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Neutrophil extracellular traps (NETs) are web-like complexes of DNA and proteins that are extruded by activated neutrophils and play critical roles as major components of the innate immune response against pathogen invasion. However, some microbes have developed strategies to evade NET attacks, leading to impaired immune defenses and persistent infections. In this study, an engineered neutrophil strategy for enhancing the antibacterial activity of NETs is developed. A nucleus-targeting photosensitizer (NCP) with strong reactive oxygen species production and a strong DNA-binding capacity is synthesized. NCP-loaded neutrophils are subsequently constructed via direct incubation of NCP with neutrophils, and the NCP is closely inserted into the nucleus DNA. Upon activation by bacteria-related toxins, NCP-coupled NETs can be released rapidly, actively trapping bacteria and providing a high local concentration of NCP around them. Both in vitro and in vivo results revealed that NCP-coupled NETs can effectively eradicate various multidrug-resistant bacteria and biofilms through photodynamic therapy, overcome bacterial immune evasion, and promote tissue recovery from severe wound infections. This design can significantly strengthen NET function, providing a non-antibiotic alternative platform for treating bacterial infectious diseases., (© 2024 Wiley‐VCH GmbH.)

Corneal Fluorescence Staining (CFS) imaging is commonly employed for assessing corneal epithelial damage. Automating the grading of CFS images can minimize subjectivity in clinical evaluations and enhance diagnostic efficiency. Existing methods typically depend on the texture and morphological information extracted from whole CFS images, often neglecting the spatial and distribution information between stained regions. This oversight hinders the accurate evaluation of corneal epithelial injury states. This study proposes a three-stage automatic corneal epithelial damage assessment model for full CFS images, optimizing grading by considering topological features among detected stained regions, which are crucial for accurately interpreting the spatial properties of objects within an image. Accurate corneal localization, robust to variations in contrast, is first achieved by integrating CFS images' intensity and phase information, subsequently by a multi-scale morphological top-hat operator concerning their prior shape to detect the stained regions. Finally, a multi-scale graph structure is constructed based on the detected stained areas, and distance-weighted topological features, along with textural and morphological features, are extracted into an automatic grading model based on an ensemble model. Experiments on an in-house dataset of CFS images annotated with six categories of Ocular Surface Staining (OSS) scores reveal that incorporating topological features achieves the highest Accuracy (0.7589), F1 score (0.7449), and AUC (0.9335). Moreover, topological features outperformed other individual features. These findings underscore the effectiveness of our proposed model in CFS grading, indicating its potential for assessing corneal epithelial damage. Additionally, the valuable insights provided by topological features into the spatial distribution patterns of staining suggest promising applications for enhancing disease classification and supporting more informed clinical decision-making in managing dry eye conditions., 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.)

CNN-based object detection models that strike a balance between performance and speed have been gradually used in polyp detection tasks. Nevertheless, accurately locating polyps within complex colonoscopy video scenes remains challenging since existing methods ignore two key issues: intra-sequence distribution heterogeneity and precision-confidence discrepancy. To address these challenges, we propose a novel Temporal-Spatial self-correction detector (TSdetector), which first integrates temporal-level consistency learning and spatial-level reliability learning to detect objects continuously. Technically, we first propose a global temporal-aware convolution, assembling the preceding information to dynamically guide the current convolution kernel to focus on global features between sequences. In addition, we designed a hierarchical queue integration mechanism to combine multi-temporal features through a progressive accumulation manner, fully leveraging contextual consistency information together with retaining long-sequence-dependency features. Meanwhile, at the spatial level, we advance a position-aware clustering to explore the spatial relationships among candidate boxes for recalibrating prediction confidence adaptively, thus eliminating redundant bounding boxes efficiently. The experimental results on three publicly available polyp video dataset show that TSdetector achieves the highest polyp detection rate and outperforms other state-of-the-art methods. The code can be available at https://github.com/soleilssss/TSdetector., 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.)

Mitochondrial viscosity serves as a critical indicator for assessing mitochondrial functionality and offers valuable insights into cellular homeostasis. Continuous, real-time monitoring of mitochondrial viscosity is indispensable for understanding and diagnosing diseases associated with these dynamic changes. In this study, we introduce a novel mitochondrial viscosity-responsive probe named "JL-JC" which is designed by using a molecular strategy, with a classic "D-π-A" molecular structure. Leveraging the distinctive twisted intramolecular charge transfer (TICT) properties of the probe, JL-JC exhibits exceptional sensitivity and a high signal-to-noise ratio, enabling precise detection of viscosity variations within its microenvironment while remaining unaffected by other factors. Upon rapid cellular uptake, JL-JC can efficiently evaluate the mitochondrial viscosity changes under diverse physiological and pathological conditions. Notably, this probe also enables viscosity imaging in zebrafish, offering insights into mitochondrial states in vivo . Our findings present JL-JC as a promising tool and potential diagnostic platform for mitochondria-related diseases.

Background: Teledentistry is the usage of information-based technologies to deliver healthcare services remotely. It is used to deliver care in regional, rural and remote regions and was particularly useful to deliver care during the COVID-19 pandemic., Objective: This systematic review and meta-analysis aimed to determine teledentistry utilisation in Australia., Methods: The databases PubMed, Google Scholar, EMBASE and Web of Science were searched from inception to June-2024. The phrases "Dental" AND "Telehealth" AND "Australia" and "Teledentistry" AND "Australia" were used. Two authors completed the study selection and data extraction. The Joanna Briggs Institute Critical Appraisal Tools were used to assess quality and bias., Results: Eighteen articles met the inclusion criteria. There were six diagnostic tests, six cross-sectional studies, 4 economic evaluations, one qualitative study and one expert opinion. Teledentistry was accurate for screening caries (average sensitivity=69.7 %, average specificity=97.4 %). There also appeared to be a non-significant negative correlation between specificity and sensitivity (r = 0.432). Opinions regarding teledentistry were mixed from clinicians but positive from patients. Teledentistry may also lead to savings for patients and healthcare providers., Conclusion: Teledentistry increases healthcare access especially for people in regional, rural and remote areas. It is an effective screening tool for caries. Whilst the opinions of clinicians were mixed, potential implementation barriers were identified which could improve opinions of clinicians and increase implementation., Clinical Importance: This study demonstrates teledentistry as a satisfactory tool for screening caries. This could be beneficial to those with difficulties visiting dentists in-person, particularly if they live in regional, rural or remote areas., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Older adults often manage multiple chronic diseases which necessitates the use of multiple medicines. Nevertheless, they also face an elevated risk of harm when medicines are used inappropriately. Studies indicate that socioeconomic disadvantage, beliefs, and health literacy may correlate with non-adherence and inappropriate medicine use. However, older adults are underrepresented in the current body of literature., Objective: To investigate the influence of beliefs and health literacy on medication-related outcomes in older adults., Methods: Participants ≥65 years living in the community were invited to complete a survey. Participants were asked to report demographics, medicines and complete three questionnaires: Self-Efficacy for Appropriate Medication use Scale (SEAMS), Beliefs about Medicines Questionnaire (BMQ) and Health Literacy Questionnaire (HLQ). Descriptive statistics, regressions and correlations were calculated., Results: A total of 154 participants were included in the analysis (35.7 % male, age range 65-110 y). Mean SEAMS score was 33.2 out of 39 (standard deviation (SD) = 8.0), reflecting high self-efficacy for adherence. Mean HLQ scores were high across the four scales measured in the survey (scales 1, 5, 6, and 9). Sixty-two participants (44.0 %) were using five or more medicines (polypharmacy) and 18 (15.4 %) reported use of a potentially inappropriate medicine. Regarding beliefs, mean BMQ-specific scores were as follows: necessity score 17.5 (SD = 5.1) and concern score 12.0 (SD = 4.0), indicating strong beliefs in the necessity of medicines and few concerns. Results of the regression analysis indicated that where the BMQ-Necessity scores were employed as the independent variable, there was statistical significance with polypharmacy (p < 0.001). Additionally, moderate positive correlations were identified between (1) necessity beliefs and both polypharmacy (r = 0.401, p < 0.001) and adherence (r = 0.477, p < 0.001), and (2) adherence and HLQ scale 5 (r = 0.343, p < 0.001), scale 6 (r = 0.326, p < 0.001) and scale 9 (r = 0.320, p < 0.001)., Conclusion: Older adults who perceive their medicines as necessary are more inclined to report use of multiple medicines, leading to polypharmacy. Additionally, older adults with stronger beliefs in the necessity of medicines and higher levels of health literacy demonstrate greater self-efficacy for adherence. Health professionals should consider evaluating necessity beliefs in older adults to manage potential non-adherence, reduce the risk of polypharmacy, and thereby mitigate the risk of suboptimal medicine use., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr Kate Wang reports a relationship with Australian Korean Foundation that includes: funding grants. If there are other authors, they 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 The Authors. Published by Elsevier Inc. All rights reserved.)

Dental, oral, and craniofacial diseases can substantially impact the quality of human life, thereby posing a serious public health concern. Although conventional therapies such as surgery have solved these problems largely, the prognosis of patients is not always satisfactory. Cell membrane-coated nanoparticles (CMCNPs) carry nanodrugs with the help of natural cell membranes, therefore utilizing their remarkable ability to interface and interact with their surrounding environment. These nanoparticles have demonstrated substantial advantages in drug targeting, prolonging blood circulation time, penetrating biofilms, and immune escape. With the assistance of CMCNPs, the therapeutic effects of dental, oral, and craniofacial diseases can reach a higher level. CMCNPs have been applied for dental, oral, and craniofacial diseases for various conditions such as head and neck cancer, periodontal disease, and oral biosignal detection. For the therapies of head and neck cancer, CMCNPs have been widely utilized as a tool of chemotherapy, phototherapy, and immunotherapy, while yet to be exploited in imaging technique. In the end, we summarized the challenges and prospectives of CMCNPs for dental, oral, and craniofacial diseases: large-scale production with uniform standards and high quantity, extensive application directions in dental, oral, and craniofacial regions (implant, endodontics), and the promotion of its clinical application., Competing Interests: Competing interests: The authors declare that they have no competing interests., (Copyright © 2024 Kang-Ning Wang et al.)

Mitochondrial DNA (mtDNA) is pivotal for mitochondrial morphology and function. Upon mtDNA damage, mitochondria undergo quality control mechanisms, including fusion, fission, and mitophagy. Real-time monitoring of mtDNA enables a deeper understanding of its effect on mitochondrial function and morphology. Controllable induction and real-time tracking of mtDNA dynamics and behavior are of paramount significance for studying mitochondrial function and morphology, facilitating a deeper understanding of mitochondria-related diseases. In this work, a fluorescent platinum complex was designed and developed that not only induces mitochondrial DNA (mtDNA) aggregation but also triggers mitochondrial autophagy (mitophagy) through the MDV pathway for damaged mtDNA clearance in living cells. Additionally, this complex allows for the real-time monitoring of these processes. This complex may serve as a valuable tool for studying mitochondrial microautophagy and holds promise for broader applications in cellular imaging and disease research.

Background: Medication use in older adults is increasing, therefore, reducing the risk of suboptimal medicine use is imperative in achieving optimal therapeutic outcomes. Research suggests that factors such as personal beliefs and beliefs about medicines may be associated with non-adherence and inappropriate medicine use., Aim: To systematically review and identify quantitative research on the influence of beliefs about medicines and the relationship with suboptimal medicine use in older adults., Method: Searches were conducted on PubMed, EMBASE, CINAHL, and PsycINFO for quantitative studies (inception to March 2023)., Inclusion Criteria: (1) exposure: participants' beliefs (personal, cultural, and medication-related), (2) outcomes: polypharmacy, potentially inappropriate medicines use, or non-adherence, and (3) participants: community-dwelling adults 65 years or above. Study selection, data extraction and quality appraisal (Joanna Briggs Institute critical appraisal checklist) were completed independently by two investigators. Data were combined in a narrative synthesis and presented in a summary of findings table., Results: Nineteen articles were included: 15 cross-sectional and four cohort studies. Outcomes of included papers were as follows; adherence (n = 18) and potentially inappropriate medicine use (n = 1). Ten studies found stronger beliefs in the necessity of medicines and/or fewer concerns led to better adherence, with one paper contradicting these findings. Three studies did not find associations between adherence and beliefs. One study confirmed an association between unnecessary drug use and a lack of belief in a "powerful other" (e.g. doctor)., Conclusion: Further investigation is necessary to (1) ascertain the importance of necessity or concern beliefs in fostering adherence and, (2) examine the influence of beliefs on polypharmacy and inappropriate medicine use., (© 2024. The Author(s).)

Eukaryotic cells regulate various cellular processes through membrane-bound and membrane-less organelles, enabling active signal communication and material exchange. Lysosomes and lipid droplets are representative organelles, contributing to cell lipophagy when their interaction and metabolism are disrupted. Our limited understanding of the interacting behaviours and physicochemical properties of different organelles during lipophagy hinders accurate diagnosis and treatment of related diseases. In this contribution, we report a fluorescent probe, PTZ, engineered for dual-targeting of lipid droplets and lysosomes. PTZ can track liquid-liquid phase separation and respond to polarity shifts through ratiometric fluorescence emission, elucidating the lipophagy process from the perspective of organelle behavior and physicochemical properties. Leveraging on the multifunctionality of PTZ, we have successfully tracked the polarity and dynamic changes of lysosomes and lipid droplets during lipophagy. Furthermore, an unknown homogeneous transition of lipid droplets and lysosomes was discovered, which provided a new perspective for understanding lipophagy processes. And this work is expected to serve as a reference for diagnosis and treatment of lipophagy-related diseases.

Visualization of the mitochondrial state is crucial for tracking cell life processes and diagnosing disease, while fluorescent probes that can accurately assess mitochondrial status are currently scarce. Herein, a fluorescent probe named " SYN " was designed and prepared, which can target mitochondria via the mitochondrial membrane potential. Upon pathology or external stimulation, SYN can be released from the mitochondria and accumulate in the nucleolus to monitor the status of mitochondria. During this process, the brightness of the nucleolus can then serve as an indicator of mitochondrial damage. SYN has demonstrated excellent photostability in live cells as well as an extremely inert fluorescence response to bioactive molecules and the physiological pH environment of live cells. Spectroscopic titration and molecular docking studies have revealed that SYN can be lit up in nucleoli due to the high viscosity of the nucleus and the strong electrostatic interaction with the phosphate backbone of RNA. This probe is expected to be an exceptional tool based on its excellent imaging properties for tracking mitochondrial state in live cells.

Background: Older people are at high risk of medicines-related harms. otentially inappropriate medicines (PIMs) list has been developed to assist clinicians and researchers to identify medicines with risks that may potentially outweigh their benefits in order to improve medication management and safety., Aim: To develop a list of PIMs for older people specific to Australia., Methods: The study obtained expert consensus through the utilisation of the Delphi technique in Australia. A total of 33 experts partook in the initial round, while 32 experts engaged in the subsequent round. The primary outcomes encompass medicines assessed as potentially inappropriate, the specific contexts in which their inappropriateness arises and potentially safer alternatives., Results: A total of 16 medicines or medicine classes had one or more medicines deemed as potentially inappropriate in older people. Up to 19 medicines or medicine classes had specific conditions that make them more potentially inappropriate, while alternatives were suggested for 16 medicines or classes., Conclusion: An explicit PIMs list for older people living in Australia has been developed containing 19 drugs/drug classes. The PIMs list is intended to be used as a guide for clinicians when assessing medication appropriateness in older people in Australian clinical settings and does not substitute individualised treatment advice from clinicians., (© 2024 The Authors. Internal Medicine Journal published by John Wiley & Sons Australia, Ltd on behalf of Royal Australasian College of Physicians.)

The signal transducer and activator of transcription 3 (STAT3), a member of the STAT family, resides in the nucleus to regulate genes essential for vital cellular functions, including survival, proliferation, self-renewal, angiogenesis, and immune response. However, continuous STAT3 activation in tumor cells promotes their initiation, progression, and metastasis, rendering STAT3 pathway inhibitors a promising avenue for cancer therapy. Nonetheless, these inhibitors frequently encounter challenges such as cytotoxicity and suboptimal biocompatibility in clinical trials. A viable strategy to mitigate these issues involves delivering STAT3 inhibitors via drug delivery systems (DDSs). This review delineates the regulatory mechanisms of the STAT3 signaling pathway and its association with cancer. It offers a comprehensive overview of the current application of DDSs for anti-STAT3 inhibitors and investigates the role of DDSs in cancer treatment. The conclusion posits that DDSs for anti-STAT3 inhibitors exhibit enhanced efficacy and reduced adverse effects in tumor therapy compared to anti-STAT3 inhibitors alone. This paper aims to provide an outline of the ongoing research and future prospects of DDSs for STAT3 inhibitors. Additionally, it presents our insights on the merits and future outlook of DDSs in cancer treatment., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Automated segmentation of liver tumors in CT scans is pivotal for diagnosing and treating liver cancer, offering a valuable alternative to labor-intensive manual processes and ensuring the provision of accurate and reliable clinical assessment. However, the inherent variability of liver tumors, coupled with the challenges posed by blurred boundaries in imaging characteristics, presents a substantial obstacle to achieving their precise segmentation. In this paper, we propose a novel dual-branch liver tumor segmentation model, SBCNet, to address these challenges effectively. Specifically, our proposed method introduces a contextual encoding module, which enables a better identification of tumor variability using an advanced multi-scale adaptive kernel. Moreover, a boundary enhancement module is designed for the counterpart branch to enhance the perception of boundaries by incorporating contour learning with the Sobel operator. Finally, we propose a hybrid multi-task loss function, concurrently concerning tumors' scale and boundary features, to foster interaction across different tasks of dual branches, further improving tumor segmentation. Experimental validation on the publicly available LiTS dataset demonstrates the practical efficacy of each module, with SBCNet yielding competitive results compared to other state-of-the-art methods for liver tumor segmentation.

Glioblastoma multiforme (GBM) is the most aggressive and lethal form of human brain tumors. Dismantling the suppressed immune microenvironment is an effective therapeutic strategy against GBM; however, GBM does not respond to exogenous immunotherapeutic agents due to low immunogenicity. Manipulating the mitochondrial electron transport chain (ETC) elevates the immunogenicity of GBM, rendering previously immune-evasive tumors highly susceptible to immune surveillance, thereby enhancing tumor immune responsiveness and subsequently activating both innate and adaptive immunity. Here, we report a nanomedicine-based immunotherapeutic approach that targets the mitochondria in GBM cells by utilizing a Trojan-inspired nanovector (ABBPN) that can cross the blood-brain barrier. We propose that the synthetic photosensitizer IrPS can alter mitochondrial electron flow and concurrently interfere with mitochondrial antioxidative mechanisms by delivering si-OGG1 to GBM cells. Our synthesized ABBPN coloaded with IrPS and si-OGG1 (ISA) disrupts mitochondrial electron flow, which inhibits ATP production and induces mitochondrial DNA oxidation, thereby recruiting immune cells and endogenously activating intracranial antitumor immune responses. The results of our study indicate that strategies targeting the mitochondrial ETC have the potential to treat tumors with limited immunogenicity.

Image segmentation achieves significant improvements with deep neural networks at the premise of a large scale of labeled training data, which is laborious to assure in medical image tasks. Recently, semi-supervised learning (SSL) has shown great potential in medical image segmentation. However, the influence of the learning target quality for unlabeled data is usually neglected in these SSL methods. Therefore, this study proposes a novel self-correcting co-training scheme to learn a better target that is more similar to ground-truth labels from collaborative network outputs. Our work has three-fold highlights. First, we advance the learning target generation as a learning task, improving the learning confidence for unannotated data with a self-correcting module. Second, we impose a structure constraint to encourage the shape similarity further between the improved learning target and the collaborative network outputs. Finally, we propose an innovative pixel-wise contrastive learning loss to boost the representation capacity under the guidance of an improved learning target, thus exploring unlabeled data more efficiently with the awareness of semantic context. We have extensively evaluated our method with the state-of-the-art semi-supervised approaches on four public-available datasets, including the ACDC dataset, M&Ms dataset, Pancreas-CT dataset, and Task&#95;07 CT dataset. The experimental results with different labeled-data ratios show our proposed method's superiority over other existing methods, demonstrating its effectiveness in semi-supervised medical image segmentation.

The efficacy of imaging-guided photodynamic therapy (PDT) is compromised by the attenuation of fluorescence and decline in reactive oxygen species (ROS) generation efficiency in the physiological environment of conventional photosensitizers, limited near-infrared (NIR) absorption, and high systemic cytotoxicity. This paper presents the synthesis of two cyclometalated Ir (III) complexes (Ir-thpy and Ir-ppy) by using a triphenylamine derivative (DPTPA) as the primary ligand and their encapsulation into an amphiphilic phospholipid to form nanoparticles (NPs). These complexes exhibit aggregation-induced emission features and remarkably enhanced ROS generation compared to Chlorin e6 (Ce6). Moreover, Ir-thpy NPs possess the unique ability to selectively target mitochondria, leading to depolarization of the mitochondrial membrane potential and ultimately triggering apoptosis. Notably, Ir-thpy NPs exhibit exceptional photocytotoxicity even towards cisplatin-resistant A549/DDP tumor cells. In vivo two-photon imaging verified the robust tumor-targeting efficacy of Ir-thpy NPs. The in vivo results unequivocally demonstrate that Ir-thpy NPs exhibit excellent tumor ablation along with remarkable biocompatibility. This study presents a promising approach for the development of multifunctional Ir-NPs for two-photon imaging-guided PDT and provides novel insights for potential clinical applications in oncology., 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 Inc. All rights reserved.)

Imaging-guided photodynamic therapy (PDT) holds great potential for tumor therapy. However, achieving the synergistic enhancement of the reactive oxygen species (ROS) generation efficiency and fluorescence emission of photosensitizers (PSs) remains a challenge, resulting in suboptimal image guidance and theranostic efficacy. The hypoxic tumor microenvironment also hinders the efficacy of PDT. Herein, we propose a "two-stage rocket-propelled" photosensitive system for tumor cell ablation. This system utilizes MitoS, a mitochondria-targeted PS, to ablate tumor cells. Importantly, MitoS can react with HClO to generate a more efficient PS, MitoSO, with a significantly improved fluorescence quantum yield. Both MitoS and MitoSO exhibit less O 2 -dependent type I ROS generation capability, inducing apoptosis and ferroptosis. In vivo PDT results confirm that this mitochondrial-specific type I-II cascade phototherapeutic strategy is a potent intervention for tumor downstaging. This study not only sheds light on the correlation between the PS structure and the ROS generation pathway but also proposes a novel and effective strategy for tumor downstaging intervention.

Normally, small-molecule fluorescent probes dependent on the mitochondrial membrane potential (MMP) are invalid for fixed cells and tissues, which limits their clinical applications when the fixation of pathological specimens is imperative. Given that mitochondrial morphology is closely associated with disease, we developed a long-chain mitochondrial probe for fixed cells and tissues, DMPQ-12 , by installing a C 12 -alkyl chain into the quinoline moiety. In fixed cells stained with DMPQ-12 , filament mitochondria and folded cristae were observed with confocal and structural illumination microscopy, respectively. In titration test with three major phospholipids, DMPQ-12 exhibited a stronger binding force to mitochondria-exclusive cardiolipin, revealing its targeting mechanism. Moreover, mitochondrial morphological changes in the three lesion models were clearly visualized in fixed cells. Finally, by DMPQ-12 , three kinds of mitochondria with different morphologies were observed in situ in fixed muscle tissues. This work breaks the conventional concept that organic fluorescent probes only stain mitochondria with normal membrane potentials and opens new avenues for comprehensive mitochondrial investigations in research and clinical settings.

Mitochondria are dynamic organelles that undergo fusion and fission events, in which the mitochondrial membrane and DNA (mtDNA) play critical roles. The spatiotemporal organization of mtDNA reflects and impacts mitochondrial dynamics. Herein, to study the detailed dynamics of mitochondrial membrane and mtDNA, we rationally develop a dual-color fluorescent probe, mtGLP, that could be used for simultaneously monitoring mitochondrial membrane and mtDNA dynamics via separate color outputs. By combining mtGLP with structured illumination microscopy to monitor mitochondrial dynamics, we discover the formation of nucleoid condensates in damaged mitochondria. We further reveal that nucleoid condensates promoted the peripheral fission of damaged mitochondria via asymmetric segregation. Through simulations, we find that the peripheral fission events occurred when the nucleoid condensates interacted with the highly curved membrane regions at the two ends of the mitochondria. Overall, we show that mitochondrial nucleoid condensates utilize peripheral fission to maintain mitochondrial homeostasis., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Corneal fluorescein staining is a key biomarker in evaluating dry eye disease. However, subjective scales of corneal fluorescein staining are lacking in consistency and increase the difficulties of an accurate diagnosis for clinicians. This study aimed to propose an automatic machine learning-based method for corneal fluorescein staining evaluation by utilizing prior information about the spatial connection and distribution of the staining region., Methods: We proposed an end-to-end automatic machine learning-based classification model that consists of staining region identification, feature signature construction, and machine learning-based classification, which fully scrutinizes the multiscale topological features together with conventional texture and morphological features. The proposed model was evaluated using retrospective data from Beijing Tongren Hospital. Two masked ophthalmologists scored images independently using the Sjögren's International Collaborative Clinical Alliance Ocular Staining Score scale., Results: A total of 382 images were enrolled in the study. A signature with six topological features, two textural features, and two morphological features was constructed after feature extraction and selection. Support vector machines showed the best classification performance (accuracy: 82.67%, area under the curve: 96.59%) with the designed signature. Meanwhile, topological features contributed more to the classification, compared with other features. According to the distribution and correlation with features and scores, topological features performed better than others., Conclusions: An automatic machine learning-based method was advanced for corneal fluorescein staining evaluation. The topological features in presenting the spatial connectivity and distribution of staining regions are essential for an efficient corneal fluorescein staining evaluation. This result implies the clinical application of topological features in dry-eye diagnosis and therapeutic effect evaluation.

The derivatives of sulfur dioxide (HSO 3 - ) formed in the biological environment play a vital role in the circulation system. Excessive SO 2 derivatives will cause serious damage to the living system. Herein, a two-photon phosphorescent probe based on Ir(III) complex (named as Ir-CN) was designed and synthesized. Ir-CN is extremely selective and sensitive to SO 2 derivatives with significant phosphorescent enhancement and increased phosphorescent lifetime. The detection limit of Ir-CN for SO 2 derivatives reaches 0.17 μM. More importantly, Ir-CN preferentially accumulates in mitochondria, so bisulfite derivatives can be detected at subcellular level, which enriching the application of metal complex probe in biological detection. In addition, both single-photon and two-photon images can clearly show that Ir-CN is targeted to mitochondria. Benefits from its good biocompatibility, Ir-CN may be used as a reliable tool to detect SO 2 derivatives in mitochondrion of living cells., 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.)

Echocardiography is an essential examination for cardiac disease diagnosis, from which anatomical structures segmentation is the key to assessing various cardiac functions. However, the obscure boundaries and large shape deformations due to cardiac motion make it challenging to accurately identify the anatomical structures in echocardiography, especially for automatic segmentation. In this study, we propose a dual-branch shape-aware network (DSANet) to segment the left ventricle, left atrium, and myocardium from the echocardiography. Specifically, the elaborate dual-branch architecture integrating shape-aware modules boosts the corresponding feature representation and segmentation performance, which guides the model to explore shape priors and anatomical dependence using an anisotropic strip attention mechanism and cross-branch skip connections. Moreover, we develop a boundary-aware rectification module together with a boundary loss to regulate boundary consistency, adaptively rectifying the estimation errors nearby the ambiguous pixels. We evaluate our proposed method on the publicly available and in-house echocardiography dataset. Comparative experiments with other state-of-the-art methods demonstrate the superiority of DSANet, which suggests its potential in advancing echocardiography segmentation.

Objectives: Given the increasing incidence of oral cancer, it is essential to provide high-risk communities, especially in remote regions, with an affordable, user-friendly tool for visual lesion diagnosis. This proof-of-concept study explored the utility and feasibility of a smartphone application that can photograph and diagnose oral lesions., Methods: The images of oral lesions with confirmed diagnoses were sourced from oral and maxillofacial textbooks. In total, 342 images were extracted, encompassing lesions from various regions of the oral cavity such as the gingiva, palate, and labial mucosa. The lesions were segregated into three categories: Class 1 represented non-neoplastic lesions, Class 2 included benign neoplasms, and Class 3 contained premalignant/malignant lesions. The images were analysed using MobileNetV3 and EfficientNetV2 models, with the process producing an accuracy curve, confusion matrix, and receiver operating characteristic (ROC) curve., Results: The EfficientNetV2 model showed a steep increase in validation accuracy early in the iterations, plateauing at a score of 0.71. According to the confusion matrix, this model's testing accuracy for diagnosing non-neoplastic and premalignant/malignant lesions was 64% and 80% respectively. Conversely, the MobileNetV3 model exhibited a more gradual increase, reaching a plateau at a validation accuracy of 0.70. The MobileNetV3 model's testing accuracy for diagnosing non-neoplastic and premalignant/malignant lesions, according to the confusion matrix, was 64% and 82% respectively., Conclusions: Our proof-of-concept study effectively demonstrated the potential accuracy of AI software in distinguishing malignant lesions. This could play a vital role in remote screenings for populations with limited access to dental practitioners. However, the discrepancies between the classification of images and the results of "non-malignant lesions" calls for further refinement of the models and the classification system used., Clinical Significance: The findings of this study indicate that AI software has the potential to aid in the identification or screening of malignant oral lesions. Further improvements are required to enhance accuracy in classifying non-malignant lesions., 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 Author(s). Published by Elsevier Ltd.. All rights reserved.)

Carotid artery intima-media thickness (CIMT) is an essential factor in signaling the risk of cardiovascular diseases, which is commonly evaluated using ultrasound imaging. However, automatic intima-media segmentation and thickness measurement are still challenging due to the boundary ambiguity of intima-media and inherent speckle noises in ultrasound images. In this work, we propose an end-to-end boundary-salience multi-branch network, BSMNet, to tackle the carotid intima-media identification from ultrasound images, where the prior shape knowledge and anatomical dependence are exploited using a parallel linear structure learning modules followed by a boundary refinement module. Moreover, we design a strip attention model to boost the thin strip region segmentation with shape priors, in which an anisotropic kernel shape captures long-range global relations and scrutinizes meaningful local salient contexts simultaneously. Extensive experimental results on an in-house carotid ultrasound (US) dataset demonstrate the promising performance of our method, which achieves about 0.02 improvement in Dice and HD95 than other state-of-the-art methods. Our method is promising in advancing the analysis of systemic arterial disease with ultrasound imaging., 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 Ltd. All rights reserved.)

Colorectal cancer is one of the malignant tumors with the highest mortality due to the lack of obvious early symptoms. It is usually in the advanced stage when it is discovered. Thus the automatic and accurate classification of early colon lesions is of great significance for clinically estimating the status of colon lesions and formulating appropriate diagnostic programs. However, it is challenging to classify full-stage colon lesions due to the large inter-class similarities and intra-class differences of the images. In this work, we propose a novel dual-branch lesion-aware neural network (DLGNet) to classify intestinal lesions by exploring the intrinsic relationship between diseases, composed of four modules: lesion location module, dual-branch classification module, attention guidance module, and inter-class Gaussian loss function. Specifically, the elaborate dual-branch module integrates the original image and the lesion patch obtained by the lesion localization module to explore and interact with lesion-specific features from a global and local perspective. Also, the feature-guided module guides the model to pay attention to the disease-specific features by learning remote dependencies through spatial and channel attention after network feature learning. Finally, the inter-class Gaussian loss function is proposed, which assumes that each feature extracted by the network is an independent Gaussian distribution, and the inter-class clustering is more compact, thereby improving the discriminative ability of the network. The extensive experiments on the collected 2568 colonoscopy images have an average accuracy of 91.50%, and the proposed method surpasses the state-of-the-art methods. This study is the first time that colon lesions are classified at each stage and achieves promising colon disease classification performance. To motivate the community, we have made our code publicly available via https://github.com/soleilssss/DLGNet., 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: Proximal humerus fractures (PHFs) are common. With the development of locking plates, open reduction and internal fixation (ORIF) of the proximal humerus can provide excellent clinical outcomes. The quality of fracture reduction is crucial in the locking plate fixation of proximal humeral fractures. The purpose of this study was to determine the impact of 3-dimensional (3D) printing technology and computer virtual technology assisted preoperative simulation on the reduction quality and clinical outcomes of 3-part and 4-part proximal humeral fractures., Method: A retrospective comparative analysis of 3-part and 4-part PHFs undergoing open reduction internal fixation was performed. Patients were divided into 2 groups according to whether computer virtual technology and 3D printed technology were used for preoperative simulation: the simulation group and the conventional group. Operative time, intraoperative bleeding, hospital stay, quality of fracture reduction, Constant scores, American Society for Shoulder and Elbow Surgery (ASES) scores, shoulder range of motion, complications, and revision surgeries were assessed., Results: This study included 67 patients (58.3%) in the conventional group and 48 patients (41.7%) in the simulation group. The patient demographics and fracture characteristics were comparable in these groups. Compared with the conventional group, the simulation group had shorter operation time and less intraoperative bleeding (P < 0.001, both). Immediate postoperative assessment of fracture reduction showed a higher incidence of greater tuberosity cranialization of < 5 mm, neck-shaft angle of 120° to 150°, and head shaft displacement of < 5 mm in the simulation group. The incidence of good reduction was 2.6 times higher in the simulation group than in the conventional group (95% CI, 1.2-5.8). At the final follow-up, the chance of forward flexion > 120° (OR 5.8, 95% CI 1.8-18.0) and mean constant score of > 65 (OR 3.4, 95% CI 1.5-7.4) was higher in the simulation group than the conventional group, as well as a lower incidence of complications in the simulation group was obtained (OR 0.2, 95% CI 0.1-0.6)., Conclusions: This study identified that preoperative simulation assisted by computer virtual technology and 3D printed technology can improve reduction quality and clinical outcomes in treatment of 3-part and 4-part PHFs., (© 2023. The Author(s).)

Background: Early identification of response to neoadjuvant chemotherapy (NAC) is instrumental in predicting patients prognosis. However, since a fixed criterion with high accuracy cannot be generalized to molecular subtypes, our study first aimed to redefine grades of clinical response to NAC in invasive breast cancer patients (IBC). And then developed a prognostic model based on clinical features and ultrasound semantics., Methods: A total of 480 IBC patients were enrolled who underwent anthracycline and taxane-based NAC between 2018 and 2020. The decrease rate of the largest diameter was calculated by ultrasound after NAC and their cut-off points were determined among subtypes. Thereafter, a nomogram was constructed based on clinicopathological and ultrasound-related data, and validated using the calibration curve, receiver operating characteristic (ROC) curve, decision curve analysis (DCA), and clinical impact curve (CIC)., Results: The optimal cut-off points for predicting pCR were 53.23%, 51.56%, 41.89%, and 53.52% in luminal B-like (HER2 negative), luminal B-like (HER2 positive), HER2 positive, and triple-negative, respectively. In addition, time interval, tumor size, molecular subtypes, largest diameter decrease rate, and change of blood perfusion were significantly associated with pCR (all p < 0.05). The prediction model based on the above variables has great predictive power and clinical value., Conclusion: Taken together, our data demonstrated that calculated cut-off points of tumor reduction rates could be reliable in predicting pathological response to NAC and developed nomogram predicting prognosis would help tailor systematic regimens with high precision., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wang, Meng, Yu, Cai, Wang, Cao and Ge.)

Wireless body area network (WBAN) is widely adopted in healthcare services, providing remote real-time and continuous healthcare monitoring. With the massive increase of detective sensor data, WBAN is largely restricted by limited storage and computation capacity, resulting in severely decreased efficiency and reliability. Mobile edge computing (MEC) technique can be combined with WBAN to resolve this issue. This paper studies the joint optimization problem of computational offloading and resource allocation (JCORA) in MEC for healthcare service scenarios. We formulate JCORA as a Markov decision process and propose a deep deterministic policy gradient-based WBAN offloading strategy (DDPG-WOS) to optimize time delay and energy consumption in interfered transmission channels. This scheme employs MEC to mitigate the computation pressure on a single WBAN and increase the transmission ability. Further, DDPG-WOS optimizes the offloading strategy-making process by considering the channel condition, transmission quality, computation ability and energy consumption. Simulation results verify the effectiveness of the proposed optimization schema in reducing energy consumption and computation latency and increasing the utility of WBAN compared to two competitive solutions., Competing Interests: Conflict of interestThe authors have no conflicts of interest to declare that are relevant to the content of this article., (© The Author(s), under exclusive licence to Springer Nature Switzerland AG 2023, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Tracking the myotendinous junction (MTJ) motion in consecutive ultrasound images is essential to assess muscle and tendon interaction and understand the mechanics' muscle-tendon unit and its pathological conditions during motion. However, the inherent speckle noises and ambiguous boundaries deter the reliable identification of MTJ, thus restricting their usage in human motion analysis. This study advances a fully automatic displacement measurement method for MTJ using prior shape knowledge on the Y-shape MTJ, precluding the influence of irregular and complicated hyperechoic structures in muscular ultrasound images. Our proposed method first adopts the junction candidate points using a combined measure of Hessian matrix and phase congruency, followed by a hierarchical clustering technique to refine the candidates approximating the position of the MTJ. Then, based on the prior knowledge of Y-shape MTJ, we finally identify the best matching junction points according to intensity distributions and directions of their branches using multiscale Gaussian templates and a Kalman filter. We evaluated our proposed method using the ultrasound scans of the gastrocnemius from 8 young, healthy volunteers. Our results present more consistent with the manual method in the MTJ tracking method than existing optical flow tracking methods, suggesting its potential in facilitating muscle and tendon function examinations with in vivo ultrasound imaging.

The methylation of the lysine residue can affect some fundamental biological processes, and specific biological effects of the methylations are often related to product specificity of methyltransferases. The question remains concerning how active-site structural features and dynamics control the activity as well as the number (1, 2, or 3) of methyl groups on methyl lysine products. SET domain containing protein 3 (SETD3) has been identified recently as the β-actin histidine73-N 3 methyltransferase, and also, it has a weak methylation activity on the H73K β-actin peptide for which the target H73 residue is mutated into K73. Interestingly, the K73 methylation activity of SETD3 increases significantly as a result of the N255 → A or N255 → F/W273 → A mutation, and the N255A product specificity also differs from that of wild-type. Here, we performed QM/MM molecular dynamics and potential of mean force (PMF) simulations for SETD3 and its mutants (N255A and N255F/W273A) to study how SETD3 and its mutants could have different product specificities and activities for the K73 methylation. The PMF simulations show that the barrier for the first methylation of K73 is higher compared to the barrier of the H73 methylation in SETD3. Moreover, the second methylation of K73 has been found to have a barrier from the free energy simulation that is higher by 2.2 kcal/mol compared to the barrier of the first methyl transfer to K73, agreeing with the suggestion that SETD3 is a monomethylase. For the first, second, and third methylations of K73 in the N255A mutant, the barriers obtained from the PMF simulations for transferring the second and third methyl groups are found to be lower relative to the barrier for the first methyl transfer. Thus, N255A can be considered as a trimethyl lysine methyltransferase. In addition, for the first K73 methylation, the activities from the PMF simulations follow the order of N255F/W273A > N255A > WT, in agreement with experiments. The examination of the structural and dynamic results at the active sites provides better understanding of different product specificities and activities for the K73 methylations in SETD3 and its mutants. It is demonstrated that the existence of well-balanced interactions at the active site leading to the near attack conformation is of crucial importance for the efficient methyl transfers. Moreover, the presence of potential interactions (e.g., the C-H···O and cation-π interactions) that are strengthening at the transition state can also be important. Furthermore, the activity as well as product specificity of the K73 methylation also seems to be controlled by certain active-site water molecules which may be released to provide extra space for the addition of more methyl groups on K73.

The penis is a vital organ of perception that transmits perceived signals to ejaculation-related centers. The penis consists of the glans penis and penile shaft, which differ considerably in both histology and innervation. This paper aims to investigate whether the glans penis or the penile shaft is the main source of sensory signals from the penis and whether penile hypersensitivity affects the whole organ or only part of it. The thresholds, latencies, and amplitudes of somatosensory evoked potentials (SSEPs) were recorded in 290 individuals with primary premature ejaculation using the glans penis and penile shaft as the sensory areas. The thresholds, latencies, and amplitudes of SSEPs from the glans penis and penile shaft in patients were significantly different (all P < 0.0001). The latency of the glans penis or penile shaft was shorter than average (indicating hypersensitivity) in 141 (48.6%) cases, of which 50 (35.5%) cases were sensitive in both the glans penis and penile shaft, 14 (9.9%) cases were sensitive in the glans penis only, and 77 (54.6%) cases were sensitive in the penile shaft only (P < 0.0001). There are statistical differences in the signals perceived through the glans penis and the penile shaft. Penile hypersensitivity does not necessarily mean that the whole penis is hypersensitive. We classify penile hypersensitivity into three categories, namely, glans penis, penile shaft, and whole-penis hypersensitivity, and we propose the new concept of penile hypersensitive zone., Competing Interests: None

Background: Prescribing medicine is integral to clinical dentistry. Infective endocarditis may be rare but fatal if left untreated. As a result, judicious prescribing of antibiotics should be implemented due to potential. To our knowledge, no Australian study has examined dental students' knowledge and perceptions about antibiotic prophylaxis for dental procedures., Methods: Australian dental students were invited to undertake the survey comprising case vignettes to investigate their medication knowledge. A total of 117 responses were received. The questions were 12 clinically relevant questions and three perception-based questions. Results were analysed using descriptive statistics as well as the chi-squared test., Results: The 117 respondents had a mean correct response of 7.34 ± 2.64 (range 3-12 out of 12). Out of 117 students, 89 (76%) answered more than half of the questions correctly. Only three students (3%) answered all the questions correctly. Nearly two-thirds felt that they knew about antibiotic prophylaxis used for dental procedures., Conclusion: Most respondents answered more than half, but not all, of the clinical questions correctly. It is crucial to highlight that dental student may never receive any more training on antimicrobial stewardship (AMS) at any point in their future careers. It may be ideal that this issue is addressed at the dental school. One way to target this is to potentially nationalised teaching delivery of dental AMS across Australia., (© 2022. The Author(s).)

Blue-phase liquid crystal (BPLC) is considered as the next-generation liquid crystal display material, but its practical application is seriously affected by a narrow temperature range and a long research period. In this paper, we used inkjet printing technology to prepare BPLC materials with high throughput, and try to use machine vision technology to test BPLC with high throughput. The "standard curve method" for establishing each printing channel and the "vector matching method" for searching the chromaticity value of the minimum distance were proposed to improve the accuracy of inkjet printing BPLC materials. For a large number of sample-phase images, we propose a machine learning method to identify the liquid crystal phase. In this paper, for the first time, the high-throughput preparation and high-throughput detection of 1080 BPLC samples with five common components by a comprehensive experimental method has been successfully realized. The results are helpful to improve the research efficiency of blue-phase materials and provide a theoretical basis and practical guidance for rapid screening of multi-component BPLC materials.

Hydrazine is widely used in industrial and agricultural production, but excessive hydrazine possesses a serious threat to human health and environment. Here two new ratiometric fluorescence probes, DDP and DDC , with the hydroxyl coumarin chalcone unit as the sensing site are developed, which can achieve colorimetric and ratiometric recognition for hydrazine with good sensitivity, excellent selectivity, and anti-interference. The calculated fluorescence limits of detections are 0.26 μM ( DDC ) and 0.14 μM ( DDP ). The ratiometric fluorescence response to hydrazine is realized through the adjustment of donor and receptor units in coumarin conjugate structure terminals, accompanied by fluorescence peak shift about 200 nm ( DDC , 188 nm; DDP , 229 nm). Stronger electropositivity in the carbon-carbon double bond is helpful to the first phase addition reaction between the probe and hydrazine. Higher phenol activity in the hydroxyl coumarin moiety will facilitate the following dihydro-pyrazole cyclization reaction. In addition, both of these probes realized the convenient detection of hydrazine vapor. The probes were also successfully applied to detect hydrazine in actual water samples, different soils, and living cells.

Background: Breast cancer has become the most frequently diagnosed cancer worldwide. Increasing evidence indicated that zinc finger proteins (ZNFs), the largest family of transcription factors, contribute to cancer development and progression. Although ZNF384 is overexpressed in several types of human cancer, the role of ZNF384 in breast cancer remains unknown. Therefore, our research focused on ZNF384 regulation of the malignant phenotype of breast cancer and the underlying molecular mechanisms., Methods: CCK-8 and colony formation assays were used to evaluate cell proliferation. Transwell and scratch assays were used to evaluate the cell migration and invasion. Chromatin immunoprecipitation (ChIP)-qPCR and luciferase reporter assays were used to confirm the target relationship between ZNF384 and zinc finger E-box binding homeobox 1 (ZEB1). Xenografts were used to monitor the targets in vivo effects., Results: We noted that ZNF384 was significantly overexpressed in breast cancer and highlighted the oncogenic mechanism of ZNF384. ZNF384 transactivated ZEB1 expression and induced an epithelial and mesenchymal-like phenotype, resulting in breast cancer metastasis. Furthermore, ZNF384 may be a target of miR-485-5p, and ZEB1 can up-regulate ZNF384 expression by repressing miR-485-5p expression. Together, we unveiled a feedback loop of ZNF384-ZEB1 in breast cancer metastasis., Conclusions: The findings suggest that ZNF384 can serve as a prognostic factor and a therapeutic target for breast cancer patients., (© 2022. The Author(s).)

Objective: Triple-negative breast cancer (TNBC) is distinguished by early recurrence and metastases, a high proclivity for treatment resistance, and a lack of targeted medicines, highlighting the importance of developing innovative therapeutic techniques. Salvia chinensis Benth (SCH) has been widely studied for its anticancer properties in a variety of cancers. However, its significance in TNBC treatment is rarely discussed. Our study investigated the anticancer effect of SCH on TNBC and the underlying mechanisms., Methods: First, we used clonogenic, cell viability, flow cytometry, and Transwell assays to assess the effect of SCH on TNBC. Bioinformatic studies, especially network pharmacology-based analysis and RNA sequencing analysis, were performed to investigate the constituents of SCH and its molecular mechanisms in the suppression of TNBC. High-performance liquid chromatography and thin-layer chromatography were used to identify two major components, quercetin and β-sitosterol. Then, we discovered the synergistic cytotoxicity of quercetin and β-sitosterol and assessed their synergistic prevention of cell migration and invasion. Breast cancer xenografts were also created using MDA-MB-231 cells to test the synergistic therapeutic impact of quercetin and β-sitosterol on TNBC in vivo . The impact on the DNA damage and repair pathways was investigated using the comet assay and Western blot analysis., Results: Our findings showed that SCH decreased TNBC cell growth, migration, and invasion while also inducing cell death. We identified quercetin and β-sitosterol as the core active components of SCH based on a network pharmacology study. According to RNA sequencing research, the p53 signaling pathway is also regarded as a critical biological mechanism of SCH treatment. The comet assay consistently showed that SCH significantly increased DNA damage in TNBC cells. Our in vivo and in vitro data revealed that the combination of quercetin and β-sitosterol induced synergistic cytotoxicity and DNA damage in TNBC cells. In particular, SCH particularly blocked the inter-strand cross-link repair mechanism and the double-strand breach repair caused by the homologous recombination pathway, in addition to inducing DNA damage. Treatment with quercetin and β-sitosterol produced similar outcomes., Conclusion: The current study provides novel insight into the previously unknown therapeutic potential of SCH as a DNA-damaging agent in TNBC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wang, Hu, Han, Zhao, Song, Sun, Lv, Jiang, Xv, Zhao and Li.)

Objectives: Pharmacists are known as medicine experts. Dentists can independently prescribe and administer medications related to dental conditions such as antimicrobials, anti-inflammatories and analgesics. However, little is known about pharmacists' knowledge and perceptions of medicines prescribed for dentistry. Therefore, this study aimed to assess community pharmacists' ability to identify the indications for dental prescriptions using hypothetical vignettes., Methods: Australian community pharmacists were invited through email and social media to undertake a web-based questionnaire consisting of nine case vignettes of dental prescriptions and their indicated uses in dental settings and two perception-based questions. The results were provided as a percentage of the correct answers to the case vignettes. In addition, Pearson chi-square tests were performed to examine associations between categorical variables., Key Findings: Of the 202 pharmacists who completed the questionnaire, the mean number of correct responses was 5 ± 2 (out of 9). More than three-quarters (78.5%) of pharmacists believed that thorough knowledge of prescriptions for dental ailments was necessary for safe and effective community pharmacy practice. In addition, nearly two-thirds (64.1%) felt confident that they could dispense medicines indicated for dental conditions safely and effectively., Conclusions: The knowledge demonstrated by participants through correct identification of the indications for dental prescription was less than optimal. Professional development courses for pharmacists in dental ailments could prove beneficial., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Royal Pharmaceutical Society.)

The nucleus is considered the ideal target for anti-tumor therapy because DNA and some enzymes in the nucleus are the main causes of cell canceration and malignant proliferation. However, nuclear target drugs with good biosafety and high efficiency in cancer treatment are rare. Herein, a nuclear-targeted material MeTPAE with aggregation-induced emission (AIE) characteristics was developed based on a triphenylamine structure skeleton. MeTPAE can not only interact with histone deacetylases (HDACs) to inhibit cell proliferation but also damage telomere and nucleic acids precisely through photodynamic treatment (PDT). The cocktail strategy of MeTPAE caused obvious cell cycle arrest and showed excellent PDT anti-tumor activity, which offered new opportunities for the effective treatment of malignant tumors., (© 2022 Wiley-VCH GmbH.)

Multi-sequence cardiac magnetic resonance (CMR) provides essential pathology information (scar and edema) to diagnose myocardial infarction. However, automatic pathology segmentation can be challenging due to the difficulty of effectively exploring the underlying information from the multi-sequence CMR data. This paper aims to tackle the scar and edema segmentation from multi-sequence CMR with a novel auto-weighted supervision framework, where the interactions among different supervised layers are explored under a task-specific objective using reinforcement learning. Furthermore, we design a coarse-to-fine framework to boost the small myocardial pathology region segmentation with shape prior knowledge. The coarse segmentation model identifies the left ventricle myocardial structure as a shape prior, while the fine segmentation model integrates a pixel-wise attention strategy with an auto-weighted supervision model to learn and extract salient pathological structures from the multi-sequence CMR data. Extensive experimental results on a publicly available dataset from Myocardial pathology segmentation combining multi-sequence CMR (MyoPS 2020) demonstrate our method can achieve promising performance compared with other state-of-the-art methods. Our method is promising in advancing the myocardial pathology assessment on multi-sequence CMR data. To motivate the community, we have made our code publicly available via https://github.com/soleilssss/AWSnet/tree/master., 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 © 2022 Elsevier B.V. All rights reserved.)

Due to the aggregation-caused quenching effect and near-infrared I poor penetration capabilities of common fluorescent molecules, their applications in visualized imaging and photoactivated treatment are limited. Therefore, new near-infrared II (NIR-II) molecule (named TST), which had the abilities of aggregation-induced emission (AIE) and photothermal therapy are synthesized. Moreover, in order to further improve its fluorescent yield and therapeutic effect, camptothecin prodrug (CPT-S-PEG) and novel immune checkpoint inhibitor AZD4635 are used to co-assemble with TST into nanoparticles for drug delivery. On account of the strong interaction of camptothecin and TST, the intramolecular rotation of TST is limited, thereby inhibiting non-radiation attenuation and promoting fluorescence generation when the nanoparticles are intact. As nanoparticles uptake by cancer cells, redox sensitive CPT-S-PEG is degraded and the nanoparticles disintegrate. The released TST enhances non-radiative attenuation and expedites photothermal conversion because of the removal of the constraint of camptothecin. Furthermore, photothermal therapy induces immunogenic cell death of cancer cells and releases abundant ATP into the tumor microenvironment to recruit immune cells. However, superfluous ATP is converted into immunosuppressive adenosine through the CD39-CD73-A2AR pathway. The AZD4635 released by photothermal disintegration of the nanoparticles just blocks this pathway timely, achieving favorable synergistic effect of photothermal therapy, chemotherapy, and immunotherapy., (© 2022 The Authors. Advanced Science published by Wiley-VCH GmbH.)

As one of the most common pathological changes in trauma and surgery practice, intestinal ischemia-reperfusion (I/R) injury is regarded as a major precipitating factor in the occurrence and development of fatal diseases. BRCA1-BRCA2-containing complex subunit 36 (BRCC36), a deubiquitinase, has been proved important in a variety of pathophysiological processes such as DNA repair, cell cycle regulation, tumorigenesis, and inflammatory response. However, the effect of BRCC36 on intestinal mucosal barrier injury after I/R has not been fully elucidated. Our research found that BRCC36 aggravated intestinal mucosal barrier injury caused by bone morphogenetic protein 2 after I/R by downregulating peroxisome proliferator-activated receptor-γ (PPARγ) signaling. These results suggested that BRCC36/PPARγ axis might serve as a potential therapeutic target for preventing intestinal mucosal barrier injury after I/R., (© The Author(s) 2021. Published by Oxford University Press on behalf of Japan Society for Bioscience, Biotechnology, and Agrochemistry.)

Inflammation exists in the microenvironment of most, if not virtually all, tumors, which greatly exacerbates the difficulty of cancer treatment. Considering the superiority of activatable photosensitizers (PSs), a novel strategy of 'making friends with the enemy' for tumor treatment was proposed. In this strategy, the "enemy" refers to inflammatory cytokines and the tumor site is targeted by detecting the enemy. Upon detection, a dichromatic fluorescence signal is released and the PS is activated specifically by the inflammatory cytokines. In this study, a multifunctional PS (TPE-PTZ-Py) was rationally designed, which can be activated specifically under the synergistic action of hypochlorous acid (HClO) (one kind of inflammatory cytokines) and acid (one typical marker of tumor), and output a ratiometric fluorescence signal simultaneously. The sulfoxide analogue (TPE-PTZO-PyH) as the response product effectively produced 1 O 2 (1.8-fold higher than that obtained with Rose Bengal) and showed high phototoxicity (IC 50 < 7.6 μM). More importantly, imaging analyses confirmed that TPE-PTZ-Py could be activated in human cervical cancer tissue. To date, several phenothiazine (PTZ)-based fluorescent probes have been developed for the selective sensing and imaging of HClO in subcellular organelles; however, this is the first phenothiazine-based nanodrug designed for the treatment of inflammation-associated tumors with a few side effects.

To investigate the role of the lncRNA growth arrest special 5 (GAS5) in ovarian clear cell carcinoma (OCCC), we measured the expression of GAS5 and miR-31-5p in OCCC tissue samples and OCCC cell lines using RT-qPCR. MTT and colony formation assays were used to measure cell viability and colony formation ability. Cell invasion was determined by Transwell assays. The binding between GAS5 and miR-31-5p as well as miR-31-5p and ARID1A was determined by dual-luciferase reporter assays. The ARID1A protein levels were detected using western blotting. Kaplan-Meier curves were used for the analysis of the 5-year survival rate of patients with OCCC. GAS5 and ARID1A levels were significantly decreased, while miR-31-5p levels were strongly elevated in the OCCC tissues and cell lines. Patients with lower GAS5/ARID1A levels had shorter overall survival times. Overexpression of GAS5 or inhibition of miR-31-5p suppressed cell viability and invasion of OCCC cells and upregulated the protein levels of ARID1A. Moreover, overexpression of miR-31-5p reversed the effects of overexpression of GAS5. Cotransfection with pcDNA3.1-GAS5 and miR-31-5p inhibitor led to the lowest cell viability and cell invasion rates. A dual-luciferase reporter assay was performed to confirm the target relationship between GAS5 and miR-31-5p, as well as between miR-31-5p and ARID1A. LncRNA GAS5 inhibited cell viability and invasion of OCCC through activation of ARID1A by sponging miR-31-5p., (© 2021 The Authors. The Kaohsiung Journal of Medical Sciences published by John Wiley & Sons Australia on behalf of Kaohsiung Medical University.)

The sequence-dependent DNA secondary structures possess structure polymorphism. To date, studies on regulated ligands mainly focus on individual DNA secondary topologies, while lack focus on quadruplex-duplex hybrids (QDHs). Here, we design an organic-metal hybrid ligand L 1 Pt(dien), which matches and selectively binds one type of QDHs with lateral duplex stem-loop (QLDH) with high affinity, while shows poor affinity for other QDHs and individual G4 or duplex DNA. The solution structure of QLDH MYT1L-L 1 Pt(dien) complex was determined by NMR. The structure reveals that L 1 Pt(dien) presents a chair-type conformation, whose large aromatic "chair surface" intercalates into the G-quadruplex-duplex interface via π-π stacking and "backrest" platinum unit interacts with duplex region through hydrogen bonding and electrostatic interactions, showing a highly matched lock-key binding mode. Our work provided guidance for spatial matching design of selectively targeting ligands to QDH structures., (© 2021 Wiley-VCH GmbH.)