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Uncoupling protein 1 (UCP1) is located at the inner membrane of mitochondria and mediates nonshivering thermogenesis. Its abnormal expression is associated with metabolic diseases, cancer, and acute kidney injury. Myeloid-derived suppressor cells (MDSCs) with immunosuppressive activity accumulate in the tumor microenvironment (TME). Here, decreased UCP1 expression in MDSCs was observed in the peripheral blood of patients with colorectal cancer and transplanted mouse tumors. Aggravated tumor progression was observed in UCP1-knockout mice and conditional knockout mice (UCP1 fl/fl -S100A8 cre ). The number of G-MDSCs and M-MDSCs increased in the transplanted tumor tissues from UCP1-deficient mice compared with those from wild-type mice. The tumor-promoting effect disappeared when the tumor-bearing mice were depleted of MDSCs by the α-DR5 administration. Adoptive transfer of tumor-derived MDSCs sharply promoted the tumor growth in vivo. Furthermore, these tumor-derived MDSCs enhanced the proliferation, reduced death, inhibited IFN-γ production of CD4 + and CD8 + T cells, and induced Treg cells ex vivo. In conclusion, MDSCs in the TME alter the metabolic pattern by decreasing UCP1 expression to enhance immunosuppressive activity for tumor escape., Competing Interests: Declaration of Competing interest The authors declare no potential conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: To investigate the potential regulatory role of gene insertion or deletion (in/del) polymorphism in the occurrence of acute T cell-mediated rejection (aTCMR) after kidney transplantation., Methods: We retrospectively analyzed the 5-year follow-up data of 133 recipients who underwent renal transplantation at the First Affiliated Hospital of Nanjing Medical University between February 1, 2010, and December 1, 2015. With target sequencing based on next-generation sequencing (NGS), tagger in/dels selection involved calculating the Hardy-Weinberg equilibrium (HWE), Minor Allele Frequency (MAF), and the linkage disequilibrium (LD) blocks. Significant in/dels associated with aTCMR were identified by intersecting the results obtained through analysis of covariance (ANCOVA) of clinical cofounders and model analysis in Rstudio using the "SNPassoc" package. Additionally, logistic models were employed to assess the associations between genotypes and the aTCMR occurrence in 5 years after surgery., Results: NFATc1 rs55741427 insertion was identified to be significantly associated with the post-surgery aTCMR(OR = 2.66, P < 0.001). We constructed a conclusive model containing the occurrence of delayed graft function (DGF) and the insertion polymorphism of rs55741427, showing a favorable predictive ability (AUC = 0.766) for aTCMR after surgery. Based on the receiver operating characteristic (ROC) curve, all cases were stratified into aTCMR high-risk and low-risk groups. Kaplan-Meier curves for two groups revealed that the aTCMR high-risk group exhibited a more unfavorable graft survival outcome (P = 0.0048)., Conclusion: Insertion mutation of rs55741427 was found to be statistically correlated with the post-surgery aTCMR during 5 years of follow-up. Our model identified DGF and insertion of rs55741427 as two crucial aTCMR-related hazards, and aTCMR high-risk group showed a worse graft prognosis., Competing Interests: Declaration of competing interest There are no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Our previous study first reported the efficacy of FURL using 365 μm fibers with holmium: yttrium aluminum garnet (Ho: YAG) laser lithotripsy. This study evaluates the 16-week safety of this procedure. A prospective cohort study was conducted, and the clinical characteristics of patients who underwent FURL using 365 μm fibers with Ho: YAG laser were retrospectively collected. Descriptive statistics were reported, and logistic regression analysis was conducted to identify risk factors influencing the stone-free rate (SFR). Infection-related laboratory parameters, including white blood cell count (WBC), procalcitonin (PCT), and C-reactive protein (CRP), were collected. Regression analysis was conducted to identify risk factors for the development of urosepsis post-surgery. Additionally, a 16-week follow-up was conducted in outpatient clinics, and kidney function was assessed. A total of 274 patients participated in this study. The 4-week stone-free rate (SFR) following FURL with 365 μm fibers of Ho: YAG laser was significantly associated with stone size and composition. No severe complications were observed following FURL procedures. There were no significant differences in white blood cell count (WBC), C-reactive protein (CRP), and procalcitonin (PCT) in peripheral blood before and after FURL procedures. Urosepsis was diagnosed in 1.82% of patients. Preoperative white blood cell count (WBC) in urine and preoperative urine culture results were identified as significant risk factors. Kidney function remained stable at 4 and 16 weeks following FURL. This prospective cohort study demonstrated the high safety of FURL with 365 μm fibers of Ho: YAG laser, as infection-related parameters during the perioperative period showed no significant differences, and kidney function remained stable throughout the 16-week follow-up., (© 2024. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

The stability of perovskite solar cells is closely related to the defects in perovskite crystals, and a large number of crystal defects are caused by the solution method. In this study, resveratrol (RES), a green natural antioxidant abundant in knotweed and grape leaves, is introduced into perovskite films to passivate the defect. RES achieves defect passivation by interacting with uncoordinated Pb 2+ in perovskite films. The defect formation energy of V Pb and Pb I on the surface of perovskite thin films is increased by RES doping, as calculated by density functional theory. The results show that the quality of the perovskite film is significantly improved, and the energy level structure of the device is optimized, and the power conversion efficiency (PCE) of the device is increased from 21.62% to 23.44%. RES can hinder the degradation of perovskite structures by O 2 - free radicals, and the device retained 88% of its initial PCE after over 1000 h in pure oxygen environment. The device retains 91% of the initial PCE after >1000 h at 25 °C and 50 ± 5% relative humidity. This work provides an idea for the use of natural and environmentally friendly additives to improve the efficiency and stability of devices., (© 2024 Wiley‐VCH GmbH.)

Background: Left bundle branch area pacing includes left bundle branch pacing (LBBP) and left ventricular septal pacing (LVSP), which is effective in patients with dyssynchronous heart failure (DHF). However, the basic mechanisms are unknown., Objectives: This study aimed to compare LBBP with LVSP and explore potential mechanisms underlying the better clinical outcomes of LBBP., Methods: A total of 24 beagles were assigned to the following groups: 1) control group; 2) DHF group, left bundle branch ablation followed by 6 weeks of AOO pacing at 200 ppm; 3) LBBP group, DHF for 3 weeks followed by 3 weeks of DOO pacing at 200 ppm; and 4) LVSP with the same interventions in the LBBP group. Metrics of electrocardiogram, echocardiography, hemodynamics, and expression of left ventricular proteins were evaluated., Results: Compared with LVSP, LBBP had better peak strain dispersion (44.67 ± 1.75 ms vs 55.50 ± 4.85 ms; P < 0.001) and hemodynamic effect (dP/dtmax improvement: 27.16% ± 7.79% vs 11.37% ± 4.73%; P < 0.001), whereas no significant differences in cardiac function were shown. The altered expressions of proteins in the lateral wall vs septum in the DHF group were partially reversed by LBBP and LVSP, which was associated with the contraction and adhesion process, separately., Conclusions: The animal study demonstrated that LBBP offered better mechanical synchrony and improved hemodynamics than LVSP, which might be explained by the reversed expression of contraction proteins. These results supported the potential superiority of left bundle branch area pacing with the capture of the conduction system in DHF model., Competing Interests: Funding Support and Author Disclosures This work was financially supported by the National Natural Science Foundation of China (No. 82100325, 82000325, 82070349), the Beijing Gold-bridge project (No. ZZ21055), Young Elite Scientists Sponsorship Program by Beijing Association for Science and Technology (No. BYESS2023392), the Peking University First Hospital Seed Foundation (No. 2020SF19), and the National High Level Hospital Clinical Research Funding (No. 2022-GSP-GG-11, 2023-GSP-GG-22, 2023-GSP-QN-40). The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate the anticaries effects of graphene oxide (GO) and graphene quantum dots (GQDs) combined with casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) on enamel in a biofilm-challenged environment., Material and Methods: GO and GQDs were synthesised using citric acid. The antibiofilm and biofilm inhibition effects for Streptococcus mutans were evaluated by scanning electron microscopy (SEM), confocal laser scanning microscopy (CLSM), and colony-forming units (CFU). Remineralisation ability was determined by assessing mineral loss, calcium-to-phosphorus ratio, and surface morphology. To create a biofilm-challenged environment, enamel blocks were immersed in S. mutans to create the lesion and then subjected to artificial saliva/biofilm cycling for 7 days. Anticaries effects of GO, GQDs, GQDs@CPP-ACP, GO@CPP-ACP, and CPP-ACP were determined by broth pH and mineral changes after 7-day pH cycling. Biocompatibility was tested using a Cell Counting Kit-8 (CCK8) assay for human gingival fibroblasts (HGF-1)., Results: GQDs and GO presented significant antibiofilm and biofilm inhibition effects compared to the CPP-ACP and control groups (P < 0.05). The enamel covered by GQDs and GO showed better crystal structure formation and less mineral loss (P < 0.05) than that covered by CPP-ACP alone. After 7 days in the biofilm-challenged environment, the GO@CPP-ACP group showed less lesion depth than the CPP-ACP and control groups (P < 0.05). GO and GQDs showed good biocompatibility compared to the control group by CCK8 (P > 0.05) within 3 days., Conclusion: GO and GQDs could improve the anti-caries effects of CPP-ACP, and CPP-ACP agents with GO or GQDs could be a potential option for enamel lesion management., Clinical Significance: GO and GQDs have demonstrated the potential to significantly enhance the anticaries effects of CPP-ACP. Incorporating these nanomaterials into CPP-ACP formulations could provide innovative and effective options for the management of enamel lesions, offering improved preventive and therapeutic strategies in dental care., Competing Interests: Declaration of competing interest All authors declared that they have no conflicts of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Allergic rhinitis (AR) is a chronic inflammatory disease of the nasal mucosa mediated by immunoglobulin E (IgE) after exposure to allergens. The bothersome symptoms of AR, such as runny nose and nasal congestion, affect millions of people worldwide. Ipratropium Bromide (IB), commonly used in clinical practice for treating AR, requires frequent administration through nasal spray and may cause significant irritation to the nasal mucosa. The induction of ROS is closely related to the initiation and symptoms of AR, and ROS will continue to accumulate during the onset of AR. To address these challenges, we have designed a drug delivery system that can be administered in liquid form and rapidly crosslink into a ROS-responsive gel in the nasal cavity. This system enables sustained ROS responsive release of IB in a high-concentration ROS environment at AR lesions, thereby alleviating AR symptoms. The gel demonstrated prolonged release of IB for up to 24 hours in rats. In the treatment of AR rat models, it improved their symptoms, reduced the expression of various inflammatory factors, suppressed MUC5AC protein expression, and decreased mucus secretion through a ROS responsive IB release pattern. Overall, this system holds promise as a better option for AR treatment and may inspire the design of nanogel-based nasal drug delivery systems., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Nowadays, orthodontics has become an important part of modern personal life to assist one in improving mastication and raising self-esteem. However, the quality of orthodontic treatment still heavily relies on the empirical evaluation of experienced doctors, which lacks quantitative assessment and requires patients to visit clinics frequently for in-person examination. To resolve the aforementioned problem, we propose a novel and practical mobile device-based framework for precisely measuring tooth movement in treatment, so as to simplify and strengthen the traditional tooth monitoring process. To this end, we formulate the tooth movement monitoring task as a multi-view multi-object pose estimation problem via different views that capture multiple texture-less and severely occluded objects (i.e. teeth). Specifically, we exploit a pre-scanned 3D tooth model and a sparse set of multi-view tooth images as inputs for our proposed tooth monitoring framework. After extracting tooth contours and localizing the initial camera pose of each view from the initial configuration, we propose a joint pose estimation scheme to precisely estimate the 3D pose of each individual tooth, so as to infer their relative offsets during treatment. Furthermore, we introduce the metric of Relative Pose Bias to evaluate the individual tooth pose accuracy in a small scale. We demonstrate that our approach is capable of reaching high accuracy and efficiency as practical orthodontic treatment monitoring requires.

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a prevalent inflammatory disorder affecting the upper respiratory tract. Recent studies have indicated an association between CRSwNP and mitochondrial metabolic disorder characterized by impaired metabolic pathways; however, the precise mechanisms remain unclear. This study aims to investigate the mitochondrial-related signature in individuals diagnosed with CRSwNP., Methods: Through the integration of differentially expressed genes (DEGs) with the mitochondrial gene set, differentially expressed mitochondrial-related genes (DEMRGs) were identified. Subsequently, the hub DEMRGs were selected using 4 integrated machine learning algorithms. Immune and mitochondrial characteristics were estimated based on CIBERSORT and ssGSEA algorithms. Bioinformatic findings were confirmed through RT-qPCR, immunohistochemistry, and ELISA for nasal tissues, as well as Western blotting analysis for human nasal epithelial cells (hNECs). The relationship between hub DEMRGs and disease severity was assessed using Spearman correlation analysis., Results: A total of 24 DEMRGs were screened, most of which exhibited lower expression levels in CRSwNP samples. Five hub DEMRGs ( ALDH1L1 , BCKDHB , CBR3 , HMGCS2 , and OXR1 ) were consistently downregulated in both the discovery and validation cohorts. The hub genes showed a high diagnostic performance and were positively correlated with the infiltration of M2 macrophages and resting mast cells. Experimental results confirmed that the 5 genes were downregulated at both the mRNA and protein levels within nasal polyp tissues. Finally, a significant and inverse relationship was identified between the expression levels of these genes and both the Lund-Mackay and Lund-Kennedy scores., Conclusion: Our findings systematically unraveled 5 hub markers correlated with mitochondrial metabolism and immune cell infiltration in CRSwNP, suggesting their potential to be based to design diagnostic and therapeutic strategies for the disease., Competing Interests: The authors declare that they conducted the research without any potential conflict of interest arising from commercial or financial relationships., (© 2024 The Authors.)

Objectives: To evaluate long-term renal graft prognosis and the role of rapamycin from a single-center in China over a 30-year follow-up., Methods: This study enrolled a total of 654 patients who underwent kidney transplantation between 1989 and 2020. The basic characteristics of the included patients were collected. Graft survival was described and compared using Kaplan-Meier curves (K-M curves). Both continuous and categorical variables were included in a multivariate Cox proportional-hazards model. Patients were divided into rapamycin-based quadruple immunosuppression regimen group (rapa group, n = 41) and conventional tacrolimus-based triple immunosuppression regimen group (control group, n = 218). The indication biopsy results of the two groups were further reviewed to compare the incidence of rejection, acute rejection, and banff score., Results: The overall 5, 10, 15, 20-year graft survival rate of our center is 87.5%, 62.4%, 46.4% and 20.9%, respectively. The median survival time after surgery is 14 years. Multiple Cox regression analysis identified BMI (p = 0.035), dialysis type (p < 0.001), immunosuppressants (p < 0.01), urine albumen (p < 0.001), globulin (p = 0.041), and blood glucose (p = 0.002) as risk factors. The 20-year, 10-year and 5-year AUC is 0.78, 0.75 and 0.75. The combination of FK506 and rapamycin was further suggested by the model to effectively improve the graft prognosis (p < 0.01, HR = 0.763). The K-M curve showed that the long-term survival rate of renal grafts in the rapa group was significantly better than that in the conventional group (p < 0.001). In addition, indication biopsy records revealed a lower possibility of immune rejection in the rapa group than that in the conventional group (p < 0.001). Banff score indicated that rapa group had less vascular inflammation in the transplanted kidney., Conclusions: In this study, a 30-year follow-up was performed in a single center, and a total graft 20-year survival rate of 20.9% was reported. The prognostic model and subgroup analysis suggested that FK506 combined with rapamycin could effectively improve the prognosis of renal transplantation, which could be explained by reduced acute rejection and less vascular inflammation., (© 2024. The Author(s).)

Energy-intensive technologies and high-precision research require energy-efficient techniques and materials. Lens-based optical microscopy technology is useful for low-energy applications in the life sciences and other fields of technology, but standard techniques cannot achieve applications at the nanoscale because of light diffraction. Far-field super-resolution techniques have broken beyond the light diffraction limit, enabling 3D applications down to the molecular scale and striving to reduce energy use. Typically targeted super-resolution techniques have achieved high resolution, but the high light intensity needed to outperform competing optical transitions in nanomaterials may result in photo-damage and high energy consumption. Great efforts have been made in the development of nanomaterials to improve the resolution and efficiency of these techniques toward low-energy super-resolution applications. Lanthanide ion-doped upconversion nanoparticles that exhibit multiple long-lived excited energy states and emit upconversion luminescence have enabled the development of targeted super-resolution techniques that need low-intensity light. The use of lanthanide ion-doped upconversion nanoparticles in these techniques for emerging low-energy super-resolution applications will have a significant impact on life sciences and other areas of technology. In this review, we describe the dynamics of lanthanide ion-doped upconversion nanoparticles for super-resolution under low-intensity light and their use in targeted super-resolution techniques. We highlight low-energy super-resolution applications of lanthanide ion-doped upconversion nanoparticles, as well as the related research directions and challenges. Our aim is to analyze targeted super-resolution techniques using lanthanide ion-doped upconversion nanoparticles, emphasizing fundamental mechanisms governing transitions in lanthanide ions to surpass the diffraction limit with low-intensity light, and exploring their implications for low-energy nanoscale applications., (© 2024. The Author(s).)

Expansion Microscopy (ExM) is a widely used super-resolution technique that enables imaging of structures beyond the diffraction limit of light. However, ExM suffers from weak labeling signals and expansion distortions, limiting its applicability. Here, we present an innovative approach called Tetrahedral DNA nanostructure Expansion Microscopy (TDN-ExM), addressing these limitations by using tetrahedral DNA nanostructures (TDNs) for fluorescence labeling. Our approach demonstrates a 3- to 10-fold signal amplification due to the multivertex nature of TDNs, allowing the modification of multiple dyes. Previous studies have confirmed minimal distortion on a large scale, and our strategy can reduce the distortion at the ultrastructural level in samples because it does not rely on anchoring agents and is not affected by digestion. This results in a brighter fluorescence, better uniformity, and compatibility with different labeling strategies and optical super-resolution technologies. We validated the utility of TDN-ExM by imaging various biological structures with improved resolutions and signal-to-noise ratios., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Aims: Glucagon-like peptide-1 receptor agonist (GLP-1RA) may promote bone formation, but conversely, they could also weaken bones due to the reduction in mechanical load associated with weight loss. However, the clinical effects in humans have not been clearly demonstrated. This meta-analysis aimed to evaluate whether GLP-1RAs affect BMD and bone turnover markers., Material and Methods: PubMed, Embase, and Scopus were searched on June 13, 2024. The eligibility criteria were: (1) human studies, (2) receiving a GLP-1RA for more than 4 weeks, (3) an untreated control group or a placebo group, (4) reporting of at least one BMD or bone turnover marker, and (5) an RCT design. The risk of bias was assessed using the Cochrane risk of bias 2 tool. Fixed- or random-effects meta-analysis was performed according to heterogeneity., Results: Seven studies were included in the meta-analysis. GLP-1RAs did not significantly change BMD in the femoral neck (mean difference [MD], 0.01 g/cm 2 ; 95% CI, -0.01-0.04 g/cm 2 ), in the total hip (MD, -0.01 g/cm 2 ; 95% CI, -0.02-0.01 g/cm 2 ), and in the lumbar spine (MD, 0 g/cm 2 ; 95% CI, -0.02-0.02 g/cm 2 ). C-terminal telopeptide of type 1 collagen (CTX), a bone resorption marker, significantly increased after GLP-1RA treatment (MD, 0.04 μg/L; 95% CI, 0.01-0.07 μg/L). GLP-1RAs did not significantly change bone formation markers such as procollagen type 1 N-terminal propeptide, bone-specific alkaline phosphatase, osteocalcin., Conclusions: GLP-1RA did not affect BMD and bone formation markers. However, GLP-1RAs led to a significant increase in CTX., (© 2024 The Author(s). Diabetes/Metabolism Research and Reviews published by John Wiley & Sons Ltd.)

Advanced glycation end products (AGEs) are formed by the Maillard reaction, a nonenzymatic process that occurs widely in cooking, food processing, and within the human body. Primarily, AGEs are formed by the glycation of reducing sugars with amino groups, and this process is heat-dependent. With changes in lifestyle, there has been an increase in the diversity of dietary habits, including those patterns associated with Western diets, which include the consumption of processed foods that are rich in AGEs. Excessive intake and exposure to AGEs are known to cause abnormalities in body function such as obesity, diabetes, and fatty liver, and the beneficial effects of AGEs in food processing in improving food flavor and quality. To obtain meaningful data regarding AGEs in a variety of food and human samples, it is necessary to more precisely characterize and analyze the AGEs extracted from samples to obtain accurate results. This review explores the recent analytical research and characterization of AGEs in foods, including casein, β-lactoglobulin, soy protein, and meat protein, and in human samples, such as glycated-albumin, hemoglobin, and plasma. Additionally, it explores the metabolic fate of AGEs in the body and the mechanisms of disease associated with metabolic abnormalities that may be caused by the consumption of foods containing AGEs. This review aims to provide an overview of the perspectives of relevant recent and future research on metabolic abnormalities caused by foods containing AGEs or by AGEs produced in the body., (© 2024 The Author(s). Comprehensive Reviews in Food Science and Food Safety published by Wiley Periodicals LLC on behalf of Institute of Food Technologists.)

Vaccination is crucial for the prevention and mitigation of avian influenza infections in China. The inactivated H7N9 vaccine, when administered to poultry, significantly lowers the risk of infection among both poultry and humans, while also markedly decreasing the prevalence of H7N9 detections. Highly pathogenic (HP) H7N9 viruses occasionally appear, whereas their low pathogenicity (LP) counterparts have been scarcely detected since 2018. However, these contributing factors remain poorly understood. We conducted an exploratory investigation of the mechanics via the application of comprehensive bioinformatic approaches. We delineated the Yangtze River Delta (YRD) H7N9 lineage into 5 clades (YRD-A to E). Our findings highlight the emergence and peak occurrence of the LP H7N9-containing YRD-E clade during the 5th epidemic wave in China's primary poultry farming areas. A more effective control of LP H7N9 through vaccination was observed compared to that of its HP H7N9 counterpart. YRD-E exhibited a tardy evolutionary trajectory, denoted by the conservation of its genetic and antigenic variation. Our analysis of YRD-E revealed only minimal amino acid substitutions along its phylogenetic tree and a few selective sweep mutations since 2016. In terms of epidemic fitness, the YRD-E was measured to be lower than that of the HP variants. Collectively, these findings underscore the conserved evolutionary patterns distinguishing the YRD-E. Given the conservation presented in its evolutionary patterns, the YRD-E LP H7N9 is hypothesized to be associated with a reduction following the mass vaccination in a relatively short period owing to its lower probability of antigenic variation that might affect vaccine efficiency.

Background: The assessment of left ventricular (LV) remodeling and its association with mineral and bone disorder (MBD) in kidney transplant recipients (KTRs) have not been systematically studied. We aimed to evaluate LV remodeling changes one year after kidney transplantation (KT) and identify their influencing factors., Methods: Ninety-five KTRs (68 males; ages 40.2 ± 10.8 years) were followed before and one year after KT. Traditional risk factors and bone metabolism indicators were assessed. Left ventricular mass index (LVMI), left ventricular ejection fraction (LVEF) and left ventricular diastolic dysfunction (LVDD) were measured using two-dimensional transthoracic echocardiography. The relationship between MBD and LV remodeling and the factors influencing LV remodeling were analyzed., Results: One year after KT, MBD was partially improved, mainly characterized by hypercalcemia, hypophosphatemia, hyperparathyroidism, 25-(OH) vitamin D deficiency, elevated bone turnover markers, and bone loss. LVMI, the prevalence of left ventricular hypertrophy (LVH), and the prevalence of LVDD decreased, while LVEF increased. LVH was positively associated with postoperative intact parathyroid hormone (iPTH) and iPTH nonnormalization. △LVMI was positively associated with preoperative type-I collagen N-terminal peptide and postoperative iPTH. LVEF was negatively associated with postoperative phosphorous. △LVEF was negatively associated with postoperative iPTH. LVDD was positively associated with postoperative lumbar spine osteoporosis. Preoperative LVMI was negatively associated with △LVMI and positively associated with △LVEF. Advanced age, increased BMI, diabetes, longer dialysis time, lower albumin level, and higher total cholesterol and low-density lipoprotein levels were associated with LV remodeling., Conclusions: LV remodeling partially improved after KT, showing a close relationship with MBD.

Purpose: To explore the characteristics of the pathogen distribution and drug resistance in bloodstream infections (BSIs) during the COVID-19 pandemic in a tertiary hospital in eastern China, and to compare them with those before the pandemic., Patients and Methods: Non-repetitive strain data of BSIs were retrospectively obtained before the COVID-19 pandemic (Pre-Pandemic, n=2698) and during the COVID-19 pandemic (Pandemic, n=2922), the distribution of pathogens and drug resistance were compared between the two groups., Results: The main pathogens of BSIs were Gram-negative bacteria (57.91%), followed by Gram-positive bacteria (32.58%), fungi and anaerobic bacteria accounting for 5.48% and 3.39%, respectively. Escherichia coli, Klebsiella pneumoniae and Staphylococcus aureus were the top 3 isolates. The proportion of Serratia marcescens, Enterobacter aerogenes, Enterococcus faecium, Enterococcus faecalis and Candida tropicalis were significantly increased, while those of Pseudomonas aeruginosa, Streptococcus sanguinis and Streptococcus pneumoniae were significantly decreased when compared to the Pre-Pandemic ( P <0.05). Carbapenem-resistant Enterobacterales (CRE) significantly elevated during the Pandemic (17.4% vs 14.4%, P =0.041); the detection of carbapenem-resistant Pseudomonas aeruginosa (CRPA) significantly ascended (39.0% vs 24.4%, P =0.016); and the proportion of carbapenem-resistant Acinetobacter baumannii (CRAB) maintained stable (78.8%). Gram-positive bacteria had the lowest resistance to linezolid, vancomycin and tigecycline, which remained a stable trend with the Pre-Pandemic (<5.0%). The isolate rates of methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) were 38.9% and 1.0%, respectively. Staphylococcus aureus showed a decrease in the isolation rate of vancomycin minimum inhibitory concentration (MIC) ≤ 0.5 μg/mL ( χ2 =7.676, P =0.006) and an increase with vancomycin MIC=1 μg/mL ( χ2 =9.008, P =0.003)., Conclusion: The pathogen distribution and drug resistance of BSIs during the COVID-19 pandemic were transformed from Pre-Pandemic and accompanied by increasing bacterial resistance. Clinical management of antibiotic application and infection control should be strengthened., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Gu et al.)

Intestinal barrier is a first line of defense that prevents entry of various harmful substances from the lumen into the systemic environment. Impaired barrier function with consequent translocation of harmful substances into systemic circulation ("leaky gut") is a central theme in many gastrointestinal, autoimmune, mental, and metabolic diseases. Probiotics have emerged as a promising strategy to maintain intestinal integrity and address "leaky gut". Using in silico, in vitro and avian in vivo analyses, we previously showed that two novel L. reuteri strains, PTA-126787 (L. reuteri 3630) and PTA-126788 (L. reuteri 3632), isolated from broiler chickens possess favorable safety profiles. Consistent with a recent study, here we show that L. reuteri 3630 and 3632 are phylogenetically similar to human L. reuteri strains. Daily administration of high doses of L. reuteri 3630 and 3632 to Sprague Dawley rats for 28 days was found to be safe with no adverse effects. More importantly, administration of L. reuteri 3630 and 3632 significantly reduced markers associated with alcohol-induced leaky gut, by downregulating inflammatory cytokines and upregulating anti-inflammatory cytokines in an alcohol model of leaky gut in mice. While L. reuteri 3630 cells and supernatant showed no activation, L. reuteri 3632 cells but not supernatant showed activation of AhR, a key transcription factor that regulates gut and immune homeostasis. L. reuteri 3630 is creamish white in morphology typical of Lactobacillus species and L. reuteri 3632 displays a unique orange pigmentation, which was stable even after passaging for 480 generations. We identified a rare polyketide biosynthetic gene cluster in L. reuteri 3632 that likely encodes for the orange-pigmented secondary metabolite. Similar to L. reuteri 3632 cells, the purified orange metabolite activated AhR. All together, these data provide evidence on the phylogenetic relatedness, safety, efficacy, and one of the likely mechanisms of action of L. reuteri 3630 and 3632 for potential probiotic applications to address "leaky gut" and associated pathologies in humans., (© 2024. The Author(s).)

The rapid development of neuromorphic computing has led to widespread investigation of artificial synapses. These synapses can perform parallel in-memory computing functions while transmitting signals, enabling low-energy and fast artificial intelligence. Robots are the most ideal endpoint for the application of artificial intelligence. In the human nervous system, there are different types of synapses for sensory input, allowing for signal preprocessing at the receiving end. Therefore, the development of anthropomorphic intelligent robots requires not only an artificial intelligence system as the brain but also the combination of multimodal artificial synapses for multisensory sensing, including visual, tactile, olfactory, auditory, and taste. This article reviews the working mechanisms of artificial synapses with different stimulation and response modalities, and presents their use in various neuromorphic tasks. We aim to provide researchers in this frontier field with a comprehensive understanding of multimodal artificial synapses., Competing Interests: Competing interests: The authors declare that they have no competing interests., (Copyright © 2024 Runze Li et al.)

Objective: This study aimed to analyse the association between lipoprotein-associated phospholipase A2 (Lp-PLA2) and 25-hydroxy-vitamin D (25[OH]D) and early diabetic kidney disease (DKD) in patients with type 2 diabetes mellitus (T2DM) and evaluate the potential roles of these two biomarkers in the clinical diagnosis of DKD., Methods: A total of 422 inpatients with T2DM were retrospectively enrolled between January 2018 and March 2022 at the First Affiliated Hospital of Nanjing Medical University. The baseline clinical parameters of each patient were determined, and their demographic characteristics were extracted from the hospital information system. The patients were separated into groups according to serum Lp-PLA2 and 25(OH)D levels and binary logistic regression analysis was used to determine independent predictors of early DKD incidence., Results: Levels of Lp-PLA2 significantly increased and those of 25(OH)D significantly decreased with DKD progression (both P  < 0.001). Lp-PLA2 concentrations were positively correlated with albuminuria levels (r = 0.37, P  < 0.001), whereas 25(OH)D levels were negatively correlation (r = -0.34, P  < 0.001). The incidence of DKD was higher in the Lp-PLA2 elevated and 25(OH)D deficient groups (all P  < 0.001). Body mass index, systemic immune-inflammatory index, serum uric acid, C-peptide, and triglyceride-glucose indices were positively associated with Lp-PLA2 levels (all P  < 0.001) and negatively associated with 25(OH)D (all P  < 0.05). Furthermore, Lp-PLA2 was an independent risk factor ( OR  = 1.003, P  = 0.015), and 25(OH)D was an independent protective factor ( OR  = 0.937, P  = 0.008) for early DKD occurrence in binary logistic regression analysis. The area under the curve for the combination of Lp-PLA2 and 25(OH)D for diagnosing DKD was 0.867, with a sensitivity of 70.4 % and a specificity of 89.5 %., Conclusions: Increased serum Lp-PLA2 and decreased 25(OH)D levels are risk factors for early DKD in patients with T2DM. The combined detection of Lp-PLA2 and 25(OH)D may enhance the diagnostic efficacy of DKD., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Modern nanofabrication technologies have propelled significant advancement of high-resolution and optically thin holograms. However, it remains a long-standing challenge to tune the complex hologram patterns at the nanoscale for temporal light field control. Here, we report femtosecond laser direct lithography of perovskites with nanoscale feature size and pixel-level temporal dynamics control for temporally programmable holograms. Specifically, under tightly focused laser irradiation, the organic molecules of layered perovskites (PEA) 2 PbI 4 can be exfoliated with nanometric thickness precision and subwavelength lateral size. This creates inorganic lead halide capping nanostructures that retard perovskite hydration, enabling tunable hydration time constant. Leveraging advanced inverse design methods, temporal holograms in which multiple independent images are multiplexed with low cross talk are demonstrated. Furthermore, cascaded holograms are constructed to form temporally holographic neural networks with programmable optical inference functionality. Our work opens up new opportunities for tunable photonic devices with broad impacts on holography display and storage, high-dimensional optical encryption and artificial intelligence., (© 2024. The Author(s).)

Cardiovascular disease (CVD) remains the leading cause of death worldwide. Patients often fail to recognize the early signs of CVDs, which display irregularities in cardiac contractility and may ultimately lead to heart failure. Therefore, continuously monitoring the abnormal changes in cardiac contractility may represent a novel approach to long-term CVD surveillance. Here, a zero-power consumption and implantable bias-free cardiac monitoring capsule (BCMC) is introduced based on the triboelectric effect for cardiac contractility monitoring in situ. The output performance of BCMC is improved over 10 times with nanoparticle self-adsorption method. This device can be implanted into the right ventricle of swine using catheter intervention to detect the change of cardiac contractility and the corresponding CVDs. The physiological signals can be wirelessly transmitted to a mobile terminal for analysis through the acquisition and transmission module. This work contributes to a new option for precise monitoring and early diagnosis of CVDs., (© 2024 Wiley‐VCH GmbH.)

Background: Iguratimod (IGU) is widely used in clinical practice due to its stable anti-inflammatory effects. Our previous studies have confirmed that the proportion of Th17/Treg balance in patients taking IGU altered significantly. This study aims to explore the role of IGU in antibody-mediated rejection (ABMR) and its potential mechanisms., Methods: We conducted bioinformatics analysis of sequencing data from the GEO database to analyze the abundance of immune cell infiltration in transplanted kidney tissues. In vivo, IGU was intervened in a mice secondary skin transplantation model and a mice kidney transplantation ABMR model, and histological morphology of the grafts were examined by pathological staining, while relevant indicators were determined through qRT-PCR, immunohistochemistry, and enzyme-linked immunosorbent assay, observed T cell differentiation by flow cytometry, and preliminarily assessed the immunosuppressive effect of IGU. In vitro, we established Th17 and Treg cell induction and stimulation differentiation culture systems and added IGU for intervention to explore its effects on their differentiation., Results: Through bioinformatics analysis, we found that Th17 and Treg may play important roles in the occurrence and development of ABMR. In vivo, we found that IGU could effectively reduce the damage caused by ABMR to the grafts, alleviate the infiltration of inflammatory cells in the graft tissues, and reduce the deposition of C4d in the grafts. Moreover, it is also found that IGU regulated the differentiation of Th17 and Treg cells in the spleen and peripheral blood and reduced the expression of IL-17A in the grafts and serum. In addition, same changes were observed in the induction and differentiation culture system of Th17 and Treg cells in vitro after the addition of IGU., Conclusion: IGU can inhibit the progression of ABMR by regulating the differentiation of Th17 and Treg cells, providing novel insights for optimizing clinical immunosuppressive treatment regimens., 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.)

This study aimed to systematically review interventions to prevent mother-to-child transmission of HIV during breastfeeding. We conducted a systematic review and meta-analysis using specific criteria to identify randomized controlled trials that focused on pregnant and breastfeeding women living with HIV and their children from birth to 2 years of age. We extensively searched electronic databases, including Web of Science, Scopus, PubMed, MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Google Scholar up to October 24, 2023. After screening 3,110 titles and abstracts, we reviewed 306 full texts. Of these, we assessed the quality and risk of bias of fifty-five articles, ultimately identifying seven studies. Four of these studies, which focused on antiretroviral therapy (ART), were included in the meta-analysis. There was little heterogeneity in study methodology and pooled estimates. The postnatal HIV transmission rate was found to be 0.01 (95%CI: 0.00 - 0.02). Therefore, the risk of mother-to-child transmission among breastfeeding mothers with HIV was significantly lower in the intervention groups than in the placebo groups. Analysis of funnel plots and Egger's test (p = 0.589) showed no evidence of publication bias. In addition to the four articles, two studies compared different ART regimens and one study compared the administration of high-dose vitamin A to the mother or the child. The results suggest that the use of ART significantly reduces the risk of postnatal HIV transmission compared with placebo. However, the effectiveness of different ART regimens or other therapies, including high-dose vitamin A, is unclear.

Multimodal deep learning plays a pivotal role in supporting the processing and learning of diverse data types within the realm of artificial intelligence generated content (AIGC). However, most photonic neuromorphic processors for deep learning can only handle a single data modality (either vision or audio) due to the lack of abundant parameter training in optical domain. Here, we propose and demonstrate a trainable diffractive optical neural network (TDONN) chip based on on-chip diffractive optics with massive tunable elements to address these constraints. The TDONN chip includes one input layer, five hidden layers, and one output layer, and only one forward propagation is required to obtain the inference results without frequent optical-electrical conversion. The customized stochastic gradient descent algorithm and the drop-out mechanism are developed for photonic neurons to realize in situ training and fast convergence in the optical domain. The TDONN chip achieves a potential throughput of 217.6 tera-operations per second (TOPS) with high computing density (447.7 TOPS/mm 2 ), high system-level energy efficiency (7.28 TOPS/W), and low optical latency (30.2 ps). The TDONN chip has successfully implemented four-class classification in different modalities (vision, audio, and touch) and achieve 85.7% accuracy on multimodal test sets. Our work opens up a new avenue for multimodal deep learning with integrated photonic processors, providing a potential solution for low-power AI large models using photonic technology., (© 2024. The Author(s).)

Uncoupling protein 1 (UCP1) catalyzes the leak of protons across the mitochondrial inner membrane for thermogenesis. Compromised NK cell activity is involved in the occurrence of nonalcoholic liver fibrosis. Here, decreased UCP1 in NK cells was identified in patients with advanced nonalcoholic fatty liver disease. Although no obvious changes were observed in the NK cells of physiologic UCP1 -/- mice (8-10 weeks old), impaired NK cell bioactivity was shown in methionine-choline-diet (MCD)-fed UCP1 -/- mice and involved in the acerbation of nonalcoholic steatohepatitis (NASH) progress to liver fibrosis. Moreover, UCP1-deficient NK cells were responsible for the aggravation of liver fibrosis, as confirmed in MCD-fed UCP1 flox/flox -NCR1 cre mice. Acerbation of liver fibrosis was also seen in wild-type mice when their endogenous NK cells were replaced with UCP1 -/- NK cells. Transcriptions of mitophagy-associated molecules in UCP1 -/- NK cells were enhanced according to RNA-seq. Electron microscopic results showed mitochondrial injuries and autophagic vesicles in MCD-fed NK WT cells, PA-treated NK WT cells, or physiologic NK KO cells. However, the co-existence of UCP1 deficiency and high lipid can synergistically induce NK cell necroptosis via DRP1 S616 accompanied with reduced mitophagy. Finally, The UCP1 in NK cells was downregulated when treated by sustained high PA (600 μM) via the PPARγ/ATF2 axis. Thus, persistent high-lipid treatment not only decreases UCP1 expression but also combines with reduced UCP1 to promote NK cell necroptosis, and it is involved in NASH progression to fibrosis., (© 2024. The Author(s).)

Non-alcoholic fatty liver disease (NAFLD) is a major issue because it is closely associated with metabolic diseases. Advanced glycation end products (AGEs) are implicated as risk factors for steatosis during NAFLD progression. AGEs influence NAFLD progression through a receptor-independent pathway involving AGE cross-link formation and a receptor-dependent pathway that binds to receptors like receptors for advanced glycation end products (RAGE). The objectives of this study are to examine the effect of Lindera obtusiloba Blume (LO) on NAFLD promoted by Nε-(carboxymethyl)lysine (CML), one of the most common dietary AGEs. The anti-glycation effects of LO were evaluated by inhibiting the AGEs formation and AGEs-collagen cross-links breaking. The efficacy of LO against NAFLD promoted by CML was assessed using both in vitro and in vivo models. NAFLD was induced in mice by feeding a high-fat diet and orally administering CML over a period of 12 weeks, and the effects of LO on lipid metabolism and its regulatory mechanisms were investigated. LO showed the effect of inhibited AGEs formation and breakage, and collagen cross-linking. Fed a high-fat diet with administered CML by gavage, LO administration resulted in a reduction in body weight, fat mass, serum triglycerides, total cholesterol, and low-density lipoprotein cholesterol levels. LO reduced hepatic CML accumulation and RAGE expression in mice fed a high-fat diet and orally administered CML. LO alleviated hepatic steatosis accompanied by lipid accumulation and histological damage by suppressing the expression of sterol regulatory element-binding protein 1c, carbohydrate response element binding protein, fatty acid synthase, stearoyl-CoA desaturase1, tumor necrosis factor-α, and interleukin-1β. LO alleviated the MAPK/NF-κB expression by attenuating CML and RAGE expression. Taken together, our results demonstrate that LO alleviates the progression of NAFLD by lowering the levels of AGEs by downregulating CML/RAGE expression.

The simultaneous detection of the orbital angular momentum (OAM) and wavelength offers new opportunities for optical multiplexing. However, because of the dispersion of lens functions for Fourier transformation, the mode conversions at distinct wavelengths cannot be achieved in the same plane. Here we propose an ultracompact achromatic complementary metal oxide semiconductor (CMOS)-integrated OAM mode detector. Specifically, a spatial multiplexed scheme, randomly interleaving the phase distributions for distributing the superposed OAM modes into preset positions at distinct wavelengths, is presented. In addition, such a nanoprinted achromatic OAM detector featuring a microscale size and a short focal length can be integrated onto a CMOS chip. Consequently, the four-bit incident light beams at three discrete wavelengths (633, 532, and 488 nm) can be distinguished with a high degree of accuracy evaluated by the average standardized Euclidean distance of ∼0.75 between the analytical and target results. Our results showcase a miniaturized platform for achieving high-capacity information processing.

Purpose: Geriatric Nutritional Risk Index (GNRI) is a simple tool for assessing the nutritional status of the aging population. This study aims to explore the clinical implication of GNRI on treatment response and long-term clinical outcomes in heart failure (HF) patients receiving cardiac resynchronization therapy (CRT)., Methods: Patients who underwent CRT implantation or upgrade at our hospital were retrospectively included. The association of GNRI and its tertiles with the echocardiographic response, all-cause mortality or heart transplantation, and the first hospitalization due to HF were investigated., Results: Totally, 647 patients were enrolled, with a median age of 60 [Interquartile Range (IQR): 52-67] years and mean score of GNRI at 107.9 ± 23.7. Super-response rates increased significantly among the GNRI T1, T2, and T3 groups (25.1%, 29.8% vs. 41.1%, P = 0.002). Patients with higher GNRI were more likely to have better LVEF improvement after multiple adjustments (OR = 1.13, 95% CI: 1.04-1.23, P = 0.010). Higher GNRI was independently associated with a lower risk of all-cause mortality or heart implantation (HR = 0.95, 95% CI: 0.93-0.96, P < 0.001) and HF hospitalization (HR = 0.96, 95% CI: 0.95-0.98, P < 0.001). The inclusion of GNRI enhanced the predictability of all-cause mortality based on traditional model, including sex, New York Heart Association functional class, left bundle branch block, QRS reduction, and N-terminal pro-B-type natriuretic peptide level (C statistics improved from 0.785 to 0.813, P = 0.007)., Conclusion: Higher GNRI was associated with better treatment response and long-term prognosis in HF patients with CRT. Evaluation of nutritional status among CRT population is necessary for individualized choice of potential responders., Competing Interests: Declaration of competing interest The authors did not receive support from any organization for the submitted work. The authors have no relevant financial or non-financial interests to disclose., (Copyright © 2024. Published by Elsevier B.V.)

GPR84 is a promising therapeutic target and biomarker for a range of diseases. In this study, we reported the discovery of BINOL phosphate (BINOP) derivatives as GPR84 antagonists. By investigating the structure-activity relationship, we identified 15S as a novel GPR84 antagonist. 15S exhibits low nanomolar potency and high selectivity for GPR84, while its enantiomer 15R is less active. Next, we rationally designed and synthesized a series of GPR84 fluorogenic probes by conjugating Nile red and compound 15S . The leading hybrid, probe F8 , not only retained GPR84 activity but also exhibited low nonspecific binding and a turn-on fluorescent signal in an apolar environment. F8 enabled visualization and detection of GPR84 in GPR84-overexpressing HEK293 cells and lipopolysaccharide-stimulated neutrophils. Furthermore, we demonstrated that F8 can detect upregulated GPR84 protein levels in mice models of inflammatory bowel disease and acute lung injury. Thus, compound F8 represents a promising tool for studying GPR84 functions.

Background: The combined association of physical activity (PA) and alcohol use (AU) with long-term mortality is yet to be investigated., Methods: For the current study, 12,621 participants aged ≥ 20 years were enrolled from the National Health and Nutrition Examination Survey (1999-2004). The study endpoint was all-cause mortality. Cox proportional hazards regression models were used to examine the combined effect of PA and AU on long-term mortality., Results: The study population was divided into young (< 60 years, N = 8,258) and old (≥ 60 years, N = 4,363) groups. The median follow-up time was 203 months. In both young and old group, sedentary lifestyle combined with even minimal AU were associated with elevated risk of death (all P < 0.05). In young group, the integration of high volume AU with any degree of PA, including sedentary PA (HR = 2.35, 95% CI 1.24-4.44, P = 0.009), low PA (HR = 1.64, 95% CI 1.01-2.68, P = 0.047), and moderate-to-vigorous PA (HR = 1.99, 95% CI 1.03-3.84, P = 0.041), was associated with an increased risk of mortality. This relationship persisted as significant after adjusting for potential confounders (all P < 0.05). In old group, combining moderate-to-vigorous PA and low volume AU (HR = 0.59, 95% CI 0.37-0.94, P = 0.027) was associated with a reduction in mortality. After adjustment, the combination of moderate-to-vigorous PA and low volume AU was independently associated with favorable prognostic outcomes (all P < 0.05)., Conclusions: In both age groups, combining sedentary lifestyle with even minimal AU was a risk factor for death. In young group, combining any level of PA with high volume AU was associated with increased mortality. In old group, combining moderate-to-vigorous PA with low volume AU was related to reduced mortality., (© 2024. The Author(s).)

H7N9 subtype avian influenza viruses (AIVs) cause 1567 human infections and have high mortality, posing a significant threat to public health. Previously, we reported that two avian-derived H7N9 isolates (A/chicken/Eastern China/JTC4/2013 and A/chicken/Eastern China/JTC11/2013) exhibit different pathogenicities in mice. To understand the genetic basis for the differences in virulence, we constructed a series of mutant viruses based on reverse genetics. We found that the PB2-E627K mutation alone was not sufficient to increase the virulence of H7N9 in mice, despite its ability to enhance polymerase activity in mammalian cells. However, combinations with PB1-V719M and/or PA-N444D mutations significantly enhanced H7N9 virulence. Additionally, these combined mutations augmented polymerase activity, thereby intensifying virus replication, inflammatory cytokine expression, and lung injury, ultimately increasing pathogenicity in mice. Overall, this study revealed that virulence in H7N9 is a polygenic trait and identified novel virulence-related residues (PB2-627K combined with PB1-719M and/or PA-444D) in viral ribonucleoprotein (vRNP) complexes. These findings provide new insights into the molecular mechanisms underlying AIV pathogenesis in mammals, with implications for pandemic preparedness and intervention strategies., (© 2024. The Author(s).)

Ferroptosis is an iron-dependent cell death form characterized by reactive oxygen species (ROS) overgeneration and lipid peroxidation. Myricetin, a flavonoid that exists in numerous plants, exhibits potent antioxidant capacity. Given that iron accumulation and ROS-provoked dopaminergic neuron death are the two main pathological hallmarks of Parkinson's disease (PD), we aimed to investigate whether myricetin decreases neuronal death through suppressing ferroptosis. The PD models were established by intraperitoneally injecting 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) into rats and by treating SH-SY5Y cells with 1-methyl-4-phenylpyridinium (MPP + ), respectively. Ferroptosis was identified by assessing the levels of Fe 2+ , ROS, malondialdehyde (MDA), and glutathione (GSH). The results demonstrated that myricetin treatment effectively mitigated MPTP-triggered motor impairment, dopamine neuronal death, and α-synuclein (α-Syn) accumulation in PD models. Myricetin also alleviated MPTP-induced ferroptosis, as evidenced by decreased levels of Fe 2+ , ROS, and MDA and increased levels of GSH in the substantia nigra (SN) and serum in PD models. All these changes were reversed by erastin, a ferroptosis activator. In vitro, myricetin treatment restored SH-SY5Y cell viability and alleviated MPP + -induced SH-SY5Y cell ferroptosis. Mechanistically, myricetin accelerated nuclear translocation of nuclear factor E2-related factor 2 (Nrf2) and subsequent glutathione peroxidase 4 (Gpx4) expression in MPP + -treated SH-SY5Y cells, two critical inhibitors of ferroptosis. Collectively, these data demonstrate that myricetin may be a potential agent for decreasing dopaminergic neuron death by inhibiting ferroptosis in PD., (© 2024. The Author(s).)

The current standard treatment for ovarian cancer consists of surgery to reduce the size of the tumor, followed by treatment with chemotherapeutic drugs, which have major side effects. Therefore, finding a new natural product drug with fewer side effects is a strategy. Delphinium brunonianum (D. brunonianum) is a traditional Tibetan medicine, mainly from southern Tibet, China, whereas the chemical constituents in this plant remain elusive. The major metabolites in the dichloromethane fraction of D. brunonianum were analyzed and purified by HPLC and various column chromatography techniques. Nine diterpenoid alkaloids (1-9) and one amide alkaloid (10) were isolated from D. brunonianum, including three novel C19-type diterpenoid alkaloids (Brunonianines D-F) (1-3). Their structures were elucidated by 1D/2D NMR, HR-ESI-MS and single-crystal X-ray diffraction analyses. All compounds were evaluated for toxicity in four tumor cell lines. Most of the compounds exhibited potent inhibitory effects on Skov-3 cell lines, with IC 50 values ranging from 2.57 to 8.05 μM. The western blotting experiment was used to further analyze the expression levels of molecules in the Bax/Bcl-2/Caspase-3 signaling pathway for compound 1. Molecular docking was performed to predict the binding modes of Brunonianine D with target proteins. In vivo experiments were also performed and evaluated in real time by monitoring the size of the Skov-3 tumor. Additionally, tumor H&E staining and the TUNEL assay used to evaluate anti-tumor effects., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Chronic allograft dysfunction (CAD) poses a significant challenge in kidney transplantation, with renal vascular endothelial-to-mesenchymal transition (EndMT) playing a vital role. While renal vascular EndMT has been verified as an important contributing factor to renal allograft interstitial fibrosis/tubular atrophy in CAD patients, its underlying mechanisms remain obscure. Currently, Src activation is closely linked to organ fibrosis development. Single-cell transcriptomic analysis in clinical patients revealed that Src is a potential pivotal mediator in CAD progression. Our findings revealed a significant upregulation of Src which closely associated with EndMT in CAD patients, allogeneic kidney transplanted rats and endothelial cells lines. In vivo, Src inhibition remarkably alleviate EndMT and renal allograft interstitial fibrosis in allogeneic kidney transplanted rats. It also had a similar antifibrotic effect in two endothelial cell lines. Mechanistically, the knockout of Src resulted in an augmented AMBRA1-mediated mitophagy in endothelial cells. We demonstrate that Src knockdown upregulates AMBRA1 level and activates mitophagy by stabilizing Parkin's ubiquitination levels and mitochondrial translocation. Subsequent experiments demonstrated that the knockdown of the Parkin gene inhibited mitophagy in endothelial cells, leading to increased production of Interleukin-6, thereby inducing EndMT. Consequently, our study underscores Src as a critical mediator of renal vascular EndMT and allograft interstitial fibrosis, exerting its impact through the regulation of AMBRA1/Parkin-mediated mitophagy., (© 2024 The Author(s). Cell Proliferation published by Beijing Institute for Stem Cell and Regenerative Medicine and John Wiley & Sons Ltd.)

Artificial intelligence has been applied to medical diagnosis and decision-making but it has not been used for classification of Class III malocclusions in children., Objective: This study aims to propose an innovative machine learning (ML)-based diagnostic model for automatically classifies dental, skeletal and functional Class III malocclusions., Methods: The collected data related to 46 cephalometric feature measurements from 4-14-year-old children ( n = 666). The data set was divided into a training set and a test set in a 7:3 ratio. Initially, we employed the Recursive Feature Elimination (RFE) algorithm to filter the 46 input parameters, selecting 14 significant features. Subsequently, we constructed 10 ML models and trained these models using the 14 significant features from the training set through ten-fold cross-validation, and evaluated the models' average accuracy in test set. Finally, we conducted an interpretability analysis of the optimal model using the ML model interpretability tool SHapley Additive exPlanations (SHAP)., Results: The top five models ranked by their area under the curve (AUC) values were: GPR (0.879), RBF SVM (0.876), QDA (0.876), Linear SVM (0.875) and L2 logistic (0.869). The DeLong test showed no statistical difference between GPR and the other models ( p > 0.05). Therefore GPR was selected as the optimal model. The SHAP feature importance plot revealed that he top five features were SN-GoMe (the ratio of the length of the anterior skull base SN to that of the mandibular base GoMe), U1-NA (maxillary incisor angulation to NA plane), Overjet (the distance between two lines perpendicular to the functional occlusal plane from U1 and L), ANB (the difference between angles SNA and SNB), and AB-NPo (the angle between the AB and N-Pog line)., Conclusions: Our findings suggest that ML models based on cephalometric data could effectively assist dentists to classify dental, functional and skeletal Class III malocclusions in children. In addition, features such as SN&#95;GoMe, U1&#95;NA and Overjet can as important indicators for predicting the severity of Class III malocclusions.

Background: The prognostic value of triglyceride-glucose (TyG) index is not yet known for older diabetic patients received right ventricular pacing (RVP). We aimed to investigate the association between TyG index and the risk of heart failure hospitalization (HFH) in older diabetic patients received RVP., Methods: This study was conducted between January 2017 and January 2018 at Fuwai Hospital, Beijing, China, and included older (age ≥ 65 years) diabetic patients that received RVP for the first time. TyG index were obtained before implantation. The primary endpoint was HFH., Results: A total of 231 patients were divided into three groups according to the tertiles of TyG index: < 8.5 (T1, N = 77), 8.5-9.1 (T2, N = 77), and > 9.1 (T3, N = 77). T3 group had higher rate of HFH (Log-rank = 11.7, P = 0.003). Multivariate analyses showed that, TyG index served as an independent predictor for HFH, both as numerical variable (HR = 1.94, 95% CI 1.21-3.11, P = 0.006), and as categorical variable (HR = 2.31, 95% CI 1.09-4.89, P = 0.03). RCS demonstrated that the risk of HFH was relatively low until TyG index exceeded 8.8, beyond which the risk began to increase rapidly (P-non-linear = 0.006)., Conclusion: Preimplantation TyG index emerges as a robust, independent predictor for HFH in older diabetic patients received RVP, and TyG index > 8.8 might be the optimal cut-off value., (© 2024. The Author(s).)

The optical memory effect in complex scattering media including turbid tissue and speckle layers has been a critical foundation for macroscopic and microscopic imaging methods. However, image reconstruction from strong scattering media without the optical memory effect has not been achieved. Here, we demonstrate image reconstruction through scattering layers where no optical memory effect exists, by developing a multistage convolutional optical neural network (ONN) integrated with multiple parallel kernels operating at the speed of light. Training this Fourier optics-based, parallel, one-step convolutional ONN with the strong scattering process for direct feature extraction, we achieve memory-less image reconstruction with a field of view enlarged by a factor up to 271. This device is dynamically reconfigurable for ultrafast multitask image reconstruction with a computational power of 1.57 peta-operations per second (POPS). Our achievement establishes an ultrafast and high energy-efficient optical machine learning platform for graphic processing.

Two unprecedented quinone compounds Rubiaxylm A (1) and Rubiaxylm B (2), along with fifteen known anthraquinones (3-17) were isolated and characterized from the roots of Rubia tibetica in Tibetan medicine. Their structures were identified through comprehensive analyses of 1D/2D NMR as well as HR-ESIMS data. Furthermore, all separated compounds were evaluated for their cytotoxic activity on A549, Caco-2, MDA-MB-231 and Skov-3 cell lines. In particular, compound 2 effectively inhibited MDA-MB-231 cells with an IC 50 value of 8.15 ± 0.20 μM. Subsequently, the anti-tumor mechanism of 2 was investigated by flow cytometry, JC-1 staining, cell scratching and cell colony. These results indicated that compound 2 could inhibit the proliferation of MDA-MB-231 cells by arresting cells in the G1 phase., Competing Interests: Declaration of competing interest We declare that there was no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Left bundle branch area pacing (LBBAP) has emerged as an alternative to biventricular pacing (BVP) for cardiac resynchronization therapy (CRT). We aimed to compare the morbidity and mortality associated with LBBAP versus BVP in patients undergoing CRT implantation., Methods: Consecutive patients who received CRT from two high-volume implantation centers were retrospectively recruited. The primary endpoint was a composite of all-cause death and heart failure hospitalization, and the secondary endpoint was all-cause death., Results: A total of 491 patients receiving CRT (154 via LBBAP and 337 via BVP) were included, with a median follow-up of 31 months. The primary endpoint was reached by 21 (13.6%) patients in the LBBAP group, as compared with 74 (22.0%) patients in the BVP group [hazard ratio (HR) 0.70, 95% confidence interval (CI) 0.43-1.14, P = 0.15]. There were 10 (6.5%) deaths in the LBBAP group, as compared with 31 (9.2%) in the BVP group (HR 0.91, 95% CI 0.44-1.86, P = 0.79). No significant difference was observed in the risk of either the primary or secondary endpoint between LBBAP and BVP after multivariate Cox regression (HR 0.74, 95% CI 0.45-1.23, P = 0.24, and HR 0.77, 95% CI 0.36-1.67, P = 0.51, respectively) or propensity score matching (HR 0.72, 95% CI 0.41-1.29, P = 0.28, and HR 0.69, 95% CI 0.29-1.65, P = 0.40, respectively)., Conclusion: LBBAP was associated with a comparable effect on morbidity and mortality relative to BVP in patients with indications for CRT., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The association between body mass index (BMI) and rapid eye-movement (REM) sleep-related behavioral disorder (RBD) in Parkinson's disease (PD) remains unknown. Our study was to investigate the association of BMI with RBD in PD patients., Methods: In this cross-sectional study, a total of 1,115 PD participants were enrolled from Parkinson's Progression Markers Initiative (PPMI) database. BMI was calculated as weight divided by height squared. RBD was defined as the RBD questionnaire (RBDSQ) score with the cutoff of 5 or more assessed. Univariable and multivariable logistic regression models were performed to examine the associations between BMI and the prevalence of RBD. Non-linear correlations were explored with use of restricted cubic spline (RCS) analysis. And the inflection point was determined by the two-line piecewise linear models., Results: We identified 426 (38.2%) RBD. The proportion of underweight, normal, overweight and obese was 2.61, 36.59, 40.36, and 20.44%, respectively. In the multivariate logistic regression model with full adjustment for confounding variables, obese individuals had an odds ratio of 1.77 (95% confidence interval: 1.21 to 2.59) with RBD compared with those of normal weight. In the RCS models with three knots, BMI showed a non-linear association with RBD. The turning points of BMI estimated from piecewise linear models were of 28.16 kg/m 2 , 28.10 kg/m 2 , and 28.23 kg/m 2 derived from univariable and multivariable adjusted logistic regression models. The effect modification by depression on the association between BMI and RBD in PD was also found in this study. Furthermore, the sensitivity analyses linked with cognition, education, and ethnic groups indicated the robustness of our results., Conclusion: The current study found a significant dose-response association between BMI and RBD with a depression-based difference in the impact of BMI on RBD in PD patients., 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 © 2024 Gu, Yuan, Yin, Li, Wang, Gu, Xu, Gao, Wu, Hu, Yuan, Cao and Ye.)

The genus Bifidobacterium has been widely used in functional foods for health promotion due to its beneficial effects on human health, especially in the gastrointestinal tract (GIT). In this study, we characterize the anti-inflammatory potential of the probiotic strain Bifidobacterium pseudocatenulatum G7, isolated from a healthy male adult. G7 secretion inhibited inflammatory response in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. Moreover, oral administration of bacteria G7 alleviated the severity of colonic inflammation in dextran sulfate sodium (DSS)-treated colitis mice, which was evidenced by a decreased disease activity index (DAI) and enhanced structural integrity of the colon. The 16S rRNA gene sequencing result illustrated that the G7 alleviated DSS-induced gut microbiota dysbiosis, accompanied by the modulated bile acids and short-chain fatty acid (SCFA) levels. Overall, our results demonstrated the potential anti-inflammatory effects of Bifidobacterium pseudocatenulatum G7 on both in vitro and in vivo models, which provided a solid foundation for further development of a novel anti-inflammatory probiotic.

The haemagglutinin-neuraminidase (HN) protein, a vital membrane glycoprotein, plays a pivotal role in the pathogenesis of Newcastle disease virus (NDV). Previously, we demonstrated that a mutation in the HN protein is essential for the enhanced virulence of JS/7/05/Ch, a velogenic variant NDV strain originating from the mesogenic vaccine strain Mukteswar. Here, we explored the effects of the HN protein during viral infection in vitro using three viruses: JS/7/05/Ch, Mukteswar, and an HN-replacement chimeric NDV, JS/MukHN. Through microscopic observation, CCK-8, and LDH release assays, we demonstrated that compared with Mukteswar and JS/MukHN, JS/7/05/Ch intensified the cellular damage and mortality attributed to the mutant HN protein. Furthermore, JS/7/05/Ch induced greater levels of apoptosis, as evidenced by the activation of caspase-3/8/9. Moreover, JS/7/05/Ch promoted autophagy, leading to increased autophagosome formation and autophagic flux. Subsequent pharmacological experiments revealed that inhibition of apoptosis and autophagy significantly impacted virus replication and cell viability in the JS/7/05/Ch-infected group, whereas less significant effects were observed in the other two infected groups. Notably, the mutant HN protein enhanced JS/7/05/Ch-induced apoptosis and autophagy by suppressing NF-κB activation, while it mitigated the effects of NF-κB on NDV infection. Overall, our study offers novel insights into the mechanisms underlying the increased virulence of NDV and serves as a reference for the development of vaccines., (© 2024. The Author(s).)

Clostridium autoethanogenum protein (CAP) is a promising protein source for aquaculture; however, how CAP influences fish quality is worth extensive research. We randomly allocated 630 turbot with initial body weights of about 180 g into 6 groups, with fishmeal-based control diet or diet with CAP replacing 15% (CAP15), 30% (CAP30), 45% (CAP45), 60% (CAP60), or 75% (CAP75) of fishmeal protein. After a 70-d feeding trial, the fillet yield ( P  = 0.015) and content of protein ( P  = 0.017), collagen ( P  < 0.001), hydroxyproline ( P  < 0.001), C20:5n-3 ( P  = 0.007), and ∑n-3/∑n-6 polyunsaturated fatty acids ratio ( P  < 0.001) in turbot muscle was found to decrease linearly with increasing CAP. However, turbot fed CAP15 diet maintained these parameters ( P  > 0.05). By contrast, the muscle hardness increased linearly with increasing CAP ( P  = 0.004), accompanied by linear reduction of muscle fiber area ( P  = 0.003) and expression of myogenesis-related genes, including cathepsin D ( ctsd P  < 0.001) and muscle ring finger protein 1 ( murf 1 , P  < 0.001). Phosphorylation of protein kinase B (Akt, P  < 0.001), target of rapamycin (TOR, P  = 0.001), eukaryotic initiation factor 4E-binding protein 1 (4E-BP1, P  < 0.001), and ribosomal protein S6 (S6, P  < 0.001) decreased linearly; however, phosphorylation of AMP-activated protein kinase (AMPK, P  < 0.001), eukaryotic initiation factor 2α (eIF2α, P  < 0.001), and the abundance of activating transcription factor 4 (ATF4, P  < 0.001) increased with increasing CAP, suggesting that the TOR signaling pathway was inhibited, and the amino acid response (AAR) and AMPK pathways were activated. Additionally, expression of genes related to protein degradation, including myogenic factor 5 ( myf 5 , P  < 0.001), myogenic differentiation ( myod , P  < 0.001), paired box 7 ( pax 7, P  < 0.001), and ctsd ( P  < 0.001), decreased linearly with increasing CAP. In conclusion, CAP could be used to replace up to 15% of fishmeal without negatively impacting turbot quality. However, higher levels of CAP decreased fillet yield, muscle protein content, and muscle fiber diameter while increasing muscle hardness, which could be attributed to the inhibition of the TOR pathway and activation of the AAR and AMPK pathways., Competing Interests: We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, and there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the content of this paper., (© 2024 The Authors.)

Background: Renal allograft interstitial fibrosis/tubular atrophy (IF/TA) constitutes the principal histopathological characteristic of chronic allograft dysfunction (CAD) in kidney-transplanted patients. While renal vascular endothelial-mesenchymal transition (EndMT) has been verified as an important contributing factor to IF/TA in CAD patients, its underlying mechanisms remain obscure. Through single-cell transcriptomic analysis, we identified Rictor as a potential pivotal mediator for EndMT. This investigation sought to elucidate the role of Rictor/mTORC2 signalling in the pathogenesis of renal allograft interstitial fibrosis and the associated mechanisms., Methods: The influence of the Rictor/mTOR2 pathway on renal vascular EndMT and renal allograft fibrosis was investigated by cell experiments and Rictor depletion in renal allogeneic transplantation mice models. Subsequently, a series of assays were conducted to explore the underlying mechanisms of the enhanced mitophagy and the ameliorated EndMT resulting from Rictor knockout., Results: Our findings revealed a significant activation of the Rictor/mTORC2 signalling in CAD patients and allogeneic kidney transplanted mice. The suppression of Rictor/mTORC2 signalling alleviated TNFα-induced EndMT in HUVECs. Moreover, Rictor knockout in endothelial cells remarkably ameliorated renal vascular EndMT and allograft interstitial fibrosis in allogeneic kidney transplanted mice. Mechanistically, Rictor knockout resulted in an augmented BNIP3-mediated mitophagy in endothelial cells. Furthermore, Rictor/mTORC2 facilitated the MARCH5-mediated degradation of BNIP3 at the K130 site through K48-linked ubiquitination, thereby regulating mitophagy activity. Subsequent experiments also demonstrated that BNIP3 knockdown nearly reversed the enhanced mitophagy and mitigated EndMT and allograft interstitial fibrosis induced by Rictor knockout., Conclusions: Consequently, our study underscores Rictor/mTORC2 signalling as a critical mediator of renal vascular EndMT and allograft interstitial fibrosis progression, exerting its impact through regulating BNIP3-mediated mitophagy. This insight unveils a potential therapeutic target for mitigating renal allograft interstitial fibrosis., (© 2024 The Author(s). Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.)

This study proposed what we believe to be a novel method for fabricating superconducting nanowire single-photon detectors (SNSPDs) with high efficiency, polarization insensitivity, and ultrafast response. To achieve these properties in niobium nitride (NbN) SNSPDs, the periodic four-split rings (PFSR) were positioned above the nanowires. This design uses the localized surface plasmon resonance to enhance the electric field around nanowires. For an incident light with a wavelength of 1550 nm, the PFSR-SNSPD structure achieved a polarization extinction ratio of 1.0064 and absorptions of 88.94% and 88.37% under TE and TM polarizations, respectively. The nanowire length was reduced by 85% using a meandering nanowire arrangement with a fill factor of 0.074.

Objective: To systematically review the literature for mid-sagittal plane establishment approaches to identify the most effective method for constructing the mid-sagittal plane for the evaluation of facial asymmetry., Materials and Methods: Six electronic databases (PubMed, Medline (via Ovid), EMBASE (via Ovid), Cochrane Library, Web of Science, and Scopus) and grey literature were searched for the studies that computed the mid-sagittal reference plane three-dimensionally, using a combination of MeSH terms and keywords. The methodological quality and the level of evidence for the included studies were analyzed using QUADAS-2 and GRADE, respectively., Results: The preliminary search yielded 6746 records, of which 42 articles that met the predefined inclusion criteria were included in the final analysis. All the included articles reported the construction of the mid-sagittal reference plane (MSP) using varied methods. The risk of bias and concerns regarding the applicability of the included studies were judged to be 'low'. The level of evidence was determined to be 'low' for the effectiveness of the technique and 'moderate' for the ease of clinical applicability., Conclusion: Despite methodological heterogeneity, this review substantiates the comparable efficacy of cephalometric and morphometric MSP construction methods. A fully automated morphometric MSP holds promise as a viable option for routine clinical use. Nevertheless, future prospective studies with an emphasis on the impact, accuracy, and clinical applicability of MSP construction techniques in cases of facial asymmetry are required., Clinical Relevance: The present review will assist clinicians in selecting the most suitable method for MSP construction, leading to improved treatment planning and ultimately more favorable treatment outcomes., (© 2024. The Author(s).)

Aim: To investigate the differences of the nasal soft and hard tissue asymmetry in postoperative patients with unilateral cleft lip and palate (UCLP) between adolescence and adulthood, and to explore the correlation of nasal soft and hard tissue asymmetry., Methods: CT data from 47 repaired UCLP patients were included and divided into two groups:1. adolescent group: 23 patients (15 males, 8 females; age: 10-12 years old). 2. adult group: 24 patients (16 males, 8 females; age:18-32 years old). The three-dimensional asymmetry in nasal soft and hard tissues was analyzed. Additionally, the correlation between nasal soft and hard tissue asymmetry was also analyzed., Results: Both the adolescent group and adult group showed asymmetries in nasal soft and hard tissues. Compared to the adolescent group, the adult group had a significantly increased horizontal asymmetry of nasal soft tissues Sbal (P < 0.05). Furthermore, the sagittal asymmetry of soft tissue Glat (P < 0.05), Sbal (P < 0.001), Sni (P < 0.001) and hard tissue LPA (P < 0.05) also increased significantly. In the adult group, there were more landmarks with a correlation between the asymmetry of nasal hard tissue and soft tissue compared to the adolescent group. There were moderate to strong correlations between nasal hard and soft tissue symmetries in the horizontal and sagittal directions (0.444 < r < 764), but no correlation in the vertical direction in the adult group (P > 0.05)., Conclusions: The asymmetry of nasal soft and hard tissues in patients with repaired UCLP becomes more apparent in the horizontal and sagittal dimensions from adolescence to adulthood. The correlation between the asymmetry of nasal hard tissue and soft tissue becomes stronger in the horizontal and sagittal dimensions. These factors should be taken into account when performing treatment for repaired UCLP patients in adolescence and adulthood., (© 2023. The Author(s), under exclusive licence to The Society of The Nippon Dental University.)

Applications of cone-beam CT (CBCT) in orthodontics have been increasingly discussed and evaluated in science and practice over the last two decades. The present work provides a comprehensive summary of current consolidated practice guidelines, cutting-edge innovative applications, and future outlooks about potential use of CBCT in orthodontics with a special focus on upper airway analysis in patients with sleep-disordered breathing. The present scoping review reveals that clinical applications of CBCT in orthodontics are broadly supported by evidence for the diagnosis of dental anomalies, temporomandibular joint disorders, and craniofacial malformations. On the other hand, CBCT imaging for upper airway analysis-including soft tissue diagnosis and airway morphology-needs further validation in order to provide better understanding regarding which diagnostic questions it can be expected to answer. Internationally recognized guidelines for CBCT use in orthodontics are existent, and similar ones should be developed to provide clear indications about the appropriate use of CBCT for upper airway assessment, including a list of specific clinical questions justifying its prescription., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Institute of Radiology and the International Association of Dentomaxillofacial Radiology.)