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Motivation: Most drugs start on their journey inside the body by binding the right target proteins. This is the reason that numerous efforts have been devoted to predicting the drug-target binding during drug development. However, the inherent diversity among molecular properties, coupled with limited training data availability, poses challenges to the accuracy and generalizability of these methods beyond their training domain., Results: In this work, we proposed a neural networks construction for high accurate and generalizable drug-target binding prediction, named Pre-trained Multi-view Molecular Representations (PMMR). The method uses pre-trained models to transfer representations of target proteins and drugs to the domain of drug-target binding prediction, mitigating the issue of poor generalizability stemming from limited data. Then, two typical representations of drug molecules, Graphs and SMILES strings, are learned respectively by a Graph Neural Network (GNN) and a Transformer to achieve complementarity between local and global features. PMMR was evaluated on drug-target affinity and interaction benchmark datasets, and it derived preponderant performance contrast to peer methods, especially generalizability in cold-start scenarios. Furthermore, our state-of-the-art method was indicated to have the potential for drug discovery by a case study of cyclin-dependent kinase 2 (CDK2)., Availability and Implementation: https://github.com/NENUBioCompute/PMMR., Supplementary Information: Supplementary data are available at Bioinformatics online., (© The Author(s) 2025. Published by Oxford University Press.)

Root canal therapy is the primary treatment method for pulpal and periapical diseases. Various advanced endodontic instruments for mechanical preparation have been marketed. The emergence of nickel-titanium rotary instruments has greatly improved the efficiency of root canal preparation. New demands have been put forward for nickel-titanium rotary instruments as a result of the deepening of clinicians' awareness of root canal anatomy system as well as the purpose and prognosis of root canal treatment. These clinical-oriented demands accelerate instrument reform and innovation. This work presents new marketed nickel-titanium systems and discusses the advantages and limitations of these systems and how they perform in terms of the efficiency and outcome of root canal preparation.

This study aimed to investigate the role of ITFG2, a protein highly expressed in cardiac tissues, in myocardial ischemic injury and its potential interactions with NEDD4-2. An in vivo myocardial infarction (MI) model was induced in mice via left anterior descending artery ligation, and ITFG2 expression was modulated using adeno-associated virus AAV9 vectors. Echocardiography was used to assess cardiac function, and primary mouse cardiomyocytes were cultured and subjected to hypoxia. ITFG2 expression was found to be significantly reduced following MI and in hypoxia-treated neonatal cardiomyocytes. Overexpression of ITFG2 improved cardiac contractility, reduced apoptosis, and stabilized calcium levels by inhibiting NEDD4-2-mediated ubiquitination of SERCA2a. Conversely, ITFG2 knockdown exacerbated calcium overload and cardiac dysfunction. Mechanistically, ITFG2 binds to NEDD4-2, decreasing its interaction with SERCA2a and preventing SERCA2a degradation. These findings suggest that ITFG2 acts as a critical inhibitor of NEDD4-2, preserving SERCA2a function and maintaining calcium homeostasis in cardiomyocytes under ischemic conditions. Therefore, ITFG2 may represent a potential therapeutic target for preventing myocardial ischemic injury and improving outcomes in MI patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Background: Currently, Vonoprazan (VPZ) and amoxicillin dual regimen (VA-dual) has not achieved satisfied efficacy as the first-line treatment for Helicobacter pylori (H. pylori) infection in China. Thus, we aimed to determine the effect of VA-dual plus Saccharomyces boulardii (S. boulardii) on H. pylori eradication rate., Methods: Naive H. pylori-infected patients were randomly allocated to the ECAB group [20-mg esomeprazole, 500-mg clarithromycin, 1000-mg amoxicillin, and 220-mg bismuth twice/day for 14 days] or the VAS group [20-mg VPZ twice/day, 750-mg amoxicillin three times/day, and 250-mg S. boulardii twice/day for 10 days]. Factors associated with eradication success were explored, and cost-effectiveness analyses were also performed., Results: Herein, 126 patients were finally included and randomly assigned to the two groups in a 1:1 ratio. The H. pylori eradication rates of VAS and ECAB groups by intention-to-treat analysis were 87.3% and 88.9% (P = 1.000) and by per-protocol analysis were 87.3% and 91.8% (P = 0.560), respectively. The ECAB group had a significantly higher incidence of adverse events than the VAS group. Superior H. pylori eradication in the VAS group was related to small body surface area and being a non-smoker. The cost-effectiveness ratio of the VAS group was less than that of the ECAB group., Conclusions: Addition of S. boulardii to VA-dual for 10 days is as effective as the 14-days bismuth-based quadruple regimen while ensuring fewer adverse events and lesser cost. This regimen is particularly suitable for low-BSA patients or non-smokers., Trial Registration: Chinese Clinical trial Registry No. ChiCTR2100055101 31/12/2021., Competing Interests: Declarations. Ethics approval and consent to participate: The study was reviewed and approved by the Clinical Medical Technical Ethics Committee of the Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical University (No. [2021] YLJSC016).This study is registered at Chinese Clinical trial Registry. The registration identification number is ChiCTR2100055101.All study participants provided informed written consent prior to study enrollment. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Genetic abnormalities of the parathyroid hormone 1 receptor (PTH1R) lead to profound craniomaxillofacial bone and dentition defects on account of inappropriate tissue metabolism and cellular differentiation. The coordinated activity of differentiation and viability in bone cells is indispensable for bone metabolism. Recent research demonstrates mesenchymal progenitors are responsive to PTH1R signaling for osteogenic differentiation, whereas the effect of PTH1R on cellular survival remains incompletely understood. Here, we report that mice with deletion of PTH1R in Prx1-positive mesenchymal cells ( Prx1Cre;PTH1R fl/fl ) exhibit decreased alveolar bone mass due in part to apoptotic response activation. The exploration of oral bone-derived mesenchymal stem cells (OMSCs) with PTH1R deficiency suggests PTH1R signaling modulates OMSCs' apoptosis by interfering mitochondrial function and morphology. The underlying molecular mechanisms are studied by transcriptome sequencing analysis, finding that inositol trisphosphate receptor-3 (IP3R-3), an endoplasmic reticulum calcium channel protein, serves as a modulator of pro-apoptosis in OMSCs. Furthermore, we find PTH1R and its downstream protein kinase A (PKA) pathway dampen IP3R-3's expression. Of note, OMSCs with IP3R-3 overexpression recapitulate the PTH1R-deletion phenotypes, while IP3R-3 silence rescues mitochondrial dysfunction. Altogether, our study uncovers the anti-apoptotic function of PTH1R signaling in OMSCs and proves that excess apoptosis partly contributes to a weakening potential of osteogenic differentiation and aberrant mandibular development.

Improvement in the sensitivity and accuracy of ECL-based biosensors, to a great extent, depends on the fabrication of high-performance electrochemiluminescence (ECL) sensors. Herein, polyethyleneimine (PEI)-grafted bimetallic ZnNi metal-organic framework (ZnNi-MOF/PEI) nanospheres were synthesized to prepare a L012-based ECL immunosensor for detecting carbohydrate antigen 15-3 (CA15-3). The introduced PEI was utilized not only as a bridging element for L012 luminophore and detection antibody (Ab 2 ) immobilization but also as a co-reactant for generating the self-enhanced ZnNi-MOF/PEI-L012@Ab 2 ECL signal probe. Furthermore, Pt nanoparticle-functionalized CeO 2 nanorods (CeO 2 -Pt) featuring high-efficiency electrocatalytic properties, as a co-reaction accelerator, could catalyze H 2 O 2 to generate abundant reactive oxygen species (ROS), further augmenting the ECL signal of ZnNi-MOF/PEI-L012@Ab 2 . In the presence of CA15-3 antigen, the capture antibody (Ab 1 )-conjugated CeO 2 -Pt complex (CeO 2 -Pt@Ab 1 ) and ZnNi-MOF/PEI-L012@Ab 2 would get closer to each other, with the formation of a "signal-on" sandwich-type ECL immunosensor. The ZnNi-MOF-assisted ECL biosensor achieved a detection limit of down to 5.75✕10 -5 U mL -1 . This work shows distinguished potential for measuring low levels of biomarkers that may help in the clinical diagnosis of breast cancer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Extending lasing wavelengths to the mid-infrared (MIR) spectrum is vital for both civilian and military applications; however, it remains challenging when employing oxide nonlinear optical crystals. In this study, we report the generation of MIR nanosecond pulses via difference frequency generation (DFG) with a near-IR pump using a newly designed langasite (LGS) crystal, La 3 (Nb 0.6 Ta 0.4 ) 0.5 Ga 5.5 O 14 (LGNT 0.4 ), which incorporates birefringence dispersion management techniques with La 3 Ga 5.5 Nb 0.5 O 14 (LGN) as a template. Due to the improved effective nonlinear coefficients and the maintained IR cutoff relative to LGN, the tunable DFG laser in LGNT 0.4 extended from 4.24 to 6.84 μm, delivering a maximum pulse energy of 16.3 μJ at 5.02 μm. To the best of our knowledge, this is the first known oxide material capable of generating tunable nanosecond pulsed lasers beyond 6 μm at μJ-level energies, demonstrating promising potential for high-intensity MIR laser systems owing to its high laser damage threshold.

Inherently chiral medium-ring derivatives have important applications in many research fields, such as materials science, molecular recognition, and asymmetric catalysis. However, the enantioselective assembly of these molecules, especially by organocatalytic strategies, remains a formidable challenge, and few methods are available. Here, we report the enantioselective NHC-catalyzed (NHC: N-heterocyclic carbenes) formal high-order (5 + 3) annulation of 1-(2-indolyl)naphthalen-2-ols with ynals. In the presence of an NHC pre-catalyst, base, Lewis acid and oxidant, this protocol enables the catalytic formation of C-C and C-O bonds, providing practical and facile access to an array of inherently chiral saddle-shaped eight-membered lactones featuring an oxocin-2-one scaffold with structural diversity in good efficiency and excellent enantiocontrol. Moreover, the scale-up preparation and representative late-stage transformations of the eight-membered lactones further demonstrate the application potential of this synthetic technology., (© 2024. The Author(s).)

Objectives: Ultrasound examination is a primary method for detecting thyroid lesions in clinical practice. Incorrect ultrasound diagnosis may lead to delayed treatment or unnecessary biopsy punctures. Therefore, our objective is to propose an artificial intelligence model to increase the precision of thyroid ultrasound diagnosis and reduce puncture rates., Methods: We consecutively collected ultrasound recordings from 672 patients with 845 nodules across two Chinese hospitals. This dataset was divided into training, validation, and internal test sets in a ratio of 7:1:2. We constructed and tested six different model variants based on different video feature distillation strategies and whether additional information from ROI (Region of Interest) scales was used. The models' performances were evaluated using the internal test set and an additional external test set containing 126 nodules from a third hospital., Results: The dual-stream model, which contains both raw-scale and ROI-scale streams with the time dimensional convolution layer, achieved the best performance on both internal and external test sets. On the internal test set, it achieved an AUROC (Area Under Receiver Operating Characteristic Curve) of 0.969 (95 % confidence interval, CI: 0.944-0.993) and an accuracy of 92.6 %, outperforming other variants (AUROC: 0.936-0.955, accuracy: 80.2%-88.3 %) and experienced radiologists (accuracy: 91.9 %). The AUROC of the best model in the external test was 0.931 (95 % CI: 0.890-0.972)., Conclusion: Integrating a dual-stream model with additional ROI scale information and the time dimensional convolution layer can improve performance in diagnosing thyroid ultrasound videos., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Objectives: This study aimed to evaluate the prognostic value of left atrial (LA) strain in patients with apical hypertrophic cardiomyopathy (ApHCM), as assessed by cardiac magnetic resonance (CMR) imaging., Methods: Four hundred and five consecutive patients with ApHCM who underwent CMR examination were retrospectively included. The study endpoint included all-cause death, heart transplant, aborted sudden cardiac death, hospitalization for heart failure, stroke, and new-onset atrial fibrillation (AF)., Results: After a median follow-up of 97 months, 75 patients (18.5%) reached the endpoint. Patients were divided into two groups based on the median LA reservoir strain of 29.4%. The group with lower LA reservoir strain had thicker maximum wall thickness, greater late gadolinium enhancement extent, and smaller end-diastolic volume index, stroke volume index, and cardiac index (all p < 0.02). For LA parameters, this subgroup showed greater diameter and volume index and worse ejection fraction, reservoir, conduit, and booster strain (all p < 0.001). In the multivariable model, age (HR 1.88, 95% CI: 1.06-3.31, p = 0.030), baseline AF (HR 2.95, 95% CI: 1.64-5.28, p < 0.001), LA volume index (LAVi) (HR 2.07, 95% CI: 1.21-3.55, p = 0.008) and LA reservoir strain (HR 2.82, 95% CI: 1.51-5.26, p = 0.001) were all associated with the outcome. Adding LAVi and LA reservoir strain in turn to the multivariable model (age and baseline AF) resulted in significant improvements in model performance (p < 0.001)., Conclusion: In ApHCM patients, LA reservoir strain is independently associated with cardiovascular risk events and has an incremental prognostic value., Clinical Relevance Statement: Left atrial reservoir strain measured by cardiac magnetic resonance is highly correlated with the prognosis of apical hypertrophic cardiomyopathy and has potential incremental value in the prognosis of major adverse cardiac events., Key Points: Left atrial (LA) strain parameters may be useful for risk stratification and treatment of apical hypertrophic cardiomyopathy (ApHCM). Apical hypertrophic cardiomyopathy (ApHCM) is independently associated with LA morphology and function. Cardiac MR examination, especially its feature-tracking technology, provides the possibility to prognosticate ApHCM at an early stage., (© 2024. The Author(s).)

Estimates of movement costs are essential for understanding energetic and life-history trade-offs. Although overall dynamic body acceleration (ODBA) derived from accelerometer data is widely used as a proxy for energy expenditure (EE) in free-ranging animals, its utility has not been tested in species that predominately use body rotations or exploit environmental energy for movement. We tested a suite of sensor-derived movement metrics as proxies for EE in two species of albatrosses, which routinely use dynamic soaring to extract energy from the wind to reduce movement costs. Birds were fitted with a combined heart-rate, accelerometer, magnetometer and GPS logger, and relationships between movement metrics and heart rate-derived V̇O2, an indirect measure of EE, were analyzed during different flight and activity modes. When birds were exclusively soaring, a metric derived from angular velocity on the yaw axis provided a useful proxy of EE. Thus, body rotations involved in dynamic soaring have clear energetic costs, albeit considerably lower than those of the muscle contractions required for flapping flight. We found that ODBA was not a useful proxy for EE in albatrosses when birds were exclusively soaring. As albatrosses spend much of their foraging trips soaring, ODBA alone was a poor predictor of EE in albatrosses. Despite the lower percentage of time flapping, the number of flaps was a useful metric when comparing EE across foraging trips. Our findings highlight that alternative metrics, beyond ODBA, may be required to estimate energy expenditure from inertial sensors in animals whose movements involve extensive body rotations., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2024. Published by The Company of Biologists Ltd.)

Dysregulation of α cells results in hyperglycemia and hyperglucagonemia in type 2 diabetes mellitus (T2DM). Mesenchymal stromal cell (MSC)-based therapy increases oxygen consumption of islets and enhances insulin secretion. However, the underlying mechanism for the protective role of MSCs in α-cell mitochondrial dysfunction remains unclear. Here, human umbilical cord MSCs (hucMSCs) were used to treat 2 kinds of T2DM mice and αTC1-6 cells to explore the role of hucMSCs in improving α-cell mitochondrial dysfunction and hyperglucagonemia. Plasma and supernatant glucagon were detected by enzyme-linked immunosorbent assay (ELISA). Mitochondrial function of α cells was assessed by the Seahorse Analyzer. To investigate the underlying mechanisms, Sirtuin 1 (SIRT1), Forkhead box O3a (FoxO3a), glucose transporter type1 (GLUT1), and glucokinase (GCK) were assessed by Western blotting analysis. In vivo, hucMSC infusion improved glucose and insulin tolerance, as well as hyperglycemia and hyperglucagonemia in T2DM mice. Meanwhile, hucMSC intervention rescued the islet structure and decreased α- to β-cell ratio. Glucagon secretion from αTC1-6 cells was consistently inhibited by hucMSCs in vitro. Meanwhile, hucMSC treatment activated intracellular SIRT1/FoxO3a signaling, promoted glucose uptake and activation, alleviated mitochondrial dysfunction, and enhanced ATP production. However, transfection of SIRT1 small interfering RNA (siRNA) or the application of SIRT1 inhibitor EX-527 weakened the therapeutic effects of hucMSCs on mitochondrial function and glucagon secretion. Our observations indicate that hucMSCs mitigate mitochondrial dysfunction and glucagon hypersecretion of α cells in T2DM via SIRT1/FoxO3a signaling, which provides novel evidence demonstrating the potential for hucMSCs in treating T2DM., (© The Author(s) 2024. Published by Oxford University Press.)

Background: The cumulative burden of hypertrophic cardiomyopathy (HCM) is significant, with a noteworthy percentage (10%-15%) of patients with HCM per year experiencing major adverse cardiovascular events (MACEs). A current risk stratification scheme for HCM had only limited accuracy in predicting sudden cardiac death (SCD) and failed to account for a broader spectrum of adverse cardiovascular events and cardiac magnetic resonance (CMR) parameters., Objectives: This study sought to develop and evaluate a machine learning (ML) framework that integrates CMR imaging and clinical characteristics to predict MACEs in patients with HCM., Methods: A total of 758 patients with HCM (67% male; age 49 ± 14 years) who were admitted between 2010 and 2017 from 4 medical centers were included. The ML model was built on the internal discovery cohort (533 patients with HCM, admitted to Fuwai Hospital, Beijing, China) by using the light gradient-boosting machine and internally evaluated using cross-validation. The external test cohort consisted of 225 patients with HCM from 3 medical centers. A total of 14 CMR imaging features (strain and late gadolinium enhancement [LGE]) and 23 clinical variables were evaluated and used to inform the ML model. MACEs included a composite of arrhythmic events, SCD, heart failure, and atrial fibrillation-related stroke., Results: MACEs occurred in 191 (25%) patients over a median follow-up period of 109.0 months (Q1-Q3: 73.0-118.8 months). Our ML model achieved areas under the curve (AUCs) of 0.830 and 0.812 (internally and externally, respectively). The model outperformed the classic HCM Risk-SCD model, with significant improvement (P < 0.001) of 22.7% in the AUC. Using the cubic spline analysis, the study showed that the extent of LGE and the impairment of global radial strain (GRS) and global circumferential strain (GCS) were nonlinearly correlated with MACEs: an elevated risk of adverse cardiovascular events was observed when these parameters reached the high enough second tertiles (11.6% for LGE, 25.8% for GRS, -17.3% for GCS)., Conclusions: ML-empowered risk stratification using CMR and clinical features enabled accurate MACE prediction beyond the classic HCM Risk-SCD model. In addition, the nonlinear correlation between CMR features (LGE and left ventricular pressure gradient) and MACEs uncovered in this study provides valuable insights for the clinical assessment and management of HCM., Competing Interests: Funding Support and Author Disclosures This study was co-funded by the National Natural Science Foundation of China (number 81930044), the National Key Research and Development Program of China (numbers 2021YFF0501404, 2021YFF0501400), and the National Natural Science Foundation of China (numbers 81971611, 81830056, 61871373). The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024. Published by Elsevier Inc.)

Cyanidin-3-O-glucoside (C3G), a natural antioxidant, plays multiple physiological or pathological roles in maintaining human health; thereby, designing advanced sensors to achieve specific recognition and high-sensitivity detection of C3G is significant. Herein, an imprinted-type electrochemiluminescence (ECL) sensing platform was developed using core-shell Ru@SiO 2 -CMIPs, which were prepared by covalent organic framework (COF)-based molecularly imprinted polymers (CMIPs) embedded in luminescent Ru@SiO 2 cores. The C3G-imprinted COF shell not only helps generate a steady-enhanced ECL signal, but also enables specific recognition of C3G. When C3G is bound to Ru@SiO 2 -CMIPs with abundant imprinted cavities, resonance energy transfer (RET) behavior is triggered, resulting in a quenched ECL response. The constructed Ru@SiO 2 -CMIPs nanoprobes exhibit ultra-high sensitivity, absolute specificity, and an ultra-low detection limit (0.15 pg mL -1 ) for analyzing C3G in food matrices. This study provides a means to construct an efficient and reliable molecular imprinting-based ECL sensor for food analysis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

A limited understanding of microbial interactions and community assembly mechanisms in constructed wetlands (CWs), particularly with different substrates, has hampered the establishment of ecological connections between micro-level interactions and macro-level wetland performance. In this study, CWs with distinct substrates (zeolite, CW&#95;A; manganese ore, CW&#95;B) were constructed to investigate the nutrient removal efficiency, microbial interactions, metabolic mechanisms, and ecological assembly for treating rural sewage with a low carbon-to-nitrogen ratio. CW&#95;B showed higher removal of ammonia nitrogen and total nitrogen by about 1.75-6.75 % and 3.42-5.18 %, respectively, compared to CW&#95;A. Candidatus&#95;Competibacter (denitrifying glycogen-accumulating bacteria) was the dominant microbial genus in CW&#95;A, whereas unclassified&#95;f&#95;Blastocatellaceae (involved in carbon and nitrogen transformation) dominated in CW&#95;B. The null model revealed that stochastic processes (drift) dominated community assembly in both CWs; however, deterministic selection accounted for a higher proportion in CW&#95;B. Compared to those in CW&#95;A, the interactions between microbes in CW&#95;B were more complex, with more key microbes involved in carbon, nitrogen, and phosphorus conversion; the synergistic cooperation of functional bacteria facilitated simultaneous nitrification-denitrification. Manganese ores favour biofilm formation, increase the activity of the electron transport system, and enhance ammonia oxidation and nitrate reduction. These results elucidated the ecological patterns exhibited by microbes under different substrate conditions thereby contributing to our understanding of how substrates shape distinct microcosms in CW systems. This study provides valuable insights for guiding the future construction and management of CWs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Polyethylene (PE) is the most productive plastic product and includes three major polymers including high-density polyethylene (HDPE), linear low-density polyethylene (LLDPE) and low-density polyethylene (LDPE) variation in the PE depends on the branching of the polymer chain and its crystallinity. Tenebrio obscurus and Tenebrio molitor larvae biodegrade PE. We subsequently tested larval physiology, gut microbiome, oxidative stress, and PE degradation capability and degradation products under high-purity HDPE, LLDPE, and LDPE powders (<300 μm) diets for 21 days at 65 ± 5% humidity and 25 ± 0.5 °C. Our results demonstrated the specific PE consumption rates by T. molitor was 8.04-8.73 mg PE ∙ 100 larvae -1 ⋅day -1 and by T. obscurus was 7.68-9.31 for LDPE, LLDPE and HDPE, respectively. The larvae digested nearly 40% of the ingested three PE and showed similar survival rates and weight changes but their fat content decreased by 30-50% over 21-day period. All the PE-fed groups exhibited adverse effects, such as increased benzoquinone concentrations, intestinal tissue damage and elevated oxidative stress indicators, compared with bran-fed control. In the current study, the digestive tract or gut microbiome exhibited a high level of adaptability to PE exposure, altering the width of the gut microbial ecological niche and community diversity, revealing notable correlations between Tenebrio species and the physical and chemical properties (PCPs) of PE-MPs, with the gut microbiome and molecular weight change due to biodegradation. An ecotoxicological simulation by T.E.S.T. confirmed that PE degradation products were little ecotoxic to Daphnia magna and Rattus norvegicus providing important novel insights for future investigations into the environmentally-friendly approach of insect-mediated biodegradation of persistent plastics., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Objective: Although ultrasound is a common tool for breast cancer screening, its accuracy is often operator-dependent. In this study, we proposed a new automated deep-learning framework that extracts video-based ultrasound data for breast cancer screening., Methods: Our framework incorporates DenseNet121, MobileNet, and Xception as backbones for both video- and image-based models. We used data from 3907 patients to train and evaluate the models, which were tested using video- and image-based methods, as well as reader studies with human experts., Results: This study evaluated 3907 female patients aged 22 to 86 years. The results indicated that the MobileNet video model achieved an AUROC of 0.961 in prospective data testing, surpassing the DenseNet121 video model. In real-world data testing, it demonstrated an accuracy of 92.59%, outperforming both the DenseNet121 and Xception video models, and exceeding the 76.00% to 85.60% accuracy range of human experts. Additionally, the MobileNet video model exceeded the performance of image models and other video models across all evaluation metrics, including accuracy, sensitivity, specificity, F1 score, and AUC. Its exceptional performance, particularly suitable for resource-limited clinical settings, demonstrates its potential for clinical application in breast cancer screening., Conclusions: The level of expertise reached by the video models was greater than that achieved by image-based models. We have developed an artificial intelligence framework based on videos that may be able to aid breast cancer diagnosis and alleviate the shortage of experienced experts., Competing Interests: Declaration of competing interest We declare that we have no financial or personal relationships with other people or organisations that can inappropriately influence our work, and there is no professional or other personal interest of any nature or kind in any product, service, and/or company that could be construed as influencing the position presented in, or the review of, the manuscript., (Copyright © 2024 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Objectives: Assessment of plaque stenosis severity allows better management of carotid source of stroke. Our objective is to create a deep learning (DL) model to segment carotid intima-media thickness and plaque and further automatically calculate plaque stenosis severity on common carotid artery (CCA) transverse section ultrasound images., Methods: Three hundred and ninety images from 376 individuals were used to train (235/390, 60%), validate (39/390, 10%), and test (116/390, 30%) on a newly proposed CANet model. We also evaluated the model on an external test set of 115 individuals with 122 images acquired from another hospital. Comparative studies were conducted between our CANet model with four state-of-the-art DL models and two experienced sonographers to re-evaluate the present model's performance., Results: On the internal test set, our CANet model outperformed the four comparative models with Dice values of 95.22% versus 90.15%, 87.48%, 90.22%, and 91.56% on lumen-intima (LI) borders and 96.27% versus 91.40%, 88.94%, 91.19%, and 92.88% on media-adventitia (MA) borders. On the external test set, our model still produced excellent results with a Dice value of 92.41%. Good consistency of stenosis severity calculation was observed between CANet model and experienced sonographers, with Intraclass Correlation Coefficient (ICC) of 0.927 and 0.702, Pearson's Correlation Coefficient of 0.928 and 0.704 on internal and external test set, respectively., Conclusions: Our CANet model achieved excellent performance in the segmentation of carotid IMT and plaques as well as automated calculation of stenosis severity., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

We report on a Kerr-lens mode-locked Tm,Ho-codoped calcium aluminate laser with in-band pumping of the Tm ions by a spatially single-mode 1678 nm Raman fiber laser. The structurally disordered CaGdAlO 4 host crystal is also codoped also with the passive Lu ion for additional inhomogeneous line broadening. The Tm,Ho,Lu:CaGdAlO 4 laser generates soliton pulses as short as 79 fs at a central wavelength of 2073.6 nm via soft-aperture Kerr-lens mode-locking. The corresponding average output power amounts to 91 mW at a pulse repetition rate of ∼86 MHz. The average output power can be scaled to 842 mW at the expense of slightly longer pulses of 155 fs at 2045.9 nm, which corresponds to a peak power of ∼58 kW. To the best of our knowledge, this represents the first demonstration of an in-band pumped Kerr-lens mode-locked Tm,Ho solid-state laser at ∼2 µm.

Early cancer diagnosis increases therapy efficiency and saves huge medical costs. Traditional blood-based cancer markers and endoscopy procedures demonstrate limited capability in the diagnosis. Reliable, non-invasive, and cost-effective methods are in high demand across the world. Worm-based diagnosis, utilizing the chemosensory neuronal system of C. elegans , emerges as a non-invasive approach for early cancer diagnosis with high sensitivity. It facilitates effectiveness in large-scale cancer screening for the foreseeable future. Here, we review the progress of a unique route of early cancer diagnosis based on the chemosensory neuronal system of C. elegans . We first introduce the basic procedures of the chemotaxis assay of C. elegans : synchronization, behavior assay, immobilization, and counting. Then, we review the progress of each procedure and the various cancer types for which this method has achieved early diagnosis. For each procedure, we list examples of microfluidics technologies that have improved the automation, throughput, and efficiency of each step or module. Finally, we envision that microfluidics technologies combined with the chemotaxis assay of C. elegans can lead to an automated, cost-effective, non-invasive early cancer screening technology, with the development of more mature microfluidic modules as well as systematic integration of functional modules.

Purpose: We aimed to develop an artificial intelligence (AI) model based on transrectal ultrasonography (TRUS) images of biopsy needle tract (BNT) tissues for predicting prostate cancer (PCa) and to compare the PCa diagnostic performance of the radiologist model and clinical model., Methods: A total of 1696 2D prostate TRUS images were involved from 142 patients between July 2021 and May 2022. The ResNet50 network model was utilized to train classification models with different input methods: original image (Whole model), BNT (Needle model), and combined image [Feature Pyramid Networks (FPN) model]. The training set, validation set, and test set were randomly assigned, then randomized 5-fold cross-validation between the training set and validation set was performed. The diagnostic effectiveness of AI models and image combination was accessed by an independent testing set. Then, the optimal AI model and image combination were selected to compare the diagnostic efficacy with that of senior radiologists and the clinical model., Results: In the test set, the area under the curve, specificity, and sensitivity of the FPN model were 0.934, 0.966, and 0.829, respectively; the diagnostic efficacy was improved compared with the Whole and Needle models, with statistically significant differences (P < 0.05), and was better than that of senior radiologists (area under the curve: 0.667). The FPN model detected more PCa compared with senior physicians (82.9% vs. 55.8%), with a 61.3% decrease in the false-positive rate and a 23.2% increase in overall accuracy (0.887 vs. 0.655)., Conclusion: The proposed FPN model can offer a new method for prostate tissue classification, improve the diagnostic performance, and may be a helpful tool to guide prostate biopsy., (© The Author(s) 2023. Published by Oxford University Press on behalf of Fellowship of Postgraduate Medicine.)

Iron and amino acids are essential nutrients for living organisms, and their deficiency or excess can cause a range of diseases. Therefore, there is considerable interest in developing sensing assays capable of detecting these nutrients with sensitivity, selectivity, and multifunctionality even in complex environments. In this report, hydrothermally synthesized blue fluorescent carbon dots (C-dots) from zinc gluconate were utilized for the detection of Fe 3+ and lysine via "on-off" and "on-off-on" mechanisms, respectively. Specifically, the Fe 3+ sensing assay achieved a broad linear range of 0-200 μM and a low limit of detection (LOD) of 1.9 μM. It is worth mentioning that the assay was also well adapted to natural aqueous environments (e.g., lake water), and its linear detection range could be extended to 0-1000 μM with a LOD of 3.3 μM. Furthermore, the assay was also effective for intracellular Fe 3+ tracking. Most importantly, the assay could also be applied for the quantitative detection of lysine with a linear range of 0-1200 μM and LOD of 8.6 μM. Systematic mechanistic studies revealed that Fe 3+ sensing was based on a static quenching process between C-dots and Fe 3+ , whereas a stronger complexation might have formed between Fe 3+ and Lys, leading to the release of C-dots and thus the recovery of fluorescence., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

We evaluated the diagnostic performance of a multimodal deep-learning (DL) model for ovarian mass differential diagnosis. This single-center retrospective study included 1,054 ultrasound (US)-detected ovarian tumors (699 benign and 355 malignant). Patients were randomly divided into training (n = 675), validation (n = 169), and testing (n = 210) sets. The model was developed using ResNet-50. Three DL-based models were proposed for benign-malignant classification of these lesions: single-modality model that only utilized US images; dual-modality model that used US images and menopausal status as inputs; and multi-modality model that integrated US images, menopausal status, and serum indicators. After 5-fold cross-validation, 210 lesions were tested. We evaluated the three models using the area under the curve (AUC), accuracy, sensitivity, and specificity. The multimodal model outperformed the single- and dual-modality models with 93.80% accuracy and 0.983 AUC. The Multimodal ResNet-50 DL model outperformed the single- and dual-modality models in identifying benign and malignant ovarian tumors., Competing Interests: The authors declare no competing interests., (© 2024 The Authors.)

Background: The risk of ductal carcinoma in situ (DCIS) identified by biopsy often increases during surgery. Therefore, confirming the DCIS grade preoperatively is necessary for clinical decision-making., Purpose: To train a three-classification deep learning (DL) model based on ultrasound (US), combining clinical data, mammography (MG), US, and core needle biopsy (CNB) pathology to predict low-grade DCIS, intermediate-to-high-grade DCIS, and upstaged DCIS., Materials and Methods: Data of 733 patients with 754 DCIS cases confirmed by biopsy were retrospectively collected from May 2013 to June 2022 (N1), and other data (N2) were confirmed by biopsy as low-grade DCIS. The lesions were randomly divided into training (n=471), validation (n=142), and test (n = 141) sets to establish the DCIS-Net. Information on the DCIS-Net, clinical (age and sign), US (size, calcifications, type, breast imaging reporting and data system [BI-RADS]), MG (microcalcifications, BI-RADS), and CNB pathology (nuclear grade, architectural features, and immunohistochemistry) were collected. Logistic regression and random forest analyses were conducted to develop Multimodal DCIS-Net to calculate the specificity, sensitivity, accuracy, receiver operating characteristic curve, and area under the curve (AUC)., Results: In the test set of N1, the accuracy and AUC of the multimodal DCIS-Net were 0.752-0.766 and 0.859-0.907 in the three-classification task, respectively. The accuracy and AUC for discriminating DCIS from upstaged DCIS were 0.751-0.780 and 0.829-0.861, respectively. In the test set of N2, the accuracy and AUC of discriminating low-grade DCIS from upstaged low-grade DCIS were 0.769-0.987 and 0.818-0.939, respectively. DL was ranked from one to five in the importance of features in the multimodal-DCIS-Net., Conclusion: By developing the DCIS-Net and integrating it with multimodal information, diagnosing low-grade DCIS, intermediate-to high-grade DCIS, and upstaged DCIS is possible. It can also be used to distinguish DCIS from upstaged DCIS and low-grade DCIS from upstaged low-grade DCIS, which could pave the way for the DCIS clinical workflow., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Bi 2 Te 3 -based alloys are the benchmark for commercial thermoelectric (TE) materials, the widespread demand for low-grade waste heat recovery and solid-state refrigeration makes it imperative to enhance the figure-of-merits. In this study, high-performance Bi 0.5 Sb 1.5 Te 3 (BST) is realized by incorporating Cu 2 GeSe 3 and Se. Concretely, the diffusion of Cu and Ge atoms optimizes the hole concentration and raises the density-of-states effective mass (m d * ), compensating for the loss of "donor-like effect" exacerbated by ball milling. The subsequent Se addition further increases m d * , enabling a total 28% improvement of room-temperature power factor (S 2 σ), reaching 43.6 µW cm -1  K -2 compared to the matrix. Simultaneously, the lattice thermal conductivity is also significantly suppressed by multiscale scattering sources represented by Cu-rich nanoparticles and dislocation arrays. The synergistic effects yield a peak ZT of 1.41 at 350 K and an average ZT of 1.23 (300-500 K) in the Bi 0.5 Sb 1.5 Te 2.94 Se 0.06 + 0.11 wt.% Cu 2 GeSe 3 sample. More importantly, the integrated 17-pair TE module achieves a conversion efficiency of 6.4%, 80% higher than the commercial one at ΔT = 200 K. These results validate that the facile composition optimization of the BST/Cu 2 GeSe 3 /Se is a promising strategy to improve the application of BST-based TE modules., (© 2023 Wiley‐VCH GmbH.)

A base-promoted olefin skeletal rearrangement strategy from para -quinone methides ( p -QMs) and N -fluoroarenesulfonamides is reported, enabling direct nitrogen insertion of olefins to produce a series of multiarylated ( Z )- N -sulfonyl amidines with complete stereoselectivity and generally good yields. Using p -QMs without o -hydroxy substituents gave triarylated N -sulfonyl amidines, whereas tetraarylated N , N '-disulfonyl amidines were synthesized with the existence of o -hydroxy groups.

A large animal model of chronic coronary artery disease (CAD) is crucial for the understanding the underlying pathophysiological processes of chronic CAD and consequences for cardiac structure and function. The goal of this study was to develop a chronic model of CAD in a swine model and to evaluate the changes of myocardial structure, myocardial motility, and myocardial viability during coronary stenosis. A total of 30 swine (including 24 experimental animals and 6 controls) were enrolled. The chronic ischemia model was constructed by using Ameroid constrictor in experimental group. The 24 experimental animals were further divided into 4 groups (6 animals in each group) and were sacrificed at 1, 2, 3 and 4 weeks after operation for pathological examination, respectively. Cardiac magnetic resonance (CMR) was performed preoperatively and weekly postoperatively until sacrificed both in experimental and control group. CMR cine images, rest/adenosine triphosphate (ATP) stress myocardial contrast perfusion and LGE were performed and analyzed. The rest wall thickening (WT) score was calculated from rest cine images. The MPRI (myocardial perfusion reserve index) and MPR (myocardial perfusion reserve) were calculated based on rest and stress perfusion images. Pathology staining including triphenyltetrazolium chloride, HE and picrosirus red staining were performed after swine were sacrificed and collagen volume fraction (CVF) was calculated. The time to formation of ischemic, hibernating, and infarcted myocardium was recorded. In experimental group, from 1w to 4w after surgery, the rest WT score decreased gradually from 35.2 ± 2.0%, 32.0 ± 2.9% to 30.5 ± 3.0% and finally 29.06 ± 1.78%, p < 0.001. Left ventricular ejection fraction was gradually impaired after modeling (58.9 ± 12.6%, 56.3 ± 10.1%, 55.3 ± 9.0%, 53.8 ± 9.9%, respectively). And the MPR and MPRI also decreased stepwise with extent of surgery time (MPRI dropped from 2.1 ± 0.4, 2.0 ± 0.2 to 1.8 ± 0.3 and finally 1.7 ± 0.1, p = 0.004; MPR dropped from 2.3 ± 0.4, 2.1 ± 0.2 to 1.9 ± 0.4 and finally 1.8 ± 0.1, p < 0.001). Stronger associations between MPR, MPRI and CVF were paralleled lower wall thickening scores in fibrosis-affected areas. The ischemic myocardium was first appeared in the first week after surgery (involving ten segments), hibernated myocardium was first appeared in the second week after surgery (involving seventeen segments). LGE was first appeared in eight swine in the third weeks after surgery (16 segments). At 4w after surgery, average 9.6 g scar tissue was found among 6 swine. At the same time, histological analysis established the presence of fibrosis and ongoing apoptosis in the infarcted area. In conclusion, our study provided valuable insights into the pathophysiological processes of chronic CAD and its consequences for cardiac structure and function in a large animal model through combining myocardial motion and stress perfusion., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Objectives: Left atrial (LA) myopathy, characterized by LA enlargement and mechanical dysfunction, is associated with worse prognosis in hypertrophic cardiomyopathy (HCM) while the impact of sarcomere mutation on LA myopathy remains unclear. We aimed to assess the association between LA myopathy and sarcomere mutation and to explore the incremental utility of LA strain in mutation prediction., Methods: A total of 105 consecutive HCM patients (mean age 47.8 ± 11.9 years, 71% male) who underwent HCM-related gene screening and cardiac MRI were retrospectively enrolled. LA volume, ejection fraction and strain indices in reservoir, conduit, and booster-pump phases were investigated respectively., Results: Fifty mutation-positive patients showed higher LA maximal volume index (59.4 ± 28.2 vs 43.8 ± 18.1 mL/m 2 , p = 0.001), lower reservoir (21.3 ± 7.9 vs 26.2 ± 6.6%, p < 0.001), and booster-pump strain (12.1 ± 5.4 vs 17.1 ± 5.0%, p < 0.001) but similar conduit strain (9.2 ± 4.5 vs 9.1 ± 4.5%, p = 0.909) compared with mutation-negative patients. In multivariate logistic regression, LA booster-pump strain was associated with sarcomere mutation (odds ratio = 0.86, 95% confidence interval: 0.77-0.96, p = 0.010) independent of maximal wall thickness, late gadolinium enhancement, and LA volume. Furthermore, LA booster-pump strain showed incremental value for mutation prediction added to Mayo II score (AUC 0.798 vs 0.709, p = 0.024)., Conclusions: In HCM, mutation-positive patients suffered worse LA enlargement and worse reservoir and booster-pump functions. LA booster-pump strain was a strong factor for sarcomere mutation prediction added to Mayo II score., Clinical Relevance Statement: The independent association between sarcomere mutation and left atrial mechanical dysfunction provide new insights into the pathogenesis of atrial myopathy and is helpful to understand the adverse prognosis regarding atrial fibrillation and stroke in mutation-positive patients., Key Points: • In patients with hypertrophic cardiomyopathy, left atrial (LA) reservoir and booster-pump function, but not conduit function, were significantly impaired in mutation-positive patients compared with mutation-negative patients. • LA booster-pump strain measured by MRI-derived feature tracking is feasible to predict sarcomere mutation with high incremental value added to Mayo II score., (© 2023. The Author(s), under exclusive licence to European Society of Radiology.)

Background: Over the past few decades, agonists binding to the benzodiazepine site of the GABA A receptor have been successfully developed as clinical drugs. Different modulators (agonist, antagonist, and reverse agonist) bound to benzodiazepine sites exhibit different or even opposite pharmacological effects, however, their structures are so similar that it is difficult to distinguish them based solely on molecular skeleton. This study aims to develop classification models for predicting the agonists., Methods: 306 agonists or non-agonists were collected from literature. Six machine learning algorithms including RF, XGBoost, AdaBoost, GBoost, SVM, and ANN algorithms were employed for model development. Using six descriptors including 1D/2D Descriptors, ECFP4, 2D-Pharmacophore, MACCS, PubChem, and Estate fingerprint to characterize chemical structures. The model interpretability was explored by SHAP method., Results: The best model demonstrated an AUC value of 0.905 and an MCC value of 0.808 for the test set. The PubMac-based model (PubMac-GB) achieved best AUC values of 0.935 for test set. The SHAP analysis results emphasized that MaccsFP62, ECFP&#95;624, ECFP&#95;724, and PubchemFP213 were the crucial molecular features. Applicability domain analysis was also performed to determine reliable prediction boundaries for the model. The PubMac-GB model was applied to virtual screening for potential GABA A agonists and the top 100 compounds were given., Conclusion: Overall, our ensemble learning-based model (PubMac-GB) achieved comparable performance and would be helpful in effectively identifying agonists of GABA A receptors., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Purpose: Prolonged exposure to plasma free fatty acids (FFAs) leads to impaired glucose tolerance (IGT) which can progress to type 2 diabetes (T2D) in the absence of timely and effective interventions. High-fat diet (HFD) leads to chronic inflammation and oxidative stress, impairing pancreatic beta cell (PBC) function. While Didymin, a flavonoid glycoside derived from citrus fruits, has beneficial effects on inflammation dysfunction, its specific role in HFD-induced IGT remains yet to be elucidated. Hence, this study aims to investigate the protective effects of Didymin on PBCs., Methods: HFD-induced IGT mice and INS-1 cells were used to explore the effect and mechanism of Didymin in alleviating IGT. Serum glucose and insulin levels were measured during the glucose tolerance and insulin tolerance tests to evaluate PBC function and insulin resistance. Next, RNA-seq analysis was performed to identify the pathways potentially influenced by Didymin in PBCs. Furthermore, we validated the effects of Didymin both in vitro and in vivo. Mitochondrial electron transport inhibitor (Rotenone) was used to further confirm that Didymin exerts its ameliorative effect by enhancing mitochondria function., Results: Didymin reduces postprandial glycemia and enhances 30-minute postprandial insulin levels in IGT mice. Moreover, Didymin was found to enhance mitochondria biogenesis and function, regulate insulin secretion, and alleviate inflammation and apoptosis. However, these effects were abrogated with the treatment of Rotenone, indicating that Didymin exerts its ameliorative effect by enhancing mitochondria function., Conclusions: Didymin exhibits therapeutic potential in the treatment of HFD-induced IGT. This beneficial effect is attributed to the amelioration of PBC dysfunction through improved mitochondrial function., (© 2024. The Author(s).)

Background: The application of artificial intelligence (AI) in the ultrasound (US) diagnosis of breast cancer (BCa) is increasingly prevalent. However, the impact of US-probe frequencies on the diagnostic efficacy of AI models has not been clearly established., Objectives: To explore the impact of using US-video of variable frequencies on the diagnostic efficacy of AI in breast US screening., Methods: This study utilized different frequency US-probes (L14: frequency range: 3.0-14.0 MHz, central frequency 9 MHz, L9: frequency range: 2.5-9.0 MHz, central frequency 6.5 MHz and L13: frequency range: 3.6-13.5 MHz, central frequency 8 MHz, L7: frequency range: 3-7 MHz, central frequency 4.0 MHz, linear arrays) to collect breast-video and applied an entropy-based deep learning approach for evaluation. We analyzed the average two-dimensional image entropy (2-DIE) of these videos and the performance of AI models in processing videos from these different frequencies to assess how probe frequency affects AI diagnostic performance., Results: The study found that in testing set 1, L9 was higher than L14 in average 2-DIE; in testing set 2, L13 was higher in average 2-DIE than L7. The diagnostic efficacy of US-data, utilized in AI model analysis, varied across different frequencies (AUC: L9 > L14: 0.849 vs. 0.784; L13 > L7: 0.920 vs. 0.887)., Conclusion: This study indicate that US-data acquired using probes with varying frequencies exhibit diverse average 2-DIE values, and datasets characterized by higher average 2-DIE demonstrate enhanced diagnostic outcomes in AI-driven BCa diagnosis. Unlike other studies, our research emphasizes the importance of US-probe frequency selection on AI model diagnostic performance, rather than focusing solely on the AI algorithms themselves. These insights offer a new perspective for early BCa screening and diagnosis and are of significant for future choices of US equipment and optimization of AI algorithms., (© 2023. The Author(s).)

Background and Objective: The incidence of stroke is rising, and it is the second major cause of mortality and the third leading cause of disability around the globe. The goal of this study was to rapidly and accurately identify carotid plaques and automatically quantify plaque burden using our automated tracking and segmentation US-video system., Methods: We collected 88 common carotid artery transection videos (11048 frames) with a history of atherosclerosis or risk factors for atherosclerosis, which were randomly divided into training, test, and validation sets using a 6:3:1 ratio. We first trained different segmentation models to segment the carotid intima and adventitia, and calculate the maximum plaque burden automatically. Finally, we statistically analyzed the plaque burden calculated automatically by the best model and the results of manual labeling by senior sonographers., Results: Of the three Artificial Intelligence (AI) models, the Robust Video Matting (RVM) segmentation model's carotid intima and adventitia Dice Coefficients (DC) were the highest, reaching 0.93 and 0.95, respectively. Moreover, the RVM model has shown the strongest correlation coefficient (0.61±0.28) with senior sonographers, and the diagnostic effectiveness between the RVM model and experts was comparable with paired-t test and Bland-Altman analysis [P= 0.632 and ICC 0.01 (95% CI: -0.24~0.27), respectively]., Conclusion: Our findings have indicated that the RVM model can be used in ultrasound carotid video. The RVM model can automatically segment and quantify atherosclerotic plaque burden at the same diagnostic level as senior sonographers. The application of AI to carotid videos offers more precise and effective methods to evaluate carotid atherosclerosis in clinical practice.

Rationale and Objectives: It is still challenging for cardiac magnetic resonance (CMR) to detect ischemic heart disease (IHD) without the use of gadolinium contrast. We aimed to evaluate the potential value of adenosine triphosphate (ATP) stress myocardial strain derived from feature tracking (FT) as a novel method for detecting IHD in a swine model., Materials and Methods: CMR cines, myocardial perfusion imaging at rest and during ATP stress, and late gadolinium enhancement were obtained in both control and IHD swine. Normal, remote, ischemic, and infarcted myocardium were analyzed. The diagnostic accuracy of myocardial strain for infarction and ischemia was assessed using coronary angiography and pathology as reference., Results: Eleven IHD swine and five healthy control swine were enrolled in this study. Strain parameters, even at rest, were associated with myocardial ischemia and infarction(all p < 0.05). The area under receiver operating characteristic curve (AUC) values of all strain parameters for detecting infarcted myocardium exceeded 0.900 (all p < 0.05). The AUC values for detecting ischemic myocardium were as follows: 0.906 and 0.847 for stress and rest radial strain, 0.763 and 0.716 for stress and rest circumferential strain, 0.758 and 0.663 for stress and rest longitudinal strain (all p < 0.001). Heat maps demonstrated that all strain parameters showed mild to moderate correlations with the stress myocardial blood flow and myocardial perfusion reserve (all p < 0.05)., Conclusion: CMR-FT-derived ATP stress myocardial strain shows promise as a noninvasive method for detecting myocardial ischemia and infarction in an IHD swine model, with rest strain parameters offering potential as a needle-free diagnostic option., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Association of University Radiologists. All rights reserved.)

Although most papillary thyroid cancers (PTCs) are deemed to have a favorable clinical course and outcome, some develop an aggressive biological behavior at diagnosis or during treatment. Single-cell RNA sequencing (scRNA-seq), which is based on quantifying the features of individual cells to resolve tumor tissue heterogeneity, was used to uncover gene regulatory relationships and trace the transcriptional trajectories underlying the malignant transformation. In this study, we performed single-cell sequencing on samples from four PTC patients and one benign thyroid tumor patient. These included two papillary thyroid microcarcinoma cancers (PTMC) patients, two age-matched advanced PTC patients with invading surrounding tissues, and one patient undergoing surgical treatment due to a benign thyroid tumor. We constructed a new PTC RNA spectrum using single-cell sequencing. Single-cell sequencing analysis indicated that there was a highly invasive subgroup in the PTC epithelial cells, the expression of SATB2 (special AT-rich binding protein-2) was related to the prognosis and clinical progress of PTC, and SATB2 could promote the proliferation, migration, and invasion of PTC cells. We found that NOTCH1 was the key target gene of SATB2, and the activation of the SATB2/NOTCH1 pathway was one of the reasons for the high carcinogenicity of this subgroup., (© 2023 Wiley Periodicals LLC.)

Background: Metabolic dysfunction-associated fatty liver disease (MAFLD) is one of the most prevalent metabolic syndromes worldwide. However, no approved pharmacological treatments are available for MAFLD. Chenpi, one kind of dried peel of citrus fruits, has traditionally been utilized as a medicinal herb for liver diseases. Didymin is a newly identified oral bioactive dietary flavonoid glycoside derived from Chenpi. In this study, we investigated the therapeutic potential of Didymin as an anti-MAFLD drug and elucidated its underlying mechanisms., Methods: High-fat diet (HFD)-induced MAFLD mice and alpha mouse liver 12 (AML12) cells were utilized to evaluate the effects and mechanisms of Didymin in the treatment of MAFLD. Liver weight, serum biochemical parameters, and liver morphology were examined to demonstrate the therapeutic efficacy of Didymin in MAFLD treatment. RNA-seq analysis was performed to identify potential pathways that could be affected by Didymin. The impact of Didymin on Sirt1 was corroborated through western blot, molecular docking analysis, microscale thermophoresis (MST), and deacetylase activity assay. Then, a Sirt1 inhibitor (EX-527) was utilized to confirm that Didymin alleviates MAFLD via Sirt1. Western blot and additional assays were used to investigate the underlying mechanisms., Results: Our results suggested that Didymin may possess therapeutic potential against MAFLD in vitro and in vivo. By promoting Sirt1 expression as well as directly binding to and activating Sirt1, Didymin triggers downstream pathways that enhance mitochondrial biogenesis and function while reducing apoptosis and enhancing lipophagy., Conclusions: These suggest that Didymin could be a promising medication for MAFLD treatment. Furthermore, its therapeutic effects are mediated by Sirt1., (© 2023. The Author(s).)

Background and Aims: Identifying patients with hypertrophic cardiomyopathy (HCM) who are candidates for implantable cardioverter defibrillator (ICD) implantation in primary prevention for sudden cardiac death (SCD) is crucial. The aim of this study was to externally validate the 2022 European Society of Cardiology (ESC) model and other guideline-based ICD class of recommendation (ICD-COR) models and explore the utility of late gadolinium enhancement (LGE) in further risk stratification., Methods: Seven hundred and seventy-four consecutive patients who underwent cardiac magnetic resonance imaging were retrospectively enrolled., Results: Forty-six (5.9%) patients reached the SCD-related endpoint during 7.4 ± 2.5 years of follow-up. Patients suffering from SCD had higher ESC Risk-SCD score (4.3 ± 2.4% vs. 2.8 ± 2.1%, P < .001) and LGE extent (13.7 ± 9.4% vs. 4.9 ± 6.6%, P < .001). Compared with the 2014 ESC model, the 2022 ESC model showed increased area under the curve (.76 vs. .63), sensitivity (76.1% vs. 43.5%), positive predictive value (16.8% vs. 13.6%), and negative predictive value (98.1% vs. 95.9%). The C-statistics for SCD prediction of 2011 American College of Cardiology (ACC)/American Heart Association (AHA), 2014 ESC, 2020 AHA/ACC, and 2022 ESC models were .68, .64, .76 and .78, respectively. Furthermore, in patients without extensive LGE, LGE ≥5% was responsible for seven-fold SCD risk after multivariable adjustment. Whether in ICD-COR II or ICD-COR III, patients with LGE ≥5% and <15% showed significantly worse prognosis than those with LGE <5% (all P < .001)., Conclusions: The 2022 ESC model performed better than the 2014 ESC model with especially improved sensitivity. LGE enabled further risk stratification based on current guidelines., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Skeletal muscle function declines in the aging process or disease; however, until now, skeletal muscle has remained one of the organs most undertreated with medication. In this study, naringenin (NAR) was found to build muscle endurance in wild-type mice of different ages by increasing oxidative myofiber numbers and aerobic metabolism, and it ameliorates muscle dysfunction in mdx mice. The transcription factor Sp1 was identified as a direct target of NAR and was shown to mediate the function of NAR on muscle. Moreover, the binding site of NAR on Sp1 was further validated as GLN-110. NAR enhances the binding of Sp1 to the CCCTGCCCTC sequence of the Esrrg promoter by promoting Sp1 phosphorylation, thus upregulating Esrrg expression. The identification of the Sp1-ERRγ transcriptional axis is of great significance in basic muscle research, and this function of NAR has potential implications for the improvement of muscle function and the prevention of muscle atrophy., Competing Interests: Declaration of interests A provisional application for the results of the article was filed with the Unites States Patent Office on March 23, 2022, and is assigned as United States Patent Application No. 63/323,146. And the subject PCT application was filed on March 23, 2023, and the application number assigned by the International Bureau is PCT/IB2023/000179., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

In this study, we have innovatively proposed a method of in-situ synthesized TiC hard phase to improve the surface mechanical properties of artificial joint materials (Ti6Al4V). In order to explore the optimum graphene oxide (GO) addition, GO/Ti6Al4V composite powders with different proportions (0, 0.5, 1.0, and 1.5 wt.%) were prepared. The homogeneously dispersed GO/Ti6Al4V composite powder was prepared on Ti6Al4V substrate by laser cladding technology. The microstructure, phase composition, and mechanical behavior of GO/Ti6Al4V composite coatings were studied by scanning electron microscope (SEM), optical microscope (OM), energy dispersive spectrometer (EDS), tribometer, hardness tester, and surface profiler. The results showed that the addition of GO could significantly improve the mechanical properties of TC4 substrate. During the preparation of the coating, the grain size of in-situ TiC phase was nanoscale and was distributed between acicular martensite, which played a critical role in enhancing the mechanical properties of the coating. The TiC phase distributed between acicular martensite refine the grain size of α ' phase and improve the cutting resistance of the coating. Nevertheless, excessive GO decreased the fluidity of the molten pool, and micro holes tended to generate in the coating, which had a negative impact on the mechanical properties of the coating. At the GO content of 0.5 wt.%, the microhardness of the GO/Ti6Al4V coating was 1.325 times that of pure Ti6Al4V. Under the friction environment of simulated body fluid solution, the average friction coefficient was approximately 0.307 and the wear rate decreased to 3.5 × 10 -7  mm 3 /N · m., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Designing innovative electrochemiluminescence (ECL) immunosensors is critical for the detection of biomarkers with a low concentration and the precise evaluation of clinical diseases. Herein, a Cu 3 (hexahydroxytriphenylene) 2 (Cu 3 (HHTP) 2 ) nanoflake-based sandwich-type ECL immunosensor was constructed for C-Reactive Protein (CRP) detection. The Cu 3 (HHTP) 2 nanoflake, an electronically conductive metal-organic framework (MOF), has a periodically arranged porous structure with a cavity size of 2 nm, which not only accommodates a large amount of Ru(bpy) 3 2+ but also confines the spatial diffusion of active species. Therefore, the Ru(bpy) 3 2+ -loaded Cu 3 (HHTP) 2 nanocomplex (Ru@CuMOF) as an ECL emitter exhibits an enhanced ECL efficiency. The ECL resonance energy transfer (ECL-RET) was accomplished by combining Ru@CuMOF used as a donor with gold nanoparticles-functionalized graphene oxide nanosheets (GO-Au) utilized as an acceptor. This should be ascribed to the fact that the ECL emission spectrum of Ru@CuMOF shows the strongest signal intensity at 615 nm, overlapping with the absorption spectrum of GO-Au at 580-680 nm. Targeted detection of CRP in human serum samples was achieved by the sandwich-type immunosensor based on the ECL-RET mechanism with a 0.26 pg mL -1 detection limit. The electro-activated hybrids of Cu 3 (HHTP) 2 and ECL emitters provide a new sensing strategy for the high-sensitivity detection of disease markers., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Purpose: To determine the association of myocardial fibrosis and left ventricular (LV) dyssynchrony measured using cardiac MRI with late gadolinium enhancement (LGE) and feature tracking (FT), respectively, with response to cardiac resynchronization therapy (CRT) for nonischemic dilated cardiomyopathy (DCM)., Materials and Methods: This retrospective study included 98 patients (mean age, 59 years ± 10 [SD]; 54 men) who had nonischemic DCM, as assessed with LGE cardiac MRI before CRT. Cardiac MRI FT-derived dyssynchrony was defined as the SD of the time-to-peak strain (TTP-SD) of the LV segments in three directions (longitudinal, radial, and circumferential). CRT response was defined as a 15% increase in LV ejection fraction (LVEF) at echocardiography at 6-month follow-up, and then, long-term cardiovascular events were assessed. The likelihood ratio test was used to evaluate the incremental prognostic value of LGE and dyssynchrony parameters., Results: Seventy-one (72%) patients showed a favorable LVEF response following CRT. LGE presence (odds ratio: 0.14 [95% CI: 0.04, 0.47], P = .002; and hazard ratio: 3.52 [95% CI: 1.37, 9.07], P = .01) and lower circumferential TTP-SD (odds ratio: 1.04 [95% CI: 1.02, 1.07], P = .002; and hazard ratio: 0.98 [95% CI: 0.96, 1.00], P = .03) were independently associated with LVEF nonresponse and long-term outcomes. Combined LGE and circumferential TTP-SD provided the highest discrimination for LVEF nonresponse (area under the receiver operating characteristic curve [AUC]: 0.89 [95% CI: 0.81, 0.94], sensitivity: 84.5% [95% CI: 74.0%, 92.0%], specificity: 85.2% [95% CI: 66.3%, 95.8%]) and long-term outcomes (AUC: 0.84 [95% CI: 0.75, 0.91], sensitivity: 76.9% [95% CI: 56.4%, 91.0%], specificity: 87.0% [95% CI: 76.7%, 93.9%])., Conclusion: Myocardial fibrosis and lower circumferential dyssynchrony assessed with pretherapy cardiac MRI were independently associated with unfavorable LVEF response and long-term events following CRT in patients with nonischemic DCM and may provide incremental value in predicting prognosis. Keywords: MR Imaging, Cardiac, Outcomes Analysis Supplemental material is available for this article . © RSNA, 2023., Competing Interests: Disclosures of conflicts of interest: Y.S. No relevant relationships. X.C. No relevant relationships. K.Y. No relevant relationships. Z.D. No relevant relationships. C.C. No relevant relationships. K.Z. No relevant relationships. H.C. No relevant relationships. K.J. No relevant relationships. M.L. No relevant relationships. S.Z. No relevant relationships., (© 2023 by the Radiological Society of North America, Inc.)

Optical anisotropy is pivotal for optical crystals, and it can be characterized by the maximum algebraic difference in refractive indices. Improving the optical anisotropy, especially for deep-ultraviolet (UV) crystals, is still a challenge and of interest. Herein, a new hydroxyfluorooxoborate, Rb[B 3 O 3 F 2 (OH) 2 ], was obtained by the heterologous isomorphic substitution strategy. Dual enhancement for the band gap and birefringence compared with the parent A[B 3 O 3 F 2 (OH) 2 ] (A = [Ph 4 P]/[Ph 3 MeP]) compounds was achieved in Rb[B 3 O 3 F 2 (OH) 2 ]. This considerable enhancement originates from the removal of organic components and the retention of a birefringence-active anionic framework. This enhancement pushes the application region from UV to deep-UV. This discovery not only expands the structural chemistry of borates but also demonstrates the viability of heterologous isomorphic substitution to design deep-UV crystals with enhanced optical property.

Background: This retrospective study aims to validate the effectiveness of artificial intelligence (AI) to detect and classify non-mass breast lesions (NMLs) on ultrasound (US) images., Methods: A total of 228 patients with NMLs and 596 volunteers without breast lesions on US images were enrolled in the study from January 2020 to December 2022. The pathological results served as the gold standard for NMLs. Two AI models were developed to accurately detect and classify NMLs on US images, including DenseNet121&#95;448 and MobileNet&#95;448. To evaluate and compare the diagnostic performance of AI models, the area under the curve (AUC), accuracy, specificity and sensitivity was employed., Results: A total of 228 NMLs patients confirmed by postoperative pathology with 870 US images and 596 volunteers with 1003 US images were enrolled. In the detection experiment, the MobileNet&#95;448 achieved the good performance in the testing set, with the AUC, accuracy, sensitivity, and specificity were 0.999 (95%CI: 0.997-1.000),96.5%,96.9% and 96.1%, respectively. It was no statistically significant compared to DenseNet121&#95;448. In the classification experiment, the MobileNet&#95;448 model achieved the highest diagnostic performance in the testing set, with the AUC, accuracy, sensitivity, and specificity were 0.837 (95%CI: 0.990-1.000), 70.5%, 80.3% and 74.6%, respectively., Conclusions: This study suggests that the AI models, particularly MobileNet&#95;448, can effectively detect and classify NMLs in US images. This technique has the potential to improve early diagnostic accuracy for NMLs., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Purpose: The objective of this research was to investigate the efficacy of various parameter combinations of Convolutional Neural Networks (CNNs) models, namely MobileNet and DenseNet121, and different input image resolutions (REZs) ranging from 64×64 to 512×512 pixels, for diagnosing breast cancer., Materials and Methods: During the period of June 2015 to November 2020, two hospitals were involved in the collection of two-dimensional ultrasound breast images for this retrospective multicenter study. The diagnostic performance of the computer models MobileNet and DenseNet 121 was compared at different resolutions., Results: The results showed that MobileNet had the best breast cancer diagnosis performance at 320×320pixel REZ and DenseNet121 had the best breast cancer diagnosis performance at 448×448pixel REZ., Conclusion: Our study reveals a significant correlation between image resolution and breast cancer diagnosis accuracy. Through the comparison of MobileNet and DenseNet121, it is highlighted that lightweight neural networks (LW-CNNs) can achieve model performance similar to or even slightly better than large neural networks models (HW-CNNs) in ultrasound images, and LW-CNNs' prediction time per image is lower., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

A novel electrochemiluminescence (ECL) aptasensor, using graphite carbonitride (g-C 3 N 4 ) capped CdS quantum dots (CdS QDs@g-C 3 N 4 ) and Au nanoparticles decorated triethanolamine (AuNPs@TEOA) as dual coreactants, was proposed for the determination of mucin 1 (MUC1). Higher ECL efficiency was acquired due to the double enhancement contribution of CdS QDs and TEOA to Ru (bpy) 3 2+ ECL. Additionally, AuNPs@TEOA also acted as nanocarrier for MUC1 aptamer immobilization. After the aptasensor was incubated in target MUC1, the decreased ECL emission was obtained because of the poor conductivity of MUC1. The ECL aptasensor displayed a good linear correlation for MUC1 in the range 0.1 pg mL -1 -1000 ng mL -1 , and the detection limit was 33 fg mL -1 . MUC1 spiked into human serum samples was quantified to assess the practicability of the ECL aptasensor., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Hypoparathyroidism (HypoPT) is a rare disease involving the parathyroid glands that is characterized by a reduced secretion or potency of the parathyroid hormone (PTH), which leads to high serum phosphorus levels and low serum calcium levels. HypoPT most commonly results from accidental damage to the glands or their removal during thyroid or other anterior neck surgery. Parathyroid/thyroid surgery has become more common in recent years, with a corresponding rise in the occurrence of HypoPT as a postoperative complication. There is a critical need for a HypoPT animal model to better understand the mechanisms underlying the effects of HypoPT on mineral ion homeostasis and to verify the therapeutic effectiveness of novel treatments. Here, a technique is reported to create acquired HypoPT in male rats by performing parathyroidectomy (PTX) using carbon nanoparticles. The rat model shows great promise over the mouse models of hypoparathyroidism. Importantly, the human PTH receptor binding region has an 84.2% sequence similarity with that of the rat, which is higher than the 73.7% similarity shared with mice. Moreover, the effects of estrogen, which can affect the PTH/PTHrP receptor signaling pathway, have not been fully investigated in male rats. Carbon nanoparticles are lymphatic tracers that stain the thyroid lymph nodes black without affecting their function, but they do not stain the parathyroid glands, which makes them easy to identify and remove. In this study, serum PTH levels were undetectable after PTX, and this resulted in significant hypocalcemia and hyperphosphatemia. Thus, the clinical state of postoperative HypoPT can be remarkably represented in the rat model. Carbon-nanoparticle-assisted PTX can, therefore, serve as an extraordinarily effective and readily implementable model for studying the pathogenesis, treatment, and prognosis of HypoPT.

Purpose: To assess the efficacy of cardiac MRI stress T1 mapping in detecting ischemic and infarcted myocardium in a miniature-swine model, using pathologic findings as the reference standard., Materials and Methods: Ten adult male Chinese miniature swine, with coronary artery stenosis induced by an ameroid constrictor, and two healthy control swine were studied. Cardiac 3-T MRI rest and adenosine triphosphate stress T1 mapping and perfusion images, along with resting and late gadolinium enhancement images, were acquired at baseline and weekly up to 4 weeks after surgery or until humanely killed. A receiver operating characteristic analysis was used to analyze the performance of T1 mapping in the detection of myocardial ischemia., Results: In the experimental group, both the infarcted myocardium (ΔT1 = 10 msec ± 2 [SD]; ΔT1 percentage = 0.7% ± 0.1) and ischemic myocardium (ΔT1 = 10 msec ± 2; ΔT1 percentage = 0.9% ± 0.2) exhibited reduced T1 reactivity compared with the remote myocardium (ΔT1 = 53 msec ± 7; ΔT1 percentage = 4.7% ± 0.6) and normal myocardium (ΔT1 = 56 msec ± 11; ΔT1 percentage = 4.9% ± 1.1). Receiver operating characteristic analysis demonstrated high diagnostic performance of ΔT1 in detecting ischemic myocardium, with an area under the curve (AUC) of 0.84 ( P < .001). Rest T1 displayed high diagnostic performance in detecting infarcted myocardium (AUC = 0.95; P < .001). When rest T1 and ΔT1 were combined, the diagnostic performance for both ischemic and infarcted myocardium were improved (AUCs, 0.89 and 0.97, respectively; all P < .001). The collagen volume fraction correlated with ΔT1, ΔT1 percentage, and Δ extracellular volume percentage ( r = -0.70, -0.70, and -0.50, respectively; P = .001, .001, and .03, respectively)., Conclusion: Using histopathologic validation in a swine model, noninvasive cardiac MRI stress T1 mapping demonstrated high performance in detecting ischemic and infarcted myocardium without the need for contrast agents. Keywords: Coronary Artery Disease, MRI, Myocardial Ischemia, Rest T1 Mapping, Stress T1 Mapping, Swine Model Supplemental material is available for this article. © RSNA, 2023See also commentary by Burrage and Ferreira in this issue., Competing Interests: Disclosures of conflicts of interest: B.Z. No relevant relationships. C.C. No relevant relationships. J.H. No relevant relationships. J.X. No relevant relationships. G.Y. No relevant relationships. X.D. No relevant relationships. G.Y. No relevant relationships. H.W. No relevant relationships. X.W. No relevant relationships. A.S. No relevant relationships. S.Z. No relevant relationships. M.L. No relevant relationships., (© 2023 by the Radiological Society of North America, Inc.)

Background: Atrial fibrillation (AF) is a highly prevalent condition that can cause or exacerbate heart failure, is an important risk factor for stroke, and is associated with pronounced morbidity and death. Genes uniquely expressed in the atria are known to be essential for maintaining atrial structure and function. Atrial tissue remodeling contributes to arrhythmia recurrence and maintenance. However, the mechanism underlying atrial remodeling remains poorly understood. This study was designed to investigate whether other uncharacterized atrial specific genes play important roles in atrial physiology and arrhythmogenesis., Methods: RNA-sequencing analysis was used to identify atrial myocyte specific and angiotensin II-responsive genes. Genetically modified, cardiomyocyte-specific mouse models (knockout and overexpression) were generated. In vivo and in vitro electrophysiological, histology, and biochemical analyses were performed to determine the consequences of CIB2 (calcium and integrin binding family member 2 protein) gain and loss of function in the atrium., Results: Using RNA-sequencing analysis, we identified CIB2 as an atrial-enriched protein that is significantly downregulated in the left atria of patients with AF and mouse models of AF from angiotensin II infusion or pressure overload. Using cardiomyocyte-specific C ib2 knockout ( Cib2 -/ - ) and atrial myocyte-specific Cib2 -overexpressing mouse models, we found that loss of C ib2 enhances AF occurrence, prolongs AF duration, and correlates with a significant increase in atrial fibrosis under stress. Conversely, Cib2 overexpression mitigates AF occurrence and atrial fibrosis triggered by angiotensin II stress. Mechanistically, we revealed that CIB2 competes with and inhibits CIB1-mediated calcineurin activation, thereby negating stress-induced structural remodeling and AF., Conclusions: Our data suggest that CIB2 represents a novel endogenous and atrial-enriched regulator that protects against atrial remodeling and AF under stress conditions. Therefore, CIB2 may represent a new potential target for treating AF., Competing Interests: Disclosures None.

Background and Objective: The value of implementing artificial intelligence (AI) on ultrasound screening for thyroid cancer has been acknowledged, with numerous early studies confirming AI might help physicians acquire more accurate diagnoses. However, the black box nature of AI's decision-making process makes it difficult for users to grasp the foundation of AI's predictions. Furthermore, explainability is not only related to AI performance, but also responsibility and risk in medical diagnosis. In this paper, we offer Explainer, an intrinsically explainable framework that can categorize images and create heatmaps highlighting the regions on which its prediction is based., Methods: A dataset of 19341 thyroid ultrasound images with pathological results and physician-annotated TI-RADS features is used to train and test the robustness of the proposed framework. Then we conducted a benign-malignant classification study to determine whether physicians perform better with the assistance of an explainer than they do alone or with Gradient-weighted Class Activation Mapping (Grad-CAM)., Results: Reader studies show that the Explainer can achieve a more accurate diagnosis while explaining heatmaps, and that physicians' performances are improved when assisted by the Explainer. Case study results confirm that the Explainer is capable of locating more reasonable and feature-related regions than the Grad-CAM., Conclusions: The Explainer offers physicians a tool to understand the basis of AI predictions and evaluate their reliability, which has the potential to unbox the "black box" of medical imaging AI., Competing Interests: Declaration of Competing Interest We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Biological materials relied on multiple synergistic structural design elements typically exhibit excellent comprehensive mechanical properties. Hierarchical incorporation of different biostructural elements into a single artificial material is a promising approach to enhance mechanical properties, but remains challenging. Herein, a biomimetic structural design strategy is proposed by coupling gradient structure with twisted plywood Bouligand structure, attempting to improve the impact resistance of ceramic-polymer composites. Via robocasting and sintering, kaolin ceramic filaments reinforced by coaxially aligned alumina nanoplatelets are arranged into Bouligand structure with a gradual transition in filament spacing along the thickness direction. After the following polymer infiltration, biomimetic ceramic-polymer composites with a gradient Bouligand (GB) structure are eventually fabricated. Experimental investigations reveal that the incorporation of gradient structure into Bouligand structure improves both the peak force and total energy absorption of the obtained ceramic-polymer composites. Computational modeling further suggests the substantial improvement in impact resistance by adopting GB structure, and clarifies the underlying deformation behavior of the biomimetic GB structured composites under impact. This biomimetic design strategy may provide valuable insights for developing lightweight and impact-resistant structural materials in the future., (© 2023 Wiley-VCH GmbH.)