WHIRLY Proteins, multi-layer regulators linking the nucleus and organelles in developmental and stress-induced senescence of plants.

Plant senescence is an integrated program of plant development that aims to remobilize nutrients and energy from senescing tissues to developing organs under developmental and stress-induced conditions. Upstream in the regulatory network, a small family of single-stranded DNA/RNA-binding proteins known as WHIRLYs occupy a central node, acting at multiple regulatory levels and via trans-localization between the nucleus and organelles. In this review, we summarize the current progress on the role of WHIRLY members in plant development and stress-induced senescence. WHIRLY proteins can be traced back in evolution to green algae. WHIRLY proteins trade off the balance of plant developmental senescence and stress-induced senescence through maintaining organelle genome stability via R-loop homeostasis, repressing the transcription at a configuration condition, recruiting RNA to impact organelle RNA editing and splicing, as evidenced in several species, WHIRLY proteins also act as retrograde signal transducers between organelles and the nucleus through protein modification and stromule or vesicle trafficking. In addition, WHIRLY proteins interact with hormones, ROS and environmental signals to orchestrate cell fate in an age-dependent manner. Finally, prospects for further research and promotion to improve crop production under environmental constraints are highlighted.

Animal-derived food allergen: A review on the available crystal structure and new insights into structural epitope.

Immunoglobulin E (IgE)-mediated food allergy is a rapidly growing public health problem. The interaction between allergens and IgE is at the core of the allergic response. One of the best ways to understand this interaction is through structural characterization. This review focuses on animal-derived food allergens, overviews allergen structures determined by X-ray crystallography, presents an update on IgE conformational epitopes, and explores the structural features of these epitopes. The structural determinants of allergenicity and cross-reactivity are also discussed. Animal-derived food allergens are classified into limited protein families according to structural features, with the calcium-binding protein and actin-binding protein families dominating. Progress in epitope characterization has provided useful information on the structural properties of the IgE recognition region. The data reveals that epitopes are located in relatively protruding areas with negative surface electrostatic potential. Ligand binding and disulfide bonds are two intrinsic characteristics that influence protein structure and impact allergenicity. Shared structures, local motifs, and shared epitopes are factors that lead to cross-reactivity. The structural properties of epitope regions and structural determinants of allergenicity and cross-reactivity may provide directions for the prevention, diagnosis, and treatment of food allergies. Experimentally determined structure, especially that of antigen-antibody complexes, remains limited, and the identification of epitopes continues to be a bottleneck in the study of animal-derived food allergens. A combination of traditional immunological techniques and emerging bioinformatics technology will revolutionize how protein interactions are characterized.

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.

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.

[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.

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.

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.

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.

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.

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.

Tomoelastography Based on Multifrequency MR Elastography for Prostate Cancer Detection: Comparison with Multiparametric MRI.

Background Multiparametric MRI is used for depiction of prostate cancer (PCa) but without consideration of the mechanical alteration of prostatic tissue by cancer. Purpose To investigate the diagnostic performance of stiffness and fluidity quantified with tomoelastography, a multifrequency MR elastography technique, for depiction of PCa compared with multiparametric MRI with Prostate Imaging Reporting and Data System (PI-RADS) version 2.1. Materials and Methods Prospective participants suspected to have PCa and healthy controls (HCs) underwent multiparametric MRI and tomoelastography between March 2019 and July 2020. Tomoelastography maps of shear-wave speed (c) and loss angle (φ) quantified stiffness and fluidity, respectively, for PCa and benign prostatic disease and for the peripheral and transition zones in HCs. Differences between entities and regions were analyzed by using analysis of variance or Kruskal-Wallis test. Diagnostic performance was assessed with area under the receiver operating characteristic curve (AUC) analysis. Results There were 73 participants with PCa (mean age, 72 years ± 7 [standard deviation]), 82 with benign prostatic disease (66 years ± 7), and 53 HCs (41 years ± 14). Mean ± standard deviation of c and φ were higher in PCa (3.4 m/sec ± 0.6 and 1.3 radian ± 0.2, respectively) than in benign prostatic disease (2.6 m/sec ± 0.3 and 1.0 radian ± 0.2, respectively; P < .001) and age-matched HCs (2.2 m/sec ± 0.1 and 0.8 radian ± 0.1, respectively; P < .001). Incorporating c and φ (AUC, 0.95; 95% CI: 0.92, 0.98) improved the diagnostic performance of PI-RADS version 2.1 (AUC, 0.85; 95% CI: 0.80, 0.91; P < .001). Multiparametric MRI combined with c and φ enabled detection of PCa with 95% (78 of 82 non-PCa) specificity, which was significantly higher than with use of multiparametric MRI alone (77% [63 of 82 non-PCa]; P < .001). In regional analysis, c combined with φ enabled differentiation of transition zone PCa from benign prostatic hyperplasia (AUC, 0.91; 95% CI: 0.83, 0.98) and peripheral zone PCa from chronic prostatitis (AUC, 0.94; 95% CI: 0.88, 1.00). Conclusion Use of tomoelastography-quantified stiffness and fluidity improved the diagnostic performance of multiparametric MRI with Prostate Imaging Reporting and Data System version 2.1 in detecting cancer in both the peripheral and transition zones. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Hectors and Lewis in this issue. An earlier incorrect version of this article appeared online. This article was corrected on March 24, 2021.

Comparison of the diagnostic performance of 2D and 3D MR elastography in staging liver fibrosis.

OBJECTIVES: To compare the diagnostic performance and image quality of state-of-the-art 2D MR elastography (MRE) and 3D MRE in the basic application of liver fibrosis staging. METHODS: This retrospective study assessed data from 293 patients who underwent 2D and 3D MRE examinations. MRE image quality was assessed with a qualitative 2-point grading system by evaluating artifacts. Two experienced analysts independently measured mean liver stiffness values. The interobserver agreement of liver stiffness measurement was assessed by the intraclass correlation coefficient (ICC). The area under the receiver operating characteristic curve (AUC) was used to assess the diagnostic performance of 2D and 3D MRE and blood-based markers for fibrosis staging using the pathology-proven liver fibrosis stage as the gold standard. RESULTS: The image quality provided by 3D MRE was graded as significantly higher than that obtained with the 2D MRE method (p < 0.01). Interobserver agreement in liver stiffness measurements was higher for 3D MRE (ICC: 3D 0.979 vs 2D 0.955). The AUC values for discriminating ≥ F1, ≥ F2, ≥ F3, and F4 fibrosis for 3D MRE (0.89, 0.92, 0.95, and 0.93) were similar to those for 2D MRE (0.89, 0.91, 0.94, and 0.92). Both the 2D and 3D MRE methods provided superior accuracy to the blood-based biomarkers, including APRI, FIB-4, and Forns index, especially for ≥ F2, ≥ F3, and F4 fibrosis stages (all p < 0.01). CONCLUSIONS: While 3D MRE offers certain advantages and opportunities for new applications of MRE, current widely deployed 2D MRE technology has comparable performance in the basic application of detecting and staging liver fibrosis. KEY POINTS: • 2D MRE and 3D MRE have comparable diagnostic performance in detecting and staging liver fibrosis. • 3D MRE has superior image quality and interobserver agreement compared to 2D MRE.

Arterial duct stent versus surgical shunt for patients with duct-dependent pulmonary circulation: a meta-analysis.

BACKGROUND: Both systemic-pulmonary shunt and arterial duct stent could be the palliation of duct-dependent pulmonary circulation. We aimed to compare the safety and efficacy of the two approaches. METHODS: The PubMed, EMBASE, and Cochrane Library databases were searched through December 2019 for studies comparing stent implantation and surgical shunt in duct-dependent pulmonary circulation. The baseline characteristics included ventricle physiology and cardiac anomaly. The main outcomes were hospital stay and total mortality. Additional outcomes included procedural complications, intensive care unit (ICU) stay, pulmonary artery growth at follow-up, and other indexes. A random- or fixed-effects model was used to summarize the estimates of the mean difference (MD)/risk ratio (RR) with 95% confidence intervals (CIs). RESULTS: In total, 757 patients with duct-dependent pulmonary circulation from six studies were included. Pooled estimates of hospital stay (MD, - 4.83; 95% CI - 7.92 to - 1.74; p < 0.05), total mortality (RR 0.44; 95% CI 0.28-0.70; p < 0.05), complications (RR 0.49; 95% CI 0.30-0.81; p < 0.05) and ICU stay (MD, - 4.00; 95% CI - 5.96 to - 2.04; p < 0.05) favored the stent group. Significant differences were found in the proportions of patients with a single ventricle (RR 0.82; 95% CI 0.68-0.98; p < 0.05) or a double ventricle (RR 1.23; 95% CI 1.07-1.41; p < 0.05) between the stent and shunt groups. Additionally, pulmonary artery growth showed no significant differences between the two groups. CONCLUSION: Arterial duct stent appears to have not inferior outcomes of procedural complications, mortality, hospital and ICU stay, and pulmonary artery growth in selected patients compared with a surgical shunt. TRIAL REGISTRATION: CRD42019147672.

Interlinked regulatory loops of ABA catabolism and biosynthesis coordinate fruit growth and ripening in woodland strawberry.

Fruit growth and ripening are controlled by multiple phytohormones. How these hormones coordinate and interact with each other to control these processes at the molecular level is unclear. We found in the early stages of Fragaria vesca (woodland strawberry) fruit development, auxin increases both widths and lengths of fruits, while gibberellin [gibberellic acid (GA)] mainly promotes their longitudinal elongation. Auxin promoted GA biosynthesis and signaling by activating GA biosynthetic and signaling genes, suggesting auxin function is partially dependent on GA function. To prevent the repressive effect of abscisic acid (ABA) on fruit growth, auxin and GA suppressed ABA accumulation during early fruit development by activating the expression of FveCYP707A4a encoding cytochrome P450 monooxygenase that catalyzes ABA catabolism. At the onset of fruit ripening, both auxin and GA levels decreased, leading to a steep increase in the endogenous level of ABA that drives fruit ripening. ABA repressed the expression of FveCYP707A4a but promoted that of FveNCED, a rate-limiting step in ABA biosynthesis. Accordingly, altering FveCYP707A4a expression changed the endogenous ABA levels and affected FveNCED expression. Hence, ABA catabolism and biosynthesis are tightly linked by feedback and feedforward loops to limit ABA contents for fruit growth and to quickly increase ABA contents for the onset of fruit ripening. These results indicate that FveCYP707A4a not only regulates ABA accumulation but also provides a hub to coordinate fruit size and ripening times by relaying auxin, GA, and ABA signals.

Abdominal perivascular epithelioid cell tumor (PEComa) without visible fat: a clinicopathologic and radiological analysis of 16 cases.

OBJECTIVE: To retrospectively review the clinicopathological features and computed tomography (CT) and magnetic resonance imaging (MRI) findings of abdominal perivascular epithelioid cell tumor without visible fat (PEComawvf). MATERIALS AND METHODS: Sixteen patients with surgically and pathologically confirmed perivascular epithelioid cell tumor without visible fat were enrolled. Their clinicopathological data and imaging findings were retrospectively reviewed. The CT and MRI features, including location, size, shape, margin, density, calcification, cystic necrosis and enhancement pattern, were analyzed. RESULTS: There were 4 males and 12 females (median age, 46 years; range, 21-65 years) in this study. All 16 patients were diagnostic asymptomatic unenhanced CT or MRI and revealed a well-defined (n = 13), oval (n = 10), mass with heterogeneous (n = 6) or homogeneous density/signal intensity (n = 7), calcification and hemorrhage was no found in any cases. On enhanced CT/MRI, markedly enhancement patterns (n = 14) were observed. The "peripheral enhancement" sign was observed in 13 cases. One in 16 cases recurrence was discovered during the follow-up period. CONCLUSIONS: Dynamic CT, MRI and pathology of PEComawvf had some characteristics of non-aggressive pattern of performance, and MRI would provide beneficial detection of microscopic fat. Enhanced imaging showed PEComawvf is characterized by a "peripheral enhancement" with a marked enhancement pattern. Knowing these characteristics could contribute to improving the understanding abdominal PEComawvf and related palliative care.

The Association between Changes in Low Parathyroid Hormone Levels and Cardiac Function Decline in Maintenance Hemodialysis Patients: A Prospective Observational Study.

OBJECTIVES: The aim of this study was to investigate a possible association between changes in low parathyroid hormone (PTH) levels and cardiac function decline in maintenance hemodialysis (MHD) patients. METHODS: A total of 150 MHD patients were included and followed for 24 months. The enrolled patients were divided into 3 groups based on their PTH status at baseline and 24 months. Factors potentially involved in changes in the PTH level and cardiac function were compared using multivariate logistic regression analysis. RESULTS: At 24 months, the presence of low PTH levels increased by 26.7%. The main independent factors for low PTH levels were a low BMI, hemoglobin, and serum albumin and high serum calcium (p < 0.05). A persistently low PTH level at 24 months was associated with a decrease in the left ventricular ejection fraction (LVEF) and increase in valvular calcification (p < 0.05). Additionally, a decrease in PTH levels from normal or high to low values was associated with a decrease in LVEF and cardiac output (CO) and an increase in valvular calcification (p < 0.05). Furthermore, compared with those of the persistently low PTH level group, LVEF values were lower at 24 months in the group with a decrease from high/normal to low PTH level (p < 0.05). CONCLUSION: Persistently low PTH levels and changes in the PTH level from high/normal to low were associated with cardiac function decline in MHD patients. Moreover, a PTH level change from high/normal to low showed a stronger correlation with cardiac function decline.

Clinical application and progress of quantitative functional magnetic resonance imaging in prostate cancer. / å®šé‡åŠŸèƒ½ç£å ±æŒ¯æˆåƒæŠ€æœ¯åœ¨å‰åˆ—è ºç™Œä¸­çš„ä¸´åºŠåº”ç”¨åŠè¿›å±•.

Magnetic resonance imaging (MRI) is a very important imaging method for diagnosis and treatment of prostate cancer (PCa) in clinical practice. As functional MRI is growing and maturing, its quantitative parameters are expected to enhance the clinical value of MRI furtherly. Intravoxel incoherent motion diffusion imaging, diffusion tensor imaging, and diffusion kurtosis imaging, which were derived from diffusion weighted imaging, have provided richer and more accurate parameters. The newly-developed magnetic resonance elastography can complement the mechanical characteristics of PCa.

Tracheoplasty for Patients with Pulmonary Artery Sling and Tracheal Stenosis: A Meta-Analysis.

We performed this meta-analysis to assess the safety and efficacy of tracheoplasty for patients with pulmonary artery sling (PAS) and tracheal stenosis. Published studies that included surgical treatment of PAS and tracheal stenosis with and without tracheoplasty were identified by searching the PubMed, EMBASE, and Cochrane Library databases until May 2020. The outcomes assessed included postoperative ventilation time, early and late mortality, and follow-up respiratory symptoms. The mean difference (MD)/risk ratio (RR) with 95% confidence intervals (CI) was estimated with a random-effects/fixed-effects model. Subgroup analysis was performed stratified by percentage of patients with tracheal rings. A total of eight studies comprising 219 patients with PAS accompanied by tracheal stenosis were included. The pooled estimates of postoperative ventilation time (MD 17.68, 95% CI 6.38 to 28.98, p < 0.01) and early mortality (RR 3.93, 95% CI 1.55 to 9.95, p < 0.01) favored the repair-only group. Late mortality (RR 1.33, 95% CI 0.48 to 3.68, p = 0.58) and respiratory symptoms (RR 1.51, 95% CI 0.50 to 4.57, p = 0.47) at follow-up showed no significant differences between the groups with repair-only and repair with tracheoplasty. The same results were found in subgroup analyses. For the surgical treatment of PAS with tracheal stenosis, repair without tracheoplasty appears to result in shorter postoperative ventilation time and lower early mortality, with no increase in late mortality or respiratory symptoms at follow-up, compared with concomitant tracheoplasty.

Comparisons of perventricular device closure, conventional surgical repair, and transcatheter device closure in patients with perimembranous ventricular septal defects: a network meta-analysis.

BACKGROUND: Treatments for perimembranous ventricular septal defects (pmVSD) mainly include conventional surgical repair (CSR), transcatheter device closure (TDC), and perventricular device closure (PDC). We aimed to perform a network meta-analysis to compare the three approaches in patients with pmVSD. METHODS: We searched for comparative studies on device closure and conventional repair for pmVSD to April 2020. A network meta-analysis was performed under the frequentist frame with risk ratio and 95% confidence interval. The main outcome was the procedural success rate. Additional outcomes were postoperative complications, including residual shunt, intra-cardiac conduction block, valvular insufficiency, incision infection, and pericardial effusion. RESULTS: Twenty-four studies of 8113 patients were included in the comparisons. The pooled estimates of success rate favored the CSR compared with the PDC. No significant differences of success rate were found in the TDC versus CSR and the PDC versus TDC. The pooled estimates of incidences of the residual shunt, new tricuspid regurgitation, incision infection, and pericardial effusion favored the PDC compared with the CSR. There were no significant differences between the PDC and TDC approaches in all outcomes except new aortic regurgitation. CONCLUSION: The PDC technique not only reduces the risk of significant complications compared with the CSR, but also produces not inferior results compared with the TDC in selected pmVSD patients. PROSPERO REGISTRATION NUMBER: CRD42019125257.

An electrochemiluminescence biosensor based on boron nitride quantum dots as novel coreactant for quantitative determination of concanavalin A.

An electrochemiluminescence (ECL) analytical platform is constructed based on boron nitride quantum dots (BNQDs) as a novel coreactant of luminol for quantitative assay of concanavalin A (Con A). Different from previous research that mainly focuses on its superior optical properties, BNQDs are used for the first time as a coreactant for boosting ECL intensity of luminol, which has a 10-fold enhancement compared with individual poly(luminol/aniline) nanorods loaded on reduced graphene oxide (PLA-rGO) using GCE. On the basis that BNQDs contain an abundance of active amino, a possible mechanism of amino oxidation facilitating ECL emission is proposed. Firstly, luminol as light spices are oxidized to luminol•- and BNQDs generate an abundance of BNQDs-NH+• via electrochemical oxidization, producing reductive intermediates BNQDs-N• in alkaline conditions. Finally, BNQDs-N• react with luminol•- to obtain the excited species AP2-*, returning to ground state and emitting light. Due to the hindrance effect of Con A, the ECL intensity decreases gradually as various concentrations of Con A are modifying the electrode surface. Therefore, a sensitive ECL biosensor for detecting Con A is constructed exhibiting a wide linear range of 1.0 pg·mL-1 to 1.0 µg·mL-1 and a low detection limit of 0.15 pg·mL-1. Graphical abstract Schematic representation of an electrochemiluminescence (ECL) biosensor based on boron nitride quantum dots (BNQDs) as an efficient coreactant of reduced graphene oxide functionalized poly(luminol/aniline) (PLA-rGO) for quantitative assay of concanavalin A (Con A).