Ensemble learning-based pretreatment MRI radiomic model for distinguishing intracranial extraventricular ependymoma from glioblastoma multiforme.

This study aims to develop an ensemble learning (EL) method based on magnetic resonance (MR) radiomic features to preoperatively differentiate intracranial extraventricular ependymoma (IEE) from glioblastoma (GBM). This retrospective study enrolled patients with histopathologically confirmed IEE and GBM from June 2016 to June 2021. Radiomics features were extracted from T1-weighted imaging (T1WI) and T2-weighted imaging (T2WI) sequence images, and classification models were constructed using EL methods and logistic regression (LR). The efficiency of the models was assessed using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis. The combined EL model, based on clinical parameters and radiomic features from T1WI and T2WI images, demonstrated good discriminative ability, achieving an area under the receiver operating characteristics curve (AUC) of 0.96 (95% CI 0.94-0.98), a specificity of 0.84, an accuracy of 0.92, and a sensitivity of 0.95 in the training set, and an AUC of 0.89 (95% CI 0.83-0.94), a specificity of 0.83, an accuracy of 0.81, and a sensitivity of 0.74 in the validation set. The discriminative efficacy of the EL model was significantly higher than that of the LR model. Favorable calibration performance and clinical applicability for the EL model were observed. The EL model combining preoperative MR-based tumor radiomics and clinical data showed high accuracy and sensitivity in differentiating IEE from GBM preoperatively, which may potentially assist in clinical management of these brain tumors.

Cobalt/Iron Bimetallic Biochar Composites for Lead(II) Adsorption: Mechanism and Remediation Performance.

The performance of nano-zero-valent iron for heavy metal remediation can be enhanced via incorporation into bimetallic carbon composites. However, few economical and green approaches are available for preparing bimetallic composite materials. In this study, novel Co/Fe bimetallic biochar composites (BC@Co/Fe-X, where X = 5 or 10 represents the CoCl2 concentration of 0.05 or 0.1 mol L-1) were prepared for the adsorption of Pb2+. The effect of the concentration of cross-linked metal ions on Pb2+ adsorption was investigated, with the composite prepared using 0.05 mol L-1 Co2+ (BC@Co/Fe-5) exhibiting the highest adsorption performance. Various factors, including the adsorption period, Pb2+ concentration, and pH, affected the adsorption of Pb2+ by BC@Co/Fe-5. Further characterisation of BC@Co/Fe-5 before and after Pb2+ adsorption using methods such as X-ray diffraction and X-ray photoelectron spectroscopy suggested that the Pb2+ adsorption mechanism involved (i) Pb2+ reduction to Pb0 by Co/Fe, (ii) Co/Fe corrosion to generate Fe2+ and fix Pb2+ in the form of PbO, and (iii) Pb2+ adsorption by Co/Fe biochar. Notably, BC@Co/Fe-5 exhibited excellent remediation performance in simulated Pb2+-contaminated water and soil with good recyclability.

Abnormal regional homogeneity and its relationship with symptom severity in cervical dystonia: a rest state fMRI study.

BACKGROUND: Although several brain networks play important roles in cervical dystonia (CD) patients, regional homogeneity (ReHo) changes in CD patients have not been clarified. We investigated to explore ReHo in CD patients at rest and analyzed its correlations with symptom severity as measured by Tsui scale. METHODS: A total of 19 CD patients and 21 gender-, age-, and education-matched healthy controls underwent fMRI scans at rest state. Data were analyzed by ReHo method. RESULTS: Patients showed increased ReHo in the right cerebellum crus I and decreased ReHo in the right superior medial prefrontal cortex (MPFC). Moreover, the right precentral gyrus, right insula, and bilateral middle cingulate gyrus also showed increased ReHo values. A significantly positive correlation was observed between ReHo value in the right cerebellum crus I and symptom severity (p < 0.05). CONCLUSIONS: Our investigation suggested abnormal ReHo existed in brain regions of the "pain matrix" and salience network (the right insula and bilateral middle cingulate gyrus), the motor network (the right precentral gyrus), the cerebellum and MPFC and further highlighted the significance of these networks in the pathology of CD.

Dissipation of sixteen pesticide residues from various applications of commercial formulations on strawberry and their risk assessment under greenhouse conditions.

Twelve commercial pesticide formulations containing sixteen active ingredients were applied on greenhouse strawberries at recommended and double doses. The dynamics and dietary risk analysis were investigated. A modified QuEChERS method based on the use of multi-walled carbon nanotubes (MWCNTs) as adsorbent followed by LC-MS/MS and GC-MS/MS detection was utilized for sample analysis. The half-lives of studied pesticides were 4.6-12.6 days and 3.8-15.8 days from two application doses. Dietary levels from the residue concentrations of the individual pesticides at harvest was contrasted with the acceptable daily intake (ADI) and acute reference dose (ARfD). The dietary risk assessment adopt the risk quotient (RQ) for chronic risk and risk probability (RP) for long-term dietary intake risk, respectively. The dietary risk induced by the studied pesticide residues in strawberry was acceptable for consumers except the pesticide fumigants. The pesticide residues at different pre-harvest intervals (PHIs) under greenhouse conditions were compared with the established maximum residue limits (MRLs). To reduce the residue levels and potential safety risk, a longer PHI or reduced application rates should be conducted.

Rapid multiplug filtration cleanup method for the determination of 124 pesticide residues in rice, wheat, and corn.

A simple and rapid multiplug filtration cleanup method based on multiwalled carbon nanotubes was developed to determine 124 pesticide residues in rice, wheat, and corn, which could be done in a few seconds without conditioning and elution steps. Various combinations of sorbents were optimized for each matrix with a dispersive solid-phase extraction procedure to get a satisfactory recovery and clean-up performance. Good linearity was obtained for all pesticides with calibration curve coefficients larger than 0.9958. Most recoveries for the majority pesticides were between 70 and 120% (n = 5) with relative standard deviations below 20%. The limit of detection was 0.1-1.3 µg/kg, and the limit of quantification was 0.2-4.3 µg/kg for the pesticides in all matrices. The work suggests that the multiplug filtration cleanup method is better than the dispersive solid-phase extraction method and it could be applied to routinely monitor pesticide residues in market samples.

Multiplug filtration cleanup method with multi-walled carbon nanotubes for the analysis of malachite green, diethylstilbestrol residues, and their metabolites in aquatic products by liquid chromatography-tandem mass spectrometry.

The food safety supervision in aquatic products has raised public concern in recent years. In this study, a liquid chromatographic-tandem mass spectrometric (LC-MS/MS) method for the simultaneous quantification and identification of four residues of the ever widely used analytes (including malachite green, leucomalachite green, diethylstilbestrol, and dienestrol) in aquaculture samples was developed. For sample preparation, a modified QuEChERS (quick, easy, cheap, effective, rugged, and safe) method was used, which was initially developed for pesticide residue analysis. For cleanup procedure, low-temperature cleanup method was combined with multiplug filtration cleanup (m-PFC) method based on multi-walled carbon nanotubes (MWCNTs). The volume of water, extraction solvent, cleanup sorbents, and m-PFC procedure were optimized for carp, striped bass, and giant salamander matrices. It was validated by analyzing four residues in each matrix spiked at three concentration levels of 0.5, 5, and 50 µg/kg (n = 5). The method was successfully validated according to the 2002/657/EC guidelines. After optimization, spike recoveries were within 73-106 % and <15 % relative standard deviations (RSDs) for all analytes in the tested matrices. Limits of quantification (LOQs) for the proposed method ranged from 0.10 to 0.50 µg/kg. Matrix-matched calibrations were performed with the coefficients of determination >0.998 between concentration levels of 0.5 and 200 µg/kg. The developed method was successfully applied to the determination of residues in market samples. Graphical abstract Flow chart of multi-plug filtration cleanup combined with low-temperature cleanup method.

Comparison of pulse glow discharge-ion mobility spectrometry and liquid chromatography with tandem mass spectrometry based on multiplug filtration cleanup for the analysis of tricaine mesylate residues in fish and water.

Analytical methods based on multiplug filtration cleanup coupled with pulse glow discharge-ion mobility spectrometry and liquid chromatography tandem mass spectrometry were developed for the analysis of tricaine mesylate residue in fish and fish-raising water samples. A silica fiber holder and an appropriate new interface were designed to make the direct introduction of the fiber into the pulse glow discharge-ion mobility spectrometry introduction mechanism. The multiplug filtration cleanup method with adsorption mixtures was optimized for the determination of tricaine mesylate in fish samples. Good linear relationships were obtained by the two methods. For fish samples, limits of detection were 6 and 0.6 µg/kg by ion mobility spectrometry and liquid chromatography with tandem mass spectrometry, respectively. The matrix effect of the established liquid chromatography tandem mass spectrometry method was negligible for fish samples but that of the ion mobility spectrometry method was not. The two methods were compared. The ion mobility spectrometry system could be used a rapid screening tool on site with the advantage of rapidity, simplicity, and portability, and the liquid chromatography tandem mass spectrometry system could be used for validation in laboratory conditions with the advantage of lower limit of detection, stability, and precision.

Analytical method for 44 pesticide residues in spinach using multi-plug-filtration cleanup based on multiwalled carbon nanotubes with liquid chromatography and tandem mass spectrometry detection.

Spinach is one of the most commonly planted vegetables worldwide. A high chlorophyll content makes spinach a complicated matrix in pesticide residue analysis. In this study, a rapid clean-up method was developed for the analysis of pesticide multi-residues in spinach followed by liquid chromatography with tandem mass spectrometry. A modified QuEChERS method with multiwalled carbon nanotubes and carbon material was adopted in the multi-Plug Filtration Cleanup procedure. This method was validated for 44 representative pesticides spiked at two concentration levels of 10 and 100 µg/kg. The pesticides of different physicochemical properties were registered on spinach in China. The recoveries were between 76 and 114% for major pesticides with relative standard deviations of less than 15%, except for quizalofop-P-ethyl, pyrimethanil, and carbendazim. Matrix-matched calibration curves were performed with the coefficients of determination higher than 0.995 for the studied pesticides for concentration levels of 10-500 µg/kg. The limits of quantitation ranged from 2 to 10 µg/kg. The developed method was successfully applied to determine pesticide residues in Chinese market spinach samples.

Platelet-rich plasma in orthopedics: Bridging innovation and clinical applications for bone repair.

In the burgeoning domain of orthopedic therapeutic research, Platelet-Rich Plasma (PRP) has firmly established its position, transforming paradigms ranging from tissue regeneration to the management of chondral lesions. This review delves into PRP's recent integrations with cutting-edge interventions such as 3D-printed scaffolds, its role in bone and cartilage defect management, and its enhanced efficacy when combined with molecules like Kartogenin (KGN) for fibrocartilage zone repair. Significant attention is paid to tissue engineering for meniscal interventions, where a combination of KGN, PRP, and bone marrow-derived mesenchymal stem cells are under exploration. Within the sphere of osteochondral regenerative therapy, the synergy of PRP with Bone Marrow Aspirate Concentrate (BMAC) represents a noteworthy leap towards cartilage regeneration. The innovative incorporation of PRP with biomaterials like hydroxyapatite and graphene oxide further underscores its versatility in supporting structural integrity and ensuring sustained growth factor release. However, while PRP's autologous and nontoxic nature makes it an inherently safe option, concerns arising from its preparation methods, particularly with bovine thrombin, necessitate caution. As of 2023, despite the burgeoning promise of PRP in bone healing, the quest for its standardization, optimization, and substantiation through rigorous clinical trials continues. This comprehensive review elucidates the contemporary applications, challenges, and future trajectories of PRP in orthopedics, aiming to spotlight areas primed for further research and exploration.

Unraveling the intrinsic mechanism behind the retention of arsenic in the co-gasification of coal and sewage sludge: Focus on the role of Ca and Fe compounds.

Minimizing the emission of arsenic (As) is one of the urgent problems during co-gasification of Shenmu coal (SM) and sewage sludge (SS). The intrinsic mechanism of As retention was obtained by analyzing the effect of different SM addition ratios on the As form transformation during co-gasification at 1000 °C under CO2 atmosphere. The results showed that the addition of SM effectively promoted the enrichment of As in the co-gasified residues. Especially, the best As retention rate of 65.71% was achieved with the 70 wt% addition ratio of SM. The addition of SM promoted the adsorption and chemical oxidation of As(III) to the less toxic As(V) through the coupling of Ca and Fe compounds in the co-gasified residues. XRD and XPS results indicated that Fe2O3 adsorbed As2O3(g) after partial conversion to Fe3O4 by the Boudouard reaction, while part of As2O3 was oxidized to As2O5 by lattice oxygen. Finally, the generated As2O5 was successively trapped by CaO and Fe2O3 to form stable Ca3(AsO4)2 and FeAsO4. HRTEM and TEM analysis comprehensively proved that As(III) was stabilized by the lattice cage of CaAl2Si2O8. In conclusion, the co-oxidation of Ca and Fe compounds and lattice stabilization simultaneously played a crucial role in the retention of As2O3(g) during co-gasification.

Soil Erosion Thickness and Seasonal Variations Together Drive Soil Nitrogen Dynamics at the Early Stage of Vegetation Restoration in the Dry-Hot Valley.

By changing the physicochemical and biological properties of soil, erosion profoundly affects soil nitrogen levels, but knowledge about the erosion impact on soil nitrogen (N) dynamics is still rather incomplete. We compared soil N contents at the early stage of vegetation self-restoration in response to soil erosion thickness (0, 10, 20, 30 and 40 cm), by conducting a simulated erosion experiment on sloping arable land in the dry-hot valley of Yunnan Province, southwestern China. The results showed total nitrogen (TN), ammonium nitrogen (NH4+-N) and nitrate nitrogen (NO3--N) contents reduced with increasing soil erosion thickness and decreased significantly at the soil erosion thickness of 10, 40 and 10 cm in the rainy season and 30, 10 and 10 cm in the dry season compared with 0 cm. Structural equation modeling (SEM) indicated that soil erosion thickness and seasonal variation were the important drivers of mineral nitrogen (NH4+-N and NO3--N) content. Soil erosion thickness indirectly affected mineral nitrogen through negative on TN, carbon content and Diazotrophs (nifH genes). Dry-wet season change had an effect on mineral nitrogen mediated by arbuscular mycorrhizal fungi (AMF) and nifH genes. We also found AMF had a promotion to nifH genes in eroded soil, which can be expected to benefit nitrogen fixing. Our findings highlight the importance of considering soil erosion thickness and sampling time for nitrogen dynamics, in particular, the investigation of nitrogen limitation, in the early stage of vegetation self-restoration.

Influence of intensive insulin therapy on vascular endothelial growth factor in patients with severe trauma.

The influence of early-stage intensive insulin therapy on the plasma levels of vascular endothelial growth factor (VEGF) and the related parameters in patients with severe trauma and the clinical implication were investigated. Sixty-four cases of severe trauma (injury severity score ≥20) with stress hyperglycemia (blood glucose >9 mmol/L) were randomly divided into intensive insulin therapy group and conventional therapy group. ELISA method, radioimmunoassay and density gradient gradation one-step process were used to determine plasma VEGF, endothelin-1 (ET-1), and the number of circulating endothelial cells (CECs) at the day of 0, 2, 3, 5 and 7 after admission. Simultaneously, the changes of CRP concentration in plasma were monitored to evaluate inflammatory response. The results showed that plasma levels of observational indexes in patients receiving early-stage intensive insulin therapy were all significantly lower than those in conventional therapy groups 2, 3, 5 and 7 days after admission [for VEGF (ng/L), 122.2±23.8 vs. 135.9±26.5, 109.6±27.3 vs. 129.0±18.4, 88.7±18.2 vs. 102.6±27.3, 54.2±26.4 vs. 85.7±35.2, P<0.05, 0.01, 0.05, 0.05 respectively; for ET-1 (ng/L), 162.8±23.5 vs. 173.7±13.2, 128.6±17.5 vs. 148.8±22.4, 96.5±14.8 vs. 125.7±14.8, 90.7±16.9 vs. 104.9±22.5, P<0.05, 0.01, 0.01, 0.01 respectively; for CRP (mg/L), 23.2±13.8 vs. 31.9±16.5, 13.6±17.3 vs. 23.5±18.4, 8.7±10.2 vs. 15.6±13.3, 5.2±9.4 vs. 10.7±11.2, all P<0.05; for CECs (/0.9 µL), 10.9±5.6 vs. 13.9±6.2, 8.5±4.9 vs. 11.3±5.3, 6.3±6.4 vs. 9.4±5.7, 4.8±7.1 vs. 7.8±4.8, all P<0.05]. It was concluded that intensive insulin therapy could antagonize the endothelium injury after trauma and reduce inflammation response quickly, which was one of important mechanisms by which intensive insulin therapy improves the prognosis of trauma patients.

Metagenomic next­generation sequencing of BALF for the clinical diagnosis of severe community­acquired pneumonia in immunocompromised patients: A single­center study.

The diagnostic methods of conventional microbiological tests (CMTs) for severe community-acquired pneumonia (SCAP) may be too complicated or impossible to use in polymicrobial infections, and it may be difficult to identify unexpected pathogens. CMTs are also limited due to the early application of broad-spectrum or prophylactic antimicrobial drugs and the fastidious or slow-growing pathogenic microorganisms. The present study aimed to investigate the value of mNGS compared with CMTs in the clinical diagnosis of SCAP in immunocompromised individuals. Therefore, 37 patients diagnosed with SCAP in immunocompromised adult patients were enrolled from the Respiratory Intensive Care Unit of the First Affiliated Hospital of Soochow University (Soochow, China) between May 1, 2019, and March 30, 2022. A bronchoalveolar lavage fluid sample from each individual was divided in half. Half was sent to the microbiology laboratory directly for examination, and the other one was sent for DNA extraction and sequencing. In addition, other relevant specimens (such as blood) were sent for CMTs, including culture or smear, T-spot, acid-fast stain, antigen detection, multiplex PCR and direct microscopic examination. Based on a composite reference standard, the diagnostic outcomes were compared between CMTs and mNGS. Among the enrolled patients, 31 patients were diagnosed with microbiologically confirmed pneumonia, with 16 (43.2%) having monomicrobial infections, while 15 (40.5%) had polymicrobial infections. Fungi were the most common etiologic pathogens in immunosuppressive individuals. Pneumocystis jirovecii (45.9%) and Aspergillus spp. (18.9%) were the most common etiologic pathogens. Initial screening test validity of mNGS [sensitivity=96.8%; specificity=33.3%; positive predictive value (PPV)=88.2%; negative predictive value (NPV)=66.6%; likelihood ratio (LR)+, 1.45; LR-, 0.10) was higher compared with that of CMTs (sensitivity=38.7%; specificity=82.3; PPV=92.3%; NPV=20.8%; LR+, 2.3; LR-, 0.74). The total diagnostic accuracy of mNGS was superior to CMTs and it was statistically significantly different [86.5% (32/37) vs. 45.9% (17/37); P<0.001]. In conclusion, the total diagnostic accuracy of mNGS was superior to CMTs for SCAP in immunocompromised patients as an important diagnostic method.

Vitamin B12 alleviates myocardial ischemia/reperfusion injury via the SIRT3/AMPK signaling pathway.

AIM: To examine the protective effect of vitamin B12 against myocardial ischemia/reperfusion (I/R) injury and elucidate its underlying mechanism of action. METHODS: Mice were subjected to myocardial I/R injury by left anterior descending coronary artery (LAD) occlusion followed by 24 h reperfusion. Cardiac function and injury were evaluated by echocardiography, triphenyl tetrazolium chloride (TTC) and cardiac troponin T (cTnT) staining, and measuring lactate dehydrogenase (LDH) levels. In addition, various molecular and biochemical methods, as well as RNA sequencing were used to determine the effects and mechanism of action of vitamin B12 on I/R injury. RESULTS: We found that high doses of vitamin B12 inhibited myocardial I/R injury. Furthermore, our data indicated that vitamin B12 supplementation alleviated cardiac dysfunction and injury by mitigating oxidative stress and apoptosis through downregulation of Nox2, the Ac-SOD2/SOD2 and Bax/Bcl-2 ratios and cleaved caspase-3 expression, and upregulation of SIRT3 expression and AMPK activity. However, these effects were largely reversed following treatment with the SIRT3 inhibitor, 3-TYP. Our RNA-sequencing data further demonstrated that vitamin B12 supplementation reduced inflammation during I/R injury. CONCLUSION: High doses of vitamin B12 supplements improved myocardial I/R injury by suppressing the accumulation of reactive oxygen species and apoptosis of myocardial tissue through modulation of the SIRT3/AMPK signaling pathway, while reducing inflammation. Our findings suggested that vitamin B12 administered at high doses could be a potential therapy for myocardial I/R damage.

Association Between Visceral Fat, Blood Pressure and Arterial Stiffness in Patients with HFpEF: A Mediation Analysis.

Purpose: To investigate the association of visceral fat with arterial stiffness of heart failure patients with preserved ejection fraction (HFpEF) and to evaluate the extent to which this association is mediated by blood pressure (BP). Patients and Methods: This cross-sectional descriptive study (clinicaltrials.gov identifier: NCT04535726) recruited 94 patients with HFpEF totally from October to December 2020. The obesity-related measurements included visceral fat area (VFA), body mass index (BMI), waist circumference (WC), hip circumference (HC), waist-hip ratio (WC/HC), abdominal circumference (AC), body fat mass and fat percentage. Brachial-ankle pulse wave velocity (baPWV) was used to estimate the degree of arterial stiffness. Mediation analysis was performed to reveal whether the effect of visceral fat area on arterial stiffness can be mediated by BP in patients with HFpEF and the extent to which this association was mediated by BP. Results: About 93.6% of HFpEF patients were accompanied with abdominal obesity. Patients in baPWV ≥1800cm/s group were older, with a higher incidence of type 2 diabetes mellitus (T2DM), hypertension and abdominal obesity. VFA, systolic BP (SBP), diastolic BP (DBP) and pulse pressure (PP) were correlated with baPWV in total group. Adjusted for age ≥75 years old, gender, smoking, T2DM, calcium channel blocker and statins, the mediation effect of systolic SBP and PP on the VFA-baPWV association were 53.3% (indirect effect was 2.28, 95% CI 0.62-4.73) and 48.4% (indirect effect was 2.07, 95% CI 0.51-4.38), respectively. DBP failed to mediate the association between VFA and baPWV (indirect effect was 0.50, 95% CI -0.41-2.14). Conclusion: The association of visceral fat with baPWV in HFpEF patients may be partly accounted for SBP or PP. Elevated SBP and PP might be important potential targets for preventing arterial stiffness in HFpEF patients.

Effect of early intensive insulin therapy on immune function of aged patients with severe trauma.

This study examined the effect of intensive insulin therapy on immune function and inflammatory factors at the early phase after severe trauma. At day 1, 3, 5, 7 after admission, subsets of CD4(+) helper T lymphocytes (Th1/Th2) and human leukocyte antigen (HLA)-DR expression on CD14(+) monocytes were flow cytometrically measured. Levels of cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-10 (IL-10) and other immunity markers, such as IgA, IgG, IgM, C3, C4 and C reaction protein (CRP) were examined in two groups. The results showed that TNF-α, IL-6 and CRP levels in the intensive insulin therapy group were significantly lower than those in the conventional therapy group, whereas IL-10 levels were substantially increased after intensive insulin therapy. C3 level at day 3, 5, 7 and C4 levels at day 5, 7 were lower in the intensive therapy group than in the conventional therapy group. Th1/Th2 ratios decreased gradually over time in both groups, and were much lower at day 3, 5, 7 in intensive therapy group. There were significant differences among day 3 to day 7 after admission in HLA-DR expression in CD14(+) monocytes. It was concluded that the intensive insulin therapy could decrease pro-inflammatory cytokines and increase anti-inflammatory cytokines in the elderly suffering from severe trauma, at the same time, with complement recovery being delayed. Moreover, intensive insulin therapy promoted immune suppression and, therefore, measures need be taken to address the issue.

Gpx3 and Egr1 Are Involved in Regulating the Differentiation Fate of Cardiac Fibroblasts under Pressure Overload.

Objectives: Although myocardial fibrosis is a common pathophysiological process associated with many heart diseases, the molecular mechanisms regulating the development of fibrosis have not been fully determined. Recently, single cell RNA sequencing (scRNA-seq) analysis has been used to examine cellular fate and function during cellular differentiation and has contributed to elucidating the mechanisms of various diseases. The main purpose of this study was to characterize the fate of cardiac fibroblasts (CFs) and the dynamic gene expression patterns in a model of cardiac pressure overload using scRNA-seq analysis. Methods: The public scRNA-seq dataset of the transverse aortic coarctation (TAC) model in mice was downloaded from the GEO database, GSE155882. First, we performed quality control, dimensionality reduction, clustering, and annotation of the data through the Seurat R package (v4.0.5). Then, we constructed the pseudotime trajectory of cell development and identified key regulatory genes using the Monocle R package (v2.22.0). Different cell fates and groups were fully characterized by Gene Set Enrichment Analysis (GSEA) analysis and Transcription factor (TF) activity analysis. Finally, we used Cytoscape (3.9.1) to extensively examine the gene regulatory network related to cell fate. Results: Pseudotime analysis showed that CFs differentiated into two distinct cell fates, one of which produced activated myofibroblasts, and the other which produced protective cells that were associated with reduced fibrosis levels, increased antioxidative stress responses, and the ability to promote angiogenesis. In the TAC model, activated CFs were significantly upregulated, while protective cells were downregulated. Treatment with the bromodomain inhibitor JQ1 reversed this change and improved fibrosis. Analysis of dynamic gene expression revealed that Gpx3 was significantly upregulated during cell differentiation into protective cells. Gpx3 expression was affected by JQ1 treatment. Furthermore, Gpx3 expression levels were negatively correlated with the different levels of fibrosis observed in the various treatment groups. Finally, we found that transcription factors Jun, Fos, Atf3, and Egr1 were upregulated in protective cells, especially Egr1 was predicted to be involved in the regulation of genes related to antioxidant stress and angiogenesis, suggesting a role in promoting differentiation into this cell phenotype. Conclusions: The scRNA-seq analysis was used to characterize the dynamic changes associated with fibroblast differentiation and identified Gpx3 as a factor that might be involved in the regulation of myocardial fibrosis under cardiac pressure overload. These findings will help to further understanding of the mechanism of fibrosis and provide potential intervention targets.

Parameters of dual-energy CT for the differential diagnosis of thyroid nodules and the indirect prediction of lymph node metastasis in thyroid carcinoma: a retrospective diagnostic study.

Background: To further investigate the differential diagnosis of thyroid nodules using dual-energy computed tomography (DECT) and explore the relationship between DECT parameters and lymph node metastasis in thyroid carcinoma for clinical practice, especially difficult diagnosis by routine imaging examination. Methods: A total of 150 patients with thyroid nodules who underwent preoperative DECT and Thyroid Imaging Report and Data System (TIRADS) classification were enrolled in this study, including 96 patients with malignant tumors and 54 with benign tumors. The DECT parameters were got form regions of interest (ROI) by an experienced radiologist team and thyroid nodules and lymph node status of all patients were identified by cytology and histopathology. Statistical analyses were performed using Student's t-test, Chi-squared test, and receiver operating characteristic (ROC) curves. Results: In the differential diagnosis of benign and malignant thyroid nodules, the optimal iodine concentration (IC) and normalized iodine concentration (NIC) cut-off values were ICa (2.835 mg/mL), NIC1a (0.690), and their corresponding area under the curve (AUC) were 0.940, 0.954 respectively; meantime, the optimal computed tomography (CT) value and slope of the spectral Hounsfield unit curve (λHU) cut-off values were 70 keVa (125.05 HU) and λHU2a (1.405), and their corresponding AUC were 0.955, 0.941 respectively. For lymph node status (with or without lymph node metastasis), the optimal IC and NIC thresholds were ICa (1.715 mg/mL) and NIC2a (0.155), and their corresponding AUC were 0.717, 0.720 respectively; meanwhile, the optimal CT value and λHU thresholds were 70 keVv (89.635 HU) and λHU2v (1.185), and their corresponding AUC were 0.729, 0.641 respectively. Conclusions: Base on our study, we think DECT is useful in differentiating malignant from benign thyroid nodules, which has potential value in the indirect prediction of lymph node metastasis in thyroid carcinoma.

Gelatin-glucosamine hydrochloride/crosslinked-cyclodextrin metal-organic frameworks@IBU composite hydrogel long-term sustained drug delivery system for osteoarthritis treatment.

Osteoarthritis (OA) is a disease of articular cartilage degradation and inflammation of the joint capsule. Combining anti-inflammatory therapy with nutritional supplement is an effective means for the treatment of OA. In this study, we prepared gelatin (Gel)-glucosamine hydrochloride (GH) mixed crosslinked-cyclodextrin metal-organic framework (G-GH/CL-CD-MOF) composite hydrogel. Polyethylene glycol diglycidyl ether was the crosslinking agent of GH and Gel to solve the problem of poor mechanical properties and water solubility at 37 °C. CL-CD-MOF was fabricated through a simple one-step chemical reaction to crosslink the hydrophilic hydroxyl groups in CD-MOF with diphenyl carbonate. Electron microscopy and x-ray diffraction analysis of CL-CD-MOF showed perfect porous morphology with a chaotic internal structure. CL-CD-MOF@IBU was prepared by immersing CL-CD-MOF in high-concentration ibuprofen (IBU) solution. CL-CD-MOF@IBU was uniformly dispersed in Gel and GH mixed solution to prepare G-GH/CL-CD-MOF@IBU composite hydrogel long-term sustained drug delivery system. The compression curve of G-GH/CL-CD-MOF composite hydrogel showed a non-linear elastic behavior. The cyclic loading-unloading compression showed that the shape of the G-GH/CL-CD-MOF composite hydrogel can be kept intact under 50% strain. On the day 14, the G-GH/CL-CD-MOF@IBU composite hydrogel was degraded by 87.1%, 61% of IBU was released. G-GH/CL-CD-MOF@IBU exhibited good biocompatibility during co-culture with MC3T3-E1 cells. Briefly, the certain mechanical properties, sustained drug release behavior, and good biocompatibility of G-GH/CL-CD-MOF@IBU composite hydrogel showed that it has potential application in OA treatment of long-term sustained nutritional supplement and anti-inflammatory synchronously.

Clinical application of MIIRMR as a salvage method in gadolinium-enhanced MRI after intra-tympanic injection.

BACKGROUND: Three-dimensional fluid-attenuated inversion-recovery (3 D-FLAIR) and real inversion-recovery (3 D-real IR) sequences are used to detect endolymphatic hydrops (EH), but medium inversion-time inversion-recovery imaging with magnitude reconstruction (MIIRMR) may be more sensitive. AIMS: We investigated the inner-ear visualisation success rate and EH detection rates of 3 D-FLAIR and 3 D-real IR, and whether salvage MIIRMR could improve EH detection. MATERIALS AND METHODS: Fifty-one patients (102 ears) with episodic or chronic vestibular syndrome were injected intra-tympanically with 8-fold diluted gadolinium, and 3 D-FLAIR and 3 D-real IR images obtained 24-h post-injection. If 3 D-FLAIR inner-ear visualisation failed, additional MIIRMR was performed. The success and EH detection rate increase by MIIRMR was calculated. The diagnostic performance of combined MIIRMR + 3D-FLAIR + 3D-real IR for Meniere's disease (MD) was evaluated. RESULTS: The success rates of 3 D-FLAIR and 3 D-real IR were 88.90% and 72.55%, respectively. MIIRMR increased the success and EH detection rates by 11.10% and 6.86%, respectively. In MD, MIIRMR increased these rates by 10.53% and 10.53%, respectively. 3 D-FLAIR + 3D-real IR + MIIRMR had 92.11% sensitivity, 79.68% specificity, 72.92% positive-predictive value, and 94.44% negative-predictive value for MD diagnosis. CONCLUSION AND SIGNIFICANCE: MIIRMR can improve success and EH detection rates when 3 D-FLAIR fails. Combined MIIRMR + 3D-FLAIR + 3D-real IR is more valuable for diagnosing MD than conventional sequences.