IL-4-induced decrease in both the number and CTLA-4 expression of Treg impairs suppression of Th2 type inflammation in severe atopic dermatitis.

BACKGROUND: Treg plays a pivotal role in the suppression of Th2 cell and the maintenance of immune homeostasis. The precise molecular mechanism underlying the disruption of Treg suppression of Th2 cell and the promotion of Th2 type inflammation in allergic diseases remains elusive. OBJECTIVE: This study aims to investigate the molecular mechanism underlying quantitative and functional changes of Treg in AD. METHODS: The molecular mechanism was investigated using flow cytometry, mRNA sequencing, co-culture experiments, co-immunoprecipitation, chromatin immunoprecipitation, and bisulfite sequencing in vitro or in AD mice model and patients with AD. RESULTS: Increased proportion of Treg was detected in mild and moderate AD. Conversely, characteristic decrease in both the number and CTLA-4 expression of Treg was relevant to serum IL-4 level in severe AD patients, which was verified under a high concentration of IL-4 treatment in vitro. The underlying mechanism is that IL-4/pSTAT6 pathway recruits DNMT1 and HDAC2 to inhibit transcriptional regulation of Foxp3 and CTLA-4 loci. High level of IL-4 impaired the suppression of Treg against Th2 cell differentiation mediated by CTLA-4, and blockade of IL-4Rα signaling in Treg restored Treg number and suppression of Th2 cell in AD model mice and patients with AD. CONCLUSION: The number of Treg is relevant to stratification of severity and serum IL-4 level in patients with AD. Abnormal high level of IL-4 epigenetically triggers a decrease in both the number and CTLA-4 expression of Treg. The reduced expression of CTLA-4 on Treg induced by IL-4 impairs suppression of Th2 cell differentiation.

Dual-layer spectral detector CT: A noninvasive preoperative tool for predicting histopathological differentiation in pancreatic ductal adenocarcinoma.

PURPOSE: To predict histopathological differentiation grades in patients with pancreatic ductal adenocarcinoma (PDAC) before surgery with quantitative and qualitative variables obtained from dual-layer spectral detector CT (DLCT). METHODS: Totally 128 patients with histopathologically confirmed PDAC and preoperative DLCT were retrospectively enrolled and categorized into the low-grade (LG) (well and moderately differentiated, n = 82) and high-grade (HG) (poorly differentiated, n = 46) subgroups. Both conventional and spectral variables for PDAC were measured. The ratio of iodine concentration (IC) values in arterial phase(AP) and venous phase (VP) was defined as iodine enhancement fraction_AP/VP (IEF_AP/VP). Necrosis was visually assessed on both conventional CT images (necrosis_con) and virtual mono-energetic images (VMIs) at 40 keV (necrosis_40keV). Forward stepwise logistic regression method was conducted to perform univariable and multivariable analysis. Receiver operating characteristic (ROC) curves and the DeLong method were used to evaluate and compare the efficiencies of variables in predicting tumor grade. RESULTS: Necrosis_con (odds ratio [OR] = 2.84, 95% confidence interval [CI]: 1.13-7.13; p < 0.001) was an independent predictor among conventional variables, and necrosis_40keV (OR = 5.82, 95% CI: 1.98-17.11; p = 0.001) and IEF_AP/VP (OR = 1.12, 95% CI:1.07-1.17; p < 0.001) were independent predictors among spectral variables for distinguishing LG PDAC from HG PDAC. IEF_AP/VP (AUC = 0.754, p = 0.016) and combination model (AUC = 0.812, p < 0.001) had better predictive performances than necrosis_con (AUC = 0.580). The combination model yielded the highest sensitivity (72%) and accuracy (79%), while IEF_AP/VP exhibited the highest specificity (89%). CONCLUSION: Variables derived from DLCT have the potential to preoperatively evaluate PDAC tumor grade. Furthermore, spectral variables and their combination exhibited superior predictive performances than conventional CT variables.

Relationship between dust allergen sensitization and cardiac autonomic function in patients with chronic obstructive pulmonary disease.

OBJECTIVE: Cardiac autonomic function predicts cardiovascular disease risk. The aim of this study was to investigate the relationship between sensitization to dust allergens and cardiac autonomic dysfunction in patients with chronic obstructive pulmonary disease (COPD), and to provide new ideas for the prevention of cardiovascular complications in these patients. METHODS: Immunoassays for sensitization to cats/dogs, cockroaches and dust mites were performed in 840 patients with COPD. Indicators of heart rate variability in these patients were used to assess cardiac autonomic function, including standard deviation of normal-to-normal intervals (SDNN), root-mean square of successive differences between normal-to-normal intervals (RMSSD), low-frequency power (LF), high-frequency power (HF), and LF/HF ratios, which were obtained based on ambulatory electrocardiographic monitoring data. The relationship between sensitization to these dust allergens and heart rate variability was explored using multivariate logistic regression. FINDINGS: The multivariate analyses showed that sensitization to total allergens was associated with reduced levels of SDNN, RMSSD, LF and HF and with increased levels of the LF/HF ratio in the patients with COPD (p < .05). CONCLUSION: Dust allergen sensitization may be associated with cardiac autonomic dysfunction in patients with COPD. Whether desensitization can prevent cardiovascular complications in these patients should be further explored.

Structural insights into the ubiquitylation strategy of the oligomeric CRL2FEM1B E3 ubiquitin ligase.

Cullin-RING E3 ubiquitin ligase (CRL) family members play critical roles in numerous biological processes and diseases including cancer and Alzheimer's disease. Oligomerization of CRLs has been reported to be crucial for the regulation of their activities. However, the structural basis for its regulation and mechanism of its oligomerization are not fully known. Here, we present cryo-EM structures of oligomeric CRL2FEM1B in its unneddylated state, neddylated state in complex with BEX2 as well as neddylated state in complex with FNIP1/FLCN. These structures reveal that asymmetric dimerization of N8-CRL2FEM1B is critical for the ubiquitylation of BEX2 while FNIP1/FLCN is ubiquitylated by monomeric CRL2FEM1B. Our data present an example of the asymmetric homo-dimerization of CRL. Taken together, this study sheds light on the ubiquitylation strategy of oligomeric CRL2FEM1B according to substrates with different scales.

KAT8-catalyzed lactylation promotes eEF1A2-mediated protein synthesis and colorectal carcinogenesis.

Aberrant lysine lactylation (Kla) is associated with various diseases which are caused by excessive glycolysis metabolism. However, the regulatory molecules and downstream protein targets of Kla remain largely unclear. Here, we observed a global Kla abundance profile in colorectal cancer (CRC) that negatively correlates with prognosis. Among lactylated proteins detected in CRC, lactylation of eEF1A2K408 resulted in boosted translation elongation and enhanced protein synthesis which contributed to tumorigenesis. By screening eEF1A2 interacting proteins, we identified that KAT8, a lysine acetyltransferase that acted as a pan-Kla writer, was responsible for installing Kla on many protein substrates involving in diverse biological processes. Deletion of KAT8 inhibited CRC tumor growth, especially in a high-lactic tumor microenvironment. Therefore, the KAT8-eEF1A2 Kla axis is utilized to meet increased translational requirements for oncogenic adaptation. As a lactyltransferase, KAT8 may represent a potential therapeutic target for CRC.

Feasibility of using 8 mL of iodinated contrast media in cerebral computed tomographic angiography with a dual-layer spectral detector.

Background: Virtual monoenergetic images (VMIs) at a low energy level can improve image quality when the amount of iodinated contrast media (CM) is reduced. The purpose was to evaluate the feasibility of using an extremely low CM volume and injection rate in cerebral computed tomography angiography (CTA) on a dual-layer spectral detector computed tomography (CT). Methods: Patients who were clinically suspected of intracranial aneurysm or cerebrovascular diseases were included in our study (from June to November 2022). In this prospective study, 80 patients were randomly enrolled into group A (8 mL of CM with a 1-mL/s flow rate) or group B (40 mL of CM with 4-mL/s flow rate). The VMIs at 40-70 keV in group A and polychromatic conventional images in the 2 groups were reconstructed. CT attenuation, image noise, contrast-to-noise ratio (CNR), and signal-to-noise ratio (SNR) were evaluated via the t-test or Mann-Whitney test (2 groups), while analysis of variance or Kruskal-Wallis test (multiple groups). Subjective image quality was assessed on a 5-point scale. Results: In group A, the subjective image quality score, CT attenuation, and CNR of the internal carotid artery (ICA) and middle cerebral artery (MCA) were the highest on VMIs at 40 keV. The image noise on VMIs at 40 keV was 5.08±0.84 Hounsfield units. The subjective image quality score, CT value of the ICA, MCA, and cerebral parenchyma on VMIs at 40 keV in group A were similar to those in group B (all P values >0.05). Compared to those in group B, the VMIs at 40 keV in group A demonstrated a significantly higher mean SNR and CNR of the ICA (mean SNR: 46.22±20.18 vs. 34.32±12.40, P=0.002; CNR: 55.47±13.43 vs. 46.18±12.30, P=0.002) and MCA [SNR: 13.66 (9.78, 20.29) vs. 9.99 (7.53, 14.00), P=0.003; CNR: 47.00±12.71 vs. 39.45±10.47, P=0.005]. Conclusions: Cerebral CTA on VMIs at 40 keV with 8 mL of CM and a 1-mL/s injection rate can provide diagnostic image quality.

Dual-energy CT improves differentiation of non-hypervascular pancreatic neuroendocrine neoplasms from CA 19-9-negative pancreatic ductal adenocarcinomas.

PURPOSE: To evaluate the utility of dual-energy CT (DECT) in differentiating non-hypervascular pancreatic neuroendocrine neoplasms (PNENs) from pancreatic ductal adenocarcinomas (PDACs) with negative carbohydrate antigen 19-9 (CA 19-9). METHODS: This retrospective study included 26 and 39 patients with pathologically confirmed non-hypervascular PNENs and CA 19-9-negative PDACs, respectively, who underwent contrast-enhanced DECT before treatment between June 2019 and December 2021. The clinical, conventional CT qualitative, conventional CT quantitative, and DECT quantitative parameters of the two groups were compared using univariate analysis and selected by least absolute shrinkage and selection operator regression (LASSO) analysis. Multivariate logistic regression analyses were performed to build qualitative, conventional CT quantitative, DECT quantitative, and comprehensive models. The areas under the receiver operating characteristic curve (AUCs) of the models were compared using DeLong's test. RESULTS: The AUCs of the DECT quantitative (based on normalized iodine concentrations [nICs] in the arterial and portal venous phases: 0.918; 95% confidence interval [CI] 0.852-0.985) and comprehensive (based on tumour location and nICs in the arterial and portal venous phases: 0.966; 95% CI 0.889-0.995) models were higher than those of the qualitative (based on tumour location: 0.782; 95% CI 0.665-0.899) and conventional CT quantitative (based on normalized conventional CT attenuation in the arterial phase: 0.665; 95% CI 0.533-0.797; all P < 0.05) models. The DECT quantitative and comprehensive models had comparable performances (P = 0.076). CONCLUSIONS: Higher nICs in the arterial and portal venous phases were associated with higher blood supply improving the identification of non-hypervascular PNENs.

Oncogenic ß-catenin-driven liver cancer is susceptible to methotrexate-mediated disruption of nucleotide synthesis.

BACKGROUND: Liver cancer is largely resistant to chemotherapy. This study aimed to identify the effective chemotherapeutics for ß-catenin-activated liver cancer which is caused by gain-of-function mutation of catenin beta 1 ( CTNNB1 ), the most frequently altered proto-oncogene in hepatic neoplasms. METHODS: Constitutive ß-catenin-activated mouse embryonic fibroblasts (MEFs) were established by deleting exon 3 ( ß-catenin Δ(ex3)/+ ), the most common mutation site in CTNNB1 gene. A screening of 12 widely used chemotherapy drugs was conducted for the ones that selectively inhibited ß-catenin Δ(ex3)/+ but not for wild-type MEFs. Untargeted metabolomics was carried out to examine the alterations of metabolites in nucleotide synthesis. The efficacy and selectivity of methotrexate (MTX) on ß-catenin-activated human liver cancer cells were determined in vitro . Immuno-deficient nude mice subcutaneously inoculated with ß-catenin wild-type or mutant liver cancer cells and hepatitis B virus ( HBV ); ß-catenin lox(ex3)/+ mice were used, respectively, to evaluate the efficacy of MTX in the treatment of ß-catenin mutant liver cancer. RESULTS: MTX was identified and validated as a preferential agent against the proliferation and tumor formation of ß-catenin-activated cells. Boosted nucleotide synthesis was the major metabolic aberration in ß-catenin-active cells, and this alteration was also the target of MTX. Moreover, MTX abrogated hepatocarcinogenesis of HBV ; ß-catenin lox(ex3)/+ mice, which stimulated concurrent Ctnnb1- activated mutation and HBV infection in liver cancer. CONCLUSION: MTX is a promising chemotherapeutic agent for ß-catenin hyperactive liver cancer. Since repurposing MTX has the advantages of lower risk, shorter timelines, and less investment in drug discovery and development, a clinical trial is warranted to test its efficacy in the treatment of ß-catenin mutant liver cancer.

Feasibility of spectral CT-derived extracellular volume fraction for differentiating aldosterone-producing from nonfunctioning adrenal nodules.

OBJECTIVE: To assess the feasibility of spectral CT-derived extracellular volume (ECV) for differentiating aldosterone-producing nodules (APN) from nonfunctioning adrenal nodules (NFN). METHODS: Sixty-nine patients with biochemically and histologically confirmed unilateral APN (34) and NFN (35) as well as 23 patients with bilateral APN (19) and NFN (27) confirmed biochemically and by adrenal vein sampling (AVS) were enrolled in this retrospective study from October 2020 to April 2022. All patients underwent contrast-enhanced spectral CT of the adrenal glands with a 10-min delayed phase. The haematocrit level was measured within 2 days of CT. An iodine density map was derived from the delayed CT. The ECV fractions of the APN and NFN were calculated and compared in the test cohort of 69 patients with unilateral adrenal nodules. The optimal cut-off value was determined to evaluate the diagnostic efficacy of the ECV fraction for differentiating APN from NFN in the validation cohort of 23 patients with bilateral adrenal nodules. RESULTS: The ECV fractions of the APN (11.17 ± 4.57%) were significantly lower (p < 0.001) than that of the NFN (24.79 ± 6.01%) in the test cohort. At cut-off ECV value of 17.16%, the optimal area under the receiver operating characteristic curve was 0.974 (95% confidence interval: 0.942-1) with 91.4% sensitivity, 93.9% specificity, and 92.8% accuracy in the test cohort and 89.5% sensitivity, 96.3% specificity, and 93.5% accuracy in the validation cohort for differentiating APN from NFN. CONCLUSION: The spectral CT-derived ECV fraction can differentiate APN from NFN with high diagnostic performance. CLINICAL RELEVANCE STATEMENT: Spectral CT-derived extracellular volume fraction could accurately differentiate between adrenal aldosterone-producing nodules and nonfunctioning nodules. It might serve as a noninvasive alternative to adrenal vein sampling in primary aldosteronism patients with bilateral adrenal nodules. KEY POINTS: • Conventional CT cannot differentiate aldosterone-producing adrenal nodules from nonfunctioning nodules. • Extracellular volume of adrenal aldosterone-producing nodules was significantly lower than that of nonfunctioning nodules and normal adrenal glands. It can accurately differentiate between aldosterone-producing and nonfunctioning adrenal nodules. • Extracellular volume may be a novel, noninvasive biomarker alternative to adrenal vein sampling for determining the functional status of bilateral adrenal nodules in patients with primary aldosteronism.

Does dual-layer spectral detector CT provide added value in predicting spread through air spaces in lung adenocarcinoma? A preliminary study.

OBJECTIVES: To examine the predictive value of dual-layer spectral detector CT (DLCT) for spread through air spaces (STAS) in clinical lung adenocarcinoma. METHODS: A total of 225 lung adenocarcinoma cases were retrospectively reviewed for demographic, clinical, pathological, traditional CT, and spectral parameters. Multivariable logistic regression analysis was carried out based on three logistic models, including a model using traditional CT features (traditional model), a model using spectral parameters (spectral model), and an integrated model combining traditional CT and spectral parameters (integrated model). Receiver operating characteristic (ROC) curve analysis and decision curve analysis (DCA) were performed to assess these models. RESULTS: Univariable analysis showed significant differences between the STAS and non-STAS groups in traditional CT features, including nodule density (p < 0.001), pleural indentation types (p = 0.006), air-bronchogram sign (p = 0.031), the presence of spiculation (p < 0.001), long-axis diameter of the entire nodule (LD) (p < 0.001), and consolidation/tumor ratio (CTR) (p < 0.001). Multivariable analysis revealed that LD > 20 mm (odds ratio [OR] = 2.271, p = 0.025) and CTR (OR = 24.208, p < 0.001) were independent predictors in the traditional model, while electronic density (ED) in the venous phase was an independent predictor in the spectral (OR = 1.062, p < 0.001) and integrated (OR = 1.055, p < 0.001) models. The area under the curve (AUC) for the integrated model (0.84) was the highest (spectral model, 0.83; traditional model, 0.80), and the difference between the integrated and traditional models was statistically significant (p = 0.015). DCA showed that the integrated model had superior clinical value versus the traditional model. CONCLUSIONS: DLCT has added value for STAS prediction in lung adenocarcinoma. CLINICAL RELEVANCE STATEMENT: Spectral CT has added value for spread through air spaces prediction in lung adenocarcinoma so may impact treatment planning in the future. KEY POINTS: • Electronic density may be a potential spectral index for predicting spread through air spaces in lung adenocarcinoma. • A combination of spectral and traditional CT features enhances the performance of traditional CT for predicting spread through air spaces.

Evaluation of microcirculation in asymptomatic cerebral infarction with multi-parameter imaging of spectral CT.

OBJECTIVE: To investigate the role of spectral CT multiparametric imaging in the evaluation of cerebral microcirculatory perfusion. METHODS: The imaging data of 145 patients with asymptomatic cerebral infarction confirmed by MR were retrospectively analyzed, and all cases underwent head CTA and cranial CT perfusion imaging (CTP) on double-layer detector spectral CT. Single energy level images (MonoE45 keV), iodine density maps, and effective atomic number maps were reconstructed based on spectral CTA data, and CT values, iodine density values, and effective atomic number values were measured in the infarcted area, healthy control area, centrum semiovale and posterior limb of the internal capsule, respectively; perfusion values, such as cerebral blood volume (CBV) values, cerebral blood flow (CBF) values, time to peak (TTP) values, and mean passage time, were measured in the above-mentioned areas on CTP images. (TTP) values, and mean time to passage (MTT) values. CT values, iodine density values, effective atomic number values, and perfused CBV, CBF, TTP, and MTT values were compared between the infarcted area and the healthy side, the center of the hemianopia, and the posterior limb of the internal capsule. The role of spectral CT parameters and perfusion parameters in the evaluation of asymptomatic cerebral infarction was analyzed. RESULTS: CT values, iodine density values, and effective atomic number values were statistically different between the infarcted area and the healthy side; CT values, iodine density values, and effective atomic number values were not statistically different between the infarcted side and the healthy side of the hemispheric centrum and the posterior limb of the internal capsule; CBV and CBF were statistically different between the infarcted side and the healthy side, and MTT and TTP were not statistically different. There were statistically significant differences in TTP between the infarcted area and the healthy side of the hemiaxial center, and no statistically significant differences in CBV, CBF, and MTT. There were no statistical differences in CBV, CBF, TTP, and MTT in the inner capsule area. ROC curve analysis of spectral CT-related parameters and CT perfusion parameters for the diagnosis of asymptomatic cerebral infarction: area under the curve of MonoE 45Kv 0.71, area under the curve of iodine density values 0.76, area under the curve of effective atomic number values 0.74; area under the curve of CBV value 0.64, area under the curve of CBF value 0.61, area under the curve of MTT value 0.50, The area under the TTP curve was 0.52. The area under the ROC curve of the multivariate logistic regression model based on spectral parameters is 0.76, which is higher than that of the logistic regression model with perfusion parameters (P < 0.05). CONCLUSION: Spectral CT can better demonstrate small intracranial ischemic lesions, and iodine density values have a better evaluation of microcirculation in asymptomatic cerebral infarcts.

Effects of different over-fired drying methods on the aroma of Lu'an Guapian tea.

Over-fired drying, a crucial process in the production of Lu'an Guapian (LAGP) tea, greatly enriches the tea's aroma. In this study, the aroma compounds of LAGP tea processed through pulley charcoal drying (PCD), roller drying (RD), roller-conveyor drying (RCD), and hot air drying (HD) were analyzed using gas chromatography-mass spectrometry. A subsequent analysis of aroma extraction dilution analysis and odor activity values revealed that (E)-ß-ionone, dimethyl sulfide, (E,E)-2,4-heptadienal, geraniol, linalool, benzeneacetaldehyde, coumarin, 2-ethyl-3,5-dimethyl-pyrazine, indole, hexanal, (Z)-jasmone, and (Z)-3-hexen-1-ol were the key contributors to the samples' aroma variation. Moreover, a quantitative descriptive analysis and aroma recombination and omission experiments analysis revealed that (E)-ß-ionone is the most critical contributor to the formation of floral aroma in tea processed using PCD, whereas (E,E)-2,4-heptadienal is responsible for the more pronounced fresh aroma in tea processed using HD. In addition, 2-ethyl-3,5-dimethyl-pyrazine contributes to the formation of a roasted aroma in tea processed using RD and RCD. The study results provide a theoretical basis for choosing the processing method, especially for drying, to obtain high-quality LAGP tea.

OLR1 Is a Pan-Cancer Prognostic and Immunotherapeutic Predictor Associated with EMT and Cuproptosis in HNSCC.

Metabolism plays a critical role in cancer. OLR1 has been implicated in cardiovascular and metabolic disorders, while its association with tumorigenesis and tumor immunity remains poorly defined in the literature. We conducted comprehensive pan-cancer analyses based on the TCGA database to examine OLR1 expression and its prognostic implications. Correlations between OLR1 expression level and tumor immunity and immunotherapy were investigated by immune infiltration, enrichment, and TIDE analysis methods. Immunohistochemistry detected OLR1 expression in HNSCC. We used the GSEA method to explore the potential signaling pathways in which OLR1 is involved, and a correlation analysis to investigate the relationships between OLR1 and epithelial-mesenchymal transition (EMT) and cuproptosis. In addition, the effects of OLR1 knockdown on the EMT process, invasion, stemness, and cuproptosis of HNSCC cells were examined by scratch, Transwell, CCK8, sphere formation, and flow cytometry, while changes in related proteins were detected using the immunoblotting method. OLR1 is highly expressed in most cancers, and it is associated with patient prognosis. OLR1 expression positively correlates with immunosuppressive cell infiltration and immune checkpoint molecules, while being negatively associated with effector T cells. Moreover, significant correlations are observed between OLR1 expression and tumor mutation burden (TMB) and microsatellite instability (MSI) in some cancers. In HNSCC, OLR1 expression is related to advanced clinicopathological factors and unfavorable outcomes. Patients with high OLR1 expression levels are prone to experience immune escape and benefit less from immune checkpoint inhibitor (ICI) therapy. Moreover, OLR1 expression may affect EMT, stemness, and cuproptosis resistance outcomes. OLR1 is an immune-related prognostic biomarker with potential as a prognostic indicator for immunotherapy, and it may also be involved in regulating the EMT process and cuproptosis in HNSCC.

Dual-Energy CT Deep Learning Radiomics to Predict Macrotrabecular-Massive Hepatocellular Carcinoma.

Background It is unknown whether the additional information provided by multiparametric dual-energy CT (DECT) could improve the noninvasive diagnosis of the aggressive macrotrabecular-massive (MTM) subtype of hepatocellular carcinoma (HCC). Purpose To evaluate the diagnostic performance of dual-phase contrast-enhanced multiparametric DECT for predicting MTM HCC. Materials and Methods Patients with histopathologic examination-confirmed HCC who underwent contrast-enhanced DECT between June 2019 and June 2022 were retrospectively recruited from three independent centers (center 1, training and internal test data set; centers 2 and 3, external test data set). Radiologic features were visually analyzed and combined with clinical information to establish a clinical-radiologic model. Deep learning (DL) radiomics models were based on DL features and handcrafted features extracted from virtual monoenergetic images and material composition images on dual phase using binary least absolute shrinkage and selection operators. A DL radiomics nomogram was developed using multivariable logistic regression analysis. Model performance was evaluated with the area under the receiver operating characteristic curve (AUC), and the log-rank test was used to analyze recurrence-free survival. Results A total of 262 patients were included (mean age, 54 years ± 12 [SD]; 225 men [86%]; training data set, n = 146 [56%]; internal test data set, n = 35 [13%]; external test data set, n = 81 [31%]). The DL radiomics nomogram better predicted MTM than the clinical-radiologic model (AUC = 0.91 vs 0.77, respectively, for the training set [P < .001], 0.87 vs 0.72 for the internal test data set [P = .04], and 0.89 vs 0.79 for the external test data set [P = .02]), with similar sensitivity (80% vs 87%, respectively; P = .63) and higher specificity (90% vs 63%; P < .001) in the external test data set. The predicted positive MTM groups based on the DL radiomics nomogram had shorter recurrence-free survival than predicted negative MTM groups in all three data sets (training data set, P = .04; internal test data set, P = .01; and external test data set, P = .03). Conclusion A DL radiomics nomogram derived from multiparametric DECT accurately predicted the MTM subtype in patients with HCC. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Chu and Fishman in this issue.

Diagnostic Ability of Perivascular Fat Attenuation Index in Predicting Atherosclerotic Plaque Formation Proximal to Myocardial Bridging of the Left Anterior Descending Artery within 3 Years.

RATIONALE AND OBJECTIVES: This study was designed to investigate the association between the perivascular fat attenuation index (FAI) and atherosclerotic plaque formation proximal to myocardial bridging (MB) of the left anterior descending artery (LAD) within 3 years. MATERIALS AND METHODS: LAD-MB patients who underwent coronary computed tomography angiography at least twice between January 2016 and December 2022 were retrospectively included in this study. In total, 99 LAD-MB patients were included in the study. Based on the formation of atherosclerotic plaques proximal to LAD-MB during follow-up, the patients were classified into two groups: LAD-MB with plaque formation and LAD-MB without plaque formation within 3 years. The anatomical features, clinical factors, and proximal perivascular FAI of LAD-MB were measured and recorded. The association of the previously mentioned factors with the presence of atherosclerotic plaque proximal to LAD-MB was determined. RESULTS: The results showed that MB length, MB stenosis, and the perivascular FAI were significant predictors of the formation of atherosclerotic plaques proximal to LAD-MB. The area under the curve of the combined predictive model incorporating MB length, MB stenosis, and the perivascular FAI was 0.901(95% confidence interval: 0.824-0.952), with higher diagnostic performance than any other single parameter (all P < 0.05). Moreover, dynamic changes in the perivascular FAI of the vascular segments proximal to LAD-MB were higher in high-risk plaques than in non-high-risk plaques (P = 0.003). CONCLUSION: The combined use of the perivascular FAI, MB length, and MB stenosis may enable prediction of the probability of atherosclerotic plaque formation proximal to LAD-MB within 3 years. Dynamic changes in perivascular FAI were associated with the vulnerability of plaques proximal to LAD-MB.

Electrospinning of Biodegradable, Monolithic Membrane with Distinct Bimodal Micron-Sized Fibers and Nanofibers for High Efficiency PMs Removal.

Atmospheric particulate matter (PMs) pollution has raised increasing public concerns, especially with the outbreak of COVID-19. The preparation of high-performance membranes for air filtration is of great significance. Herein, the biosynthetic polymer poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) was adopted to create a hierarchical structure and biodegradable nonwoven membrane for PMs filtration through a facile directly electrospinning method. The as-prepared membranes with hierarchical structure contain abundant nanowires (5-100 nm) and microfibers (2-5 µm) with different diameter (1000-5000 nm). We have achieved realization of formation mechanisms of such bimodal micro- and nanofibers, which stem from the branching of microfiber at early stage of electrospinning. The PHBV membranes exhibit a very high PM0.3 removal efficiency of 99.999% and PM2.5 removal efficiency of 100% with 0.077% standard atmospheric pressure in the air flow speed of 5.3 cm/s. More importantly, the PHBV membranes can be completely disintegrated within 1 week under composted conditions, indicating the great biodegradability of PHBV membranes. Our work provides insights for the development of biodegradable, high performance air filters for pollutants, molds, bacteria, and viruses.

Adaptive sliding mode fault-tolerant attitude control for flexible satellites based on T-S fuzzy disturbance modeling.

This paper investigates the fault tolerance problem of flexible satellites subject to actuator faults and multiple disturbances. An adaptive sliding mode fault tolerant control (ASMFTC) approach based on Takagi-Sugeno (T-S) fuzzy disturbance observer (TSFDO) is presented for attitude control system (ACS) under loss of actuator effectiveness, environmental disturbance torque and elastic modal generated by flexible appendages. Compared with the traditional disturbance observer based control (DOBC) methods, the T-S fuzzy technology is applied to estimate the unknown nonlinear elastic modal. Then, the energy bounded disturbance is eliminated by designing an adaptive sliding mode controller. The proposed ASMFTC design can guarantee the sliding surface to approach zero. Finally, the effectiveness of the control method proposed in this paper is further verified by comparative simulation.

Metabolite analysis and sensory evaluation reveal the effect of roasting on the characteristic flavor of large-leaf yellow tea.

Roasting is essential for processing large-leaf yellow tea (LYT). However, the effect of the roasting on the metabolic and sensory profiles of LYT remains unknown. Herein, the metabolomics and sensory quality of LYT at five roasting degrees were evaluated by liquid/gas chromatography mass spectrometry and quantitative descriptive analysis. A higher degree of roasting resulted in a significantly stronger crispy rice, fried rice, and smoky-burnt aroma (p < 0.05), which is closely associated with heterocyclic compound accumulation (concentrations: 6.47 ± 0.27 - 1065.00 ± 5.58 µg/g). Amino acids, catechins, flavonoid glycosides and N-ethyl-2-pyrrolidone-substituted flavan-3-ol varied with roasting degree. The enhancement of crispy-rice and burnt flavor coupled with the reduction of bitterness and astringency. Correlations analysis revealed the essential compounds responsible for roasting degree, including 2,3-diethyl-5-methylpyrazine, hexanal, isoleucine, N-ethyl-2-pyrrolidone-substituted flavan-3-ol (EPSF), and others. These findings provide a theoretical basis for improving the specific flavors of LYT.

Identification of a Favorable Prognostic Subgroup in Oral Squamous Cell Carcinoma: Characterization of ITGB4/PD-L1high with CD8/PD-1high.

Integrin ß4 (ITGB4) is a member of the integrin family, which plays a crucial role in mediating cell adhesion to the extracellular matrix. Recent studies have demonstrated that ITGB4 is involved in tumorigenesis and metastasis during the development of cancer. However, the role of ITGB4 in oral squamous cell carcinoma (OSCC) remains unclear. A Multiplex immunohistochemistry (OPAL™, mIHC) assay was employed to stain ITGB4, ALDH1, PD-L1, cytokeratin (CK), CD8 and PD-1 in a human OSCC tissue microarray, containing 26 normal oral epithelium samples, 21 oral epithelium dysplasia samples and 76 OSCC samples. The expression pattern and clinicopathological characteristics of ITGB4 were analyzed and compared with those of PD-1, PD-L1, ALDH1 and CD8. The correlation between subgroups of tumor cells, including ITGB4+PD-L1+ and ITGB4+ALDH1+, and subgroups of T cells, including CD8+ and CD8+PD-1+, was evaluated using two-tailed Pearson's statistics. A Kaplan-Meier curve was built, and a log-rank test was performed to analyze the survival rate of different subgroups. The mIHC staining results show that ITGB4 was mostly expressed in the tumor cells, with a significant increase in the OSCC specimens compared with normal oral epithelium and oral epithelium dysplasia. The paired analysis, conducted between the OSCC tumor tissue and normal paracancer mucosa, confirmed the results. The study further revealed that ITGB4+PD-L1+ cancer cells, but not ITGB4+ALDH1+ cancer cells, were significantly associated with the infiltration of CD8+ T cells (positivity p = 0.005, positive number p = 0.03). Additionally, ITGB4+PD-L1+ tumor cells were positively correlated with CD8+PD-1+ T cells (positivity p = 0.02, positive number p = 0.03). Most intriguingly, the subgroup of ITGB4/PD-L1high with CD8/PD-1high displayed the best prognosis compared with the other considered subgroups. The results show that the expression of ITGB4 was increased in OSCC compared with normal oral mucosa. Furthermore, a specific subgroup with high levels of expression of ITGB4/PD-L1 and CD8/PD-1 was found to have a relatively better prognosis compared with the other subgroups. Ultimately, this study sheds light on the potential role of ITGB4 in OSCC and provides a basis for further investigation.

Efficacy and confounding factors of CT attenuation value differences in distinguishing acute and old vertebral compression fractures: a retrospective study.

PURPOSE: To evaluate the influence of various factors on CT attenuation values (HUs) of acute and old fracture vertebra, and to determine the efficacy of HU differences (△HUs) in the differentiation of the two type of fractures. MATERIALS AND METHODS: A total of 113 acute and 71 old fracture vertebrae confirmed by MRI were included. Four HUs measured at the mid-sagittal, upper 1/3 axial, mid-axial, and lower 1/3 axial planes of each vertebra were obtained. The △HUs between fracture vertebra and its control counterpart was calculated. Receiver operating characteristic (ROC) curve analysis was used and the areas under the ROC curve (AUC) were calculated to evaluate the efficacy of HUs and △HUs. To evaluate the effect of height reduction, region, age and gender on HUs and △HUs, one-way analysis of variance, Pearson correlation analysis and t-test were used. RESULTS: The HUs and △HUs at the upper 1/3 axial plane achieved the highest AUCs of 0.801 and 0.839, respectively. The HUs decreased gradually from Thoracic to Lumbar in control group of acute fracture. While no significant differences were found in the HUs among the 3 localizations in both fracture groups (all P > 0.05). The HUs were negatively correlated with age in all groups. The HUs of male were significantly higher than female patients in all groups (all P < 0.05). While △HU was not significantly different between males and females (all P > 0.05). CONCLUSION: The vertebral HUs at the upper 1/3 axial plane are more likely to identify acute fractures. △HUs were beneficial in eliminating interfering factors.