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1.
Opt Express ; 32(8): 13065-13081, 2024 Apr 08.
Article in English | MEDLINE | ID: mdl-38859286

ABSTRACT

In order to improve the safety of spacecraft, the research on artificial neural network and digital twin technology based on, to our best knowledge, a novel fiber Bragg grating (FBG) sensor array is proposed for intelligent sensing monitoring of spacecraft on-orbit collisions. Femtosecond FBG arrays were fabricated on the novel oxide-doped fiber by point-by-point writing technique. The femtosecond FBG is analyzed using the time-dependent perturbation theory of quantum mechanics. The FBG array can achieve high-temperature measurement of 1100 °C and large strain measurement of 15000 µÎµ. The sensing arrays were deployed on the surface of the spacecraft. Constructed the multi-layer perceptron neural network structure and convolutional neural network structure. 1200 samples were trained. Conducted model accuracy testing. The accuracy rate is above 98%, and accuracy verification has been implemented. The digital twin model was designed based on various data such as strain and temperature of the spacecraft structure under impact monitored by FBG sensors. A precise mapping has been formed between the physical entities of spacecraft and digital twins. Empower spacecraft with functions such as self-monitoring, judgment, and response. To ensure the stable and safe operation of spacecraft.

2.
Int J Chron Obstruct Pulmon Dis ; 19: 1167-1175, 2024.
Article in English | MEDLINE | ID: mdl-38826698

ABSTRACT

Purpose: To develop a novel method for calculating small airway resistance using computational fluid dynamics (CFD) based on CT data and evaluate its value to identify COPD. Patients and Methods: 24 subjects who underwent chest CT scans and pulmonary function tests between August 2020 and December 2020 were enrolled retrospectively. Subjects were divided into three groups: normal (10), high-risk (6), and COPD (8). The airway from the trachea down to the sixth generation of bronchioles was reconstructed by a 3D slicer. The small airway resistance (RSA) and RSA as a percentage of total airway resistance (RSA%) were calculated by CFD combined with airway resistance and FEV1 measured by pulmonary function test. A correlation analysis was conducted between RSA and pulmonary function parameters, including FEV1/FVC, FEV1% predicted, MEF50% predicted, MEF75% predicted and MMEF75/25% predicted. Results: The RSA and RSA% were significantly different among the three groups (p<0.05) and related to FEV1/FVC (r = -0.70, p < 0.001; r = -0.67, p < 0.001), FEV1% predicted (r = -0.60, p = 0.002; r = -0.57, p = 0.004), MEF50% predicted (r = -0.64, p = 0.001; r = -0.64, p = 0.001), MEF75% predicted (r = -0.71, p < 0.001; r = -0.60, p = 0.002) and MMEF 75/25% predicted (r = -0.64, p = 0.001; r = -0.64, p = 0.001). Conclusion: Airway CFD is a valuable method for estimating the small airway resistance, where the derived RSA will aid in the early diagnosis of COPD.


Subject(s)
Airway Resistance , Hydrodynamics , Lung , Predictive Value of Tests , Pulmonary Disease, Chronic Obstructive , Tomography, X-Ray Computed , Humans , Pulmonary Disease, Chronic Obstructive/physiopathology , Pulmonary Disease, Chronic Obstructive/diagnostic imaging , Male , Retrospective Studies , Female , Middle Aged , Aged , Forced Expiratory Volume , Lung/physiopathology , Lung/diagnostic imaging , Vital Capacity , Computer Simulation , Radiographic Image Interpretation, Computer-Assisted , Respiratory Function Tests/methods
3.
Commun Biol ; 7(1): 703, 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38849461

ABSTRACT

Novelty and appropriateness are two fundamental components of creativity. However, the way in which novelty and appropriateness are separated at behavioral and neural levels remains poorly understood. In the present study, we aim to distinguish behavioral and neural bases of novelty and appropriateness of creative idea generation. In alignment with two established theories of creative thinking, which respectively, emphasize semantic association and executive control, behavioral results indicate that novelty relies more on associative abilities, while appropriateness relies more on executive functions. Next, employing a connectome predictive modeling (CPM) approach in resting-state fMRI data, we define two functional network-based models-dominated by interactions within the default network and by interactions within the limbic network-that respectively, predict novelty and appropriateness (i.e., cross-brain prediction). Furthermore, the generalizability and specificity of the two functional connectivity patterns are verified in additional resting-state fMRI and task fMRI. Finally, the two functional connectivity patterns, respectively mediate the relationship between semantic association/executive control and novelty/appropriateness. These findings provide global and predictive distinctions between novelty and appropriateness in creative idea generation.


Subject(s)
Creativity , Executive Function , Magnetic Resonance Imaging , Semantics , Humans , Executive Function/physiology , Male , Female , Adult , Young Adult , Connectome , Brain/physiology , Brain/diagnostic imaging
4.
Heliyon ; 10(11): e31668, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38845907

ABSTRACT

Background: Postoperative sleep disturbance (PSD) occurs frequently in patients who undergo major abdominal surgical procedures. Dexmedetomidine is a promising agent to improve the quality of sleep for surgical patients. We designed this trial to investigate the effects of two different doses of intraoperative dexmedetomidine on the occurrence of PSD in elderly patients who have major abdominal surgery. Methods: In this randomized, double-blind, controlled trial, 210 elderly patients aged ≥65 years will be randomized, with an allocation ratio of 1:1:1, to two dexmedetomidine groups (intraoperative infusion of 0.3 or 0.6 µg/kg/h) and a normal saline placebo group. The primary endpoint is the occurrence of PSD on the first night after surgery, assessed using the Athens Insomnia Scale. The secondary endpoints are (1) the incidence of PSD during the 2nd, 3rd, 5th, 7th, and 30th nights postoperatively; (2) pain at rest and on movement at 24 and 48 h postoperatively, assessed using the Numerical Rating Scale; (3) the incidence of postoperative delirium during 0-7 days postoperatively or until hospital discharge, assessed using the 3-min Confusion Assessment Method; (4) depressive symptoms during 0-7 days postoperatively or until hospital discharge, assessed using the 15-items Geriatric Depression Scale; and (5) quality of recovery on postoperative days 1, 2, and 3, assessed using the 15-items Quality of Recovery Scale. Patients' sleep data will also be collected by Xiaomi Mi Band 7 for further analysis. Discussion: The findings of this trial will provide clinical evidence for improving the quality of sleep among elderly patients undergoing major abdominal surgery. Ethics and dissemination: This trial was approved by the Ethics Committee of the First Affiliated Hospital of Soochow University (No. 2023-160). The results will be published in a peer-reviewed journal. Trial registration: Chinese Clinical Trial Registry (ChiCTR2300073163).

5.
Front Endocrinol (Lausanne) ; 15: 1327903, 2024.
Article in English | MEDLINE | ID: mdl-38846495

ABSTRACT

Objectives: To research the connection between the indexes of the indexes of triglyceride-glucose (TyG) combined with obesity indices and the initial neurological severity and short-term outcome of new-onset acute ischemic stroke. Methods: Data of patients with acute ischemic stroke admitted to the Stroke Ward of the Affiliated Hospital of Beihua University from November 2021 to October 2023, were collected. The two indexes were calculated by combining TyG and obesity indices: TyG-body mass index (TyG-BMI) and TyG-waist circumference (TyG-WC). The National Institute of Health Stroke Scale (NIHSS) was used to assess and group patients with neurological deficits within 24 hours of admission: mild stroke (NIHSS ≤5) and moderate-severe stroke (NIHSS >5). Short-term prognosis was evaluated using the modified Rankin Scale (mRS) at discharge or 14 days after onset of the disease and grouped: good outcome (mRS ≤2) and poor outcome (mRS >2). According to the quartiles of TyG-BMI and TyG-WC, the patients were placed into four groups: Q1, Q2, Q3 and Q4. Multi-factor logistic regression analysis was utilized to evaluate the correlation of TyG-BMI and TyG-WC with the severity and short-term outcome. Results: The study included 456 patients. After adjusting for multiple variables, the results showed that compared with the quartile 1, patients in quartile 4 of TyG-BMI had a reduced risk of moderate-severe stroke [Q4: OR: 0.407, 95%CI (0.185-0.894), P = 0.025]; Patients in quartiles 2, 3 and 4 of TyG-BMI had sequentially lower risk of short-term adverse outcomes [Q2: OR: 0.394, 95%CI (0.215-0.722), P = 0.003; Q3: OR: 0.324, 95%CI (0.163-0.642), P = 0.001; Q4: OR: 0.158, 95%CI (0.027-0.349), P <0.001]; Patients in quartiles 3 and 4 of TyG-WC had sequentially lower risk of moderate-severe stroke [Q3: OR: 0.355, 95%CI (0.173-0.728), P = 0.005; Q4: OR: 0.140, 95%CI (0.056-0.351), P <0.001]; Patients in quartiles 3 and 4 of TyG-WC had sequentially lower risk of short-term adverse outcomes [Q3: OR: 0.350, 95%CI (0.175-0.700), P = 0.003; Q4: OR: 0.178, 95%CI (0.071-0.451), P <0.001]. Conclusions: TyG-WC and TyG-BMI were correlated with the severity and short-term outcome of new-onset acute ischemic stroke. As TyG-WC and TyG-BMI increased, stroke severity decreased and short-term outcome was better.


Subject(s)
Blood Glucose , Body Mass Index , Ischemic Stroke , Severity of Illness Index , Triglycerides , Humans , Male , Female , Ischemic Stroke/blood , Middle Aged , Aged , Triglycerides/blood , Prognosis , Blood Glucose/analysis , Blood Glucose/metabolism , Waist Circumference , Obesity/blood , Obesity/complications
6.
J Immunol ; 2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38856632

ABSTRACT

Psoriasis is a common inflammatory skin disorder with no cure. Mesenchymal stem cells (MSCs) have immunomodulatory properties for psoriasis, but the therapeutic efficacies varied, and the molecular mechanisms were unknown. In this study, we improved the efficacy by enhancing the immunomodulatory effects of umbilical cord-derived MSCs (UC-MSCs). UC-MSCs stimulated by TNF-α and IFN-γ exhibited a better therapeutic effect in a mouse model of psoriasis. Single-cell RNA sequencing revealed that the stimulated UC-MSCs overrepresented a subpopulation expressing high tryptophanyl-tRNA synthetase 1 (WARS1). WARS1-overexpressed UC-MSCs treat psoriasis-like skin inflammation more efficiently than control UC-MSCs by restraining the proinflammatory macrophages. Mechanistically, WARS1 maintained a RhoA-Akt axis and governed the immunomodulatory properties of UC-MSCs. Together, we identify WARS1 as a master regulator of UC-MSCs with enhanced immunomodulatory capacities, which paves the way for the directed modification of UC-MSCs for escalated therapeutic efficacy.

7.
J Cardiothorac Surg ; 19(1): 307, 2024 May 31.
Article in English | MEDLINE | ID: mdl-38822379

ABSTRACT

BACKGROUND: Accurate prediction of visceral pleural invasion (VPI) in lung adenocarcinoma before operation can provide guidance and help for surgical operation and postoperative treatment. We investigate the value of intratumoral and peritumoral radiomics nomograms for preoperatively predicting the status of VPI in patients diagnosed with clinical stage IA lung adenocarcinoma. METHODS: A total of 404 patients from our hospital were randomly assigned to a training set (n = 283) and an internal validation set (n = 121) using a 7:3 ratio, while 81 patients from two other hospitals constituted the external validation set. We extracted 1218 CT-based radiomics features from the gross tumor volume (GTV) as well as the gross peritumoral tumor volume (GPTV5, 10, 15), respectively, and constructed radiomic models. Additionally, we developed a nomogram based on relevant CT features and the radscore derived from the optimal radiomics model. RESULTS: The GPTV10 radiomics model exhibited superior predictive performance compared to GTV, GPTV5, and GPTV15, with area under the curve (AUC) values of 0.855, 0.842, and 0.842 in the three respective sets. In the clinical model, the solid component size, pleural indentation, solid attachment, and vascular convergence sign were identified as independent risk factors among the CT features. The predictive performance of the nomogram, which incorporated relevant CT features and the GPTV10-radscore, outperformed both the radiomics model and clinical model alone, with AUC values of 0.894, 0.828, and 0.876 in the three respective sets. CONCLUSIONS: The nomogram, integrating radiomics features and CT morphological features, exhibits good performance in predicting VPI status in lung adenocarcinoma.


Subject(s)
Adenocarcinoma of Lung , Lung Neoplasms , Neoplasm Invasiveness , Neoplasm Staging , Nomograms , Tomography, X-Ray Computed , Humans , Male , Female , Lung Neoplasms/pathology , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/surgery , Middle Aged , Tomography, X-Ray Computed/methods , Adenocarcinoma of Lung/surgery , Adenocarcinoma of Lung/diagnostic imaging , Adenocarcinoma of Lung/pathology , Neoplasm Staging/methods , Aged , Retrospective Studies , Pleura/diagnostic imaging , Pleura/pathology , Pleural Neoplasms/diagnostic imaging , Pleural Neoplasms/surgery , Pleural Neoplasms/pathology , Radiomics
8.
Pestic Biochem Physiol ; 202: 105932, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38879298

ABSTRACT

The marine antifungal peptide epinecidin-1 (EPI) have been shown to inhibit Botrytis cinerea growth, while the molecular mechanism have not been explored based on omics technology. This study aimed to investigate the molecular mechanism of EPI against B. cinerea by transcriptome technology. Our findings indicated that a total of 1671 differentially expressed genes (DEGs) were detected in the mycelium of B. cinerea treated with 12.5 µmol/L EPI for 3 h, including 773 up-regulated genes and 898 down-regulated genes. Cluster analysis showed that DEGs (including steroid biosynthesis, (unsaturated) fatty acid biosynthesis) related to cell membrane metabolism were significantly down-regulated, and almost all DEGs involved in DNA replication were significantly inhibited. In addition, it also induced the activation of stress-related pathways, such as the antioxidant system, ATP-binding cassette transporter (ABC) and MAPK signaling pathways, and interfered with the tricarboxylic acid (TCA) cycle and oxidative phosphorylation pathways related to mitochondrial function. The decrease of mitochondrial related enzyme activities (succinate dehydrogenase, malate dehydrogenase and adenosine triphosphatase), the decrease of mitochondrial membrane potential and the increase content of hydrogen peroxide further confirmed that EPI treatment may lead to mitochondrial dysfunction and oxidative stress. Based on this, we speculated that EPI may impede the growth of B. cinerea through its influence on gene expression, and may lead to mitochondrial dysfunction and oxidative stress.


Subject(s)
Antifungal Agents , Botrytis , Mitochondria , Oxidative Stress , Botrytis/drug effects , Oxidative Stress/drug effects , Mitochondria/drug effects , Mitochondria/metabolism , Antifungal Agents/pharmacology , Gene Expression Profiling , Membrane Potential, Mitochondrial/drug effects
9.
Nat Commun ; 15(1): 4948, 2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38862486

ABSTRACT

Seasonal storage of solar thermal energy through supercooled phase change materials (PCM) offers a promising solution for decarbonizing space and water heating in winter. Despite the high energy density and adaptability, natural PCMs often lack the necessary supercooling for stable, long-term storage. Leveraging erythritol, a sustainable mid-temperature PCM with high latent heat, we introduce a straightforward method to stabilize its supercooling by incorporating carrageenan (CG), a bio-derived food thickener. By improving the solid-liquid interfacial energy with the addition of CG the latent heat of erythritol can be effectively locked at a very low temperature. We show that the composite PCM can sustain an ultrastable supercooled state below -30 °C, which guarantees no accidental loss of the latent heat in severe cold regions on Earth. We further demonstrate that the common ultrasonication method can be used as the key to unlocking the latent heat stored in the CG-thickened erythritol, showing its great potential to serve as a high-performance, eco-friendly PCM for long-term seasonal solar energy storage.

10.
Cardiovasc Diabetol ; 23(1): 161, 2024 May 07.
Article in English | MEDLINE | ID: mdl-38715070

ABSTRACT

BACKGROUND: The association between the triglyceride-glucose (TyG) index and subclinical left ventricular (LV) systolic dysfunction in obese patients remains unclear. This study aimed to investigate the relationship between the TyG index and LV global longitudinal strain (GLS) in obese patients. METHODS: A total of 1028 obese patients from January 2019 to January 2024 were included in the present study. Clinical parameters and biochemical and echocardiographic data were obtained from the participants. LV GLS was obtained from the GE EchoPAC workstation for evaluating subclinical LV function. The TyG index was calculated as Ln (fasting TG [mg/dL] × fasting glucose [mg/dL]/2). LV GLS was compared between obese patients with a high TyG index and those with a low TyG index. RESULTS: Obese patients with a high TyG index had greater incidences of hypertension, diabetes mellitus and hyperlipidaemia. The LV GLS was significantly lower in the high TyG index group than in the low TyG index group (P = 0.01). After adjusting for sex, age, body mass index, heart rate, hypertension, diabetes mellitus, dyslipidaemia, blood urea nitrogen, serum creatinine, LV mass and LV hypertrophy, the TyG index remained an independent risk indicator related to an LV GLS < 20% (OR: 1.520, 95% CI: 1.040 to 2.221; P = 0.031). CONCLUSIONS: We concluded that an increase in the TyG index is independently associated with subclinical LV systolic dysfunction in obese patients.


Subject(s)
Asymptomatic Diseases , Biomarkers , Blood Glucose , Obesity , Triglycerides , Ventricular Dysfunction, Left , Ventricular Function, Left , Humans , Male , Female , Ventricular Dysfunction, Left/physiopathology , Ventricular Dysfunction, Left/blood , Ventricular Dysfunction, Left/diagnostic imaging , Ventricular Dysfunction, Left/diagnosis , Ventricular Dysfunction, Left/epidemiology , Obesity/diagnosis , Obesity/blood , Obesity/physiopathology , Obesity/epidemiology , Obesity/complications , Middle Aged , Triglycerides/blood , Blood Glucose/metabolism , Biomarkers/blood , Adult , Risk Factors , Risk Assessment , Systole , Aged , Cross-Sectional Studies , Predictive Value of Tests , Retrospective Studies
11.
J Int Med Res ; 52(5): 3000605241241000, 2024 May.
Article in English | MEDLINE | ID: mdl-38749910

ABSTRACT

Ileostomy diverts the flow of feces, which can result in malnutrition in the distal part of the intestine. The diversity of the gut microbiota consequently decreases, ultimately leading to intestinal dysbiosis and dysfunction. This condition can readily result in diversion colitis (DC). Potential treatment strategies include interventions targeting the gut microbiota. In this case study, we effectively treated a patient with severe DC by ileostomy and allogeneic fecal microbiota transplantation (FMT). A 69-year-old man presented with a perforated malignant tumor in the descending colon and an iliac abscess. He underwent laparoscopic radical sigmoid colon tumor resection and prophylactic ileostomy. Follow-up colonoscopy 3 months postoperatively revealed diffuse intestinal mucosal congestion and edema along with granular inflammatory follicular hyperplasia, leading to a diagnosis of severe DC. After two rounds of allogeneic FMT, both the intestinal mucosal bleeding and edema significantly improved, as did the diversity of the gut microbiota. The positive outcome of allogeneic FMT in this case highlights the potential advantages that this procedure can offer patients with DC. However, few studies have focused on allogeneic FMT, and more in-depth research is needed to gain a better understanding.


Subject(s)
Colitis , Fecal Microbiota Transplantation , Gastrointestinal Microbiome , Ileostomy , Humans , Male , Aged , Fecal Microbiota Transplantation/methods , Colitis/microbiology , Colitis/therapy , Transplantation, Homologous/methods , Treatment Outcome , Colonoscopy
12.
Int J Nanomedicine ; 19: 4651-4665, 2024.
Article in English | MEDLINE | ID: mdl-38799698

ABSTRACT

Introduction: Recently, nanobubbles (NBs) have gained significant traction in the field of tumor diagnosis and treatment owing to their distinctive advantages. However, the application of NBs is limited due to their restricted size and singular reflection section, resulting in low ultrasonic reflection. Methods: We synthesized a nano-scale ultrasound contrast agent (IR783-SiO2NPs@NB) by encapsulating SiO2 nanoparticles in an IR783-labeled lipid shell using an improved film hydration method. We characterized its physicochemical properties, examined its microscopic morphology, evaluated its stability and cytotoxicity, and assessed its contrast-enhanced ultrasound imaging capability both in vitro and in vivo. Results: The results show that IR783-SiO2NPs@NB had a "donut-type" composite microstructure, exhibited uniform particle size distribution (637.2 ± 86.4 nm), demonstrated excellent stability (30 min), high biocompatibility, remarkable tumor specific binding efficiency (99.78%), and an exceptional contrast-enhanced ultrasound imaging capability. Conclusion: Our newly developed multiple scattering NBs with tumor targeting capacity have excellent contrast-enhanced imaging capability, and they show relatively long contrast enhancement duration in solid tumors, thus providing a new approach to the structural design of NBs.


Subject(s)
Contrast Media , Nanoparticles , Particle Size , Silicon Dioxide , Ultrasonography , Contrast Media/chemistry , Ultrasonography/methods , Animals , Nanoparticles/chemistry , Silicon Dioxide/chemistry , Humans , Cell Line, Tumor , Mice , Neoplasms/diagnostic imaging , Microbubbles , Mice, Nude , Mice, Inbred BALB C , Indoles
13.
Front Neurosci ; 18: 1368552, 2024.
Article in English | MEDLINE | ID: mdl-38716255

ABSTRACT

Probucol has been utilized as a cholesterol-lowering drug with antioxidative properties. However, the impact and fundamental mechanisms of probucol in obesity-related cognitive decline are unclear. In this study, male C57BL/6J mice were allocated to a normal chow diet (NCD) group or a high-fat diet (HFD) group, followed by administration of probucol to half of the mice on the HFD regimen. Subsequently, the mice were subjected to a series of behavioral assessments, alongside the measurement of metabolic and redox parameters. Notably, probucol treatment effectively alleviates cognitive and social impairments induced by HFD in mice, while exhibiting no discernible influence on mood-related behaviors. Notably, the beneficial effects of probucol arise independently of rectifying obesity or restoring systemic glucose and lipid homeostasis, as evidenced by the lack of changes in body weight, serum cholesterol levels, blood glucose, hyperinsulinemia, systemic insulin resistance, and oxidative stress. Instead, probucol could regulate the levels of nitric oxide and superoxide-generating proteins, and it could specifically alleviate HFD-induced hippocampal insulin resistance. These findings shed light on the potential role of probucol in modulating obesity-related cognitive decline and urge reevaluation of the underlying mechanisms by which probucol exerts its beneficial effects.

14.
Mycology ; 15(2): 272-281, 2024.
Article in English | MEDLINE | ID: mdl-38813477

ABSTRACT

Shiraia-like fungi, which are rare parasitic fungi found around bamboo, play an important role in traditional medicine. Their main active component, hypocrellin, is widely used in medicine, food, and cosmetics. By comparing strains with different hypocrellin yields, we identified a transcription factor (SbTF) in the hypocrellin biosynthesis pathway. SbTF from high-yielding zzz816 and low-yielding CNUCC C72 differed in its protein structure. Subsequently, SbTF from high-yielding zzz816 was overexpressed in several strains. This stabilised the yield in zzz816 and significantly increased the yield in low-yielding CNUCC C72. Comparing downstream non-essential genes between wild type and SbTF-overexpressing CNUCC C72 showed that SbMNF was significantly up-regulated. Therefore, it was selected for further study. SbMNF overexpression increased the hypocrellin yield in low-yielding CNUCC C72 and altered the composition of compounds in high-yielding CNUCC 1353PR and zzz816. This involved an increased elsinochrome C yield in CNUCC 1353PR and an increased hypocrellin B yield in zzz816 (by 2 and 70.3 times that in the corresponding wild type, respectively). This study is the first to alter hypocrellin synthesis to alter the levels of one bioactive agent compared to another. The results provide new insights regarding genetic modification and will help to optimise fungal fermentation.

15.
Eur Radiol ; 2024 May 15.
Article in English | MEDLINE | ID: mdl-38748243

ABSTRACT

OBJECTIVE: To comprehensively assess the impact of aging, cigarette smoking, and chronic obstructive pulmonary disease (COPD) on pulmonary physiology using 129Xe MR. METHODS: A total of 90 subjects were categorized into four groups, including healthy young (HY, n = 20), age-matched control (AMC, n = 20), asymptomatic smokers (AS, n = 28), and COPD patients (n = 22). 129Xe MR was utilized to obtain pulmonary physiological parameters, including ventilation defect percent (VDP), alveolar sleeve depth (h), apparent diffusion coefficient (ADC), total septal wall thickness (d), and ratio of xenon signal from red blood cells and interstitial tissue/plasma (RBC/TP). RESULTS: Significant differences were found in the measured VDP (p = 0.035), h (p = 0.003), and RBC/TP (p = 0.003) between the HY and AMC groups. Compared with the AMC group, higher VDP (p = 0.020) and d (p = 0.048) were found in the AS group; higher VDP (p < 0.001), d (p < 0.001) and ADC (p < 0.001), and lower h (p < 0.001) and RBC/TP (p < 0.001) were found in the COPD group. Moreover, significant differences were also found in the measured VDP (p < 0.001), h (p < 0.001), ADC (p < 0.001), d (p = 0.008), and RBC/TP (p = 0.032) between the AS and COPD groups. CONCLUSION: Our findings indicate that pulmonary structure and functional changes caused by aging, cigarette smoking, and COPD are various, and show a progressive deterioration with the accumulation of these risk factors, including cigarette smoking and COPD. CLINICAL RELEVANCE STATEMENT: Pathophysiological changes can be difficult to comprehensively understand due to limitations in common techniques and multifactorial etiologies. 129Xe MRI can demonstrate structural and functional changes caused by several common factors and can be used to better understand patients' underlying pathology. KEY POINTS: Standard techniques for assessing pathophysiological lung function changes, spirometry, and chest CT come with limitations. 129Xe MR demonstrated progressive deterioration with accumulation of the investigated risk factors, without these limitations. 129Xe MR can assess lung changes related to these risk factors to stage and evaluate the etiology of the disease.

16.
bioRxiv ; 2024 Apr 28.
Article in English | MEDLINE | ID: mdl-38712164

ABSTRACT

The Christchurch mutation (R136S) on the APOE3 (E3S/S) gene is associated with low tau pathology and slowdown of cognitive decline despite the causal PSEN1 mutation and high levels of amyloid beta pathology in the carrier1. However, the molecular effects enabling E3S/S mutation to confer protection remain unclear. Here, we replaced mouse Apoe with wild-type human E3 or E3S/S on a tauopathy background. The R136S mutation markedly mitigated tau load and protected against tau-induced synaptic loss, myelin loss, and spatial learning. Additionally, the R136S mutation reduced microglial interferon response to tau pathology both in vivo and in vitro, suppressing cGAS-STING activation. Treating tauopathy mice carrying wild-type E3 with cGAS inhibitor protected against tau-induced synaptic loss and induced similar transcriptomic alterations to those induced by the R136S mutation across brain cell types. Thus, cGAS-STING-IFN inhibition recapitulates the protective effects of R136S against tauopathy.

17.
Toxicol Appl Pharmacol ; 487: 116975, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38762191

ABSTRACT

Kidney renal clear cell carcinoma (KIRC) is a highly immune-infiltrated kidney cancer with the highest mortality rate and the greatest potential for invasion and metastasis. Solute carrier family 11 member1 (SLC11A1) is a phagosomal membrane protein located in monocytes and plays a role in innate immunity, autoimmune diseases, and infection, but its expression and biological role in KIRC is still unknown. In this study, we sought to investigate the potential value of SLC11A1 according to tumor growth and immune response in KIRC. TIMER and UALCAN database was used to analyze the expression feature and prognostic significance of SLC11A1 and its correlation with immune-related biomarkers in KIRC. Proliferation, migration, and invasion were measured using colony formation, EdU, and transwell assays. Role of SLC11A1 on KIRC tumor growth was examined by the xenograft tumor model in vivo. Effects of KIRC cells on macrophage polarization and the proliferation and apoptosis of CD8+ T cells were analyzed using flow cytometry assays. Herein, SLC11A1 was highly expressed in KIRC tissues and cell lines. SLC11A1 downregulation repressed KIRC cell proliferation, migration, invasion, macrophage, and lymphocyte immunity in vitro, as well as hindered tumor growth in vivo. SLC11A1 is significantly correlated with immune cell infiltration and immune-related biomarkers. In KIRC patients, SLC11A1 is highly expressed and positively correlated with the immune-related factors CCL2 and PD-L1. SLC11A1 induced CCL2 and PD-L1 expression, thereby activating the JAK/STAT3 pathway. SLC11A1 deficiency constrained KIRC cell malignant phenotypes and immune response via regulating CCL2 and PD-L1-mediated JAK/STAT3 pathway, providing a promising therapeutic target for KIRC treatment.


Subject(s)
Carcinoma, Renal Cell , Cation Transport Proteins , Cell Proliferation , Kidney Neoplasms , Tumor Microenvironment , Carcinoma, Renal Cell/pathology , Carcinoma, Renal Cell/genetics , Carcinoma, Renal Cell/immunology , Carcinoma, Renal Cell/metabolism , Humans , Kidney Neoplasms/pathology , Kidney Neoplasms/immunology , Kidney Neoplasms/genetics , Animals , Cell Line, Tumor , Cation Transport Proteins/genetics , Cation Transport Proteins/metabolism , Mice , Cell Movement , Disease Progression , Mice, Nude , CD8-Positive T-Lymphocytes/immunology , Apoptosis , Female , Chemokine CCL2/metabolism , Chemokine CCL2/genetics , Male , Signal Transduction , Neoplasm Invasiveness , Gene Expression Regulation, Neoplastic , Mice, Inbred BALB C
19.
Transl Psychiatry ; 14(1): 229, 2024 May 30.
Article in English | MEDLINE | ID: mdl-38816410

ABSTRACT

Depression is a prevalent mental disorder with a complex biological mechanism. Following the rapid development of systems biology technology, a growing number of studies have applied proteomics and metabolomics to explore the molecular profiles of depression. However, a standardized resource facilitating the identification and annotation of the available knowledge from these scattered studies associated with depression is currently lacking. This study presents ProMENDA, an upgraded resource that provides a platform for manual annotation of candidate proteins and metabolites linked to depression. Following the establishment of the protein dataset and the update of the metabolite dataset, the ProMENDA database was developed as a major extension of its initial release. A multi-faceted annotation scheme was employed to provide comprehensive knowledge of the molecules and studies. A new web interface was also developed to improve the user experience. The ProMENDA database now contains 43,366 molecular entries, comprising 20,847 protein entries and 22,519 metabolite entries, which were manually curated from 1370 human, rat, mouse, and non-human primate studies. This represents a significant increase (more than 7-fold) in molecular entries compared to the initial release. To demonstrate the usage of ProMENDA, a case study identifying consistently reported proteins and metabolites in the brains of animal models of depression was presented. Overall, ProMENDA is a comprehensive resource that offers a panoramic view of proteomic and metabolomic knowledge in depression. ProMENDA is freely available at https://menda.cqmu.edu.cn .


Subject(s)
Depression , Metabolomics , Proteomics , Animals , Humans , Rats , Mice , Depression/metabolism , Brain/metabolism , Disease Models, Animal , Databases, Factual
20.
Article in English | MEDLINE | ID: mdl-38696270

ABSTRACT

Respiratory viral infections remain a leading cause of morbidity and mortality. Using a murine model of human metapneumovirus (HMPV), we identified recruitment of a C1q-expressing inflammatory monocyte population concomitant with viral clearance by adaptive immune cells. Genetic ablation of C1q led to reduced CD8+ T cell function. Production of C1q by a myeloid lineage was necessary to enhance CD8+ T cell function. Activated and dividing CD8+ T cells expressed a C1q receptor, gC1qR. Perturbation of gC1qR signaling led to altered CD8+ T cell IFN-γ production, metabolic capacity, and cell proliferation. Autopsy specimens from fatal respiratory viral infections in children demonstrated diffuse production of C1q by an interstitial population. Humans with severe COVID-19 infection also demonstrated upregulation of gC1qR on activated and rapidly dividing CD8+ T cells. Collectively, these studies implicate C1q production from monocytes as a critical regulator of CD8+ T cell function following respiratory viral infection. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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