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PM2.5 pollution in China has decreased dramatically, but how its health effects change is not clear. There are 120 old industrial cities in China, where the sources, composition, and health effects of PM2.5 may be significantly different with other cities. Huangshi, an old industrial city in central China, underwent intense green transformations from 2015 to 2018. In this study, we collected ambient PM2.5 samples in 2015 and 2018 at an urban site in Huangshi. The average PM2.5 concentration decreased from 83.44 ± 48.04 µg/m3 in 2015 to 68.03 ± 39.41 µg/m3 in 2018. However, the average volume-normalized dithiothreitol (DTTv) of PM2.5 increased from 1.38 ± 0.45 nmol/min/m3 to 2.14 ± 1.31 nmol/min/m3 and the DTT normalized by particulate mass (DTTm) increased from 20.6 ± 10.1 pmol/min/µg to 40.07 ± 21.9 pmol/min/µg, indicating increased exposure risk and inherent toxicity. The increased toxicity of PM2.5 might be related to the increased trace elements (TEs) concentrations. The positive matrix factorization and multiple linear regression methods were employed to quantify the contributions of emission sources to PM2.5 and DTTv. The results showed that the contribution of coal combustion, industry, and dust to PM2.5 decreased significantly from 2015 to 2018, while that of vehicle emission and secondary sources increased. Despite the decreased fraction of coal combustion and industry sources, their contribution to DTTv increased slightly, which was caused by the increased intrinsic toxicity. The increased intrinsic toxicity was possibly caused by increased TEs, such as Pb, Cu, and V. Besides, the contribution of vehicle emission to DTTv also increased. Overall, these results provide valuable insights into the effectiveness of controlling strategies in reducing particulate health impacts in old industrial cities, and stress the necessity of formulating toxicity-oriented controlling strategies, with special attention to TEs from coal combustion and industry sources as well as vehicle emissions.
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MRI offers new opportunities for detailed visualization of the different layers of the esophageal wall, as well as early detection and accurate characterization of esophageal lesions. Staging of esophageal tumors including extramural extent of disease, and status of the adjacent organ can also be performed by MRI with higher accuracy compared to other imaging modalities including CT and esophageal endoscopy. Although MDCT appears to be the primary imaging modality that is indicated for preoperative staging of esophageal cancer to assess tumor resectability, MDCT is considered less accurate in T staging. This review aims to update radiologists about emerging imaging techniques and the imaging features of various esophageal masses, emphasizing the imaging features that differentiate between esophageal masses, demonstrating the critical role of MRI in esophageal masses. CRITICAL RELEVANCE STATEMENT: MRI features may help differentiate mucosal high-grade neoplasia from early invasive squamous cell cancer of the esophagus, also esophageal GISTs from leiomyomas, and esophageal malignant melanoma has typical MR features. KEY POINTS: MRI can accurately visualize different layers of the esophagus potentially has a role in T staging. MR may accurately delineate esophageal fistulae, especially small mediastinal fistulae. MRI features of various esophageal masses are helpful in the differentiation.
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Objective: To explore the clinical effect of laser acupuncture combined with Schroth therapy on adolescent idiopathic scoliosis (AIS). Method: This was a retrospective study. Eighty AIS patients were admitted to The Second People's Hospital of Dalian from March 2021 to March 2022 and divided into control group and experimental group according to the treatment method, with 40 cases in each group. The control group received Schroth therapy, and the experimental group received Schroth therapy and laser acupuncture therapy (MLS® laser). All treatments are performed five times a week for four consecutive weeks we compared the clinical effects of the two groups before treatment, six months and 12 months after treatment, and compared the improvement of Cobb angle, axial trunk rotation (ATR), musculoskeletal stiffness(The PulStarG3 system), and gait evaluation (Micro-Electro-Mechanical System(MEMS) between the two groups of patients. Result: After four weeks of treatment, the spinal condition of both groups of patients improved. After treatment, the experimental group showed greater improvement in Cobb angle, ATR, spinal range of motion, gait parameters, and clinical efficacy compared to the control group (p<0.05). Conclusion: Laser acupuncture combined with Schroth therapy is safe and effective in the treatment of AIS, and is more effective in correcting scoliosis and related problems of AIS.
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BACKGROUND: To assess the feasibility and diagnostic performance of the fractional order calculus (FROC), continuous-time random-walk (CTRW), diffusion kurtosis imaging (DKI), intravoxel incoherent motion (IVIM), mono-exponential (MEM) and stretched exponential models (SEM) for predicting response to neoadjuvant chemotherapy (NACT) in patients with esophageal squamous cell carcinoma (ESCC). MATERIALS AND METHODS: This study prospectively included consecutive ESCC patients with baseline and follow up MR imaging and pathologically confirmed cT1-4aN + M0 or T3-4aN0M0 and underwent radical resection after neoadjuvant chemotherapy (NACT) between July 2019 and January 2023. Patients were divided into pCR (TRG 0) and non-pCR (TRG1 + 2 + 3) groups according to tumor regression grading (TRG). The Pre-, Post- and Delta-treatment models were built. 18 predictive models were generated according to different feature categories, based on six models by five-fold cross-validation. Areas under the curve (AUCs) of the models were compared by using DeLong method. RESULTS: Overall, 90 patients (71 men, 19 women; mean age, 64 years ± 6 [SD]) received NACT and underwent baseline and Post-NACT esophageal MRI, with 29 patients in the pCR group and 61 patients in the non-pCR group. Among 18 predictive models, The Pre-, Post-, and Delta-CTRW model showed good predictive efficacy (AUC = 0.722, 0.833 and 0.790). Additionally, the Post-FROC model (AUC = 0.907) also exhibited good diagnostic performance. CONCLUSIONS: Our study indicates that the CTRW model, along with the Post-FROC model, holds significant promise for the future of NACT efficacy prediction in ESCC patients.
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This research evaluated a microalgae consortium (MC) in a pilot-scale tubular photobioreactor for municipal wastewater (MWW) treatment, compared with an aeration column photobioreactor. Transitioning from suspended MC to a microalgae-microbial biofilm (MMBF) maintained treatment performance despite increasing influent from 50 L to 150 L in a 260 L system. Carbon and nitrogen removal were effective, but phosphorus removal varied due to biofilm shading and the absence of phosphorus-accumulating organisms. High influent flow caused MMBF detachment due to shear stress. Stabilizing and re-establishing the MMBF showed that a stable phycosphere influenced microbial diversity and interactions, potentially destabilizing the MMBF. Heterotrophic nitrification-aerobic denitrification bacteria were crucial for MC equilibrium. Elevated gene expression related to nitrogen fixation, organic nitrogen metabolism, and nitrate reduction confirmed strong microalgal symbiosis, highlighting MMBF's treatment potential. This study supports the practical application of microalgae in wastewater treatment.
Subject(s)
Biofilms , Denitrification , Heterotrophic Processes , Microalgae , Nitrogen , Photobioreactors , Wastewater , Microalgae/metabolism , Wastewater/microbiology , Photobioreactors/microbiology , Nitrogen/metabolism , Phosphorus , Water Purification/methods , Aerobiosis , Carbon/metabolism , Carbon/pharmacology , Waste Disposal, Fluid/methodsABSTRACT
Microglia are innate immune cells in the brain and show exceptional heterogeneity. They are key players in brain physiological development regulating synaptic plasticity and shaping neuronal networks. In pathological disease states, microglia-induced synaptic pruning mediates synaptic loss and targeting microglia was proposed as a promising therapeutic strategy. However, the effect of microglia depletion and subsequent repopulation on dendritic spine density and neuronal function in the adult brain is largely unknown. In this study, we investigated whether pharmacological microglia depletion affects dendritic spine density after long-term permanent microglia depletion and after short-term microglia depletion with subsequent repopulation. Long-term microglia depletion using colony-stimulating-factor-1 receptor (CSF1-R) inhibitor PLX5622 resulted in increased overall spine density, especially of mushroom spines, and increased excitatory postsynaptic current amplitudes. Short-term PLX5622 treatment with subsequent repopulation of microglia had an opposite effect resulting in activated microglia with increased synaptic phagocytosis and consequently decreased spine density and reduced excitatory neurotransmission, while Barnes maze and elevated plus maze testing was unaffected. Moreover, RNA sequencing data of isolated repopulated microglia showed an activated and proinflammatory phenotype. Long-term microglia depletion might be a promising therapeutic strategy in neurological diseases with pathological microglial activation, synaptic pruning, and synapse loss. However, repopulation after depletion induces activated microglia and results in a decrease of dendritic spines possibly limiting the therapeutic application of microglia depletion. Instead, persistent modulation of pathological microglia activity might be beneficial in controlling synaptic damage.
Subject(s)
Brain , Dendritic Spines , Mice, Inbred C57BL , Microglia , Animals , Microglia/drug effects , Microglia/metabolism , Dendritic Spines/drug effects , Male , Mice , Excitatory Postsynaptic Potentials/drug effects , Excitatory Postsynaptic Potentials/physiology , Phagocytosis/physiology , Phagocytosis/drug effects , Neuronal Plasticity/physiology , Neuronal Plasticity/drug effects , Mice, Transgenic , Receptors, Granulocyte-Macrophage Colony-Stimulating Factor/antagonists & inhibitors , Receptors, Granulocyte-Macrophage Colony-Stimulating Factor/metabolism , Organic ChemicalsABSTRACT
MCPH1 has been identified as the causal gene for primary microcephaly type 1, a neurodevelopmental disorder characterized by reduced brain size and delayed growth. As a multifunction protein, MCPH1 has been reported to repress the expression of TERT and interact with transcriptional regulator E2F1. However, it remains unclear whether MCPH1 regulates brain development through its transcriptional regulation function. This study showed that the knockout of Mcph1 in mice leads to delayed growth as early as the embryo stage E11.5. Transcriptome analysis (RNA-seq) revealed that the deletion of Mcph1 resulted in changes in the expression levels of a limited number of genes. Although the expression of some of E2F1 targets, such as Satb2 and Cdkn1c, was affected, the differentially expressed genes (DEGs) were not significantly enriched as E2F1 target genes. Further investigations showed that primary and immortalized Mcph1 knockout mouse embryonic fibroblasts (MEFs) exhibited cell cycle arrest and cellular senescence phenotype. Interestingly, the upregulation of p19ARF was detected in Mcph1 knockout MEFs, and silencing p19Arf restored the cell cycle and growth arrest to wild-type levels. Our findings suggested it is unlikely that MCPH1 regulates neurodevelopment through E2F1-mediated transcriptional regulation, and p19ARF-dependent cell cycle arrest and cellular senescence may contribute to the developmental abnormalities observed in primary microcephaly.
Subject(s)
Cell Cycle Checkpoints , Cellular Senescence , Cyclin-Dependent Kinase Inhibitor p16 , Microcephaly , Animals , Mice , Cell Cycle Checkpoints/genetics , Cell Cycle Proteins/genetics , Cell Cycle Proteins/metabolism , Cellular Senescence/genetics , Cyclin-Dependent Kinase Inhibitor p16/genetics , Cyclin-Dependent Kinase Inhibitor p16/metabolism , Cyclin-Dependent Kinase Inhibitor p16/deficiency , E2F1 Transcription Factor/genetics , E2F1 Transcription Factor/metabolism , Fibroblasts/metabolism , Mice, Knockout , Microcephaly/genetics , Microcephaly/metabolism , Microcephaly/pathologyABSTRACT
OBJECTIVE: This study aimed to investigate the impact of Dickkopf 2 (DKK2) on the progression of oral squamous cell carcinoma (OSCC) and explore its role in the PI3K/AKT signaling transduction pathway. MATERIALS AND METHODS: The study initially examined the expression of the DKK2 gene in OSCC tissues and normal tissues. Simultaneously, the expression of DKK2 in HOK cells and OSCC cells was verified, and changes in DKK2 expression under hypoxic conditions were detected. DKK2 overexpression and knockdown were performed in SCC-15 and CAL-27 cells. Subsequently, the effects of DKK2 on the proliferation, migration and invasion of OSCC were detected. Western blotting was employed to detect the expression of key proteins in the DKK2/PI3K/AKT signaling axis before and after transfection, and further explore the relevant molecular mechanisms. RESULTS: Compared to normal tissues, DKK2 expression was elevated in OSCC tissues. The expression of DKK2 in the SCC-15 and CAL-27 cell lines was higher than that in HOK cells, and hypoxic conditions could promote DKK2 expression. DKK2 overexpression promoted cell proliferation, migration, and invasion, while DKK2 knockdown inhibited these processes. DKK2 overexpression activated the PI3K/AKT pathway, while DKK2 knockdown suppressed this pathway. CONCLUSION: This study suggests that hypoxic conditions enhance the expression of DKK2 in OSCC. DKK2 regulates the proliferation, migration, and invasion of OSCC through the PI3K/AKT signaling pathway.
Subject(s)
Carcinoma, Squamous Cell , Cell Movement , Cell Proliferation , Intercellular Signaling Peptides and Proteins , Mouth Neoplasms , Phosphatidylinositol 3-Kinases , Proto-Oncogene Proteins c-akt , Signal Transduction , Humans , Intercellular Signaling Peptides and Proteins/metabolism , Intercellular Signaling Peptides and Proteins/genetics , Mouth Neoplasms/pathology , Mouth Neoplasms/metabolism , Mouth Neoplasms/genetics , Proto-Oncogene Proteins c-akt/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Cell Line, Tumor , Cell Proliferation/genetics , Cell Movement/genetics , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/metabolism , Carcinoma, Squamous Cell/genetics , Disease Progression , Gene Expression Regulation, Neoplastic , Neoplasm InvasivenessABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Ginkgo biloba is a traditional Chinese medicine extracted from the Ginkgophyta and is commonly used in the treatment of cardiovascular diseases in China. Clinical trials have demonstrated the clinical benefits of Ginkgo biloba extract (GBE) preparations for patients with unstable angina pectoris (UAP). AIM OF THE STUDY: The efficacy of different GBE preparations in treating UAP may vary, leading to a lack of guidance for physicians when choosing GBE preparations. How to make choices among different GBE preparations is a topic worthy of investigation. In order to clarify the efficacy differences among different GBE preparations, provide a reference for their optimal use conditions, this study was conducted. MATERIALS AND METHODS: This study included literature from eight databases from inception to November 2023. It included UAP patients, with the control group receiving conventional treatment and the treatment group receiving different GBE preparations in addition to conventional treatment. Angina efficacy, electrocardiogram (ECG) improvement, and frequency of angina were chosen as outcomes. This study employed a systematic review and Bayesian network meta-analysis, and the surface under the cumulative ranking (SUCRA) curve was used for estimating the efficacy ranking. RESULTS: A total of 98 studies involving 9513 patients and 9 interventions were included. Compared with conventional treatment, GBE preparations combined with conventional treatment had better efficacy in angina symptoms and ECG improvement. According to the SUCRA ranking, Shuxuening injection was most effective in improving angina symptoms and reducing the frequency of angina. Among oral GBE preparations, Ginkgo tablets had the best performance in improving angina symptoms and ECG manifestations, and reducing the frequency of angina. There was no significant difference in the incidence of adverse events between the treatment group and the control group, and all adverse events were mild and self-limiting. Compared with oral preparations, the incidence of adverse events for injections was higher. CONCLUSIONS: GBE preparations may alleviate angina symptoms and myocardial ischemia in the treatment of UAP with favorable safety. Shuxuening injection may be the most effective among all GBE preparations in improving angina symptoms, while Ginkgo tablets may perform best among oral formulations. The optimal use of GBE injection may be for rapidly alleviating angina symptoms and myocardial ischemia in patients with UAP, and oral formulation of GBE may be more suitable for the long-term treatment of patients with milder symptoms. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022361487, ID: CRD42022361487.
Subject(s)
Angina, Unstable , Ginkgo biloba , Plant Extracts , Humans , Plant Extracts/therapeutic use , Plant Extracts/adverse effects , Plant Extracts/administration & dosage , Angina, Unstable/drug therapy , Network Meta-Analysis , Treatment Outcome , Ginkgo ExtractABSTRACT
The thermophysical properties and elemental abundances of the noble gases in terrestrial materials can provide unique insights into the Earth's evolution and mantle dynamics. Here, we perform extensive ab initio molecular dynamics simulations to determine the melting temperature and sound velocity of neon up to 370 GPa and 7500 K to constrain its physical state and storage capacity, together with to reveal its implications for the deep interior of the Earth. It is found that solid neon can exist stably under the lower mantle and inner core conditions, and the abnormal melting of neon is not observed under the entire temperature (T) and pressure (P) region inside the Earth owing to its peculiar electronic structure, which is substantially distinct from other heavier noble gases. An inspection of the reduction for sound velocity along the Earth's geotherm evidences that neon can be used as a light element to account for the low-velocity anomaly and density deficit in the deep Earth. A comparison of the pair distribution functions and mean square displacements of MgSiO3-Ne and Fe-Ne alloys further reveals that MgSiO3 has a larger neon storage capacity than the liquid iron under the deep Earth condition, indicating that the lower mantle may be a natural deep noble gas storage reservoir. Our results provide valuable information for studying the fundamental behavior and phase transition of neon in a higher T-P regime, and further enhance our understanding for the interior structure and evolution processes inside the Earth.
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Autophagy during myocardial ischemia/reperfusion (MI/R) exacerbates cardiomyocyte injury. Melatonin (Mel) alleviates myocardial damage by regulating mitochondrial function and mitophagy, but the role of mitophagy in melatonin-induced cardioprotection remains unclear. This study aimed to explore the roles of sirtuin3 (SIRT3) and retinoid-related orphan nuclear receptor-α (RORα) in mitophagy during simulated ischemia reperfusion (SIR) in H9c2 cells. Our data showed that mitophagy was excessively activated after SIR injury, which was consistent with reduced cell survival, enhanced oxidative responses and mitochondrial dysfunction in H9c2 myocytes. Melatonin greatly enhanced cell viability, reduced oxidative stress and improved mitochondrial function. The effects of melatonin protection were involved in excessive mitophagy inhibition, as demonstrated by the reduced levels of mitophagy-linked proteins, including Parkin, Beclin1, NIX and BNIP3, and the LC3 II/LC3 I ratio and elevations in p62. Additionally, the decreases in SIRT3 and RORα in H9c2 myocytes after SIR were reversed by melatonin, and the above effects of melatonin were eliminated by small interfering RNA (siRNA)-mediated knockdown of SIRT3 and RORα. In brief, SIRT3 and RORα are two prospective targets in the cardioprotection of melatonin against mitophagy during SIR in H9c2 myocytes.
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Predicting the trajectories of pedestrians is an important and difficult task for many applications, such as robot navigation and autonomous driving. Most of the existing methods believe that an accurate prediction of the pedestrian intention can improve the prediction quality. These works tend to predict a fixed destination coordinate as the agent intention and predict the future trajectory accordingly. However, in the process of moving, the intention of a pedestrian could be a definite location or a general direction and area, and may change dynamically with the changes of surrounding. Thus, regarding the agent intention as a fixed 2-d coordinate is insufficient to improve the future trajectory prediction. To address this problem, we propose Dynamic Target Driven Network for pedestrian trajectory prediction (DTDNet), which employs a multi-precision pedestrian intention analysis module to capture this dynamic. To ensure that this extracted feature contains comprehensive intention information, we design three sub-tasks: predicting coarse-precision endpoint coordinate, predicting fine-precision endpoint coordinate and scoring scene sub-regions. In addition, we propose a original multi-precision trajectory data extraction method to achieve multi-resolution representation of future intention and make it easier to extract local scene information. We compare our model with previous methods on two publicly available datasets (ETH-UCY and Stanford Drone Dataset). The experimental results show that our DTDNet achieves better trajectory prediction performance, and conducts better pedestrian intention feature representation.
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The S-phase checkpoint involving CHK1 is essential for fork stability in response to fork stalling. PARP1 acts as a sensor of replication stress and is required for CHK1 activation. However, it is unclear how the activity of PARP1 is regulated. Here, we found that UFMylation is required for the efficient activation of CHK1 by UFMylating PARP1 at K548 during replication stress. Inactivation of UFL1, the E3 enzyme essential for UFMylation, delayed CHK1 activation and inhibits nascent DNA degradation during replication blockage as seen in PARP1-deficient cells. An in vitro study indicated that PARP1 is UFMylated at K548, which enhances its catalytic activity. Correspondingly, a PARP1 UFMylation-deficient mutant (K548R) and pathogenic mutant (F553L) compromised CHK1 activation, the restart of stalled replication forks following replication blockage, and chromosome stability. Defective PARP1 UFMylation also resulted in excessive nascent DNA degradation at stalled replication forks. Finally, we observed that PARP1 UFMylation-deficient knock-in mice exhibited increased sensitivity to replication stress caused by anticancer treatments. Thus, we demonstrate that PARP1 UFMylation promotes CHK1 activation and replication fork stability during replication stress, thus safeguarding genome integrity.
Subject(s)
Checkpoint Kinase 1 , DNA Replication , Poly (ADP-Ribose) Polymerase-1 , Animals , Poly (ADP-Ribose) Polymerase-1/metabolism , Poly (ADP-Ribose) Polymerase-1/genetics , Checkpoint Kinase 1/metabolism , Checkpoint Kinase 1/genetics , Mice , Humans , DNA Damage , Ubiquitin-Protein Ligases/metabolism , Ubiquitin-Protein Ligases/geneticsABSTRACT
OBJECTIVE: This systematic review aims to evaluate the effectiveness of universal school-based transdiagnostic interventions in promoting the mental health of children and adolescents. It compares and discusses interventions targeting the prevention of mental disorders versus the promotion of mental health. Additionally, the roles of teachers and psychologists as intervention conductors are examined. METHODS: A comprehensive search of the Psycinfo, Pubmed, and Web of Science databases was conducted without any time restrictions to identify relevant literature on universal school-based transdiagnostic interventions promoting children and adolescents' mental health. RESULTS AND DISCUSSION: The findings reveal that universal school-based transdiagnostic promotion/prevention programs have a small to medium overall effect size. These interventions demonstrate a broad coverage of different aspects of children and adolescents' mental health. However, the relative effectiveness of teacher-led versus psychologist-led interventions remains unclear. Interventions focused on preventing mental disorders exhibit a higher effect size, albeit on a narrower range of mental health aspects for children and adolescents. SIGNIFICANCE: This study enhances our understanding of universal school-based transdiagnostic interventions and their impact on children and adolescents' mental health. Further research is needed to elucidate the comparative efficacy of teacher-led and psychologist-led interventions and to explore the specific dimensions of mental health targeted by these interventions.
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BACKGROUND: To evaluate the postoperative morbidity and mortality of patients undergoing cardiovascular surgery during the 2022 nationwide Omicron variant infection wave in China. METHODS: This retrospective cohort study included 403 patients who underwent cardiovascular surgery for the first time during the 2022 wave of the pandemic within 1 month. Among them, 328 patients were preoperatively diagnosed with COVID-19 Omicron variant infection during the pandemic, and 75 patients were negative. The association between Omicron variant exposure and postoperative prognosis was explored by comparing patients with and without COVID-19 exposure. The primary outcome was in-hospital death after cardiovascular surgery. The secondary outcomes were major postoperative morbidity, including myocardial infarction (MI), acute kidney injury (AKI), postoperative mechanical ventilation hours, ICU stay hours, and postoperative length of stay. The data were analyzed using inverse probability of treatment weighting (IPTW) to minimize bias. RESULTS: We identified 403 patients who underwent cardiovascular surgery, 328 (81.39%) had Omicron variant infections. In total, 10 patients died in the hospital. Omicron variant infection was associated with a much greater risk of death during cardiovascular surgery after adjustment for IPTW (2.8% vs. 1.3%, adjusted OR 2.185, 95%CI = 1.193 to 10.251, P = 0.041). For major postoperative morbidity, there were no significant differences in terms of myocardial infarction between the two groups (adjusted OR = 0.861, 95%CI = 0.444 to 1.657, P = 0.653), acute kidney injury (adjusted OR = 1.157, 95%CI = 0.287 to 5.155, P = 0.820), postoperative mechanical ventilation hours (B -0.375, 95%CI=-8.438 to 7.808, P = 0.939), ICU stay hours (B 2.452, 95%CI=-13.269 to 8.419, P = 0.660) or postoperative stay (B -1.118, 95%CI=-2.237 to 1.154, P = 0.259) between the two groups. CONCLUSION: Perioperative COVID-19 infection was associated with an increased risk of in-hospital death among patients who underwent cardiovascular surgery during the Omicron variant wave of the pandemic.
Subject(s)
Acute Kidney Injury , COVID-19 , Myocardial Infarction , Humans , Pandemics , Retrospective Studies , Hospital Mortality , COVID-19/epidemiology , Postoperative Complications/epidemiology , SARS-CoV-2 , Morbidity , Myocardial Infarction/epidemiology , Acute Kidney Injury/epidemiology , Acute Kidney Injury/etiologyABSTRACT
In mammalian brain development, WNT signaling balances proliferation and differentiation of neural progenitor cells, and is essential for the maintenance of regular brain development. JADE1 is a candidate transcription co-factor essential for DNA replication, cell division, and cell cycle regulation. In 293T cells, JADE1 is stabilized by von Hippel-Lindau protein pVHL, promotes the ß-catenin ubiquitination and thus blunts canonical WNT signaling. Furthermore, JADE1 inhibits ß-catenin-induced ectopic axis formation in Xenopus embryos. However, JADE1's role in mammalian brain development remains unknown. Here, we generated a new Jade1 knockout mouse line using CRISPR-Cas9 technology. We found that JADE1 null resulted in decreased survival rate, reduced body weight and brain weight in mice. However, histological analysis revealed a normal brain development. Furthermore, Jade1 null neural progenitor cells proliferated normally in vivo and in vitro. RNA-seq analysis further showed that JADE1 loss did not affect the cerebral cortex gene expression. Our findings indicate that JADE1 is dispensable for developing the cerebral cortex in mice.
Subject(s)
Brain , Homeodomain Proteins , Animals , Mice , beta Catenin/metabolism , Brain/growth & development , Brain/metabolism , Cell Differentiation , Cell Proliferation , Homeodomain Proteins/metabolism , Mammals/metabolism , Mice, Knockout , Wnt Signaling Pathway/physiologyABSTRACT
OBJECTIVES: To investigate the MRI radiomics signatures in predicting pathologic response among patients with locally advanced esophageal squamous cell carcinoma (ESCC), who received neoadjuvant chemotherapy (NACT). METHODS: Patients who underwent NACT from March 2015 to October 2019 were prospectively included. Each patient underwent esophageal MR scanning within one week before NACT and within 2-3 weeks after completion of NACT, prior to surgery. Radiomics features extracted from T2-TSE-BLADE were randomly split into the training and validation sets at a ratio of 7:3. According to the progressive tumor regression grade (TRG), patients were stratified into two groups: good responders (GR, TRG 0 + 1) and poor responders (non-GR, TRG 2 + 3). We constructed the Pre/Post-NACT model (Pre/Post-model) and the Delta-NACT model (Delta-model). Kruskal-Wallis was used to select features, logistic regression was used to develop the final model. RESULTS: A total of 108 ESCC patients were included, and 3/2/4 out of 107 radiomics features were selected for constructing the Pre/Post/Delta-model, respectively. The selected radiomics features were statistically different between GR and non-GR groups. The highest area under the curve (AUC) was for the Delta-model, which reached 0.851 in the training set and 0.831 in the validation set. Among the three models, Pre-model showed the poorest performance in the training and validation sets (AUC, 0.466 and 0.596), and the Post-model showed better performance than the Pre-model in the training and validation sets (AUC, 0.753 and 0.781). CONCLUSIONS: MRI-based radiomics models can predict the pathological response after NACT in ESCC patients, with the Delta-model exhibiting optimal predictive efficacy. CLINICAL RELEVANCE STATEMENT: MRI radiomics features could be used as a useful tool for predicting the efficacy of neoadjuvant chemotherapy in esophageal carcinoma patients, especially in selecting responders among those patients who may be candidates to benefit from neoadjuvant chemotherapy. KEY POINTS: ⢠The MRI radiomics features based on T2WI-TSE-BLADE could potentially predict the pathologic response to NACT among ESCC patients. ⢠The Delta-model exhibited the best predictive ability for pathologic response, followed by the Post-model, which similarly had better predictive ability, while the Pre-model performed less well in predicting TRG.
Subject(s)
Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Humans , Esophageal Squamous Cell Carcinoma/diagnostic imaging , Esophageal Squamous Cell Carcinoma/drug therapy , Esophageal Neoplasms/diagnostic imaging , Esophageal Neoplasms/drug therapy , Neoadjuvant Therapy , Radiomics , Magnetic Resonance Imaging , Retrospective StudiesABSTRACT
Excessive or uncontrolled mitophagy may result in a drastic shortage of healthy mitochondrial for ATP supply after reperfusion, leading to irreversible myocardial damage. Melatonin, a hormone produced by the pineal gland, has been proven to ameliorate myocardial ischemia-reperfusion (I/R) injury via regulating mitophagy. However, its underlying mechanism has not been fully elucidated. The present study focused on the role of mitophagy in the cardioprotective effects of melatonin by using the myocardial I/R rat model. The rats were pretreated with or without the apelin inhibitor ML221, the sirtuin 3 (SIRT3) inhibitor 3-TYP and then subjected to I/R injury, with melatonin administrated 10 min before reperfusion. The effects of melatonin on myocardial infarct size, biomarkers of myocardial injury, oxidative stress, and mitochondrial function were detected, and the expression of apelin, SIRT3, and mitophagy-related proteins were also measured. Excessive mitophagy was activated after I/R injury and was correlated with oxidative stress and mitochondrial dysfunction. Melatonin pretreatment ameliorated myocardial injury by decreasing oxidative stress, restoring mitochondrial function, and inhibiting excessive mitophagy. However, ML221 or 3-TYP disrupted these beneficial effects of melatonin on I/R injury. Taken together, these results suggest that melatonin pretreatment ameliorates myocardial I/R injury through regulating the apelin/SIRT3 pathway to inhibit excessive mitophagy.
Subject(s)
Melatonin , Myocardial Reperfusion Injury , Reperfusion Injury , Sirtuin 3 , Rats , Animals , Myocardial Reperfusion Injury/drug therapy , Myocardial Reperfusion Injury/prevention & control , Myocardial Reperfusion Injury/metabolism , Sirtuin 3/metabolism , Melatonin/pharmacology , Melatonin/therapeutic use , Melatonin/metabolism , Mitophagy , ApelinABSTRACT
Wash water from fresh vegetables and root vegetables is an important vehicle for foodborne virus transmission. However, there is lack of assessing rapid viral inactivation strategies in wash water characterized by a high soil content at the post-harvest stage. Considering the significance of food safety during the washing stage for fresh and root vegetable produce prior to marketing, we assessed the inactivation efficacy by using chlorine dioxide (ClO2) and peracetic acid (PAA) against a surrogate of human norovirus (murine norovirus 1, MNV-1) and hepatitis A virus (HAV), in wash water containing black soil and clay loam. The results indicated that MNV-1 and HAV were reduced to the process limit of detection (PLOD), with reductions ranging from 4.89 to 6.35 log10 PFU, and 4.63 to 4.96 log10 PFU when treated with ClO2 at 2.5 ppm for 10 mins. Comparatively, when treated with 500 ppm of PAA for 10 mins, MNV-1 and HAV were maximum reduced to 1.75 ± 0.23 log10 PFU (4.50 log10 PFU reduction) and 2.13 ± 0.12 log10 PFU (2.72 log10 PFU reduction). This demonstrated the efficacy of ClO2 in eliminating foodborne viruses in soil-rich wash water. When we validated the recovery of the virus from two types of wash water, the pH (9.24 ± 0.33 and 5.95 ± 0.05) had no impact on the recovery of MNV-1, while the recovery of HAV was less than 1 %. By adjusting the pH to a neutral level, recovery of HAV and its RNA levels was increased to 15.94 and 3.89 %. Thus, this study emphasized the critical role of pH in the recovery of HAV from the complex soil-rich aqueous environment, and the efficacy of ClO2 serving as a pivotal reference for the development of control strategies against foodborne viruses in the supply chain of fresh and root vegetables.
Subject(s)
Disinfection , Hepatitis A virus , Animals , Mice , Humans , Disinfection/methods , Peracetic Acid/pharmacology , Soil , Water , VegetablesABSTRACT
Essential oils (EOs) have been used for centuries as flavor enhancers in foods, and owing to their antimicrobial properties, they have potential as natural food preservatives. However, their effect on food-borne viruses is unknown. Therefore, in this study, the virucidal effects of three EOs (cinnamon, clove, and thyme) on the infectivity of the hepatitis A virus (HAV) were investigated. Different concentrations of each EO (0.05, 0.1, 0.5, and 1%) were mixed with viral suspensions in accordance with ASTM E1052-11:2011 and incubated for 1 h at room temperature. The EOs exhibited a concentration-dependent effect in the suspension tests, and HAV titers decreased by approximately 1.60 log PFU/mL when treated with EOs at the highest concentration of 1%. The antiviral effect of EOs treated at 1% for 1 h was also evidenced in surface disinfection tests according to the OECD:2013, as approximately 2 log PFU/mL reduction on hard food-contact surfaces (stainless steel and polypropylene) and approximately 2 and 1.4 log PFU/mL reduction on low-density polyethylene and kraft (soft food-contact surfaces), respectively. Moreover, RT-qPCR results revealed that HAV genome copies were negligibly reduced until treated with a high concentration (1%) in suspension and carrier tests. Overall, our findings highlighted the potential of cinnamon, clove, and thyme EOs as natural disinfectants capable of limiting HAV (cross-) contamination conveyed by food-contact surfaces. These findings advance our knowledge of EOs as antimicrobials and their potential in the food sector as alternative natural components to reduce viral contamination and improve food safety.