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Abstract Background The incidence of non-tuberculous mycobacterium infection has shown a gradual increasing trend in recent years, among which cutaneous manifestations as an important aspect. This study aimed to describe the clinical features and microbiological findings in 6 cases of primary cutaneous nontuberculous mycobacterium infection. Methods In this retrospective study from June 2021 to June 2022, the clinical data and microbiological results of six cases diagnosed with primary cutaneous non-tuberculous mycobacterium infection in department of dermatology, Hangzhou Third People’s Hospital were analyzed. Results All six cases were primary cutaneous non-tuberculous mycobacterium infections, four of which had a history of trauma or exposure, and two had an underlying disease that could lead to compromised immunity. All patients presented with erythema nodular skin lesions, four on the upper or lower extremities, one on the face, and one on the right hip. The histopathological findings of five patients who underwent biopsy were granulomatous inflammatory changes with mixed infiltration. Laboratory cultures using tissue or tissue fluid were all successful, including four Mycobacterium marinum, one Mycobacterium abscessus, and one Mycobacterium avium. Metagenomics next-generation sequencing detected results consistent with culture colonies in only two cases. With the exception of case 4, all patients responded well to oral medication, with a course of treatment ranging from 4 months to 1 year, and the prognosis was good. Conclusions The clinical features of primary cutaneous non-tuberculous mycobacterium infection are often lacking in specificity, and the identification of related strains is difficult for a variety of reasons. Although the results of metagenomics next-generation sequencing are useful for pathogen spectrum identification, its diagnostic value should be carefully reevaluated under certain circumstances. Patients with suspected triggers who do not respond well to conventional treatments should be suspected as atypical infection and potential immunosuppression. If diagnosed and treated promptly, the prognosis of primary cutaneous non-tuberculous mycobacterium infection is generally good.

Abstract Charge density waves (CDWs) are pervasive orders in solids that usually enhance the effective mass (m*) and reduce the Fermi velocity ( $${v}_{{{{\rm{F}}}}}$$ v F ) of carriers. Here, we report on the inverse — a reduced m* and an enhanced $${v}_{{{{\rm{F}}}}}$$ v F correlated with the growth of the CDW order in CuTe with gapped, practically linearly dispersing bands — reminiscent of emergent CDW-gapped topological semimetals. Using momentum-dependent electron energy-loss spectroscopy (q-EELS), we simultaneously capture m* and $${v}_{{{{\rm{F}}}}}$$ v F of the CDW-related, practically linearly dispersing electrons by plasmon dispersions across the transition (335 K, TCDW), with m* of 0.28 m0 (m0, the electron rest mass) and $${v}_{{{{\rm{F}}}}}$$ v F of ~ 0.005c (c, the speed of light) at 300 K. With the growth of the CDW order-parameter strength toward 100 K, the electrons become lighter and move faster by ~ 20%. Thorough inspection below TCDW unveils the essential role of the increasing opening of the CDW gap. CuTe is a rich platform for the exploration of CDW/correlation physics with q-EELS established as a useful probe for this type of physics.

Purpose Total neoadjuvant therapy (TNT) is becoming the standard of care for locally advanced rectal cancer. However, surgery is deferred for months after completion, which may lead to fibrosis and increased surgical difficulty. The aim of this study was to assess whether TNT (TNT-RAPIDO) is associated with increased difficulty of total mesorectal excision (TME) compared with long-course chemoradiotherapy (LCRT) and upfront surgery. Methods Twelve laparoscopic videos of low anterior resection with TME for rectal cancer were prospectively collected from January 2020 to October 2021, with 4 videos in each arm. Seven colorectal surgeons assessed the videos independently, graded the difficulty of TME using a visual analog scale and attempted to identify which category the videos belonged to. Results The median age was 67 years, and 10 patients were male. The median interval to surgery from radiotherapy was 13 weeks in the LCRT group and 24 weeks in the TNT-RAPIDO group. There was no significant difference in the visual analog scale for difficulty in TME between the 3 groups (LCRT, 3.2; TNT-RAPIDO, 4.6; upfront, 4.1; P=0.12). A subgroup analysis showed similar difficulty between groups (LCRT 3.2 vs. TNT-RAPIDO 4.6, P=0.05; TNT-RAPIDO 4.6 vs. upfront 4.1, P=0.54). During video assessments, surgeons correctly identified the prior treatment modality in 42% of the cases. TNT-RAPIDO videos had the highest recognition rate (71%), significantly outperforming both LCRT (29%) and upfront surgery (25%, P=0.01). Conclusion TNT does not appear to increase the surgical difficulty of TME.

Owing to their exceptional piezoelectric effects, piezoelectric materials play a crucial role in high-end technologies and contribute significantly to the national economy. Bismuth layer-structured ferroelectrics (BLSFs) possess high Curie temperatures, making them a focal point of research in high-temperature piezoelectric sensor devices. However, their poor piezoelectric performance and low direct-current (DC) electrical resistivity hinder their effective deployment in high-temperature applications. To overcome these shortcomings, we employed composition optimization by partially substituting bismuth ions with rare-earth praseodymium ions. This approach enhances the piezoelectric performance and improves the DC electrical resistivity by preventing the loss of volatile bismuth ions and stabilizing the bismuth oxide layer (Bi2O2)2+, thereby reducing the concentration of oxygen vacancies. Consequently, we achieved a large piezoelectric constant d33 of 23.5 pC/N in praseodymium-substituted Bi5Ti3FeO15, which is three times higher than that of pure Bi5Ti3FeO15 (7.1 pC/N), along with a high Curie temperature TC of 778 °C. Additionally, the optimal composition of 4 mol% praseodymium-substituted Bi5Ti3FeO15 exhibits good thermal stability of electromechanical coupling characteristics up to 300 °C. This study holds promise for a wide array of high-temperature piezoelectric applications and has the potential to accelerate the development of high-temperature piezoelectric sensor technologies.

Abstract This cross-sectional survey aims to determine whether cotinine exposure would enhance the relationship between blood manganese (Mn) and non-alcoholic fatty liver disease (NAFLD) in children using the NHANES database. Restricted cubic spline (RCS) and logistic regression analyses were adopted to determine the potential relationship. Besides, we tested the robustness of the results by performing trend tests and subgroup analyses. The study finally enrolled 866 children aged 18 years and below. Blood Mn was linearly linked to NAFLD and the risk of NAFLD was increased with the blood Mn elevation (P

Abstract Coastal urbanization is a key driver of mangrove loss, yet its global impacts on mangroves have yet to be thoroughly understood. Here we present a fine-scale assessment of the hidden impacts of urbanization on mangroves mediated by climate, and the joint effects of urbanization and climate at the global scale. Surprisingly, both urbanization and climate had positive impacts on mangrove growth and carbon stock in some regions, which is different from the general belief of the adverse impacts from previous research. In total, 27.3% of global mangroves received positive impacts from urbanization regarding their extent and carbon stock, among which 59.5% are indirectly mediated by climate. Moreover, mangroves in subtropical/temperate climate zones experienced more indirect positive impacts from urbanization, which enhances local climate conditions for growth by altering temperature, rainfall and sea levels. These findings suggest the feasibility of facilitating mangrove conservation through effective urban planning to achieve coastal sustainability.

Heritage usually represents how the past is valued today. This paper, however, introduces a new perspective based on historical materialism, which is evident in modern Asian architecture. It argues that contemporary Asian architecture moves away from traditional historicism and embraces different ways of relating to history. The paper explores the idea of “living heritage”, which is shaped by the postcolonial nature of current Asian architecture and urban planning. The core idea is that immediate historicity, the presence of appreciated historical values, creates a unique quality called “display-ness”. This concept involves not just physical, visual, and spatial aspects, but also how a place is institutionalised. As evidence, modern heritage is influenced by global political dynamics. In Asia, the quality of architecture has shifted from modernism to what might be called colonial modernity, showing a new focus on hybridity. By comparing Japan and Singapore, this paper illustrates this idea of display-ness, which suggests a blend of future urban developments and cultural history in the present.

Abstract Metformin, a widely used oral hypoglycemic drug, has emerged as a potential therapeutic agent for cancer treatment. While initially known for its role in managing diabetes, accumulating evidence suggests that metformin exhibits anticancer properties through various mechanisms. Several cellular or animal experiments have attempted to elucidate the role of non-coding RNA molecules, including microRNAs and long non-coding RNAs, in mediating the anticancer effects of metformin. The present review summarized the current understanding of the mechanisms by which non-coding RNAs modulate the response to metformin in cancer cells. The regulatory roles of non-coding RNAs, particularly miRNAs, in key cellular processes such as cell proliferation, cell death, angiogenesis, metabolism and epigenetics, and how metformin affects these processes are discussed. This review also highlights the role of lncRNAs in cancer types such as lung adenocarcinoma, breast cancer, and renal cancer, and points out the need for further exploration of the mechanisms by which metformin regulates lncRNAs. In addition, the present review explores the potential advantages of metformin-based therapies over direct delivery of ncRNAs, and this review highlights the mechanisms of non-coding RNA regulation when metformin is combined with other therapies. Overall, the present review provides insights into the molecular mechanisms underlying the anticancer effects of metformin mediated by non-coding RNAs, offering novel opportunities for the development of personalized treatment strategies in cancer patients.

This study investigated the clinical efficacy of Carbon dioxide (CO2) laser therapy combined with photodynamic therapy in male patients with condyloma acuminatum. A retrospective analysis was conducted on 120 male patients with genital warts treated at our hospital. Based on different treatment methods, they were divided into a control group and an observation group, each consisting of 60 cases. The control group received CO2laser treatment, while the observation group received photodynamic therapy and CO2 laser treatment. Levels of lymphocyte chemotactic factor (LTN), human beta-defensin-2 (HBD-2), B-cell lymphoma-2 (Bcl-2), interleukin-12 (IL-12), tumor necrosis factor-alpha (TNF-α), T lymphocytes (CD3+), inducible T cells (CD4+), suppressive T cells (CD8+), Male Sexual Function Index (MSFI) scores, Chinese version of the Genital Warts Quality of Life Scale (CECA10) scores, incidence of adverse reactions, recurrence rate, and total treatment effectiveness were compared between groups. After therapy, both groups showed reduced levels of Bcl-2 and TNF-α, but increased levels of IL-12. The observation group had significantly lower Bcl-2, TNF-α and greater IL-12 levels than the control group (p < 0.05). After therapy, both groups showed increased levels of CD3+ and CD4+ but lower levels of CD8+ than before treatment. The observation group had significantly greater CD3+ and CD4+ levels, but lower CD8+ levels than the control group (p < 0.05). The observation group had significantly higher CD3+ and CD4+ levels and lower CD8+ levels compared to the control group (p < 0.05). The incidence of complications in the observation group was significantly lower than in the control group (p < 0.05). CO2 laser therapy combined with 5-aminolevulinic acid photodynamic therapy demonstrates efficacy in treating male genital warts. This therapy can significantly reduce inflammation, improve immune function, and help improve quality-of-life.

The exploration of the first member of Permian Maokou Formation (Maokou 1) in the Weiyuan area of southern Sichuan Basin has been limited. Previous analyses of cast thin sections and argon ion electron microscopy based on earlier drilling data suggested that talc pores were the primary reservoir spaces, with talc formation significantly contributing to the reservoir. However, the latest drilling data shows substantial differences in the types of reservoir spaces and the genesis of the Maokou 1 marlstone reservoirs compared to earlier understanding. It is necessary to further clarify the main controlling factors for the development of these reservoirs in the Maokou 1 member. Through core observation, thin section identification, physical property analysis, nitrogen adsorption, argon ion polishing scanning electron microscopy, and quantitative pore characterization, the primary reservoir spaces and types of the Maokou 1 marlstone were analyzed from both qualitative and quantitative perspectives. The main controlling factors for the development of these reservoirs were identified by combining total organic carbon (TOC) content determination, rare earth element analysis, and whole rock X-ray diffraction. High-quality reservoirs in the Maokou 1 member of the Weiyuan area are developed in marlstone, characterized by low porosity and permeability fractures and pore-type reservoirs, predominantly Type Ⅲ with some Type Ⅱ reservoirs. The main reservoir spaces include corroded pores, organic matter pores, and talc pores and fractures, with pore development closely related to TOC content. Talc formation, dolomitization, and silicification did not significantly contribute to secondary reservoir spaces, and their contribution to porosity is minimal. The development of marlstone reservoirs is jointly controlled by early dissolution, sedimentary facies, and organic matter abundance. Early dissolution is the key to the formation of corroded pores and fractures, while high primary productivity and high organic matter settling rate of the inner gentle slope shallow water environment provided the material basis for the formation of organic matter pores. This understanding provides theoretical support for the exploration of similar oil and gas reservoirs in the basin.

Abstract Aim To provide an overview of the various influencing factors related to the positive aspects of caring for dementia patients by family caregivers. Design A systematic mixed studies review. Methods The Preferred Reporting Items for Systematic Reviews guided this protocol as reported. Peer-reviewed studies published in English from 1997 to the present will be searched via information sources, gray literature, and the following databases: Web of Science, PsycINFO, PubMed, EMBASE, CINAHL and the Cochrane Central Register of Controlled Trials. Eligible trials will also be retrieved from ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform. This will be a mixed studies review. The Mixed Method Appraisal Tool will be used for the mixed-method studies. The Newcastle–Ottawa Scale for case–control and cohort studies and the JBI quality scale for cross-sectional and interventional (i.e., randomized or quasi-experimental) studies will be consulted. The Joanna Briggs Institute Critical Appraisal Checklist for Qualitative Research will be used for the qualitative studies. All the data will be extricated with JBI data extraction tools. The convergent synthesis method will be used in the review. Discussion This systematic review will synthesize and analyze the factors that influence the positive aspects of caring for dementia patients by family caregivers. Conclusion The findings will help decision-makers to adopt more appropriate and effective interventions for caregivers of people with dementia. Patient or public contributions This review protocol will ascertain the factors affecting the mediation of and path to improved caregiving, explore the factors’ action mechanisms, and examine the controlling factors to design a more targeted intervention program to improve caregiving, thus improving dementia patients’ outcomes and care. Contributions of the findings will include evidence of strategies that address ongoing dementia caregiving issues and the identification of areas for future research.

Optical imaging in the second near-infrared (NIR-II; 900–1880 nm) window is currently a popular research topic in the field of biomedical imaging. This study aimed to explore the application value of NIR-II fluorescence imaging in foot and ankle surgeries. A lab-established NIR-II fluorescence surgical navigation system was developed and used to navigate foot and ankle surgeries which enabled obtaining more high-spatial-frequency information and a higher signal-to-background ratio (SBR) in NIR-II fluorescence images compared to NIR-I fluorescence images; our result demonstrates that NIR-II imaging could provide higher-contrast and larger-depth images to surgeons. Three types of clinical application scenarios (diabetic foot, calcaneal fracture, and lower extremity trauma) were included in this study. Using the NIR-II fluorescence imaging technique, we observed the ischemic region in the diabetic foot before morphological alterations, accurately determined the boundary of the ischemic region in the surgical incision, and fully assessed the blood supply condition of the flap. NIR-II fluorescence imaging can help surgeons precisely judge surgical margins, detect ischemic lesions early, and dynamically trace the perfusion process. We believe that portable and reliable NIR-II fluorescence imaging equipment and additional functional fluorescent probes can play crucial roles in precision surgery.

Abstract Purpose This study was designed to investigate the function of RAD51AP1 in the self-renewal and chemosensitivity of CD133 positive (CD133+) ovarian cancer (OC) stem-like cells. Methods CD133+ (CD133 positive) OVCAR4 and CD133 negative (CD133−) OVCAR4 cells were separated from OVCAR4 by flow cytometry. Then, the separated CD133+OVCAR4 cells were divided into the following groups: Vector group; RAD51AP1 group; siNC group; si-RAD51AP1 group. Next, sphere-formation assay and colony forming assay were used to evaluate the self-renewal and proliferation ability of cells; western blot to detect the expression of RAD51AP1, transforming growth factor beta 1 (TGF-β1) and SMAD4 proteins in tissues and cells; qRT-PCR to assess the mRNA levels of sex-determining region Y-box 2 (SOX2), octamer-binding transcription factor 4 (OCT4), NANOG and Kruppel-like factor 4 (KLF4). Results The performance of CD133+OVCAR4 cells was much better than that of CD133−OVCAR4 cells in sphere-formation assay and colony forming assay. Besides, compared with adjacent group and CD133−OVCAR4 cells, the expression level of RAD51AP1 increased significantly in OC group and CD133+OVCAR4 cells. Moreover, the over-expression of RAD51AP1 promoted the self-renewal and proliferation of CD133+OVCAR4 cells. On the contrary, knocking down the expression level of RAD51AP1 could inhibit the self-renewal and proliferation of CD133+OVCAR4 cells and improve the sensitivity of cells to chemotherapy drugs. Conclusion The findings of this study showed that RAD51AP1 was highly expressed in OC tissue and CD133+OVCAR4 cells, and regulated the self-renewal and chemosensitivity of tumor cells through the TGF-β1/SMAD4 signaling pathway.

The Tibetan Plateau (TP) has undergone significant warming and humidification in recent years, resulting in rapid permafrost degradation and spatiotemporal variations in hydrological processes, such as subsurface water transport, hydrothermal conversion, and runoff generation. Understanding the mechanisms of hydrological processes in permafrost areas under changing climate is crucial for accurately evaluating hydrological responses on the TP. This study comprehensively discusses the permafrost hydrological processes of the TP under changing climate. Topics include climate conditions and permafrost states, subsurface water transport under freeze–thaw conditions, development of thermokarst lakes and hydrothermal processes, and runoff response during permafrost degradation. This study offers a comprehensive understanding of permafrost changes and their hydrological responses, contributing significantly to water security and sustainable development on the TP.

As artificial intelligence (AI) technology rapidly develops and is deployed, students increasingly need to understand and learn AI-related skills for future employment. This study investigates how students' AI learning anxiety and AI job replacement anxiety affect intrinsic/extrinsic learning motivations and subsequent AI learning intention. The moderating effect of learning self-efficacy is also examined. An online survey instrument collected data from a sample of students in Taiwan, and partial least-squares structural equation modeling (PLS-SEM) technique was employed to test the proposed model. The results indicate AI learning anxiety negatively affects learning motivations, but AI job replacement anxiety has a positive impact on extrinsic motivation. Learning self-efficacy and intrinsic/extrinsic motivations positively affect learning intention. Learning self-efficacy positively moderates the influence of intrinsic learning motivation on student AI learning intention but negatively moderates the influence of extrinsic learning motivation on student AI learning intention. The findings highlight the importance of AI anxiety and can be used to guide course design in an AI learning setting.

This study investigates the individual difference antecedents of students' behavioural intention to use VR-based learning systems, especially from an integrated perspective of Big Five personality traits and perceived physiological vulnerability to IT use (PPVITU). Data collected from 149 respondents are tested against the research model using the partial least squares structural equation method (PLS-SEM). The results indicate that extraversion and neuroticism positively affect perceived usefulness, conscientiousness negatively influences usefulness, and agreeableness and neuroticism have positive effects on perceived enjoyment. Furthermore, this study finds that musculoskeletal discomfort: neck and shoulder back pain (one PPVITU component) positively influences perceived ease of use. The findings of this study provide several important theoretical and practical implications for promoting VR-based learning system use behaviour.

International recognition of Special Educational Needs Coordinators (SENCos) as agents of change for students with special educational needs calls for a deeper understanding of SENCo agency. However, literature on teacher agency for inclusion has paid little attention to SENCos. Taking a sociocultural view of agency, this qualitative case study collected rich data from five primary school SENCos in New Zealand via semi-structured individual interviews, work-shadowing and relevant documents. The findings showed that the SENCos exercised agency for inclusion through advocacy for students with SEN, commitment to the SENCo role, professional competence, self-efficacy, participation in decision-making, and collaboration with a wide range of people. The findings point to the need to conceptualise SENCo agency as a temporal, ecological process that involves engagement with culture, structure and resources in specific contexts.

As an important construct in the cognitive process, comprehension monitoring has received much scholarly attention. Researchers have recognized comprehension monitoring as an ability closely linked with children's reading comprehension ability and working memory capacity. Evidence is also abundant to prove that comprehension monitoring skill develops with age. It remains unclear, however, how these factors interact during reading, particularly in low-grade children. Many previous empirical studies have only employed online or offline measurements to examine children's monitoring performance, which might lead to unsolid conclusions. In this study, we utilized both online eye-tracking measures and offline probe interviews to quantify the developmental features (i.e., evaluation and regulation) of comprehension monitoring skills among Chinese beginning readers. The results indicated that the comprehension monitoring performance, as quantified by eye-tracking measures, was positively related to their reading comprehension ability and working memory capacity. Moreover, the first-graders' performances lacked online regulation skills during the error-detecting tasks, while second-graders had relatively developed online monitoring performance. Additionally, the eye-tracking measures were found as a predictor for children's performances in probe interviews, as the readers with high comprehension ability and working memory capacity successfully reported more errors embedded in the self-designed reading materials. Therefore, the findings support the claim that children's comprehension monitoring is a developing skill associated with reading comprehension and working memory capacity and further question the existence of comprehension monitoring skills in beginning readers, especially first-graders.

The latest review published in Nature Reviews Drug Discovery by Michael W. Mullowney and co-authors focuses on the use of artificial intelligence techniques, specifically machine learning, in natural product drug discovery. The authors discussed various applications of AI in this field, such as genome and metabolome mining, structural characterization of natural products, and predicting targets and biological activities of these compounds. They also highlighted the challenges associated with creating and managing large datasets for training algorithms, as well as strategies to address these obstacles. Additionally, the authors examine common pitfalls in algorithm training and offer suggestions for avoiding them.

AbstractFeline infectious peritonitis (FIP) is a fatal illness caused by a mutated feline coronavirus (FCoV). This disease is characterized by its complexity, resulting from systemic infection, antibody-dependent enhancement (ADE), and challenges in accessing effective therapeutics. Extract derived from Vigna radiata (L.) R. Wilczek (VRE) exhibits various pharmacological effects, including antiviral activity. This study aimed to investigate the antiviral potential of VRE against FCoV, addressing the urgent need to advance the treatment of FIP. We explored the anti-FCoV activity, antiviral mechanism, and combinational application of VRE by means of in vitro antiviral assays. Our findings reveal that VRE effectively inhibited the cytopathic effect induced by FCoV, reduced viral proliferation, and downregulated spike protein expression. Moreover, VRE blocked FCoV in the early and late infection stages and was effective under in vitro ADE infection. Notably, when combined with VRE, the polymerase inhibitor GS-441524 or protease inhibitor GC376 suppressed FCoV more effectively than monotherapy. In conclusion, this study characterizes the antiviral property of VRE against FCoV in vitro, and VRE possesses therapeutic potential for FCoV treatment.

Abstract Objectives STAT3 is a transcriptional activator of breast cancer oncogenes, suggesting that it could be a potential therapeutic target for breast cancer. Therefore, this study investigated the potential application of C188-9, a STAT3 signal pathway inhibitor, in the treatment of breast cancer through a novel pre-clinical platform with patient-specific primary cells (PSPCs). Methods PSPCs were isolated from breast cancer samples obtained via biopsy or surgery from fifteen patient donors with their full acknowledgements. PSPCs were treated with C188-9 or other chemotherapeutic agents, and then analyzed with cell viability assay. Western blot assay and real-time quantitative PCR were also used to determine the expression and activity of STAT3 signaling pathway of corresponding PSPCs. Results C188-9 treatment at normal (experimental) concentration had valid inhibition on PSPCs proliferation. Meanwhile, treatment at a low (clinic-relevant) concentration of C188-9 for an extended period reduced cell viability of PSPCs still more than some of other traditional chemotherapy drugs. In addition, C188-9 decreased expression level of pSTAT3 in PSPCs from some, but not all patient samples. The treatment of C188-9 reduced cell viability of the breast cancer samples through inhibiting the STAT3 to C-myc signaling pathway. Conclusions In this study, we tested a novel drug C188-9 at a low, clinic-relevant concentration, together with several traditional chemotherapy agents. PSPCs from ten out of fifteen patient donors were sensitive to C188-9, while some of traditional chemotherapy agents failed. This finding suggested that C188-9 could have treatment effects only on those ten PSPC patient donors, indicating the future personalized utilization of PSPCs.

Abstract Doxorubicin (DOX) is an important chemotherapeutic agent for the treatment of hematologic tumors and breast carcinoma. However, its clinical application is limited owing to severe cardiotoxicity. Pyroptosis is a form of programmed cell death linked to DOX-induced cardiotoxicity. Bone mesenchymal stem cell–derived exosomes (BMSC-Exos) and endothelial progenitor cells-derived exosomes (EPC-Exos) have a protective role in the myocardium. Here we found that BMSC-Exos could improve DOX-induced cardiotoxicity by inhibiting pyroptosis, but EPC-Exos couldn’t. Compared with EPCs-Exo, BMSC-Exo-overexpressing lncRNA GHET1 more effectively suppressed pyroptosis, protecting against DOX-induced cardiotoxicity. Further studies showed that lncRNA GHET1 effectively decreased the expression of Nod-like receptor protein 3 (NLRP3), which plays a vital role in pyroptosis by binding to IGF2 mRNA-binding protein 1 (IGF2BP1), a non-catalytic posttranscriptional enhancer of NLRP3 mRNA. In summary, lncRNA GHET1 released by BMSC-Exo ameliorated DOX-induced pyroptosis by targeting IGF2BP1 to reduce posttranscriptional stabilization of NLRP3.

Abstract The acquisition of ectopic fibroblast growth factor receptor 1 (FGFR1) expression is well documented in prostate cancer (PCa) progression, notably in conferring tumor growth advantage and facilitating metastasis. However, how FGFR1 contributes to PCa progression is not fully revealed. Here we report that ectopic FGFR1 in PCa cells promotes transferrin receptor 1 (TFR1) expression and expands the labile iron pool (LIP), and vice versa. We further demonstrate that FGFR1 stabilizes iron regulatory proteins 2 (IRP2) and therefore, upregulates TFR1 via promoting IRP2 binding to the IRE of TFR1. Deletion of FGFR1 in DU145 cells decreases the LIP, which potentiates the anticancer efficacy of iron chelator. Intriguingly, forced expression of IRP2 in FGFR1 depleted cells reinstates TFR1 expression and LIP, subsequently restoring the tumorigenicity of the cells. Together, our results here unravel a new mechanism by which FGFR1 drives PCa progression and suggest a potential novel target for PCa therapy.

Abstract Lower back pain (LBP) is a common condition closely associated with intervertebral disc degeneration (IDD), causing a significant socioeconomic burden. Inflammatory activation in degenerated discs involves pro-inflammatory cytokines, dysregulated regulatory cytokines, and increased levels of nerve growth factor (NGF), leading to further intervertebral disc destruction and pain sensitization. Macrophage polarization is closely related to autophagy. Based on these pathological features, a structured biomimetic nanoparticle coated with TrkA-overexpressing macrophage membranes (TMNP@SR) with a rapamycin-loaded mesoporous silica core is developed. TMNP@SR acted like sponges to adsorbe inflammatory cytokines and NGF and delivers the autophagy regulator rapamycin (RAPA) into macrophages through homologous targeting effects of the outer engineered cell membrane. By regulating autophagy activation, TMNP@SR promoted the M1-to-M2 switch of macrophages to avoid continuous activation of inflammation within the degenerated disc, which prevented the apoptosis of nucleus pulposus cells. In addition, TMNP@SR relieved mechanical and thermal hyperalgesia, reduced calcitonin gene-related peptide (CGRP) and substance P (SP) expression in the dorsal root ganglion, and downregulated GFAP and c-FOS signaling in the spinal cord in the rat IDD model. In summary, TMNP@SR spontaneously inhibits the aggravation of disc inflammation to alleviate disc degeneration and reduce the ingress of sensory nerves, presenting a promising treatment strategy for LBP induced by disc degeneration. Graphical Abstract

Abstract The minimally invasive injection of tissue engineering scaffolds is of interest as it requires a smaller incision and quickens recovery. However, the engineering of scaffolds capable of injection remains a challenge. Here, we report on a shrunken scaffold inspired by the shrinking of puffed food in a humid environment. A scaffold is freeze-dried to remove water then placed in a humid atmosphere. The humidity causes the dry scaffold to shrink by up to 90%. In addition, the humidity treatment reduces the scaffolds modulus minimizing the foreign body response after implantation. The scaffolds can rapidly swell into their original size and shape after application. A tool for the delivery of the minimally invasive scaffolds is developed and we demonstrate the potential for minimally invasive delivery using this shrinking technique.

Background: Uncorrected refractive error is a major cause of vision impairment worldwide and its increasing prevalent necessitates effective screening and management strategies. Meanwhile, deep learning, a subset of Artificial Intelligence, has significantly advanced ophthalmological diagnostics by automating tasks that required extensive clinical expertise. Although recent studies have investigated the use of deep learning models for refractive power detection through various imaging techniques, a comprehensive systematic review on this topic is has yet be done. This review aims to summarise and evaluate the performance of ocular image-based deep learning models in predicting refractive errors. Main text: We search on three databases (PubMed, Scopus, Web of Science) up till June 2023, focusing on deep learning applications in detecting refractive error from ocular images. We included studies that had reported refractive error outcomes, regardless of publication years. We systematically extracted and evaluated the continuous outcomes (sphere, SE, cylinder) and categorical outcomes (myopia), ground truth measurements, ocular imaging modalities, deep learning models, and performance metrics, adhering to PRISMA guidelines. Nine studies were identified and categorised into three groups: retinal photo-based (n ​= ​5), OCT-based (n ​= ​1), and external ocular photo-based (n ​= ​3).For high myopia prediction, retinal photo-based models achieved AUC between 0.91 and 0.98, sensitivity levels between 85.10% and 97.80%, and specificity levels between 76.40% and 94.50%. For continuous prediction, retinal photo-based models reported MAE ranging from 0.31D to 2.19D, and R2 between 0.05 and 0.96. The OCT-based model achieved an AUC of 0.79–0.81, sensitivity of 82.30% and 87.20% and specificity of 61.70%–68.90%. For external ocular photo-based models, the AUC ranged from 0.91 to 0.99, sensitivity of 81.13%–84.00% and specificity of 74.00%–86.42%, MAE ranges from 0.07D to 0.18D and accuracy ranges from 81.60% to 96.70%. The reported papers collectively showed promising performances, in particular the retinal photo-based and external eye photo -based DL models. Conclusions: The integration of deep learning model and ocular imaging for refractive error detection appear promising. However, their real-world clinical utility in current screening workflow have yet been evaluated and would require thoughtful consideration in design and implementation.

Abstract Neutrophils are emerging as an important player in skeletal muscle injury and repair. Neutrophils accumulate in injured tissue, thus releasing inflammatory factors, proteases and neutrophil extracellular traps (NETs) to clear muscle debris and pathogens when skeletal muscle is damaged. During the process of muscle repair, neutrophils can promote self-renewal and angiogenesis in satellite cells. When neutrophils are abnormally overactivated, neutrophils cause collagen deposition, functional impairment of satellite cells, and damage to the skeletal muscle vascular endothelium. Heterotopic ossification (HO) refers to abnormal bone formation in soft tissue. Skeletal muscle injury is one of the main causes of traumatic HO (tHO). Neutrophils play a pivotal role in activating BMPs and TGF-β signals, thus promoting the differentiation of mesenchymal stem cells and progenitor cells into osteoblasts or osteoclasts to facilitate HO. Furthermore, NETs are specifically localized at the site of HO, thereby accelerating the formation of HO. Additionally, the overactivation of neutrophils contributes to the disruption of immune homeostasis to trigger HO. An understanding of the diverse roles of neutrophils will not only provide more information on the pathogenesis of skeletal muscle injury for repair and HO but also provides a foundation for the development of more efficacious treatment modalities for HO.

Abstract Objective Based on the Omaha problem classification system, a sensitivity outcome index system for home nursing of elderly liver transplant patients was established. Methods Through a comprehensive literature review and rigorous application of the Delphi method, a panel of 20 experts completed two rounds of effective letter consultation to obtain expert consensus opinions. The contents of indicators were determined based on this process, and the analytic hierarchy process was employed to confirm the weightage assigned to each indicator. Consequently, we established a sensitivity outcome index system for home care in elderly liver transplant patients. Results The effective recovery rate of the questionnaire in two rounds of expert consultation was 100%, and the proportion of experts who gave opinions was 55% and 15%, respectively, indicating that the experts were highly active. The expert authority coefficients were calculated as 0.904 and 0.905, respectively, indicating a high degree of expert authority. In the second round, Kendall’s coordination coefficients for primary, secondary, and tertiary indicators were determined to be 0.419, 0.418, and 0.394 (P

Abstract Background Malnutrition is linked to a higher risk of unfavorable outcomes in various illnesses. The present investigation explored the correlation between inadequate nutritional condition and outcomes in older individuals diagnosed with hyperlipidemia. Methods The geriatric nutritional risk index (GNRI) was used to evaluate the nutritional status. All patients were divided into two groups according to GNRI. A Kaplan-Meier analysis was used to assess the survival rates of different groups at risk of malnutrition. In addition, GNRI was used in COX proportional risk regression models to evaluate its predictive effect on both overall mortality and cardiovascular mortality among patients with hyperlipidemia. Furthermore, the study employed restricted cubic splines (RCS) to examine the nonlinear correlation between GNRI and mortality. Results The study included 4,532 elderly individuals diagnosed with hyperlipidemia. During a median follow-up duration of 139 months, a total of 1498 deaths from all causes and 410 deaths from cardiovascular causes occurred. The Kaplan-Meier analysis demonstrated significantly poorer survival among individuals at risk of malnutrition, as indicated by the GNRI. In the malnutrition risk group, the modified COX proportional hazards model revealed that a decrease in GNRI was associated with a higher risk of all-cause mortality (HR=1.686, 95% CI 1.212-2.347) and cardiovascular mortality (HR=3.041, 95% CI 1.797-5.147). Furthermore, the restricted cubic splines revealed a non-linear association between GNRI and both all-cause mortality and cardiovascular mortality (p-value for non-linearity = 0.0039, p-value for non-linearity=0.0386). Conclusions In older patients with hyperlipidemia, lower levels of GNRI are associated with mortality. The GNRI could potentially be used to predict all-cause mortality and cardiovascular mortality.

Abstract Objectives To assess the effectiveness of HRCT-based radiomics in predicting rapidly progressive interstitial lung disease (RP-ILD) and mortality in anti-MDA5 positive dermatomyositis-related interstitial lung disease (anti-MDA5 + DM-ILD). Methods From August 2014 to March 2022, 160 patients from Institution 1 were retrospectively and consecutively enrolled and were randomly divided into the training dataset (n = 119) and internal validation dataset (n = 41), while 29 patients from Institution 2 were retrospectively and consecutively enrolled as external validation dataset. We generated four Risk-scores based on radiomics features extracted from four areas of HRCT. A nomogram was established by integrating the selected clinico-radiologic variables and the Risk-score of the most discriminative radiomics model. The RP-ILD prediction performance of the models was evaluated by using the area under the receiver operating characteristic curves, calibration curves, and decision curves. Survival analysis was conducted with Kaplan-Meier curves, Mantel-Haenszel test, and Cox regression. Results Over a median follow-up time of 31.6 months (interquartile range: 12.9–49.1 months), 24 patients lost to follow-up and 46 patients lost their lives (27.9%, 46/165). The Risk-score based on bilateral lungs performed best, attaining AUCs of 0.869 and 0.905 in the internal and external validation datasets. The nomogram outperformed clinico-radiologic model and Risk-score with AUCs of 0.882 and 0.916 in the internal and external validation datasets. Patients were classified into low- and high-risk groups with 50:50 based on nomogram. High-risk group patients demonstrated a significantly higher risk of mortality than low-risk group patients in institution 1 (HR = 4.117) and institution 2 cohorts (HR = 7.515). Conclusion For anti-MDA5 + DM-ILD, the nomogram, mainly based on radiomics, can predict RP-ILD and is an independent predictor of mortality.

Abstract Background The atherogenic index of plasma (AIP) is a simple and reliable marker of insulin resistance and is closely associated with various cardiovascular diseases (CVDs). However, the relationships between AIP and left ventricular (LV) geometric indicators have not been adequately assessed. This study was carried out to investigate the association between AIP and LV geometric abnormalities in obstructive sleep apnea (OSA) patients. Methods This retrospective cross-sectional study included a total of 618 OSA patients (57.3 ± 12.4 years, 73.1% males, BMI 28.1 ± 4.2 kg/m2) who underwent echocardiography. Patients with OSA were diagnosed with clinical symptoms and an apnea-hypopnea index ≥ 5.0. LV hypertrophy (LVH) was defined as left ventricular mass index (LVMIh2.7) ≥ 50.0 g/m2.7 for men and 47.0 g/m2.7 for women. AIP was calculated as log10 (TG/HDL-C). Results Compared with the non-LVH group, AIP was significantly higher in the LVH group (0.19 ± 0.29 vs 0.24 ± 0.28, P = 0.024) and the concentric LVH group (0.18 ± 0.29, 0.19 ± 0.30, 0.20 ± 0.26 and 0.29 ± 0.29 in the control, concentric remodeling, eccentric hypertrophy and concentric hypertrophy groups, respectively, P = 0.021). Meanwhile, in the group of patients with the highest AIP tertile, the levels of LVMIh2.7 (42.8 ± 10.5, 43.2 ± 9.3 and 46.1 ± 12.1 in the T1, T2 and T3 groups, respectively, P = 0.003), and the prevalence of LVH (25.2%, 24.0% and 34.6% in the T1, T2 and T3 groups, respectively, P = 0.032) and concentric LVH (10.7%, 9.8% and 20.2% in the T1, T2 and T3 groups, respectively, P = 0.053) were higher compared with those in the other groups. Positive correlations between AIP and LV geometric indicators including the LVMIh2.7, LVMIBSA, LV mass (LVM), diastolic left ventricular inner diameter (LVIDd), diastolic left ventricular posterior wall thickness (PWTd) and diastolic interventricular septal thickness (IVSTd), were revealed according to correlation analysis (P

Abstract The biomechanical aspects of adjacent segment degeneration after Adult Idiopathic Scoliosis (AdIS) corrective surgery involving postoperative changes in motion and stress of adjacent segments have yet to be investigated. The objective of this study was to evaluate the biomechanical effects of corrective surgery on adjacent segments in adult idiopathic scoliosis by finite element analysis. Based on computed tomography data of the consecutive spine from T1–S1 of a 28-year-old male patient with adult idiopathic scoliosis, a three-dimensional finite element model was established to simulate the biomechanics. Two posterior long-segment fixation and fusion operations were designed: Strategy A, pedicle screws implanted in all segments of both sides, and Strategy B, alternate screws instrumentation on both sides. The range of motion (ROM), Maximum von Mises stress value of intervertebral disc (IVD), and Maximum von Mises stress of the facet joint (FJ) at the fixation adjacent segment were calculated and compared with data of the preoperative AdIS model. Corrective surgery decreased the IVD on the adjacent segments, increased the FJ on the adjacent segments, and decreased the ROM of the adjacent segments. A greater decrease of Maximum von Mises stress was observed on the distal adjacent segment compared with the proximal adjacent segment. The decrease of Maximum von Mises stress and increment of Maximum von Mises stress on adjacent FJ in strategy B was greater than that in strategy A. Under the six operation modes, the change of the Maximum von Mises stress on the adjacent IVD and FJ was significant. The decrease in ROM in the proximal adjacent segment was greater than that of the distal adjacent segment, and the decrease of ROM in strategy A was greater than that in strategy B. This study clarified the biomechanical characteristics of adjacent segments after AdIS corrective surgery, and further biomechanical analysis of two different posterior pedicle screw placement schemes by finite element method. Our study provides a theoretical basis for the pathogenesis, prevention, and treatment of adjacent segment degeneration after corrective surgery for AdIS.