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Background and Aims: Arterial pressure-volume index (API) is a non-invasive tool for assessing small-to-medium-sized arterial stiffness. This study aimed to investigate the potential age- and sex-related differences in the API and explore the practical implications of such differences., Methods and Results: The study analysed 7620 subjects for whom API measurements were available. Linear regression and restrictive cubic spline models were used to investigate the associations between potential risk conditions and the API. Additionally, this study employed a backward stepwise regression method to identify the independent factors associated with a high API. Middle-aged to older women had higher API values and a higher prevalence of high API than men in the same age group. However, the opposite was observed among younger individuals, with women having lower API values than men. This study also identified a J-shaped relationship between API and age, where API values began to increase at a certain age and rapidly increased after that. In women, the API started to increase at 31 years of age and rapidly increased after 54 years of age. In men, the API started to increase at 38 years of age, followed by a rapid increase after 53 years of age., Conclusion: This study's observation of a significant age-sex interaction in small-to-medium-sized arterial stiffening offers a valuable explanation for cardiovascular disease risk and provides important parameters for using API measurements to evaluate such risk., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest relevant to this study., (Copyright © 2023. Published by Elsevier B.V.)

Clinical application of doxorubicin (DOX) is heavily hindered by DOX cardiotoxicity. Several theories were postulated for DOX cardiotoxicity including DNA damage and DNA damage response (DDR), although the mechanism(s) involved remains to be elucidated. This study evaluated the potential role of TBC domain family member 15 (TBC1D15) in DOX cardiotoxicity. Tamoxifen-induced cardiac-specific Tbc1d15 knockout ( Tbc1d15 CKO ) or Tbc1d15 knockin ( Tbc1d15 CKI ) male mice were challenged with a single dose of DOX prior to cardiac assessment 1 week or 4 weeks following DOX challenge. Adenoviruses encoding TBC1D15 or containing shRNA targeting Tbc1d15 were used for Tbc1d15 overexpression or knockdown in isolated primary mouse cardiomyocytes. Our results revealed that DOX evoked upregulation of TBC1D15 with compromised myocardial function and overt mortality, the effects of which were ameliorated and accentuated by Tbc1d15 deletion and Tbc1d15 overexpression, respectively. DOX overtly evoked apoptotic cell death, the effect of which was alleviated and exacerbated by Tbc1d15 knockout and overexpression, respectively. Meanwhile, DOX provoked mitochondrial membrane potential collapse, oxidative stress and DNA damage, the effects of which were mitigated and exacerbated by Tbc1d15 knockdown and overexpression, respectively. Further scrutiny revealed that TBC1D15 fostered cytosolic accumulation of the cardinal DDR element DNA-dependent protein kinase catalytic subunit (DNA-PKcs). Liquid chromatography-tandem mass spectrometry and co-immunoprecipitation denoted an interaction between TBC1D15 and DNA-PKcs at the segment 594-624 of TBC1D15. Moreover, overexpression of TBC1D15 mutant (∆594-624, deletion of segment 594-624) failed to elicit accentuation of DOX-induced cytosolic retention of DNA-PKcs, DNA damage and cardiomyocyte apoptosis by TBC1D15 wild type. However, Tbc1d15 deletion ameliorated DOX-induced cardiomyocyte contractile anomalies, apoptosis, mitochondrial anomalies, DNA damage and cytosolic DNA-PKcs accumulation, which were canceled off by DNA-PKcs inhibition or ATM activation. Taken together, our findings denoted a pivotal role for TBC1D15 in DOX-induced DNA damage, mitochondrial injury, and apoptosis possibly through binding with DNA-PKcs and thus gate-keeping its cytosolic retention, a route to accentuation of cardiac contractile dysfunction in DOX-induced cardiotoxicity., Competing Interests: The authors declare no conflicts of interest., (© 2023 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.)

Background: Clear cell renal cell carcinoma (ccRCC) is a common malignant tumor of the urinary system characterized by abundant immunocytes infiltration. The impact of guanosine triphosphatases (GTPases) of immunity-associated proteins (GIMAPs) on the tumor immune microenvironment (TIME) and prognosis of ccRCC is unclear., Methods: The expression of GIMAPs in ccRCC was determined through multiple datasets (ONCOMINE, TCGA and UALCAN). The relationship between GIMAP family members was analyzed through Spearman correlation analysis. The interaction among the GIMAPs protein was analyzed using STRING. Prognostic values of GIMAPs were evaluated by Survival analysis, Lasso and Cox regression analysis; Prognostic risk model and nomogram were constructed. The correlation between GIMAPs and TIME was explored using TIMER, Cibersort and Pearson correlation analysis. Gene set enrichment analysis (GSEA) was performed to discuss their function and mechanism in ccRCC., Results: GIMAPs were over-expressed in ccRCC and significantly related to overall survival (OS) of the patients. GIMAPs were positively correlated with each other, the risk model based on GIMAPs had good prognostic value in ccRCC. GIMAPs mainly expressed in TIME and were associated with abundant immunocytic infiltration in ccRCC, the risk model also had close correlation with TIME. Our results showed GIMAPs may affect the development of ccRCC by regulating the amount and antitumor activity of immunocytes in TIME., Conclusions: GIMAPs were over-expressed in ccRCC, and their expression levels were significantly related to the OS of patients and immunocytic infiltration in TIME. GIMAPs are potential therapeutic targets and prognostic biomarkers for ccRCC., Competing Interests: The authors declare no conflict of interest., (© 2023 The Author(s). Published by IMR Press.)

Objective: To compare cardiac function indicators between mild and moderate to severe COVID-19 patients and to try to identify the sequence and directivity in cardiac muscle injury of COVID-19 patients., Methods: From December 2022 to January 2023, all patients with laboratory-confirmed SARS-CoV-2 infection in Shanghai General Hospital Jiading Branch were enrolled. The clinical classification was stratified into mild, moderate, or severe groups. We collected the clinical and laboratory information, transthoracic echocardiographic and speckle-tracking echocardiographic parameters of patients and compared the differences among different groups., Results: The values of echocardiographic parameters in mild group were lower than that in moderate or severe group ( P  < 0.05) except LVEF. The values of LVEF of mild and moderate group were higher than severe group ( P  < 0.05). There were no significant differences between moderate and severe group. Positive correlations were observed between left ventricular global longitudinal strain (LVGLS) and myoglobin ( r  = 0.72), E/e' and age ( r  = 0.79), E/e' and BNP ( r  = 0.67). The multivariate analysis shows that SpO 2 (OR = 0.360, P  = 0.02), LVGLS (OR = 3.196, P  = 0.003) and E/e' (OR = 1.307, P  = 0.036) were the independent risk factors for mild cases progressing to moderate or severe. According to the receiver operating characteristic (ROC) curves, when all the COVID-19 patients was taken as the sample size, the area under the curve (AUC) of the LVGLS was the highest (AUC = 0.861). The AUC of the LVGLS was higher than LVGCS (AUC = 0.565, P  < 0.001)., Conclusion: When mild COVID-19 progresses to moderate or severe, both systolic and diastolic functions of the heart are impaired. LVGLS was the independent risk factor for mild cases progressing to moderate or severe cases. Longitudinal changes may manifest earlier than circumferential changes as myocardial disease progresses in COVID-19., 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., (© 2023 Wang, Chen, Jin, Wu, Zhang, Sun, Shen, Du, Wang and Li.)

Background: To explore the value of a novel ventricular-vascular coupling index (VVI) system in relation to age, gender and body mass index (BMI)., Methods: A total of 239 volunteers with single-center and cross-sectional health screening were enrolled in the study. Subjects were divided according to age (young [18-44 years], middle-age [45-59 years], old [60-80 years]), gender (male, female), and BMI (overweight/obese [BMI ≥ 24], control [BMI < 24]). The left ventricle end-diastolic volume (LVEDV) and left ventricle end-systolic volume (LVESV) provided the left ventricular structure index, while the TDI e ' provided the functional index. Also derived from routine echocardiography were the effective arterial elastance (Ea), left ventricular end-systolic elastance (Ees), and VVI. The novel VVI systems were arterial velocity pulse index (AVI), left ventricular global longitudinal strain (LVGLS), and the AVI to LVGLS ratio (AVI/LVGLS)., Results: (1) Middle-age and elderly subjects had higher Ea and lower LVGLS compared to young subjects. AVI and AVI/LVGLS increased progressively from young to middle-age to old subjects. (2) Females had higher Ea, Ees and LVGLS than male subjects. No significant differences in AVI and AVI/LVGLS were observed between males and females. (3) No significant differences in Ea, Ees, VVI, AVI, LVGLS and AVI/LVGLS were observed between the overweight/obese and control groups. (4) AVI/LVGLS was negatively correlated with LVEDV and LVESV and with TDI e ' . LVEDV, LVESV and TDI e ' were independent predictors of AVI/LVGLS. (5) The diagnostic performance of AVI/LVGLS was higher than that of VVI in the young and middle-age groups. The diagnostic efficacy of AVI/LVGLS was higher than that of VVI in the young and old groups, and the diagnostic efficacy of AVI was higher than that of Ea. The difference in diagnostic efficacy between LVGLS and Ees was not statistically significant. The differences in diagnostic efficacy between AVI/LVGLS and VVI, AVI and Ea, and LVGLS and Ees were not statistically significant in the middle-age and old groups., Conclusions: The novel index system of ventricular-vascular coupling described here (AVI, LVGLS, and AVI/LVGLS) was more effective than traditional indexes in detecting differences in cardiovascular function between different ages groups., Clinical Trial Registration: The study protocol was registered on the official website of China Clinical Trial Registration Center (ChiCTR2000035937)., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2023 The Author(s). Published by IMR Press.)

Introduction: Endoscopic evaluation is crucial for predicting the invasion depth of esophagus squamous cell carcinoma (ESCC) and selecting appropriate treatment strategies. Our study aimed to develop and validate an interpretable artificial intelligence-based invasion depth prediction system (AI-IDPS) for ESCC., Methods: We reviewed the PubMed for eligible studies and collected potential visual feature indices associated with invasion depth. Multicenter data comprising 5,119 narrow-band imaging magnifying endoscopy images from 581 patients with ESCC were collected from 4 hospitals between April 2016 and November 2021. Thirteen models for feature extraction and 1 model for feature fitting were developed for AI-IDPS. The efficiency of AI-IDPS was evaluated on 196 images and 33 consecutively collected videos and compared with a pure deep learning model and performance of endoscopists. A crossover study and a questionnaire survey were conducted to investigate the system's impact on endoscopists' understanding of the AI predictions., Results: AI-IDPS demonstrated the sensitivity, specificity, and accuracy of 85.7%, 86.3%, and 86.2% in image validation and 87.5%, 84%, and 84.9% in consecutively collected videos, respectively, for differentiating SM2-3 lesions. The pure deep learning model showed significantly lower sensitivity, specificity, and accuracy (83.7%, 52.1% and 60.0%, respectively). The endoscopists had significantly improved accuracy (from 79.7% to 84.9% on average, P = 0.03) and comparable sensitivity (from 37.5% to 55.4% on average, P = 0.27) and specificity (from 93.1% to 94.3% on average, P = 0.75) after AI-IDPS assistance., Discussion: Based on domain knowledge, we developed an interpretable system for predicting ESCC invasion depth. The anthropopathic approach demonstrates the potential to outperform deep learning architecture in practice., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Fusobacterium nucleatum (Fn) infection and microRNAs (miRNAs) are closely associated with colorectal cancer (CRC) development, but the mechanism by which Fn regulates tumor-suppressive miRNAs via exosomes and facilitates CRC metastasis remains unclear. Here, we identified that Fn infection significantly increased exosomal miR-122-5p levels in the serum of CRC patients and CRC cell culture supernatants through two miRNA panels of high-throughput sequencing and RT-qPCR analysis. In Fn -infected patients, the serum exosomal levels of miR-122-5p were negatively associated with their expression levels of tissues. Downregulated miR-122-5p was demonstrated to enhance the migration, invasion, and metastasis abilities of CRC cells in vivo and in vitro . Secretion of miR-122-5p into exosomes is mediated by hnRNPA2B1. Mechanistically, Fn activated the TGF-β1/Smads signaling pathway to promote EMT by regulation of the miR-122-5p/FUT8 axis. In conclusion, Fn infection may stimulate CRC cells to excrete exosome-wrapped miR-122-5p, and activate the FUT8/TGF-β1/Smads axis to promote metastasis., Competing Interests: The authors declare no competing interests., (© 2023 The Author(s).)

Background: Arterial stiffness played an important role in the development of cardiovascular disease (CVD) events. The aim of this study was to verify the relative importance of arterial stiffness for different CVD risk scores in a large sample of Chinese women., Methods: We measured arterial velocity pulse index (AVI) and CVD risk scores in 2220 female participants (mean age 57 years). Framingham Risk Score (FRS), and the prediction for Atherosclerotic Cardiovascular Disease Risk in China (China-PAR) were used to estimate CVD risk, respectively. The relationships between AVI and risk scores were investigated by linear regressions and restricted cubic spline (RCS) analysis. To determine the relative importance of AVI in predicting CVD risk scores, random forest analysis was used., Results: There was a significant positive correlation between AVI and FRS, China-PAR in all subgroup groups stratified by age, blood pressure and BMI. AVI showed higher importance in predicting CVD risk scores in FRS model, compared with these traditional risk factors. In China-PAR model, although AVI was not as predictive as SBP, it had better predictive power than many known risk factors such as lipids. Furthermore, AVI had significant J-shaped associations both with FRS and China-PAR scores., Conclusions: AVI was significantly associated with CVD risk score. In FRS and China-PAR model, AVI showed relatively high importance in predicting CVD risk scores. These findings may support the use of arterial stiffness measurements in CVD risk assessment., 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., (© 2023 Jin, Chen, Wu, Zhang, Sun, Shen, Du, Wang and Li.)

Objective: Uncorrected obesity is accompanied by unfavorable structural and functional changes in the heart, known as obesity cardiomyopathy. Recent evidence has revealed a crucial role for mitochondria-associated endoplasmic reticulum membranes (MAMs) in obesity-induced cardiac complication. Syntaxin 17 (STX17) serves as a scaffolding molecule localized on MAMs although its role in obesity heart complication remains elusive., Methods and Materials: This study examined the role of STX17 in MAMs and mitochondrial Ca 2+ homeostasis in HFD-induced obesity cardiomyopathy using tamoxifen-induced cardiac-specific STX17 knockout (STX17 cko ) and STX17 overexpression mice using intravenously delivered recombinant adeno-associated virus serotype-9 (AAV9-cTNT-STX17)., Results: STX17 levels were significantly elevated in plasma from obese patients and heart tissues of HFD-fed mice. Our data revealed that cardiac STX17 knockout alleviated cardiac remodeling and dysfunction in obese hearts without eliciting any notable effect itself, while STX17 overexpression aggravated cardiac dysfunction in obese mice. STX17 deletion and STX17 overexpression annihilated and aggravated, respectively, HFD-induced oxidative stress (O 2 - production) and mitochondrial injury in the heart. Furthermore, STX17 transfection facilitated obesity-induced MAMs formation in cardiomyocytes and evoked excess mitochondrial Ca 2+ influx, dependent upon interaction with mitochondrial Ca 2+ uniporter dominant negative β (MCUb) through Habc domain. Our data also suggested that STX17 promoted ubiquitination and degradation of MCUb through the E3 ligase parkin in the face of palmitate challenging., Conclusion: Taken together, our results identified a novel role for STX17 in facilitating obesity-induced MAMs formation, and subsequently mitochondrial Ca 2+ overload, mitochondrial O 2 - accumulation, lipid peroxidation, resulting in cardiac impairment. Our findings denoted therapeutic promises of targeting STX17 in obesity., (Copyright © 2023. Published by Elsevier Inc.)

Recent studies have reported that Fusobacterium nucleatum (Fn) is associated with gastric cancer (GC). Cancer-derived exosomes contain key regulatory noncoding RNAs and are a crucial medium of intercellular communication. However, the function and regulatory mechanism of exosomes (Fn-GCEx) secreted from Fn-infected GC cells remains unclear. In this study, Fn-GCEx enhanced the proliferation, migration, and invasion capacity of GC cells in vitro, as well as tumor growth and metastasis in vivo. HOTTIP was also upregulated in GC cells treated with Fn-GCEx. Moreover, knockdown of HOTTIP weakened the effects of Fn-GCEx in recipient GC cells. Mechanistically, HOTTIP promoted EphB2 expression by sponging microRNA (miR)-885-3p, thus activating the PI3K/AKT pathway in Fn-GCEx treated GC cells. Overall, Fn infection induced the upregulation of exosomal HOTTIP from GC cells that subsequently promoted GC progression through the miR-885-3p/EphB2/PI3K/AKT axis. Herein, we identify a potential molecular pathway and therapeutic target for GC., (© 2023 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

White light endoscopy is the most pivotal tool for detecting early gastric neoplasms. Previous artificial intelligence (AI) systems were primarily unexplainable, affecting their clinical credibility and acceptability. We aimed to develop an explainable AI named ENDOANGEL-ED (explainable diagnosis) to solve this problem. A total of 4482 images and 296 videos with focal lesions from 3279 patients from eight hospitals were used for training, validating, and testing ENDOANGEL-ED. A traditional sole deep learning (DL) model was trained using the same dataset. The performance of ENDOANGEL-ED and sole DL was evaluated on six levels: internal and external images, internal and external videos, consecutive videos, and man-machine comparison with 77 endoscopists in videos. Furthermore, a multi-reader, multi-case study was conducted to evaluate the ENDOANGEL-ED's effectiveness. A scale was used to compare the overall acceptance of endoscopists to traditional and explainable AI systems. The ENDOANGEL-ED showed high performance in the image and video tests. In man-machine comparison, the accuracy of ENDOANGEL-ED was significantly higher than that of all endoscopists in internal (81.10% vs. 70.61%, p < 0.001) and external videos (88.24% vs. 78.49%, p < 0.001). With ENDOANGEL-ED's assistance, the accuracy of endoscopists significantly improved (70.61% vs. 79.63%, p < 0.001). Compared with the traditional AI, the explainable AI increased the endoscopists' trust and acceptance (4.42 vs. 3.74, p < 0.001; 4.52 vs. 4.00, p < 0.001). In conclusion, we developed a real-time explainable AI that showed high performance, higher clinical credibility, and acceptance than traditional DL models and greatly improved the diagnostic ability of endoscopists., (© 2023. The Author(s).)

Breast cancer threatens the health of women worldwide, and its molecular subtypes largely determine the therapy and prognosis of patients. However, an uncomplicated and accurate method to identify subtypes is currently lacking. This study utilized photoacoustic spectral analysis (PASA) based on the partial least squares discriminant algorithm (PLS-DA) to identify molecular breast cancer subtypes at the biomacromolecular level in vivo. The area of power spectrum density (APSD) was extracted to semi-quantify the biomacromolecule content. The feature wavelengths were obtained via the variable importance in projection (VIP) score and the selectivity ratio (Sratio), to identify the biomarkers. The PASA achieved an accuracy of 84%. Most of the feature wavelengths fell into the collagen-dominated absorption waveband, which was consistent with the histopathological results. This paper proposes a successful method for identifying molecular breast cancer subtypes and proves that collagen can be treated as a biomarker for molecular breast cancer subtyping., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Purpose: The purpose of this study was to analyze and compare the clinical characteristics of patients with 30-day planned and unplanned readmissions and to identify patients at high risk for unplanned readmissions. This will facilitate a better understanding of these readmissions and improve and optimize resource utilization for this patient population., Methods: A retrospective cohort descriptive study was conducted at the West China Hospital (WCH), Sichuan University from January 1, 2015, to December 31, 2020. Discharged patients (≥ 18 years old) were divided into unplanned readmission and planned readmission groups according to 30-day readmission status. Demographic and related information was collected for each patient. Logistic regression analysis was used to assess the association between unplanned patient characteristics and the risk of readmission., Results: We identified 1,118,437 patients from 1,242,496 discharged patients, including 74,494 (6.7%) 30-day planned readmissions and 9,895 (0.9%) unplanned readmissions. The most common diseases of planned readmissions were antineoplastic chemotherapy (62,756/177,749; 35.3%), radiotherapy sessions for malignancy (919/8,229; 11.2%), and systemic lupus erythematosus (607/4,620; 13.1%). The most common diseases of unplanned readmissions were antineoplastic chemotherapy (2038/177,747; 1.1%), age-related cataract (1061/21,255; 5.0%), and unspecified disorder of refraction (544/5,134; 10.6%). There were statistically significant differences between planned and unplanned readmissions in terms of patient sex, marital status, age, length of initial stay, the time between discharge, ICU stay, surgery, and health insurance., Conclusion: Accurate information on 30-day planned and unplanned readmissions facilitates effective planning of healthcare resource allocation. Identifying risk factors for 30-day unplanned readmissions can help develop interventions to reduce readmission rates., (© 2023. The Author(s).)

Background and Objective: The new non-invasive arterial stiffness indices, arterial pressure volume index (API) is explored as a novel marker of residual stress in the wall of the peripheral muscular arteries at zero-stress state in clinical settings. The present study aimed to study the association of API with cardiovascular disease (CVD) risk in China (China-PAR)., Methods: According to China-PAR score, participants were divided into three groups: low risk (< 5%), medium risk (5-9.9%), and high risk (≥ 10.0%). API ≥ 31 was defined as high API, and the incidences of high API were compared. Logistic regression models were used to analyze the risk factors of high API and high risk China-PAR categories. The association between China-PAR and API was analyzed by restrictive cubic spline., Results: The study included 4311 participants. After adjustments for confounding factors, high API was independent factor associated with high risk China-PAR categories, and the probability of high API was 1.366 times higher than that in normal API subjects. While, the independent factors associated with high API were BMI, blood pressure and heart rate. Furthermore, API had a significant U-shaped association with China-PAR. CVD risk was lowest with API of 19 units, the fastest increase at 26 units and the flattest starting point at 59 units., Conclusion: API, an indicator of arterial stiffness and residual stress, had a U-shaped association with China-PAR score and might play an important role in predicting CVD risk in Chinese natural populations., (© 2023. The Author(s).)

Disseminated intravascular coagulation (DIC) is a complex, life-threatening syndrome associated with the end-stage of different coagulation disorders. Early prediction of the risk of DIC development is an urgent clinical need to reduce adverse outcomes. However, effective approaches and models to identify early DIC are still lacking. In this study, a novel interpretable deep learning based time series is used to predict the risk of DIC. The study cohort included ICU patients from a 4300-bed academic hospital between January 1, 2019, and January 1, 2022. Experimental results show that our model achieves excellent performance (AUC: 0.986, Accuracy: 95.7%, and F1:0.935). Gradient-weighted Class Activation Mapping (Grad-CAM) was used to explain how predictive models identified patients with DIC. The decision basis of the model was displayed in the form of a heat map. The model can be used to identify high-risk patients with DIC early, which will help in the early intervention of DIC patients and improve the treatment effect., (© 2022. The Author(s).)

Herein, we designed a dual-response shape transformation and charge reversal strategy with chemo-photodynamic therapy to improve the blood circulation time, tumor penetration and retention, which finally enhanced the anti-tumor effect. In the system, hydrophobic photosensitizer chlorin e6 (Ce6), hydrophilic chemotherapeutic drug berberrubine (BBR) and matrix metalloproteinase-2 (MMP-2) response peptide (PLGVRKLVFF) were coupled by linkers to form a linear triblock molecule BBR-PLGVRKLVFF-Ce6 (BPC), which can self-assemble into nanoparticles. Then, positively charged BPC and polyethylene glycol-histidine (PEG-His) were mixed to form PEG-His@BPC with negative surface charge and long blood circulation time. Due to the acidic tumor microenvironment, the PEG shell was detached from PEG-His@BPC attributing to protonation of the histidine, which achieved charge reversal, size reduction and enhanced tumor penetration. At the same time, enzyme cutting site was exposed, and the spherical nanoparticles could transform into nanofibers following the enzymolysis by MMP-2, while BBR was released to kill tumors by inducing apoptosis. Compared with original nanoparticles, the nanofibers with photosensitizer Ce6 retained within tumor site for a longer time. Collectively, we provided a good example to fully use the intrinsic properties of different drugs and linkers to construct tumor microenvironment-responsive charge reversal and shape transformable nanoparticles with synergistic antitumor effect., Competing Interests: The authors declare no conflicts of interest., (© 2022 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.)

Background: Prompt diagnosis of early gastric cancer (EGC) is crucial for improving patient survival. However, most previous computer-aided-diagnosis (CAD) systems did not concretize or explain diagnostic theories. We aimed to develop a logical anthropomorphic artificial intelligence (AI) diagnostic system named ENDOANGEL-LA (logical anthropomorphic) for EGCs under magnifying image enhanced endoscopy (M-IEE)., Methods: We retrospectively collected data for 692 patients and 1897 images from Renmin Hospital of Wuhan University, Wuhan, China between Nov 15, 2016 and May 7, 2019. The images were randomly assigned to the training set and test set by patient with a ratio of about 4:1. ENDOANGEL-LA was developed based on feature extraction combining quantitative analysis, deep learning (DL), and machine learning (ML). 11 diagnostic feature indexes were integrated into seven ML models, and an optimal model was selected. The performance of ENDOANGEL-LA was evaluated and compared with endoscopists and sole DL models. The satisfaction of endoscopists on ENDOANGEL-LA and sole DL model was also compared., Findings: Random forest showed the best performance, and demarcation line and microstructures density were the most important feature indexes. The accuracy of ENDOANGEL-LA in images (88.76%) was significantly higher than that of sole DL model (82.77%, p  = 0.034) and the novices (71.63%, p <0.001), and comparable to that of the experts (88.95%). The accuracy of ENDOANGEL-LA in videos (87.00%) was significantly higher than that of the sole DL model (68.00%, p <0.001), and comparable to that of the endoscopists (89.00%). The accuracy (87.45%, p <0.001) of novices with the assistance of ENDOANGEL-LA was significantly improved. The satisfaction of endoscopists on ENDOANGEL-LA was significantly higher than that of sole DL model., Interpretation: We established a logical anthropomorphic system (ENDOANGEL-LA) that can diagnose EGC under M-IEE with diagnostic theory concretization, high accuracy, and good explainability. It has the potential to increase interactivity between endoscopists and CADs, and improve trust and acceptability of endoscopists for CADs., Funding: This work was partly supported by a grant from the Hubei Province Major Science and Technology Innovation Project (2018-916-000-008) and the Fundamental Research Funds for the Central Universities (2042021kf0084)., Competing Interests: We declare no competing interests., (© 2022 The Authors.)

Myocardial infarction (MI) is a major cause of morbidity and mortality worldwide. Modern therapeutic strategies targeting the infarct border area have been shown to benefit overall cardiac function after MI. However, there is no non-invasive diagnostic technique to precisely demarcate the MI boundary till to now. In this study, the feasibility of demarcating the MI border using dual-wavelength photoacoustic spectral analysis (DWPASA) was investigated. To quantify specific molecular characteristics before and after MI, "the ratio of the areas of the power spectral densities ( R APSD )" was computed from the DWPASA results. Compared to the normal tissue, MI tissue was shown to contain more collagen, resulting in higher R APSD values ( p  < 0.001). Cross-sectional MI lengths and the MI area border demarcated in two dimensions by DWPASA were in substantial agreement with Masson staining (ICC = 0.76, p  < 0.001, IoU = 0.72). R APSD has been proved that can be used as an indicator of disease evolution to distinguish normal and pathological tissues. These findings indicate that the DWPASA method may offer a new diagnostic solution for determining MI borders., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Pathology is currently the gold standard for grading prostate cancer (PCa). However, pathology takes considerable time to provide a final result and is significantly dependent on subjective judgment. In this study, wavelet transform-based photoacoustic power spectrum analysis (WT-PASA) was used for grading PCa with different Gleason scores (GSs). The tumor region was accurately identified via wavelet transform time-frequency analysis. Then, a linear fitting was conducted on the photoacoustic power spectrum curve of the tumor region to obtain the quantified spectral parameter slope . The results showed that high GSs have small glandular cavity structures and higher heterogeneity, and consequently, the slopes at both 1210 nm and 1310 nm were high ( p  < 0.01). The classification accuracy of the PA time frequency spectrum (PA-TFS) of tumor region using ResNet-18 was 89% at 1210 nm and 92.7% at 1310 nm. Further, the testing time was less than 7 mins. The results demonstrated that identification of PCa can be rapidly and objectively realized using WT-PASA., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Authors.)

Gastric cancer (GC) is one of the leading causes of cancer-related death worldwide. MicroRNAs (miRNAs) are known to be important regulators of GC. This study aims to investigate the role of miRNA (miR)-497 in GC. We demonstrated that the expression of miR-497 was downregulated in human GC tissues. After N-methyl-N-nitrosourea treatment, the incidence of GC in miR-497 knockout mice was significantly higher than that in wild-type mice. miR-497 overexpression suppressed GC cell proliferation, cell-cycle progression, colony formation, anti-apoptosis ability, and cell migration and invasion capacity. Additionally, miR-497 overexpression decreased the expression levels of cell division cycle 42 (CDC42) and integrin β1 (ITGB1) and inhibited the phosphorylation of focal adhesion kinase (FAK), paxillin (PXN), and serine-threonine protein kinase (AKT). Furthermore, overexpression of miR-497 inhibited the metastasis of GC cells in vivo , which could be counteracted by CDC42 restoration. Furthermore, the focal adhesion of GC cells was found to be regulated by miR-497/CDC42 axis via ITGB1/FAK/PXN/AKT signaling. Collectively, it is concluded that miR-497 plays an important role in the repression of GC tumorigenesis and progression, partly via the CDC42/ITGB1/FAK/PXN/AKT pathway., Competing Interests: The authors declare no competing interests., (© 2021 The Authors.)

The tubular structures and dendritic distributions of blood vessels emit anisotropic photoacoustic (PA) signals with different intensities and frequency components at different angles. Therefore, spectral analysis of PA signals from a single angle cannot accurately determine the physical characteristics of microvessels. This study investigated the feasibility of using the PA power azimuth spectrum (PA-PAS) method to evaluate microvessel structures. We mapped the acoustic power spectrum of the PA signals along the azimuth direction. Based on a frequency-domain analysis of the broadband PA signal, we calculated the spectral parameter power-weighted mean frequency (PWMF). The results demonstrate that the PA signal information of the microvessel is mainly concentrated in the direction of its width. In addition, the PWMF decreases linearly with the microvascular size. The experimental findings exhibit good agreement with the simulation results, thus demonstrating that this approach can effectively differentiate the sizes of microvessels., Competing Interests: The authors declare that there are no conflicts of interest., (© 2021 The Author(s).)

In this study, we investigated the feasibility of using photoacoustic time-frequency spectral analysis (PA-TFSA) for evaluating the bone mineral density (BMD) and bone structure. Simulations and ex vivo experiments on bone samples with different BMDs and mean trabecular thickness (MTT) were conducted. All photoacoustic signals were processed using the wavelet transform-based PA-TFSA. The power-weighted mean frequency (PWMF) was evaluated to obtain the main frequency component at different times. The y-intercept , midband-fit , and slope of the linearly fitted curve of the PWMF over time were also quantified. The results show that the osteoporotic bone samples with lower BMD and thinner MTT have higher frequency components and lower acoustic frequency attenuation over time, thus higher y-intercept , midband-fit , and slope . The midband-fit and slope were found to be sensitive to the BMD; therefore, both parameters could be used to distinguish between osteoporotic and normal bones ( p < 0.05)., Competing Interests: The authors report no declarations of interest., (© 2021 The Author(s).)

The CaO-MgO-SiO 2 -based bioactive glass-ceramic coating (named M2) on Ti-6Al-4V alloy has been proven to behave well in vitro . But how to make full sense of its performances in terms of osteogenesis and osseointegration in vivo matters very much. For this, the M2-coated Ti-6Al-4V cylinders were prepared by atmospheric plasma spraying (APS) and implanted into New Zealand rabbit for 1, 2 and 3 months, respectively, by setting commercial HA-coated Ti-6Al-4V as the control. It is encouraging that, the two groups bonded with the surrounding tissues stably and newly formed bone grew towards or around the implants after 3-month implantation according to radiographic images. From the histological sections, it is obvious that, compared to the control, the M2-coated implant was more favorable for the osteogenesis and neo- vascularisation in the whole experimental process and demonstrated a better osseointegration with the host bone, indicating the former possessed better osteoconductivity, osteoinductivity and osteogenic ability. The study indicated that the M2-coated Ti-6Al-4V implant exerted a great potential to substitute the commercial HA-coated Ti-6Al-4V implant in repairing load-bearing bone defects., (© 2019 Published by Elsevier Ltd.)

In this paper, we reported the in situ fabrication of highly luminescent formamidinium lead bromide (FAPbBr 3 ) nanocrystal thin films by dropping toluene as an anti-solvent during the spin-coating with a perovskite precursor solution using 3,3-diphenylpropylamine bromide (DPPA-Br) as a ligand. The resulting films are uniform and composed of 5-20 nm FAPbBr 3 perovskite nanocrystals. By monitoring the solvent mixing of anti-solvent and precursor solution on the substrates, we illustrated the difference between the ligand-assisted reprecipitation (LARP) process and the nanocrystal-pinning (NCP) process. This understanding provides a guideline for film optimization, and the optimized films obtained through the in situ LARP process exhibit strong photoluminescence emission at 528 nm, with quantum yields up to 78% and an average photoluminescence lifetime of 12.7 ns. In addition, an exciton binding energy of 57.5 meV was derived from the temperature-dependent photoluminescence measurement. More importantly, we achieved highly efficient pure green perovskite based light-emitting diode (PeLEDs) devices with an average external quantum efficiency (EQE) of 7.3% (maximum EQE is 16.3%) and an average current efficiency (CE) of 29.5 cd A -1 (maximum CE is 66.3 cd A -1 ) by adapting a conventional device structure of ITO/PEDOT:PSS/TFB/perovskite film/TPBi/LiF/Al. It is expected that the in situ LARP process provides an effective methodology for the improvement of the performance of PeLEDs.

In the present study, the dissolution behavior of the CaO-MgO-SiO 2 -based multiphase bioceramic powders as well as the effects of released ions on osteogenesis was investigated. In the dissolution process, Ca, Mg, and Si ions could be dissolved out from the powders. The incorporation of Mg could slow down the degradation rate of the powders so that to reduce the local concentration of Ca and Si ions. In return, the dissolution of Ca and Si ions leading to the formation of a porous SiO 2 -rich layer could enhance the readsorption of free Mg ions in solution and thus down-regulate the concentration of Mg ions. In addition, the released ions exhibited both positive and negative synergistic effects on osteogenesis with a concentration-dependent manner. Trace amount of released Si ions could stimulate cell proliferation and osteogenic differentiation in the presence of Ca and Mg ions. The optimal concentration of Ca-Mg-Si ion combination to promote osteogenesis was existed in the 1/4 diluted extract, whereas a slightly inhibitory effect on cell proliferation and ALP activity was observed in the 1/2 diluted extract with higher concentration of Ca and Si ions . All above results suggested that the ion dissolution behavior of the CaO-MgO-SiO 2 -based multiphase bioceramic could be regulated via adjustment of the composition so that released ions could be maintained at an appropriate composite concentration to cooperatively regulate the osteogenesis. This research provided an experimental basis for further optimization and application of CaO-MgO-SiO 2 -based multiphase bioceramics with controlled ion dissolution and excellent physicochemical and biological properties. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 3159-3168, 2017., (© 2017 Wiley Periodicals, Inc.)