Sexual stage-specific A-to-I mRNA editing is mediated by tRNA-editing enzymes in fungi.

A-to-I RNA editing catalyzed by adenosine-deaminase-acting-on-RNA (ADARs) was assumed to be unique to metazoans because fungi and plants lack ADAR homologs. However, genome-wide messenger RNA (mRNA) editing was found to occur specifically during sexual reproduction in filamentous ascomycetes. Because systematic characterization of adenosine/cytosine deaminase genes has implicated the involvement of TAD2 and TAD3 orthologs in A-to-I editing, in this study, we used genetic and biochemical approaches to characterize the role of FgTAD2, an essential adenosine-deaminase-acting-on-tRNA (ADAT) gene, in mRNA editing in Fusarium graminearum. FgTAD2 had a sexual-stage-specific isoform and formed heterodimers with enzymatically inactive FgTAD3. Using a repeat-induced point (RIP) mutation approach, we identified 17 mutations in FgTAD2 that affected mRNA editing during sexual reproduction but had no effect on transfer RNA (tRNA) editing and vegetative growth. The functional importance of the H352Y and Q375*(nonsense) mutations in sexual reproduction and mRNA editing were confirmed by introducing specific point mutations into the endogenous FgTAD2 allele in the wild type. An in vitro assay was developed to show that FgTad2-His proteins purified from perithecia, but not from vegetative hyphae, had mRNA editing activities. Moreover, the H352Y mutation affected the enzymatic activity of FgTad2 to edit mRNA but had no effect on its ADAT activity. We also identified proteins co-purified with FgTad2-His by mass spectrometry analysis and found that two of them have the RNA recognition motif. Taken together, genetic and biochemical data from this study demonstrated that FgTad2, an ADAT, catalyzes A-to-I mRNA editing with the stage-specific isoform and cofactors during sexual reproduction in fungi.

Experimental evidence for the functional importance and adaptive advantage of A-to-I RNA editing in fungi.

Adenosine-to-inosine (A-to-I) editing is the most prevalent type of RNA editing in animals, and it occurs in fungi specifically during sexual reproduction. However, it is debatable whether A-to-I RNA editing is adaptive. Deciphering the functional importance of individual editing sites is essential for the mechanistic understanding of the adaptive advantages of RNA editing. Here, by performing gene deletion for 17 genes with conserved missense editing (CME) sites and engineering underedited (ue) and overedited (oe) mutants for 10 CME sites using site-specific mutagenesis at the native locus in Fusarium graminearum, we demonstrated that two CME sites in CME5 and CME11 genes are functionally important for sexual reproduction. Although the overedited mutant was normal in sexual reproduction, the underedited mutant of CME5 had severe defects in ascus and ascospore formation like the deletion mutant, suggesting that the CME site of CME5 is co-opted for sexual development. The preediting residue of Cme5 is evolutionarily conserved across diverse classes of Ascomycota, while the postediting one is rarely hardwired into the genome, implying that editing at this site leads to higher fitness than a genomic A-to-G mutation. More importantly, mutants expressing only the underedited or the overedited allele of CME11 are defective in ascosporogenesis, while those expressing both alleles displayed normal phenotypes, indicating that concurrently expressing edited and unedited versions of Cme11 is more advantageous than either. Our study provides convincing experimental evidence for the long-suspected adaptive advantages of RNA editing in fungi and likely in animals.

A non-pheromone GPCR is essential for meiosis and ascosporogenesis in the wheat scab fungus.

Meiosis is essential for generating genetic diversity and sexual spores, but the regulation of meiosis and ascosporogenesis is not clear in filamentous fungi, in which dikaryotic and diploid cells formed inside fruiting bodies are not free living and independent of pheromones or pheromone receptors. In this study, Gia1, a non-pheromone GPCR (G protein-coupled receptor) with sexual-specific expression in Fusarium graminearum, is found to be essential for ascosporogenesis. The gia1 mutant was normal in perithecium development, crozier formation, and karyogamy but failed to undergo meiosis, which could be partially rescued by a dominant active mutation in GPA1 and activation of the Gpmk1 pathway. GIA1 orthologs have conserved functions in regulating meiosis and ascosporogenesis in Sordariomycetes. GIA1 has a paralog, GIP1, in F. graminearum and other Hypocreales species which is essential for perithecium formation. GIP1 differed from GIA1 in expression profiles and downstream signaling during sexual reproduction. Whereas the C-terminal tail and IR3 were important for intracellular signaling, the N-terminal region and EL3 of Gia1 were responsible for recognizing its ligand, which is likely a protein enriched in developing perithecia, particularly in the gia1 mutant. Taken together, these results showed that GIA1 encodes a non-pheromone GPCR that regulates the entry into meiosis and ascosporogenesis via the downstream Gpmk1 MAP kinase pathway in F. graminearum and other filamentous ascomycetes.

FgSnt1 of the Set3 HDAC complex plays a key role in mediating the regulation of histone acetylation by the cAMP-PKA pathway in Fusarium graminearum.

The cAMP-PKA pathway is critical for regulating growth, differentiation, and pathogenesis in fungal pathogens. In Fusarium graminearum, mutants deleted of PKR regulatory-subunit of PKA had severe defects but often produced spontaneous suppressors. In this study eleven pkr suppressors were found to have mutations in FgSNT1, a component of the Set3C histone deacetylase (HDAC) complex, that result in the truncation of its C-terminal region. Targeted deletion of the C-terminal 98 aa (CT98) in FgSNT1 suppressed the defects of pkr in growth and H4 acetylation. CT98 truncation also increased the interaction of FgSnt1 with Hdf1, a major HDAC in the Set3 complex. The pkr mutant had no detectable expression of the Cpk1 catalytic subunit and PKA activities, which was not suppressed by mutations in FgSNT1. Cpk1 directly interacted with the N-terminal region of FgSnt1 and phosphorylated it at S443, a conserved PKA-phosphorylation site. CT98 of FgSnt1 carrying the S443D mutation interacted with its own N-terminal region. Expression of FgSNT1S443D rescued the defects of pkr in growth and H4 acetylation. Therefore, phosphorylation at S443 and suppressor mutations may relieve self-inhibitory binding of FgSnt1 and increase its interaction with Hdf1 and H4 acetylation, indicating a key role of FgSnt1 in crosstalk between cAMP signaling and Set3 complex.

Comparative physiological and transcriptome analysis between potassium-deficiency tolerant and sensitive sweetpotato genotypes in response to potassium-deficiency stress.

BACKGROUND: Sweetpotato is a typical ''potassium (K+) favoring'' food crop, which root differentiation process needs a large supply of potassium fertilizer and determine the final root yield. To further understand the regulatory network of the response to low potassium stress, here we analyze physiological and biochemical characteristics, and investigated root transcriptional changes in two sweetpotato genotypes, namely, - K tolerant "Xu32" and - K susceptible"NZ1". RESULT: We found Xu32 had the higher capability of K+ absorption than NZ1 with better growth performance, higher net photosynthetic rate and higher chlorophyll contents under low potassium stress, and identified 889 differentially expressed genes (DEGs) in Xu32, 634 DEGs in NZ1, 256 common DEGs in both Xu32 and NZ1. The Gene Ontology (GO) term in molecular function enrichment analysis revealed that the DEGs under low K+ stress are predominately involved in catalytic activity, binding, transporter activity and antioxidant activity. Moreover, the more numbers of identified DEGs in Xu32 than that in NZ1 responded to K+-deficiency belong to the process of photosynthesis, carbohydrate metabolism, ion transport, hormone signaling, stress-related and antioxidant system may result in different ability to K+-deficiency tolerance. The unique genes in Xu32 may make a great contribution to enhance low K+ tolerance, and provide useful information for the molecular regulation mechanism of K+-deficiency tolerance in sweetpotato. CONCLUSIONS: The common and distinct expression pattern between the two sweetpotato genotypes illuminate a complex mechanism response to low potassium exist in sweetpotato. The study provides some candidate genes, which can be used in sweetpotato breeding program for improving low potassium stress tolerance.

Unraveling the Electron Transfer Effect of Single-Metal Ce-N4 Sites via Mesopore-Coupling for Boosted Oxygen Reduction Activity.

The development of cerium (Ce) single-atom (SA) electrocatalysts for oxygen reduction reaction (ORR) with high active-site utilization and intrinsic activity has become popular recently but remains challenging. Inspired by an interesting phenomenon that pore-coupling with single-metal cerium sites can accelerate the electron transfer predicted by density functional theory calculations, here, a facile strategy is reported for directional design of a highly active and stable Ce SA catalyst (Ce SA/MC) by the coupling of single-metal Ce-N4 sites and mesopores in nanocarbon via pore-confinement-pyrolysis of Ce/phenanthroline complexes combined with controlling the formation of Ce oxides. This catalyst delivers a comparable ORR catalytic activity with a half-wave potential of 0.845 V versus RHE to the Pt/C catalyst. Also, a Ce SA/MC-based zinc-air battery (ZAB) has exhibited a higher energy density (924 Wh kgZn -1 ) and better long-term cycling durability than a Pt/C-based ZAB. This proposed strategy may open a door for designing efficient rare-earth metal catalysts with single-metal sites coupling with porous structures for next-generation energy devices.

The transcription factor CitZAT5 modifies sugar accumulation and hexose proportion in citrus fruit.

Sugars are fundamental to plant developmental processes. For fruits, the accumulation and proportion of sugars play crucial roles in the development of quality and attractiveness. In citrus (Citrus reticulata Blanco.), we found that the difference in sweetness between mature fruits of "Gongchuan" and its bud sport "Youliang" is related to hexose contents. Expression of a SuS (sucrose synthase) gene CitSUS5 and a SWEET (sugars will eventually be exported transporter) gene CitSWEET6, characterized by transcriptome analysis at different developmental stages of these 2 varieties, revealed higher expression levels in "Youliang" fruit. The roles of CitSUS5 and CitSWEET6 were investigated by enzyme activity and transient assays. CitSUS5 promoted the cleavage of sucrose to hexoses, and CitSWEET6 was identified as a fructose transporter. Further investigation identified the transcription factor CitZAT5 (ZINC FINGER OF ARABIDOPSIS THALIANA) that contributes to sucrose metabolism and fructose transportation by positively regulating CitSUS5 and CitSWEET6. The role of CitZAT5 in fruit sugar accumulation and hexose proportion was investigated by homologous transient CitZAT5 overexpression, -VIGS, and -RNAi. CitZAT5 modulates the hexose proportion in citrus by mediating CitSUS5 and CitSWEET6 expression, and the molecular mechanism explained the differences in sugar composition of "Youliang" and "Gongchuan" fruit.

Inhibitor of cardiolipin biosynthesis-related enzyme MoGep4 confers broad-spectrum anti-fungal activity.

Plant pathogens cause devastating diseases, leading to serious losses to agriculture. Mechanistic understanding of pathogenesis of plant pathogens lays the foundation for the development of fungicides for disease control. Mitophagy, a specific form of autophagy, is important for fungal virulence. The role of cardiolipin, mitochondrial signature phospholipid, in mitophagy and pathogenesis is largely unknown in plant pathogenic fungi. The functions of enzymes involved in cardiolipin biosynthesis and relevant inhibitors were assessed using a set of assays, including genetic deletion, plant infection, lipidomics, chemical-protein interaction, chemical inhibition, and field trials. Our results showed that the cardiolipin biosynthesis-related gene MoGEP4 of the rice blast fungus Magnaporthe oryzae regulates growth, conidiation, cardiolipin biosynthesis, and virulence. Mechanistically, MoGep4 regulated mitophagy and Mps1-MAPK phosphorylation, which are required for virulence. Chemical alexidine dihydrochloride (AXD) inhibited the enzyme activity of MoGep4, cardiolipin biosynthesis and mitophagy. Importantly, AXD efficiently inhibited the growth of 10 plant pathogens and controlled rice blast and Fusarium head blight in the field. Our study demonstrated that MoGep4 regulates mitophagy, Mps1 phosphorylation and pathogenesis in M. oryzae. In addition, we found that the MoGep4 inhibitor, AXD, displays broad-spectrum antifungal activity and is a promising candidate for fungicide development.

The use of longitudinal CT-based radiomics and clinicopathological features predicts the pathological complete response of metastasized axillary lymph nodes in breast cancer.

BACKGROUND: Accurate assessment of axillary status after neoadjuvant therapy for breast cancer patients with axillary lymph node metastasis is important for the selection of appropriate subsequent axillary treatment decisions. Our objectives were to accurately predict whether the breast cancer patients with axillary lymph node metastases could achieve axillary pathological complete response (pCR). METHODS: We collected imaging data to extract longitudinal CT image features before and after neoadjuvant chemotherapy (NAC), analyzed the correlation between radiomics and clinicopathological features, and developed models to predict whether patients with axillary lymph node metastasis can achieve axillary pCR after NAC. The clinical utility of the models was determined via decision curve analysis (DCA). Subgroup analyses were also performed. Then, a nomogram was developed based on the model with the best predictive efficiency and clinical utility and was validated using the calibration plots. RESULTS: A total of 549 breast cancer patients with metastasized axillary lymph nodes were enrolled in this study. 42 independent radiomics features were selected from LASSO regression to construct a logistic regression model with clinicopathological features (LR radiomics-clinical combined model). The AUC of the LR radiomics-clinical combined model prediction performance was 0.861 in the training set and 0.891 in the testing set. For the HR + /HER2 - , HER2 + , and Triple negative subtype, the LR radiomics-clinical combined model yields the best prediction AUCs of 0.756, 0.812, and 0.928 in training sets, and AUCs of 0.757, 0.777 and 0.838 in testing sets, respectively. CONCLUSIONS: The combination of radiomics features and clinicopathological characteristics can effectively predict axillary pCR status in NAC breast cancer patients.

miR-410 Regulates Helper T Cell Differentiation in Ovalbumin-Induced Asthma through the PI3K-AKT-VEGF Signaling Pathway.

INTRODUCTION: Asthma has been attributed to Th1/Th2 imbalance and inappropriate Th2 responses to environmental allergens. MicroRNAs (miRNAs), 21 to 23 RNA molecules, are first found in mammals and have been implicated in various biological activities. Our previous study found that miR-410 effectively ameliorates airway inflammation in the ovalbumin (OVA)-induced asthma murine model. However, the role of miR-410 in regulating helper T (Th) cell differentiation is not clear. In the present study, we aimed to explore the regulatory effects of miR-410 on the differentiation of Th cells through both in vivo and in vitro studies. METHODS: Dual-luciferase reporter assay was used to find if miR-410 has any direct binding position with VEGF mRNAs. PBMC and CD4+ T cells were isolated and stimulated with OVA. The miR-410 mimics and inhibitors were transfected into CD4+ T cells. The differentiation of Th cells was evaluated by enzyme-linked immunosorbent assay (ELISA) for the concentration of IL-4, IFN-γ, and TGF-ß levels in supernatants. Western Blot was used to detect protein expression and phosphorylation of PI3K and AKT. BALB/c mice were kept in a specific pathogen-free condition and received sterile OVA-free food and water. OVA-induced asthmatic mice model was established. ELISA was used to measure the bronchoalveolar lavage fluid (BALF) concentrations of IL-4, IFN-γ, TGF-ß, and VEGF. Hematoxylin and eosin staining and immunohistochemical staining were conducted to analyze inflammatory cell infiltration, pathological changes, and the expression of VEGF. RESULTS: Dual-luciferase reporter assay showed that miR-410 has no direct binding position with VEGF mRNAs. In the OVA-primed mononuclear cells compared to normal cells, IFN-γ and TGF-ß were decreased while IL-4 and VEGF were increased. This change was reversed while miRNA-410 mimics were transfected into CD4+ T cells. Besides, the OVA-primed CD4+ T cells treated with miR-410 decrease the proliferation of cytokine of Th2 cells as well as phosphorylation of PI3K, and AKT. In OVA-induced asthma mice, IFN-γ and TGF-ß were decreased in BALF while the IL-4 and VEGF were increased. OVA-induced mice with asthma treated with miR-410 mimics showed marked reductions in the infiltration of inflammatory cells as well as IL-4 and VEGF in BALF. The immunohistochemical staining of the expression of VEGF also decreased in OVA-induced asthma mice with the instillation of miR-410. CONCLUSIONS: In this study, we revealed that miR-410 could regulate the differentiation of Th cells via the PI3K-AKT-VEGF signaling pathway in asthma.

Signal enhancement ratio of multi-phase contrast-enhanced MRI: an imaging biomarker for survival in pancreatic adenocarcinoma.

OBJECTIVES: To evaluate signal enhancement ratio (SER) for tissue characterization and prognosis stratification in pancreatic adenocarcinoma (PDAC), with quantitative histopathological analysis (QHA) as the reference standard. METHODS: This retrospective study included 277 PDAC patients who underwent multi-phase contrast-enhanced (CE) MRI and whole-slide imaging (WSI) from three centers (2015-2021). SER is defined as (SIlt - SIpre)/(SIea - SIpre), where SIpre, SIea, and SIlt represent the signal intensity of the tumor in pre-contrast, early-, and late post-contrast images, respectively. Deep-learning algorithms were implemented to quantify the stroma, epithelium, and lumen of PDAC on WSIs. Correlation, regression, and Bland-Altman analyses were utilized to investigate the associations between SER and QHA. The prognostic significance of SER on overall survival (OS) was evaluated using Cox regression analysis and Kaplan-Meier curves. RESULTS: The internal dataset comprised 159 patients, which was further divided into training, validation, and internal test datasets (n = 60, 41, and 58, respectively). Sixty-five and 53 patients were included in two external test datasets. Excluding lumen, SER demonstrated significant correlations with stroma (r = 0.29-0.74, all p < 0.001) and epithelium (r = -0.23 to -0.71, all p < 0.001) across a wide post-injection time window (range, 25-300 s). Bland-Altman analysis revealed a small bias between SER and QHA for quantifying stroma/epithelium in individual training, validation (all within ± 2%), and three test datasets (all within ± 4%). Moreover, SER-predicted low stromal proportion was independently associated with worse OS (HR = 1.84 (1.17-2.91), p = 0.009) in training and validation datasets, which remained significant across three combined test datasets (HR = 1.73 (1.25-2.41), p = 0.001). CONCLUSION: SER of multi-phase CE-MRI allows for tissue characterization and prognosis stratification in PDAC. CLINICAL RELEVANCE STATEMENT: The signal enhancement ratio of multi-phase CE-MRI can serve as a novel imaging biomarker for characterizing tissue composition and holds the potential for improving patient stratification and therapy in PDAC. KEY POINTS: Imaging biomarkers are needed to better characterize tumor tissue in pancreatic adenocarcinoma. Signal enhancement ratio (SER)-predicted stromal/epithelial proportion showed good agreement with histopathology measurements across three distinct centers. Signal enhancement ratio (SER)-predicted stromal proportion was demonstrated to be an independent prognostic factor for OS in PDAC.

Screening and Evaluation of Children's Sensitively Toxic Chemicals in New Mosquito Repellent Products Based on a Nationwide Investigation.

New mosquito repellent products (NMRPs) are emerging popular repellents among children. There are increasing reports on children's sensitization reactions caused by NMRPs, while regulations on their productions, sales, or usage are still lacking. One of the reasons could be the missing comprehensive risk assessment. We first conducted a nationwide investigation on children's NMRP usage preferences. Then, we high-throughput screened volatile or semivolatile organic chemicals (VOCs/SVOCs) in five representative NMRPs by the headspace gas chromatography-orbitrap high-resolution mass spectrometry analytical method. After that, toxic compounds were recognized based on the toxicity forecaster (ToxCast) database. A total of 277 VOCs/SVOCs were recognized, and 70 of them were identified as toxic compounds. In a combination of concentrations, toxicities, absorption, distribution, metabolism, and excretion characteristics in the body, 28 chemicals were finally proposed as priority-controlled compounds in NMRPs. Exposure risks of recognized toxic chemicals through NMRPs by inhalation and dermal intake for children across the country were also assessed. Average daily intakes were in the range of 0.20-7.31 mg/kg/day for children in different provinces, and the children in southeastern coastal provinces were found to face higher exposure risks. By controlling the high-priority chemicals, the risks were expected to be reduced by about 46.8% on average. Results of this study are therefore believed to evaluate exposure risks, encourage safe production, and promote reasonable management of NMRPs.

Comparative outcomes of autologous cultured melanocytes transplantation and non-cultured epidermal cell suspension transplantation in piebaldism patients: A retrospective study.

PURPOSE: To compare the efficacy and safety of autologous cultured melanocytes transplantation (CMT) and non-cultured epidermal cell suspension transplantation (NCES) in the treatment of piebaldism. PATIENTS AND METHODS: A retrospective study was conducted on 30 anatomically based lesions from nine piebaldism patients who underwent either CMT (n = 7) or NCES (n = 23) between 2018 and 2020. The extent of repigmentation and colour matching was evaluated in all recipient sites using a digital imaging analysis system. In addition, adverse effects have also been assessed by follow-up results. RESULTS: More than 75% repigmentation was achieved in 100% (7/7) and 60.9% (14/23) of the 30 lesions with the CMT and NCES, respectively. There were significant differences between the two methods in terms of repigmentation. The majority of patients had colour mismatches, and there was no discernible difference between the two surgical techniques. Adverse reactions rarely occurred. CONCLUSION: The present study suggested that autologous CMT may provide better repigmentation in piebaldism patients than NCES with no significant side effects.

Evaluation of disease severity and prediction of severe cases in children hospitalized with influenza A (H1N1) infection during the post-COVID-19 era: a multicenter retrospective study.

BACKGROUND: The rebound of influenza A (H1N1) infection in post-COVID-19 era recently attracted enormous attention due the rapidly increased number of pediatric hospitalizations and the changed characteristics compared to classical H1N1 infection in pre-COVID-19 era. This study aimed to evaluate the clinical characteristics and severity of children hospitalized with H1N1 infection during post-COVID-19 period, and to construct a novel prediction model for severe H1N1 infection. METHODS: A total of 757 pediatric H1N1 inpatients from nine tertiary public hospitals in Yunnan and Shanghai, China, were retrospectively included, of which 431 patients diagnosed between February 2023 and July 2023 were divided into post-COVID-19 group, while the remaining 326 patients diagnosed between November 2018 and April 2019 were divided into pre-COVID-19 group. A 1:1 propensity-score matching (PSM) was adopted to balance demographic differences between pre- and post-COVID-19 groups, and then compared the severity across these two groups based on clinical and laboratory indicators. Additionally, a subgroup analysis in the original post-COVID-19 group (without PSM) was performed to investigate the independent risk factors for severe H1N1 infection in post-COIVD-19 era. Specifically, Least Absolute Shrinkage and Selection Operator (LASSO) regression was applied to select candidate predictors, and logistic regression was used to further identify independent risk factors, thus establishing a prediction model. Receiver operating characteristic (ROC) curve and calibration curve were utilized to assess discriminative capability and accuracy of the model, while decision curve analysis (DCA) was used to determine the clinical usefulness of the model. RESULTS: After PSM, the post-COVID-19 group showed longer fever duration, higher fever peak, more frequent cough and seizures, as well as higher levels of C-reactive protein (CRP), interleukin 6 (IL-6), IL-10, creatine kinase-MB (CK-MB) and fibrinogen, higher mechanical ventilation rate, longer length of hospital stay (LOS), as well as higher proportion of severe H1N1 infection (all P < 0.05), compared to the pre-COVID-19 group. Moreover, age, BMI, fever duration, leucocyte count, lymphocyte proportion, proportion of CD3+ T cells, tumor necrosis factor α (TNF-α), and IL-10 were confirmed to be independently associated with severe H1N1 infection in post-COVID-19 era. A prediction model integrating these above eight variables was established, and this model had good discrimination, accuracy, and clinical practicability. CONCLUSIONS: Pediatric H1N1 infection during post-COVID-19 era showed a higher overall disease severity than the classical H1N1 infection in pre-COVID-19 period. Meanwhile, cough and seizures were more prominent in children with H1N1 infection during post-COVID-19 era. Clinicians should be aware of these changes in such patients in clinical work. Furthermore, a simple and practical prediction model was constructed and internally validated here, which showed a good performance for predicting severe H1N1 infection in post-COVID-19 era.

Application of deep learning algorithms in classification and localization of implant cutout for the postoperative hip.

OBJECTIVE: This study aims to explore the feasibility of employing convolutional neural networks for detecting and localizing implant cutouts on anteroposterior pelvic radiographs. MATERIALS AND METHODS: The research involves the development of two Deep Learning models. Initially, a model was created for image-level classification of implant cutouts using 40191 pelvic radiographs obtained from a single institution. The radiographs were partitioned into training, validation, and hold-out test datasets in a 6/2/2 ratio. Performance metrics including the area under the receiver operator characteristics curve (AUROC), sensitivity, and specificity were calculated using the test dataset. Additionally, a second object detection model was trained to localize implant cutouts within the same dataset. Bounding box visualizations were generated on images predicted as cutout-positive by the classification model in the test dataset, serving as an adjunct for assessing algorithm validity. RESULTS: The classification model had an accuracy of 99.7%, sensitivity of 84.6%, specificity of 99.8%, AUROC of 0.998 (95% CI: 0.996, 0.999) and AUPRC of 0.774 (95% CI: 0.646, 0.880). From the pelvic radiographs predicted as cutout-positive, the object detection model could achieve 95.5% localization accuracy on true positive images, but falsely generated 14 results from the 15 false-positive predictions. CONCLUSION: The classification model showed fair accuracy for detection of implant cutouts, while the object detection model effectively localized cutout. This serves as proof of concept of using a deep learning-based approach for classification and localization of implant cutouts from pelvic radiographs.

Assessment of Left Ventricular Longitudinal Systolic Function Using Global Tissue Motion Annular Displacement in Patients with Chronic Severe Aortic Regurgitation.

Background: In patients with chronic aortic regurgitation (AR), the left ventricle (LV) develops compensatory mechanisms to sustain its function. LV global longitudinal strain (GLS) is a key means to detect subclinical LV dysfunction, even when LV ejection fraction (LVEF) remains within the normal range. Compared to GLS, Tissue motion annular displacement (TMAD) is a simpler strain-based method to assess LV systolic function. This study investigated the correlation among TMAD parameters, LVEF, and GLS, and determined the diagnostic value and threshold of TMAD parameters for left ventricular systolic dysfunction. Methods: A prospective study was conducted at a single center. The case and control groups consisted of patients with chronic severe AR and healthy volunteers, respectively. Speckle-tracking echocardiography (STE) was used to assess the GLS and TMAD parameters in the apical 4-chamber and apical 2-chamber. Subsets of participants were analyzed for inter- and intra-observer variability and analysis time. A correlation analysis was performed among the TMAD parameters, LVEF, and GLS. Receiver operating characteristic curves and the area under the curves (AUCs) were used to evaluate the predictive value of the TMAD parameters for LVEF <50% and GLS > -18%. Results: This study involved 96 patients with severe chronic AR and 45 healthy volunteers. Compared to GLS, TMAD demonstrated superior intra- and inter-observer consistency and shorter average analysis time. Biplane global Midpt% showed the highest correlation with GLS and LVEF among all the TMAD parameters, with r values of 0.81 and 0.74, respectively. Furthermore, global Midpt% had AUCs of 0.89 and 0.92 for predicting LVEF< 50% and GLS > -18%, respectively. Conclusion: The TMAD global Midpt% has the potential to replace GLS in clinical practice and find wide applications.

Prenatal diagnosis and appearance of nasal chondromesenchymal hamartoma in a fetus: A case report.

We report a case of fetal nasal chondromesenchymal hamartoma (NCMH) first noted on prenatal ultrasound at 34 weeks. A solid-cystic mass which predominantly hyperechoicgenic and relatively clear margin, was located on the left nasal cavity and pharynx, with anterior extension and moderate blood flow. Further follow-up ultrasound examination depicted an enlargement of the tumor. Fetal magnetic resonance imaging (MRI) showed an inhomogeneous signal lesion involving the ethmoid sinuses, nasal cavity, and pharynx. The infant, delivered via cesarean section at 37 + 5 weeks, required urgent neonatology intervention due to respiratory difficulties. Neonatal MRI and computer tomography were subsequently performed at 1 day after birth. Surgical excision occurred at 7 days, confirming NCMH via histological examination. Awareness of this entity, is essential to avoid potentially harmful therapies, especially in prenatal period. Considered NCMH in diagnosis when fetal nasal masses presenting with predominantly high-level echo, well-defined margins and moderate vascularity.

Toroidal Dipole BIC-Driven Highly Robust Perfect Absorption with a Graphene-Loaded Metasurface.

Achieving perfect absorption in few-layer two-dimensional (2D) materials plays a crucial role in applications such as optoelectronics and sensing. However, the underlying mechanisms of all reported works imply a strongly inherent dependence of the central wavelength on the structural parameters. Here, we propose a structure-parameter-deviation immune method for achieving perfect absorption at any desired wavelength by harnessing the toroidal dipole-bound state in the continuum (TD BIC). We experimentally demonstrate the versatile design with a monolayer-graphene-loaded compound grating structure. Such a TD BIC built upon the TE31 mode allows for the transition from BIC to quasi-BIC without breaking the structural symmetry, enabling the stable resonance wavelength while tailoring the quality factors via variation of the gap distance. Comparison with traditional literature further reveals the superiority of our method in realizing highly robust perfect absorption, with a wavelength stability ratio of >15. Remarkably, this approach can be straightforwardly applied to other 2D materials.

Rabies Virus Infection Causes Pyroptosis of Neuronal Cells.

Rabies virus (RABV) is a neurotropic virus that causes fatal neurological disease, raising serious public health issues and attracting extensive attention in society. To elucidate the molecular mechanism of RABV-induced neuronal damage, we used hematoxylin-eosin staining, transmission electron microscopy, transcriptomics analysis, and immune response factor testing to investigate RABV-infected neurons. We successfully isolated the neurons from murine brains. The specificity of the isolated neurons was identified by a monoclonal antibody, and the viability of the neurons was 83.53-95.0%. We confirmed that RABV infection induced serious damage to the neurons according to histochemistry and transmission electron microscope (TEM) scanning. In addition, the transcriptomics analysis suggested that multiple genes related to the pyroptosis pathway were significantly upregulated, including gasdermin D (Gsdmd), Nlrp3, caspase-1, and IL-1ß, as well as the chemokine genes Ccl2, Ccl3, Ccl4, Ccl5, Ccl7, Ccl12, and Cxcl10. We next verified this finding in the brains of mice infected with the rRC-HL, GX074, and challenge virus standard strain-24 (CVS-24) strains of RABV. Importantly, we found that the expression level of the Gsdmd protein was significantly upregulated in the neurons infected with different RABV strains and ranged from 691.1 to 5764.96 pg/mL, while the basal level of mock-infected neurons was less than 100 pg/mL. Taken together, our findings suggest that Gsdmd-induced pyroptosis is involved in the neuron damage caused by RABV infection.

A systematic analysis on global epidemiology and burden of foot fracture over three decades.

PURPOSE: To comprehensively analyze the geographic and temporal trends of foot fracture, understand its health burden by age, sex, and sociodemographic index (SDI), and explore its leading causes from 1990 to 2019. METHODS: The datasets in the present study were generated from the Global Burden of Diseases Study 2019, which included foot fracture data from 1990 to 2019. We extracted estimates along with the 95% uncertainty interval (UI) for the incidence and years lived with disability (YLDs) of foot fracture by location, age, gender, and cause. The epidemiology and burden of foot fracture at the global, regional, and national level was exhibited. Next, we presented the age and sex patterns of foot fracture. The leading cause of foot fracture was another focus of this study from the viewpoint of age, sex, and location. Then, Pearson's correlations between age-standardized rate (ASR), SDI, and estimated annual percentage change were calculated. RESULTS: The age-standardized incidence rate was 138.68 (95% UI: 104.88 - 182.53) per 100,000 persons for both sexes, 174.24 (95% UI: 134.35 - 222.49) per 100,000 persons for males, and 102.19 (95% UI: 73.28 - 138.00) per 100,000 persons for females in 2019. The age-standardized YLDs rate was 5.91 (95% UI: 3.58 - 9.25) per 100,000 persons for both genders, 7.35 (95% UI: 4.45 - 11.50) per 100,000 persons for males, and 4.51 (95% UI: 2.75 - 7.03) per 100,000 persons for females in 2019. The global incidence and YLDs of foot fracture increased in number and decreased in ASR from 1990 to 2019. The global geographical distribution of foot fracture is uneven. The incidence rate for males peaked at the age group of 20 - 24 years, while that for females increased with advancing age. The incidence rate of older people was rising, as younger age incidence rate declined from 1990 to 2019. Falls, exposure to mechanical forces, and road traffic injuries were the 3 leading causes of foot fracture. Correlations were observed between ASR, estimated annual percentage change, and SDI. CONCLUSIONS: The burden of foot fracture remains high globally, and it poses an enormous public health challenge, with population ageing. It is necessary to allocate more resources to the high-risk populations. Targeted realistic intervention policies and strategies are warranted.