3D MR elastography-based stiffness as a marker for predicting tumor grade and subtype in cervical cancer.

BACKGROUND: Increasing evidence has indicated that high tissue stiffness (TS) may be a potential biomarker for evaluation of tumor aggressiveness. PURPOSE: To investigate the value of magnetic resonance elastography (MRE)-based quantitative parameters preoperatively predicting the tumor grade and subtype of cervical cancer (CC). STUDY TYPE: Retrospective. POPULATION: Twenty-five histopathology-proven CC patients and 7 healthy participants. FIELD STRENGTH/SEQUENCE: 3.0T, magnetic resonance imaging (MRI) (LAVA-flex) and MRE with a three-dimensional spin-echo echo-planar imaging. ASSESSMENT: The regions of interest (ROIs) were manually drawn by two observers in tumors to measure mean TS, storage modulus (G'), loss modulus (G″) and damping ratio (DR) values. Surgical specimens were evaluated for tumor grades and subtypes. STATISTICAL TESTS: Intraclass correlation coefficient (ICC) was expressed in terms of inter-observer agreements. t-test or Mann-Whitney nonparametric test was used to compare the complex modulus and apparent diffusion coefficient (ADC) values between different tumor groups. Area under the receiver operating characteristic curve (AUC) analysis was used to evaluate the diagnostic performance. RESULTS: The TS of endocervical adenocarcinoma (ECA) group was significantly higher than that in squamous cell carcinoma (SCC) group (5.27 kPa vs. 3.44 kPa, P = 0.042). The TS also showed significant difference between poorly and well/moderately differentiated CC (5.21 kPa vs. 3.47 kPa, P = 0.038), CC patients and healthy participants (4.18 kPa vs. 1.99 kPa, P < 0.001). The cutoff value of TS to discriminate ECA from SCC was 4.10 kPa (AUC: 0.80), while it was 4.42 kPa to discriminate poorly from well/moderately differentiated CC (AUC: 0.83), and 2.25 kPa to distinguish normal cervix from CC (AUC: 0.88), respectively. There were no significant difference in G″, DR and ADC values between any subgroups except for comparison of healthy participants and CC patients (P = 0.001, P = 0.004, P < 0.001, respectively). DATA CONCLUSION: 3D MRE-assessed TS shows promise as a potential biomarker to preoperatively assess tumor grade and subtype of CC.

The emotion filmmaker: Temporal memory, time-emotion integration, and affective style.

Emotional experiences are temporally dynamic, but prior work suggests that temporal features are usually neglected in remembered emotion. For instance, retrospective emotion evaluations are often biased by discrete salient timepoints, such as the peak and end moments, at the expense of objective event duration (i.e., peak-end effects and duration neglect). However, how these retrospective emotion biases originate, as well as their significance for emotional functioning, remain unclear. Here, we test the hypothesis that retrospective emotion biases are related to fundamental limits of temporal processing and memory capacity. Further, we examine whether these limits have implications for emotional functioning. Participants (n = 60) underwent a novel paradigm comprising affectively-rich movie sequences while providing emotion ratings continuously (moment-by-moment) and retrospectively. Temporal memory for previously watched emotional movie sequences and dispositional negativity were measured. Our findings revealed a greater "end" bias as the duration of emotional-movie sequences increased, suggesting that limitations in temporal processing capacity may contribute to retrospective emotion biases. Critically, temporal-memory errors were associated with larger retrospective emotion biases and with individual differences in dispositional negativity. Collectively, these results indicate that retrospective emotion biases may stem partly from mnemonic temporal errors that are emotionally maladaptive. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Business decision-making of power generators in competitive electricity market.

This paper presents a theoretical framework for the business decision-making process of the power generators as price takers when considering the participation of energy storage. The framework assesses rational valuation, optimal sales strategies, and hedging options for power plants with and without a gross sales constraint. The valuation and optimal sales strategy problems are analyzed using a risk-neutral pricing approach, dynamic programming principles, and the trinomial tree model suitable for the regime switching model. The formulation of a price risk hedging scheme flexible and widely used over-the-counter electricity derivative, the electricity contract for difference, as a tool for hedging electricity spot price risk. The minimum variance hedge ratio and its corresponding hedging efficiency formula are derived. In the section of numerical simulations, we first use the EM algorithm to calibrate the electricity spot model based on electricity spot price data of Nord Pool. Numerical simulations are then conducted on the operational decision-making of power generators under three different forms of energy storage. The results of the simulations provide a basis for power generators to evaluate the real-time value of power plants, to select optimal real-time power sales, and to determine the optimal timing of power plant transfer and storage methods.

Amorphous bismuth and GO co-doped WO3 electrochromic film with fast-switching time and long-term stability.

The sol-gel process for fabricating electrochromic thin films is straightforward, offering advantages such as low cost and ease of compositional control. Herein we prepared GO-Bi-WO3 films with improved electrochromic performance using a simple sol-gel spin-coating method. The sample shows a fast-switching time (1.8 s for coloring and 1.8 s for bleaching), large optical modulation (85% at 630 nm), excellent stability (86.4% retention after 10 200 cycles), and high coloration efficiency (65.9 cm2 C-1). This work indicates the electrochromic performance of WO3-based films can be enhanced by incorporating GO, which provides an effective strategy for the rapid, safe, and efficient fabrication of electrochromic thin films.

Head-to-head comparison of 18F-FAPI and 18F-FDG PET/CT in staging and therapeutic management of hepatocellular carcinoma.

BACKGROUND: Fluorine 18 (18F) fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) has limitations in staging hepatocellular carcinoma (HCC). The recently introduced 18F-labeled fibroblast-activation protein inhibitor (FAPI) has shown promising prospects in detection of HCC lesions. This study aimed to investigate the initial staging and restaging performance of 18F-FAPI PET/CT compared to 18F-FDG PET/CT in HCC. METHODS: This prospective study enrolled histologically confirmed HCC patients from March 2021 to September 2022. All patients were examined with 18F-FDG PET/CT and 18F-FAPI PET/CT within 1 week. The maximum standard uptake value (SUVmax), tumor-to-background ratio (TBR), and diagnostic accuracy were compared between the two modalities. RESULTS: A total of 67 patients (57 men; median age, 57 [range, 32-83] years old) were included. 18F-FAPI PET showed higher SUVmax and TBR values than 18F-FDG PET in the intrahepatic lesions (SUVmax: 6.7 vs. 4.3, P < 0.0001; TBR: 3.9 vs. 1.7, P < 0.0001). In diagnostic performance, 18F-FAPI PET/CT had higher detection rate than 18F-FDG PET/CT in intrahepatic lesions [92.2% (238/258) vs 41.1% (106/258), P < 0.0001] and lymph node metastases [97.9% (126/129) vs 89.1% (115/129), P = 0.01], comparable in distant metastases [63.6% (42/66) vs 69.7% (46/66), P > 0.05]. 18F-FAPI PET/CT detected primary tumors in 16 patients with negative 18F-FDG, upgraded T-stages in 12 patients and identified 4 true positive findings for local recurrence than 18F-FDG PET, leading to planning therapy changes in 47.8% (32/67) of patients. CONCLUSIONS: 18F-FAPI PET/CT identified more primary lesions, lymph node metastases than 18F-FDG PET/CT in HCC, which is helpful to improve the clinical management of HCC patients. TRIAL REGISTRATION: Clinical Trials, NCT05485792 . Registered 1 August 2022, Retrospectively registered.

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.

Clinical significance of CD155 expression and correlation with cellular components of tumor microenvironment in gastric adenocarcinoma.

Introduction: CD155 is recently emerging as a promising target in malignancies. However, the relationship between CD155 expression and tumor microenvironment (TME) cell infiltration in gastric adenocarcinoma (GAC) has rarely been clarified. Methods: We measured CD155 expression in specimens of gastric precancerous disease and GAC by immunohistochemistry. The association of CD155 expression with GAC progression and cells infiltration in TME was evaluated through 268 GAC tissues and public dataset analysis. Results: We showed that the expression of CD155 was positively correlated with the pathological development of gastric precancerous disease (r = 0.521, P < 0.0001). GAC patients with high CD155 expression had a poorer overall survival (P = 0.033). Moreover, CD155 expression correlated with aggressive clinicopathological features including tumor volume, tumor stage, lymph node involvement, and cell proliferation (P <0.05). Remarkably, CD155 expression positively related to the infiltration of CD68+ macrophages in TME (P = 0.011). Meanwhile, the positive correlation was observed between CD155 and CD31 (P = 0.026). In addition, patients with high CD155 expression combined with low CD3, CD4, CD8, IL-17, IFN-γ or CD19 expression as well as those with high CD155 and α-SMA expression showed significantly worse overall survival (P < 0.05). Conclusions: CD155 may play a pivotal role in the development of GAC through both immunological and non-immunological mechanisms and be expected to become a novel target of immunotherapy in GAC patients.

Berberine Alleviates Doxorubicin-Induced Myocardial Injury and Fibrosis by Eliminating Oxidative Stress and Mitochondrial Damage via Promoting Nrf-2 Pathway Activation.

Doxorubicin (DOX)-related cardiotoxicity has been recognized as a serious complication of cancer chemotherapy. Effective targeted strategies for myocardial protection in addition to DOX treatment are urgently needed. The purpose of this paper was to determine the therapeutic effect of berberine (Ber) on DOX-triggered cardiomyopathy and explore the underlying mechanism. Our data showed that Ber markedly prevented cardiac diastolic dysfunction and fibrosis, reduced cardiac malondialdehyde (MDA) level and increased antioxidant superoxide dismutase (SOD) activity in DOX-treated rats. Moreover, Ber effectively rescued the DOX-induced production of reactive oxygen species (ROS) and MDA, mitochondrial morphological damage and membrane potential loss in neonatal rat cardiac myocytes and fibroblasts. This effect was mediated by increases in the nuclear accumulation of nuclear erythroid factor 2-related factor 2 (Nrf2) and levels of heme oxygenase-1 (HO-1) and mitochondrial transcription factor A (TFAM). We also found that Ber suppressed the differentiation of cardiac fibroblasts (CFs) into myofibroblasts, as indicated by decreased expression of α-smooth muscle actin (α-SMA), collagen I and collagen III in DOX-treated CFs. Pretreatment with Ber inhibited ROS and MDA production and increased SOD activity and the mitochondrial membrane potential in DOX-challenged CFs. Further investigation indicated that the Nrf2 inhibitor trigonelline reversed the protective effect of Ber on both cardiomyocytes and CFs after DOX stimulation. Taken together, these findings demonstrated that Ber effectively alleviated DOX-induced oxidative stress and mitochondrial damage by activating the Nrf2-mediated pathway, thereby leading to the prevention of myocardial injury and fibrosis. The current study suggests that Ber is a potential therapeutic agent for DOX-induced cardiotoxicity that exerts its effects by activating Nrf2.

Crystal Structure Analysis of Sarcoplasmic-Calcium-Binding Protein: An Allergen in Scylla paramamosain.

The structure of allergenic proteins provides important information about the binding of allergens to antibodies. In this study, the crystal structure of Scy p 4 with a resolution of 1.60 Å was obtained by X-ray diffraction. Epitope mapping of Scy p 4 revealed that linear epitopes are located on the surface of Scy p 4. Also, conformational epitopes are mostly located in the structural conservative region. Further structural comparison, surface electrostatic potential, and hydrogen bond force analysis showed that mutation of Asp70 and Asp18/20/70 would lead to calcium-binding capacity being lost and destruction of allergenicity. Furthermore, a comparative analysis of structure showed that sarcoplasmic-calcium-binding protein (SCP) had high sequence, secondary, and spatial structural identity in crustaceans, which may be an important factor leading to cross-reactivity among crustaceans. The structure of Scy p 4 provides a template for epitope evaluation and localization of SCPs, which will help to reveal cross-reactivity among species.

The value of quantitative MR elastography-based stiffness for assessing the microvascular invasion grade in hepatocellular carcinoma.

OBJECTIVES: To evaluate the potential diagnostic value of MR elastography (MRE)-based stiffness to noninvasively predict the microvascular invasion (MVI) grade in hepatocellular carcinoma (HCC). METHODS: One hundred eighty-five patients with histopathology-proven HCC who underwent MRI and MRE examinations before hepatectomy were retrospectively enrolled. According to the three-tiered MVI grading system, the MVI was divided into negative-MVI (n = 89) and positive-MVI (n = 96) groups, and the latter group was categorized into mild-MVI (n = 49) and severe-MVI (n = 47) subgroups. Logistic regression and area under the receiver operating characteristic curve (AUC) analyses were used to determine the predictors associated with MVI grade and analyze their performances, respectively. RESULTS: Among the 185 patients, tumor size ≥ 50 mm (p = 0.031), tumor stiffness (TS)/liver stiffness (LS) > 1.47 (p = 0.001), TS > 4.33 kPa (p < 0.001), and nonsmooth tumor margin (p = 0.006) were significant independent predictors for positive-MVI. Further analyzing the subgroups, tumor size ≥ 50 mm (p < 0.001), TS > 5.35 kPa (p = 0.001), and AFP level > 400 ng/mL (p = 0.044) were independently associated with severe-MVI. The models incorporating MRE and clinical-radiological features together performed better for evaluating positive-MVI (AUC: 0.846) and severe-MVI (AUC: 0.802) than the models using clinical-radiological predictors alone (AUC: positive-/severe-MVI, 0.737/0.743). Analysis of recurrence-free survival and overall survival showed the predicted positive-MVI/severe-MVI groups based on combined models had significantly poorer prognoses than predicted negative-MVI/mild-MVI groups, respectively (all p < 0.05). CONCLUSIONS: MRE-based stiffness was an independent predictor for both the positive-MVI and severe-MVI. The combination of MRE and clinical-radiological models might be a useful tool for evaluating HCC patients' prognoses underwent hepatectomy by preoperatively predicting the MVI grade. KEY POINTS: • The severe-microvascular invasion (MVI) grade had the highest tumor stiffness (TS), followed by mild-MVI and non-MVI, and there were significances among the three different MVI grades. • MR elastography (MRE)-based stiffness value was an independent predictor of positive-MVI and severe-MVI in hepatocellular carcinoma (HCC) preoperatively. • When combined with clinical-radiological models, MRE could significantly improve the predictive performance for MVI grade. Patients with predicted positive-MVI/severe-MVI based on the combined models had worse recurrence-free survival and overall survival than those with negative-MVI/mild-MVI, respectively.

[18F]FAPI PET/CT in the evaluation of focal liver lesions with [18F]FDG non-avidity.

PURPOSE: This prospective study was aimed to investigate the potential utility of [18F]fibroblast activation protein inhibitor (FAPI) PET/CT for evaluating focal liver lesions (FLLs) with [18F]FDG non-avidity. METHODS: From January 2021 to March 2022, this prospective study included 80 FLLs that were not avid on [18F]FDG PET/CT from 37 patients, then underwent [18F]FAPI PET/CT. All patients with FLL(s) with biopsy-proof or follow-up confirmation were categorized into four subgroups (20 hepatocellular carcinomas [HCCs]/5 non-HCC malignancies/4 inflammatory FLLs/8 benign noninflammatory FLLs). The diagnostic value of [18F]FAPI for detecting liver malignancy was determined by visual evaluation. Differences in the maximum standardized uptake value (SUVmax) and lesion-to-background ratio (LBR) obtained from [18F]FAPI PET/CT among the four subgroups were analyzed by semiquantitative analysis. RESULTS: Among the thirty-seven enrolled participants (34 males; median age 57 years, range 48-67 years), on visual evaluation, the sensitivity, specificity, and accuracy of [18F]FAPI PET for detecting liver malignancy in the patient-based analysis were 96.0% (24/25), 58.3% (7/12), and 83.8% (31/37), respectively. On semiquantitative analysis, the SUVmax and LBR of [18F]FAPI PET in liver malignancy (33 HCC lesions; 19 non-HCC malignant lesions) were significantly higher than those in 11 benign noninflammatory FLLs [HCC: SUVmax: 6.4 vs. 4.5, P = 0.017; LBR: 5.1 vs. 1.5, P = 0.003; non-HCC: SUVmax: 5.5 vs. 4.5, P = 0.008; LBR: 4.4 vs. 1.5, P = 0.042]. Notably, there was no significant difference in the SUVmax of [18F]FAPI PET between 33 HCC lesions and 17 inflammatory FLLs (6.4 vs. 8.2, P = 0.37), but the LBR of [18F]FAPI PET in HCC were significantly lower than that in inflammatory FLLs (5.1 vs. 9.1, P = 0.003). CONCLUSIONS: [18F]FAPI PET/CT shows high sensitivity in detecting HCC and non-HCC malignancy with [18F]FDG non-avidity. [18F]FAPI might be a promising radiopharmaceutical for the differential diagnosis of benign noninflammatory FLLs and liver malignancy with [18F]FDG non-avidity.

Hypoallergenic derivatives of Scylla paramamosain heat-stable allergens alleviated food allergy symptoms in Balb/c mice.

The design of hypoallergenic derivatives is a new strategy for allergen-specific immunotherapy. Although hypoallergenic derivatives of Scylla paramamosain (mud crab) heat-stable tropomyosin (TM) and myosin light chain (MLC) have been preliminarily explored, their allergenicity in vivo needs to be further studied. In this work, recombinant allergens (wtTM, wtMLC) and hypoallergenic derivatives (mtTM, mtMLC) were purified. IgE-binding frequencies of wtTM and wtMLC in 177 crab-sensitised patients were 32.8% and 11.9%, respectively. In the Balb/c mouse model, mtTM and mtMLC caused mild intestinal inflammation, did not activate T-helper (Th) 2 immune response (interleukin-4, anaphylactic mediator, IgE, and IgG1 antibodies were not significantly increased) but could significantly promote the production of interleukin-10, which equilibrated Th1/Th2 cells, thus alleviating allergic symptoms. Moreover, mtTM and mtMLC-induced rabbit/mice anti-IgG antibodies could effectively block wtTM and wtMLC binding to patients' sera IgE in vitro. These results indicate that hypoallergenic derivatives offer the promise for an immunotherapeutic regimen for crab allergy.

Identification of the Immunoglobulin E Epitope of Arginine Kinase, an Important Allergen from Crassostrea angulata.

Arginine kinase (AK) was identified as an allergen in Crassostrea angulata. However, little information is available about its epitopes. In this study, AK from C. angulata was registered to the World Health Organization/International Union of Immunological Societies allergen nomenclature committee to be named as Cra a 2. The immunoglobulin G/immunoglobulin E-binding capacity of Cra a 2 was significantly reduced after chemical denaturation treatment. Further, eight linear mimotopes and five conformational mimotopes of Cra a 2 were obtained using phage panning. In addition to six linear epitopes that have been identified, two linear epitopes were verified by a synthetic peptide, of which L-Cra a 2-2 was conserved in shellfish. Four conformational epitopes were verified by site-directed mutation, among which mutation of C-Cra a 2-1 affected the structure and reduced the immunoreactivity of Cra a 2 most significantly. Overall, the identified epitopes may lay a foundation for the development of hypoallergenic oyster products through food processing.

IgE Epitope Analysis for Scy p 1 and Scy p 3, the Heat-Stable Myofibrillar Allergens in Mud Crab.

Tropomyosin (Scy p 1) and myosin light chain (Scy p 3) are investigated to be important heat-stable allergens in Scylla paramamosain. However, the epitopes of Scy p 1 and Scy p 3 are limited. In this study, recombinant Scy p 1 and Scy p 3 had similar IgE-binding capacity to natural proteins. Mimotopes of Scy p 1 and Scy p 3 were analyzed by bioinformatics, phage display, and one-bead-one-compound technology. Ten linear epitopes of Scy p 1 and seven linear epitopes of Scy p 3 were identified by synthetic peptides and inhibition dot blot. Meanwhile, three conformational epitopes of Scy p 1 and seven conformational epitopes of Scy p 3 were verified by site-directed mutagenesis and the serological test. Furthermore, strong IgE-binding epitopes of Scy p 1 and Scy p 3 were conserved in multiple crustaceans. Overall, these epitopes could enhance our understanding of crab allergens, which lay the foundation for a cross-reaction.

Characterization, Epitope Identification, and Cross-reactivity Analysis of Tropomyosin: An Important Allergen of Crassostrea angulata.

Oyster is a common shellfish product in China, which is associated with food allergy. However, there is still lack of research on allergens in oysters. In this study, tropomyosin (TM), an important allergen of Crassostrea angulata, was purified and identified by mass spectrometry. Subsequently, TM was cloned and expressed, with a sequence of size 852 bp, encoding 284 amino acid residues. The results of circular dichroism, digestion assay, inhibition enzyme-linked immunosorbent assay, and basophil activation test showed that recombinant TM had similar physicochemical properties and immunological properties to native TM. Furthermore, two conformational mimotopes were obtained and 10 IgE linear epitopes were verified. Meanwhile, different degrees of cross-reactivity were observed between C. angulata TM and the other 8 shellfish TMs using antibodies and serological analysis, which may relate to the 3 conserved epitope regions. These findings are expected to provide a theoretical basis for the molecular diagnosis of oyster allergy and cross-reactivity among shellfish.

WHIRLY1 recruits the histone deacetylase HDA15 repressing leaf senescence and flowering in Arabidopsis.

Leaf senescence is controlled by a complex regulatory network in which robustness is ensured by the activity of transcription factors and epigenetic regulators. However, how these coordinate the process of leaf senescence remains poorly understood. We found that WHIRLY1 interacts with Histone Deacetylase (HDA)15, a Reduced Potassium Dependence3 (RPD3)/HDA1-type HDA, by using green fluorescent protein-nanotrap-mass spectrum assays. The development-dependent interaction between WHIRLY1 and HDA15 was further confirmed by bimolecular fluorescence complementation assays and co-immunoprecipitation assays in Arabidopsis. Multi-omics genome-wide transcriptome and H3K9 acetylome enrichment analysis showed that HDA15 delays leaf senescence and flowering by repressing the expression of the positive regulators of leaf senescence and flowering, such as LOX2 and LARP1C, and reducing H3K9ac levels at these loci; WHIRLY1 and HDA15 co-target to the region near the transcription start site of a subset of nutrient recycling-related genes (e.g., Glutathione S-transferases 10, non-coding RNA, and photosystem II protein D1 synthesizer attenuator PDIL1-2), as well as WRKY53 and ELF4, and co-repress their expression by removing H3K9 acetylation. Our study revealed a key transcription regulatory node of nutrient recycling and senescence-associated genes involved in leaf senescence and flowering via the recruitment of HDA15 by the single-stranded DNA/RNA-binding protein WHIRLY1.

MR Elastography-Based Shear Strain Mapping for Assessment of Microvascular Invasion in Hepatocellular Carcinoma.

OBJECTIVES: To evaluate the potential of MR elastography (MRE)-based shear strain mapping to noninvasively predict the presence of microvascular invasion (MVI) in hepatocellular carcinoma (HCC). METHODS: Fifty-nine histopathology-proven HCC patients with conventional 60-Hz MRE examinations (+/-MVI, n = 34/25) were enrolled retrospectively between December 2016 and October 2019, with one subgroup comprising 29/59 patients (+/-MVI, n = 16/13) who also underwent 40- and 30-Hz MRE examinations. Octahedral shear strain (OSS) maps were calculated, and the percentage of peritumoral interface length with low shear strain (i.e., a low-shear-strain length, pLSL, %) was recorded. For OSS-pLSL, differences between the MVI (+) and MVI (-) groups and diagnostic performance at different MRE frequencies were analyzed using the Mann-Whitney test and area under the receiver operating characteristic curve (AUC), respectively. RESULTS: The peritumor OSS-pLSL was significantly higher in the MVI (+) group than in the MVI (-) group at the three frequencies (all p < 0.01). The AUC of peritumor OSS-pLSL for predicting MVI was good/excellent in all frequency groups (60-Hz: 0.73 (n = 59)/0.80 (n = 29); 40-Hz: 0.84; 30-Hz: 0.90). On further analysis of the 29 cases with all frequencies, the AUCs were not significantly different. As the frequency decreased from 60-Hz, the specificity of OSS increased at 40-Hz (53.8-61.5%) and further increased at 30-Hz (53.8-76.9%), and the sensitivity remained high at lower frequencies (100.0-93.8%) (all p > 0.05). CONCLUSIONS: MRE-based shear strain mapping is a promising technique for noninvasively predicting the presence of MVI in patients with HCC, and the most recommended frequency for OSS is 30-Hz. KEY POINTS: • MR elastography (MRE)-based shear strain mapping has the potential to predict the presence of microvascular invasion (MVI) in hepatocellular carcinoma preoperatively. • The low interface shear strain identified at tumor-liver boundaries was highly correlated with the presence of MVI.

MicroRNA840 (MIR840) accelerates leaf senescence by targeting the overlapping 3'UTRs of PPR and WHIRLY3 in Arabidopsis thaliana.

MicroRNAs negatively regulate gene expression by promoting target mRNA cleavage and/or impairing its translation, thereby playing a crucial role in plant development and environmental stress responses. In Arabidopsis, the MIR840 gene is located within the overlapping 3'UTR of the PPR and WHIRLY3 (WHY3) genes, both being predicted targets of miR840* and miR840, the short maturation products of MIR840. Gain- and loss-of-function of MIR840 in Arabidopsis resulted in opposite senescence phenotypes. The highest expression levels of the MIR840 precursor transcript pre-miR840 were observed at senescence initiation, and pre-miR840 expression is significantly correlated with a reduction in PPR, but not WHY3, transcript levels. Although a reduction of transcript level of PPR, but not WHY3 transcript levels were not significantly affected by MIR840 overexpression, its protein levels were strongly reduced. Mutating the cleavage sites or replacing the target sequences abolishes the miR840*/miR840-mediated degradation of PPR transcripts and accumulation of WHY3 protein. In support for this, concurrent knockdown of both PPR and WHY3 in wild-type plants resulted in a senescence phenotype resembling that of the MIR840-overexpressing plant. This indicates that both PRR and WHY3 are targets in the MIR840-mediated senescence pathway. Moreover, single knockout mutants of PPR and WHY3 show a convergent upregulated subset of senescence-associated genes, which are also found among those induced by MIR840 overexpression. Our data provide evidence for a regulatory role of MIR840 in plant senescence.

Two hypo-allergenic derivatives lacking the dominant linear epitope of Scy p 1 and Scy p 3.

Scylla paramamosain frequently elicits IgE-mediated type-I hypersensitivity reactions. Molecular candidates for crab allergen-specific immunotherapy have not been studied previously. In this study, reduced and alkylated (red/alk) derivatives with destroyed conformational epitopes and mutant derivatives (mtALLERGEN) with deleted heat/digestion-stable linear epitopes were produced of tropomyosin and myosin light chain. Structural changes and the allergenicity of derivatives was analyzed. Compared with wild-type allergens, red/alk derivatives had dramatically altered protein structures, whereas mtALLERGEN showed slightly structural effects. Enzyme linked immunosorbent assay revealed the heterogeneous epitope-recognition patterns with derivatives among 29 crab-sensitised patients, of whom 13% and 62% recognised conformational and linear epitopes, respectively, whereas 25% recognised both epitope types to the same extent. Furthermore, mtALLERGEN could not bind to IgE or induce basophil activation in some patients. These results imply that hypo-allergenic derivatives of crab myofibril allergens that specifically lacked linear epitopes may serve as viable candidates for immunotherapy.

Differentiating the clinical and computed tomography imaging features of mixed epithelial and stromal tumors of the kidney to establish a treatment plan.

OBJECTIVE: To differentiate the clinical features and computed tomography imaging features in the two types of mixed epithelial and stromal tumor of the kidney (MESTK) and to establish a treatment plan for the MESTK types. METHODS: Seventeen patients who underwent multidetector computed tomography (MDCT) before surgery and had a pathological diagnosis of MESTK were enrolled. Their clinical information (R.E.N.A.L. nephrometry score (R.E.N.A.L.-NS), radical nephrectomy (RN), partial nephrectomy (PN), etc.) were collected. The radiological features included renal sinus fat invagination (SFI), maximal diameter (MD), capsule and septa of the tumor, etc., were also analyzed. They were divided into two types according to the MDsolid /MDtumor ratio (solid type with >60%; cystic type with ≤60%). An independent-sample t-test and Fisher exact test were used to assess the differences between the two groups. RESULTS: MESTKs demonstrated a variable multi-septate cystic and solid components with a delayed enhancement. There were nine patients for solid type and eight patients for cystic type. Compared with solid type, the lesions in cystic type have larger MD (81.00 ± 37.91 vs. 41.22 ± 24.19, p = 0.020), higher R.E.N.A.L.-NS (10.03 ± 0.50 vs. 8.95 ± 1.26, p < 0.001), higher RN (75.00% vs. 22.22%, p = 0.015), larger SFI (87.5% vs. 33.3%, p = 0.05), more septa (100% vs. 0%, p < 0.001), and more capsule (100% vs. 11.1%, p < 0.001). CONCLUSION: Cystic type MESTK has more hazardous features (such as larger MD, higher R.E.N.A.L.-NS, more RN, greater SFI, multiple septa) compared with solid type, suggesting that RN is more suitable for cystic type and PN for solid type.