Immune isolation-enabled nanoencapsulation of donor T cells: a promising strategy for mitigating GVHD and treating AML in preclinical models.

BACKGROUND: In allogeneic-hematopoietic stem cell transplantation for acute myeloid leukemia (AML), donor T cells combat leukemia through the graft-versus-leukemia (GVL) effect, while they also pose a risk of triggering life-threatening graft-versus-host disease (GVHD) by interacting with recipient cells. The onset of GVHD hinges on the interplay between donor T cells and recipient antigen-presenting cells (APCs), sparking T-cell activation. However, effective methods to balance GVHD and GVL are lacking. METHODS: In our study, we crafted nanocapsules by layering polycationic aminated gelatin and polyanionic alginate onto the surface of T cells, examining potential alterations in their fundamental physiological functions. Subsequently, we established an AML mouse model and treated it with transplantation of bone marrow cells (BMCs) combined with encapsulated T cells to investigate the GVL and anti-GVHD effects of encapsulated T cells. In vitro co-culture was employed to probe the effects of encapsulation on immune synapses, co-stimulatory molecules, and tumor-killing pathways. RESULTS: Transplantation of BMCs combined with donor T cells selectively encapsulated onto AML mice significantly alleviates GVHD symptoms while preserving essential GVL effects. Encapsulated T cells exerted their immunomodulatory effects by impeding the formation of immune synapses with recipient APCs, thereby downregulating co-stimulatory signals such as CD28-CD80, ICOS-ICOSL, and CD40L-CD40. Recipient mice receiving encapsulated T-cell transplantation exhibited a marked increase in donor Ly-5.1-BMC cell numbers, accompanied by unaltered in vivo expression levels of perforin and granzyme B. While transient inhibition of donor T-cell cytotoxicity in the tumor microenvironment was observed in vitro following single-cell nanoencapsulation, subsequent restoration to normal antitumor activity ensued, attributed to selective permeability of encapsulated vesicle shells and material degradation. Moreover, the expression of apoptotic proteins and FAS-FAS ligand pathway at normal levels was still observed in leukemia tumor cells. CONCLUSIONS: Encapsulated donor T cells effectively mitigate GVHD while preserving the GVL effect by minimizing co-stimulatory signaling with APCs through early immune isolation. Subsequent degradation of nanocapsules restores T-cell cytotoxic efficacy against AML cells, mediated by cytotoxic pathways. Using transplant-encapsulated T cells offers a promising strategy to suppress GVHD while preserving the GVL effect.

Enhancing enzymatic catalysis efficiency: Immobilizing laccase on HHSS for synergistic bisphenol A adsorption and biodegradation through optimized external surface utilization.

Laccase, a prominent enzyme biomacromolecule, exhibits promising catalytic efficiency in degrading phenolic compounds like bisphenol A (BPA). The laccase immobilized on conventional materials frequently demonstrates restricted loading and suboptimal catalytic performance. Hence, there is a pressing need to optimized external surface utilization to enhance catalytic performance. Herein, we synthesized amino-functionalized modified silica particles with a hierarchical hollow silica spherical (HHSS) structure for laccase immobilization via crosslinking, resulting in HHSS-LE biocatalysts. Through Box-Behnken design (BBD) and response surface methodology (RSM), we achieved a remarkably high enzyme loading of up to 213.102 mg/g. The synergistic effect of adsorption by HHSS and degradation by laccase facilitated efficient removal of BPA. The HHSS-LE demonstrated superior BPA removal capabilities, with efficiencies exceeding 100 % in the 50-200 mg/L BPA concentration range. Compared to MCM-41 and solid silica spheres (SSS), HHSS showed the highest enzyme loading capacity and catalytic activity, underscoring its superior external surface utilization rate per unit mass. Remarkably, the HHSS-LE biocatalyst exhibited remarkable recyclability even after 11 successive cycles of reuse. By preparing high immobilization rate with efficient external surface utilization, this study lays the foundation for the design of universally applicable and efficient enzyme immobilization catalysts.

Natural Attenuation of Groundwater Uranium in Post-Neutral-Mining Sites Evidenced from Multiple Isotopes and Dissolved Organic Matter.

Although natural attenuation is an economic remediation strategy for uranium (U) contamination, the role of organic molecules in driving U natural attenuation in postmining aquifers is not well-understood. Groundwaters were sampled to investigate the chemical, isotopic, and dissolved organic matter (DOM) compositions and their relationships to U natural attenuation from production wells and postmining wells in a typical U deposit (the Qianjiadian U deposit) mined by neutral in situ leaching. Results showed that Fe(II) concentrations and δ34SSO4 and δ18OSO4 values increased, but U concentrations decreased significantly from production wells to postmining wells, indicating that Fe(III) reduction and sulfate reduction were the predominant processes contributing to U natural attenuation. Microbial humic-like and protein-like components mediated the reduction of Fe(III) and sulfate, respectively. Organic molecules with H/C > 1.5 were conducive to microbe-mediated reduction of Fe(III) and sulfate and facilitated the natural attenuation of dissolved U. The average U attenuation rate was -1.07 mg/L/yr, with which the U-contaminated groundwater would be naturally attenuated in approximately 11.2 years. The study highlights the specific organic molecules regulating the natural attenuation of groundwater U via the reduction of Fe(III) and sulfate.

Percutaneous endocardial septal radiofrequency ablation on syncope in patients with hypertrophic obstructive cardiomyopathy: a short-term safety and efficacy study.

Background: Syncope is a serious consequence in patients with hypertrophic obstructive cardiomyopathy (HOCM). Percutaneous endocardial septal radiofrequency ablation (PESA) has emerged as a promising intervention to alleviate symptoms and enhance the quality of life for HOCM patients. However, little is known about the effects of PESA on syncope in HOCM. The authors aimed to study the effects of PESA on syncope in patients with HOCM. Materials and methods: Nineteen patients with HOCM and syncope were enrolled. The left ventricular outflow tract gradient (LVOTG) of the patients was more than 50 mmHg despite medication. The participants underwent PESA under the guidance of intracardiac echocardiography (ICE) combined with a three-dimensional electrophysiological mapping system. The patients were followed for 3 (3-5.5) months. Results: The mean age of the patients was 54.8±13.7 years. Out of the 19 participants, 7 (37%) were females. During the follow-up, the syncope was completely alleviated in 14 patients (73.7%) or the syncope episodes were reduced greater than or equal to 80% in 16 patients (84.2%). The mean NYHA functional class significantly improved from 2.2±0.7 at baseline to 1.7±0.6 during follow-up (P=0.002). The LVOTG and septal thickness showed a decreasing trend from baseline to follow-up (LVOTG: P=0.083, septal thickness: P=0.086). Conclusion: The authors' investigation provides evidence supporting the effectiveness of PESA in reducing syncope episodes in patients with HOCM.

Sodium chloride promotes macrophage pyroptosis and aggravates rheumatoid arthritis by activating SGK1 through GABA receptors Slc6a12.

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by synovial inflammation and the production of autoantibodies. Previous studies have indicated an association between high-salt diets (HSD) and an increased risk of RA, yet the underlying mechanisms remain unclear. Macrophage pyroptosis, a pro-inflammatory form of cell death, plays a pivotal role in RA. In this study, we demonstrate that HSD exacerbates the severity of arthritis in collagen-induced arthritis (CIA) mice, correlating with macrophage infiltration and inflammatory lesions. Given the significant alterations observed in macrophages from CIA mice subjected to HSD, we specifically investigate the impact of HSD on macrophage responses in the inflammatory milieu of RA. In our in vitro experiments, pretreatment with NaCl enhances LPS-induced pyroptosis in RAW.264.7 and THP-1 cells through the p38 MAPK/NF-κB signaling pathway. Subsequent experiments reveal that Slc6a12 inhibitors and SGK1 silencing inhibit sodium-induced activation of macrophage pyroptosis and the p38 MAPK/NF-κB signaling pathway, whereas overexpression of the SGK1 gene counteracts the effect of sodium on macrophages. In conclusion, our findings verified that high salt intake promotes the progression of RA and provided a detailed elucidation of the activation of macrophage pyroptosis induced by sodium transportation through the Slc6a12 channel.

Artificial intelligence assistance for fetal development: evaluation of an automated software for biometry measurements in the mid-trimester.

BACKGROUND: This study presents CUPID, an advanced automated measurement software based on Artificial Intelligence (AI), designed to evaluate nine fetal biometric parameters in the mid-trimester. Our primary objective was to assess and compare the CUPID performance of experienced senior and junior radiologists. MATERIALS AND METHODS: This prospective cross-sectional study was conducted at Shenzhen University General Hospital between September 2022 and June 2023, and focused on mid-trimester fetuses. All ultrasound images of the six standard planes, that enabled the evaluation of nine biometric measurements, were included to compare the performance of CUPID through subjective and objective assessments. RESULTS: There were 642 fetuses with a mean (±SD) age of 22 ± 2.82 weeks at enrollment. In the subjective quality assessment, out of 642 images representing nine biometric measurements, 617-635 images (90.65-96.11%) of CUPID caliper placements were determined to be accurately placed and did not require any adjustments. Whereas, for the junior category, 447-691 images (69.63-92.06%) were determined to be accurately placed and did not require any adjustments. In the objective measurement indicators, across all nine biometric parameters and estimated fetal weight (EFW), the intra-class correlation coefficients (ICC) (0.843-0.990) and Pearson correlation coefficients (PCC) (0.765-0.978) between the senior radiologist and CUPID reflected good reliability compared with the ICC (0.306-0.937) and PCC (0.566-0.947) between the senior and junior radiologists. Additionally, the mean absolute error (MAE), percentage error (PE), and average error in days of gestation were lower between the senior and CUPID compared to the difference between the senior and junior radiologists. The specific differences are as follows: MAE (0.36-2.53 mm, 14.67 g) compared to (0.64- 8.13 mm, 38.05 g), PE (0.94-9.38%) compared to (1.58-16.04%), and average error in days (3.99-7.92 days) compared to (4.35-11.06 days). In the time-consuming task, CUPID only takes 0.05-0.07 s to measure nine biometric parameters, while senior and junior radiologists require 4.79-11.68 s and 4.95-13.44 s, respectively. CONCLUSIONS: CUPID has proven to be highly accurate and efficient software for automatically measuring fetal biometry, gestational age, and fetal weight, providing a precise and fast tool for assessing fetal growth and development.

Glutamine Metabolism Promotes Renal Fibrosis through Regulation of Mitochondrial Energy Generation and Mitochondrial Fission.

Fibroblast activation and proliferation is an essential phase in the progression of renal fibrosis. Despite the recognized significance of glutamine metabolism in cellular growth and proliferation, its precise pathophysiological relevance in renal fibrosis remains uncertain. Therefore, this study aims to investigate the involvement of glutamine metabolism in fibroblast activation and its possible mechanism. Our findings highlight the importance of glutamine metabolism in fibroblast activation and reveal that patients with severe fibrosis exhibit elevated serum glutamine levels and increased expression of kidney glutamine synthetase. Furthermore, the deprivation of glutamine metabolism in vitro and in vivo could inhibit fibroblast activation, thereby ameliorating renal fibrosis. It was also detected that glutamine metabolism is crucial for maintaining mitochondrial function and morphology. These effects may partially depend on the metabolic intermediate α-ketoglutaric acid. Moreover, glutamine deprivation led to upregulated mitochondrial fission in fibroblasts and the activation of the mammalian target of rapamycin / mitochondrial fission process 1 / dynamin-related protein 1 pathway. Thus, these results provide compelling evidence that the modulation of glutamine metabolism initiates the regulation of mitochondrial function, thereby facilitating the progression of renal fibrosis. Consequently, targeting glutamine metabolism emerges as a novel and promising avenue for therapeutic intervention and prevention of renal fibrosis.

Isolation, identification, and pathogenicity of Pseudomonas glycinae causing ginseng bacterial soft rot in China.

By tissue separation method, tie-back experiment, and hypersensitive response test in potato, strain XJFL-1 was isolated and identified as the pathogen of ginseng bacterial soft rot in Liaoning Provence, China. The morphological characteristics of XJFL-1 were conformed to the Pseudomonads genus. Microbial fatty acid identification showed the principal cellular fatty acid traits of XLFJ-1 corresponded with Pseudomonas spp. API 50CH test results allowed the differentiation of strain XJFL-1 and MS586T from other closely related Pseudomonas species. The molecular identification, including 16S rRNA analysis and multilocus sequence typing (MLST) analysis, showed that XJFL-1 was in the same branch as P. glycinae MS586T. The genome of XJFL-1 was 6,296,473 bp, with an average guanine/cytosine (G + C) content of 60.72 %. Comparative genomics analysis using ANIb and GGDC algorithms indicated that the maximum value was observed between XJFL-1 and P. glycinae MS586T. The above morphological, cell morphology, and molecular biological identification results supported to identification of XJFL-1 as P. glycinae. This is the first report of P. glycinae as the plant pathogen causing ginseng bacterial root rot in China, which complements the biological significance of the species to a certain extent, enriches the pathogens of ginseng bacterial soft rot, and provides a theoretical basis for further investigation.

The HIF-1/ BNIP3 pathway mediates mitophagy to inhibit the pyroptosis of fibroblast-like synoviocytes in rheumatoid arthritis.

BACKGROUND: Synovial hypoxia, a critical pathological characteristic of rheumatoid arthritis (RA), significantly contributes to synovitis and synovial hyperplasia. In response to hypoxic conditions, fibroblast-like synoviocytes (FLS) undergo adaptive changes involving gene expression modulation, with hypoxia-inducible factors (HIF) playing a pivotal role. The regulation of BCL2/adenovirus e1B 19 kDa protein interacting protein 3 (BNIP3) and nucleotide-binding oligomerization segment-like receptor family 3 (NLRP3) expression has been demonstrated to be regulated by HIF-1. The objective of this study was to examine the molecular mechanism that contributes to the aberrant activation of FLS in response to hypoxia. Specifically, the interaction between BNIP3-mediated mitophagy and NLRP3-mediated pyroptosis was conjointly highlighted. METHODS: The research methodology employed Western blot and immunohistochemistry techniques to identify the occurrence of mitophagy in synovial tissue affected by RA. Additionally, the levels of mitophagy under hypoxic conditions were assessed using Western blot, immunofluorescence, quantitative polymerase chain reaction (qPCR), and CUT&Tag assays. Pyroptosis was observed through electron microscopy, fluorescence microscopy, and Western blot analysis. Furthermore, the quantity of reactive oxygen species (ROS) was measured. The silencing of HIF-1α and BNIP3 was achieved through the transfection of short hairpin RNA (shRNA) into cells. RESULTS: In the present study, a noteworthy increase in the expression of BNIP3 and LC3B was observed in the synovial tissue of patients with RA. Upon exposure to hypoxia, FLS of RA exhibited BNIP3-mediated mitophagy and NLRP3 inflammasome-mediated pyroptosis. It appears that hypoxia regulates the expression of BNIP3 and NLRP3 through the transcription factor HIF-1. Additionally, the activation of mitophagy has been observed to effectively inhibit hypoxia-induced pyroptosis by reducing the intracellular levels of ROS. CONCLUSION: In summary, the activation of FLS in RA patients under hypoxic conditions involves both BNIP3-mediated mitophagy and NLRP3 inflammasome-mediated pyroptosis. Additionally, mitophagy can suppress hypoxia-induced FLS pyroptosis by eliminating ROS and inhibiting the HIF-1α/NLRP3 pathway.

LaVO4: Eu3+ nano-islands onto silica for achieving fluorescence enhancement and their detection of Fe3+ ions and anti-counterfeiting applications.

Rare earth (RE) composite fluorescent materials are favored by researchers in the field of anti-counterfeiting and ion sensing due to their fascinating optical properties. Ultra-small RE fluorescent nanoparticles are anchored on inorganic carriers by a simple preparation method to improve luminous intensity and hydrophilicity, which has not been explored yet. Herein, LaVO4: Eu3+ nano-islands anchored on silica with high fluorescence intensity and easy formation of stable colloidal solution is designed. Through a simple and mild hydrothermal approach, ultra-small LaVO4: Eu3+ nano-islands are highly dispersed on the surface of hierarchical hollow silica sphere (HHSS) to expose more luminescent centers. Remarkably, the stable HHSS@LaVO4: Eu3+ colloidal solution displayed highly sensitive and selective sensor for Fe3+ ions. The "island-sea synergy" structure formed by the LaVO4: Eu3+ nano-islands and the surrounding silica surface makes HHSS@LaVO4: Eu3+ to be an outstanding sensor for the effective detection of iron ions in water. In addition, HHSS@LaVO4: Eu3+ phosphor exhibit unique properties for anti-counterfeiting and encryption applications. These findings provide a promising strategy for the carrierisation of RE luminescent materials to improve optical properties and enable broader applications.

hIgD-Fc-Ig fusion protein regulates T cell functions by inhibiting TCR signaling pathway in adjuvant arthritis rats.

This study aimed to investigate the effect of hIgD-Fc-Ig on TCR-Lck-Erk activated by IgD in adjuvant arthritis (AA) rats. Wistar rats were divided into the normal, AA model, hIgD-Fc-Ig (1 mg/kg, 3 mg/kg and 9 mg/kg) and Etanercept (3 mg/kg) groups. The overall index of AA rats was measured every 3 days. The pathologic examination of knee joints and the proliferation of the spleen and thymus of AA rats were detected by H&E staining and CCK-8. The blood flow signal of knee joints of experimental rats was examined by US. The articular bone injury was detected by X-ray. The changes in PBMCs and spleen T cell subsets were detected by flow cytometry. The expression of CD3ε, p-Lck, p-Zap70, Ras, and p-Erk in rat spleens was detected by immunofluorescence and WB. Rat spleen T cells or Jurkat cells treated by IgD to observe the effect of hIgD-Fc-Ig on TCR and its downstream protein expression. The results showed that hIgD-Fc-Ig had a therapeutic effect on AA rats by reducing the secondary inflammation, improving pathological changes. hIgD-Fc-Ig can reduce the ratio of Th cells of PBMCs of AA rats, the ratio of Th, Th1, Th17 cells and increase the ratio of Th2, Treg cells of AA rat spleens. hIgD-Fc-Ig could down-regulate the expression of CD3ε, p-Lck, p-Zap70, Ras, p-Erk in vivo or in vitro. In conclusion, hIgD-Fc-Ig could alleviate the symptoms of AA rats and regulate T cells through TCR-Lck-Erk signaling pathway and maybe a new promising biological agent for RA.

Avoiding Unnecessary Systematic Biopsy in Clinically Significant Prostate Cancer: Comparison Between MRI-Based Radiomics Model and PI-RADS Category.

BACKGROUND: MRI-targeted biopsy (MRTB) improves the clinically significant prostate cancer (csPCa) detection rate with fewer biopsy cores in men with suspected PCa. However, whether concurrent systematic biopsy (SB) can be avoided in patients undergoing MRTB remains unclear. PURPOSE: To evaluate the potential value of MRI-based radiomics models in avoiding unnecessary SB in biopsy-naïve patients. STUDY TYPE: Retrospective. POPULATION: A total of 226 patients (mean age 66.6 ± 9.02 years) with suspicion of PCa (PI-RADS score ≥ 3) and received combined cognitive MRTB with SB were retrospectively recruited and randomly divided into training (N = 180) and test (N = 46) cohorts at an 8:2 ratio. FIELD STRENGTH/SEQUENCE: A 3.0 T, biparametric MRI (bpMRI) including T2-weighted imaging (T2WI) and apparent diffusion coefficient (ADC) map. ASSESSMENT: The whole prostate gland (PG) and the index lesion (IL) were delineated. Three radiomics models of bpMRIPG , bpMRIIL , and bpMRIPG+IL were constructed, respectively, and the performance of each radiomics model was compared with that of PI-RADS assessment. STATISTICAL TESTS: The least absolute shrinkage and selection operator (LASSO) regression method was used to select texture features. The area under the curve (AUC) and decision curve analysis were used to estimate the models. RESULTS: The bpMRIPG+IL radiomics model exhibited good discrimination, calibration, and net benefits, which would reduce the SB biopsy in 71.2% and 71.4% of men with PI-RADS ≥ 5 lesions in the training and test cohorts, respectively. DATA CONCLUSION: A bpMRIPG+IL radiomics model may outperform PI-RADS category in help reducing unnecessary SB in biopsy-naïve patients. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 6.

Machine learning-based combined nomogram for predicting the risk of pulmonary invasive fungal infection in severely immunocompromised patients.

Background: Early and accurate diagnosis of invasive fungal infection (IFI) is pivotal for the initiation of effective antifungal therapy for patients with hematologic malignancies. Methods: This retrospective study involved 235 patients with hematologic malignancies and pulmonary infections diagnosed as IFIs (n=118) or bacterial pneumonia (n=117). Patients were randomly divided into training (n=188) and validation (n=47) datasets. Four feature selection methods with nine classifiers were implemented to select the optimal machine learning (ML) model using five-fold cross-validation. A radiomic signature was constructed using a linear ML algorithm, and a radiomic score (Radscore) was calculated. The combined model was developed with the Radscore, the significant clinical and radiologic factors were selected using multivariable logistic regression, and the results were presented as a clinical radiomic nomogram. A prospective pilot study was also conducted to compare the classification performance of the combined nomogram with practicing radiologists. Results: Significant differences were found in the Radscore between IFI and bacterial pneumonia patients in the training (0.683 vs. -0.724, P<0.001) and validation set (0.353 vs. -0.717, P=0.002). The combined model showed good discrimination performance in the validation cohort [area under the curve (AUC) =0.844] and outperformed the clinical (AUC =0.696) and radiomics (AUC =0.767) model alone (both P<0.05). Conclusions: The clinical radiomic nomogram can serve as a promising predictive tool for IFI in patients with hematologic malignancies.

A Cascaded Multi-Task Generative Framework for Detecting Aortic Dissection on 3-D Non-Contrast-Enhanced Computed Tomography.

Contrast-enhanced computed tomography (CE-CT) is the gold standard for diagnosing aortic dissection (AD). However, contrast agents can cause allergic reactions or renal failure in some patients. Moreover, AD diagnosis by radiologists using non-contrast-enhanced CT (NCE-CT) images has poor sensitivity. To address this issue, we propose a novel cascaded multi-task generative framework for AD detection using NCE-CT volumes. The framework includes a 3D nnU-Net and a 3D multi-task generative architecture (3D MTGA). Specifically, the 3D nnU-Net was employed to segment aortas from NCE-CT volumes. The 3D MTGA was then employed to simultaneously synthesize CE-CT volumes, segment true & false lumen, and classify the patient as AD or non-AD. A theoretical formulation demonstrated that the 3D MTGA could increase the Jensen-Shannon Divergence (JSD) between AD and non-AD for each NCE-CT volume, thus indirectly improving the AD detection performance. Experiments also showed that the proposed framework could achieve an average accuracy of 0.831, a sensitivity of 0.938, and an F1-score of 0.847 in comparison with seven state-of-the-art classification models used by three radiologists with junior, intermediate, and senior experiences, respectively. The experimental results indicate that the proposed framework obtains superior performance to state-of-the-art models in AD detection. Thus, it has great potential to reduce the misdiagnosis of AD using NCE-CT in clinical practice. The source codes and supplementary materials for our framework are available at https://github.com/yXiangXiong/CMTGF.

Genome-Resolved Metagenomic Analysis of Groundwater: Insights into Arsenic Mobilization in Biogeochemical Interaction Networks.

High-arsenic (As) groundwaters, a worldwide issue, are critically controlled by multiple interconnected biogeochemical processes. However, there is limited information on the complex biogeochemical interaction networks that cause groundwater As enrichment in aquifer systems. The western Hetao basin was selected as a study area to address this knowledge gap, offering an aquifer system where groundwater flows from an oxidizing proximal fan (low dissolved As) to a reducing flat plain (high dissolved As). The key microbial interaction networks underpinning the biogeochemical pathways responsible for As mobilization along the groundwater flow path were characterized by genome-resolved metagenomic analysis. Genes associated with microbial Fe(II) oxidation and dissimilatory nitrate reduction were noted in the proximal fan, suggesting the importance of nitrate-dependent Fe(II) oxidation in immobilizing As. However, genes catalyzing microbial Fe(III) reduction (omcS) and As(V) detoxification (arsC) were highlighted in groundwater samples downgradient flow path, inferring that reductive dissolution of As-bearing Fe(III) (oxyhydr)oxides mobilized As(V), followed by enzymatic reduction to As(III). Genes associated with ammonium oxidation (hzsABC and hdh) were also positively correlated with Fe(III) reduction (omcS), suggesting a role for the Feammox process in driving As mobilization. The current study illustrates how genomic sequencing tools can help dissect complex biogeochemical systems, and strengthen biogeochemical models that capture key aspects of groundwater As enrichment.

Preparation and adsorption performance of functionalization cellulose-based composite aerogel.

Herein, functionalization cellulose-based composite aerogels with the addition of carboxyl cellulose nanofibers (CNF), montmorillonite (MMT) and polyethyleneimine (PEI) were fabricated by solution blending and freeze-drying technology. MMT was blended into the cellulose framework as a reinforcing agent. PEI combined with cellulose through amidation reaction, and the synergism of hydrogen bond and chemical bond helped the CNF/MMT/PEI composite aerogels (CMP) with good mechanical properties. The morphology, chemical structure and thermal stability of the CMP were characterized. The adsorption properties and mechanism of the CMP were discussed, using Congo red (CR) dye as an adsorbate. The results showed that the CMP formed a three-dimensional network structure with abundant pores. The addition of PEI regulated the surface charge distribution of cellulose and improved the adsorption performance of CMP for CR with the adsorption capacity of 3114 mg/g calculated by the Langmuir model. The adsorption process of CMP-30 for CR was more in line with the pseudo-second-order kinetic model and Langmuir isotherm model, indicating chemical adsorption of a single molecular layer. After functionalized by octadecyl trichlorosilane (OTS), the contact angle of the aerogel surface was 151.80°. Meanwhile, the CMP-30 was transformed from hydrophilic and lipophilic properties to hydrophobic and lipophilic properties.

[Research on real-time detection system of catheter delivering force in vascular interventional robots].

In existing vascular interventional surgical robots, it is difficult to accurately detect the delivery force of the catheter/guidewire at the slave side. Aiming to solve this problem, a real-time force detection system was designed for vascular interventional surgical (VIS) robots based on catheter push force. Firstly, the transfer process of catheter operating forces in the slave end of the interventional robot was analyzed and modeled, and the design principle of the catheter operating force detection system was obtained. Secondly, based on the principle of stress and strain, a torque sensor was designed and integrated into the internal transmission shaft of the slave end of the interventional robot, and a data acquisition and processing system was established. Thirdly, an ATI high-precision torque sensor was used to build the experimental platform, and the designed sensor was tested and calibrated. Finally, sensor test experiments under ideal static/dynamic conditions and simulated catheter delivery tests based on actual human computed tomography (CT) data and vascular model were carried out. The results showed that the average relative detection error of the designed sensor system was 1.26% under ideal static conditions and 1.38% under ideal dynamic stability conditions. The system can detect on-line catheter operation force at high precision, which is of great significance towards improving patient safety in interventional robotic surgery.

The ROS/GRK2/HIF-1α/NLRP3 Pathway Mediates Pyroptosis of Fibroblast-Like Synoviocytes and the Regulation of Monomer Derivatives of Paeoniflorin.

Hypoxia is an important factor in the development of synovitis in rheumatoid arthritis (RA). The previous study of the research group found that monomeric derivatives of paeoniflorin (MDP) can alleviate joint inflammation in adjuvant-induced arthritis (AA) rats by inhibiting macrophage pyroptosis. This study revealed increased levels of hypoxia-inducible factor- (HIF-) 1α and N-terminal p30 fragment of GSDMD (GSDMD-N) in fibroblast-like synoviocytes (FLS) of RA patients and AA rats, while MDP significantly inhibited their expression. Subsequently, FLS were exposed to a hypoxic environment or treated with cobalt ion in vitro. Western blot and immunofluorescence analysis showed increased expression of G protein-coupled receptor kinase 2 (GRK2), HIF-1α, nucleotide-binding oligomerization segment-like receptor family 3 (NLRP3), ASC, caspase-1, cleaved-caspase-1, and GSDMD-N. Electron microscopy revealed FLS pyroptosis after exposure in hypoxia. Next, corresponding shRNAs were transferred into FLS to knock down hypoxia-inducible factor- (HIF-) 1α, and in turn, NLRP3 and western blot results confirmed the same. The enhanced level of GSDMD was reversed under hypoxia by inhibiting NLRP3 expression. Knockdown and overexpression of GRK2 in FLS revealed GRK2 to be a positive regulator of HIF-1α. Levels of GRK2 and HIF-1α were inhibited by eliminating excess reactive oxygen species (ROS). Furthermore, MDP reduced FLS pyroptosis through targeted inhibition of GRK2 phosphorylation. According to these findings, hypoxia induces FLS pyroptosis through the ROS/GRK2/HIF-1α/NLRP3 pathway, while MDP regulates this pathway to reduce FLS pyroptosis.

Automatic machine learning based on native T1 mapping can identify myocardial fibrosis in patients with hypertrophic cardiomyopathy.

OBJECTIVES: To investigate the feasibility of automatic machine learning (autoML) based on native T1 mapping to predict late gadolinium enhancement (LGE) status in hypertrophic cardiomyopathy (HCM). METHODS: Ninety-one HCM patients and 44 healthy controls who underwent cardiovascular MRI were enrolled. The native T1 maps of HCM patients were classified as LGE ( +) or LGE (-) based on location-matched LGE images. An autoML pipeline was implemented using the tree-based pipeline optimization tool (TPOT) for 3 binary classifications: LGE ( +) and LGE (-), LGE (-) and control, and HCM and control. TPOT modeling was repeated 10 times to obtain the optimal model for each classification. The diagnostic performance of the best models by slice and by case was evaluated using sensitivity, specificity, accuracy, and microaveraged area under the curve (AUC). RESULTS: Ten prediction models were generated by TPOT for each of the 3 binary classifications. The diagnostic accuracy obtained with the best pipeline in detecting LGE status in the testing cohort of HCM patients was 0.80 by slice and 0.79 by case. In addition, the TPOT model also showed discriminability between LGE (-) patients and control (accuracy: 0.77 by slice; 0.78 by case) and for all HCM patients and controls (accuracy: 0.88 for both). CONCLUSIONS: Native T1 map analysis based on autoML correlates with LGE ( +) or (-) status. The TPOT machine learning algorithm could be a promising method for predicting myocardial fibrosis, as reflected by the presence of LGE in HCM patients without the need for late contrast-enhanced MRI sequences. KEY POINTS: • The tree-based pipeline optimization tool (TPOT) is a machine learning algorithm that could help predict late gadolinium enhancement (LGE) status in patients with hypertrophic cardiomyopathy. • The TPOT could serve as an adjuvant method to detect LGE by using information from native T1 maps, thus avoiding the need for contrast agent. • The TPOT also detects native T1 map alterations in LGE-negative patients with hypertrophic cardiomyopathy.