Automated Design of Fault Diagnosis CNN Network for Satellite Attitude Control Systems.

Despite the dominance of unsupervised and self-supervised anomaly detection methods in the current satellite fault diagnosis domain, supervised anomaly detection offers a superior alternative for high-sensitivity detection and lightweight deployment requirements specific to subsystems or components, such as attitude control systems (ACSs). This article addresses the issues of over-design and insufficient accuracy in the CNN network design for satellite ACS fault diagnosis by introducing the modified particle swarm optimization-advanced convolution blocks-based CNN (MPSO-ACBCNN) method. First, we present the ACBCNN, a lightweight, flexible-layer CNN architecture. This architecture leverages advanced convolution blocks (ACBs), which incorporate numerous efficient design elements to enhance feature extraction capabilities within power spectral density (PSD) graphs of various fault samples, and employs classical dense connection methods to prevent the issue of gradient vanishing. Second, we devise the MPSO-ACBCNN algorithm to optimize the ACBCNN fault diagnosis architecture for specified ACS using MPSO. In MPSO-ACBCNN, several optimizations to the canonical PSO are implemented, including the fitness design that balances the tradeoff between total parameter quantity and the training effectiveness, and methods to ensure feasible solutions, etc. Finally, numerical experimental results demonstrate the effectiveness and superiority of MPSO-ACBCNN in fault diagnosis for ACS.

miR-153 promotes neural differentiation by activating the cell adhesion/Ca2+ signaling pathway and targeting ion channel activity in HT-22 cells by bioinformatic analysis.

MicroRNAs have been studied extensively in neurodegenerative diseases. In a previous study, miR-153 promoted neural differentiation and projection formation in mouse hippocampal HT-22 cells. However, the pathways and molecular mechanism underlying miR-153-induced neural differentiation remain unclear. To explore the molecular mechanism of miR-153 on neural differentiation, we performed RNA sequencing on miR-153-overexpressed HT-22 cells. Based on RNA sequencing, differentially expressed genes (DEGs) and pathways in miR-153-overexpressed cells were identified. The Database for Annotation, Visualization and Integrated Discovery and Gene Set Enrichment Analysis were used to perform functional annotation and enrichment analysis of DEGs. Targetscan predicted the targets of miR-153. The Search Tool for the Retrieval of Interacting Genes and Cytoscape, were used to construct protein-protein interaction networks and identify hub genes. Q-PCR was used to detect mRNA expression of the identified genes. The expression profiles of the identified genes were compared between embryonic days 9.5 (E9.5) and E11.5 in the embryotic mouse brain of the GDS3442 dataset. Cell Counting Kit-8 assay was used to determine cell proliferation and cellular susceptibility to amyloid ß-protein (Aß) toxicity in miR-153-overexpressed cells. The results indicated that miR-153 increased cell adhesion/Ca2+ (Cdh5, Nrcam, and P2rx4) and Bdnf/Ntrk2 neurotrophic signaling pathway, and decreased ion channel activity (Kcnc3, Kcna4, Clcn5, and Scn5a). The changes in the expression of the identified genes in miR-153-overexpressed cells were consistent with the expression profile of GDS3442 during neural differentiation. In addition, miR-153 overexpression decreased cellular susceptibility to Aß toxicity in HT-22 cells. In conclusion, miR-153 overexpression may promote neural differentiation by inducing cell adhesion and the Bdnf/Ntrk2 pathway, and regulating electrophysiological maturity by targeting ion channels. MiR-153 may play an important role in neural differentiation; the findings provide a useful therapeutic direction for neurodegenerative diseases.

Outcomes of Heart Transplantation From Donation After Circulatory Death: An Up-to-Date Systematic Meta-analysis.

BACKGROUND: Donation after circulatory death (DCD) heart transplantation (HTx) significantly expands the donor pool and reduces waitlist mortality. However, high-level evidence-based data on its safety and effectiveness are lacking. This meta-analysis aimed to compare the outcomes between DCD and donation after brain death (DBD) HTxs. METHODS: Databases, including MEDLINE, Embase, CINAHL, and the Cochrane Central Register of Controlled Trials, were systematically searched for randomized controlled trials and observational studies reporting the outcomes of DCD and DBD HTxs published from 2014 onward. The data were pooled using random-effects models. Risk ratios (RRs) with 95% confidence intervals (CIs) were used as the summary measures for categorical outcomes and mean differences were used for continuous outcomes. RESULTS: Twelve eligible studies were included in the meta-analysis. DCD HTx was associated with lower 1-y mortality rate (DCD 8.13% versus DBD 10.24%; RR = 0.75; 95% CI, 0.59-0.96; P = 0.02) and 5-y mortality rate (DCD 14.61% versus DBD 20.57%; RR = 0.72; 95% CI, 0.54-0.97; P = 0.03) compared with DBD HTx. CONCLUSIONS: Using the current DCD criteria, HTx emerges as a promising alternative to DBD transplantation. The safety and feasibility of DCD hearts deserve further exploration and investigation.

Targeted depletion of PD-1-expressing cells induces immune tolerance through peripheral clonal deletion.

Thymic negative selection of the T cell receptor (TCR) repertoire is essential for establishing self-tolerance and acquired allograft tolerance following organ transplantation. However, it is unclear whether and how peripheral clonal deletion of alloreactive T cells induces transplantation tolerance. Here, we establish that programmed cell death protein 1 (PD-1) is a hallmark of alloreactive T cells and is associated with clonal expansion after alloantigen encounter. Moreover, we found that diphtheria toxin receptor (DTR)-mediated ablation of PD-1+ cells reshaped the TCR repertoire through peripheral clonal deletion of alloreactive T cells and promoted tolerance in mouse transplantation models. In addition, by using PD-1-specific depleting antibodies, we found that antibody-mediated depletion of PD-1+ cells prevented heart transplant rejection and the development of experimental autoimmune encephalomyelitis (EAE) in humanized PD-1 mice. Thus, these data suggest that PD-1 is an attractive target for peripheral clonal deletion and induction of immune tolerance.

Progress of engineered bacteria for tumour therapy.

Finding novel therapeutic modalities, improving drug delivery efficiency and targeting, and reducing the immune escape of tumor cells are currently hot topics in the field of tumor therapy. Bacterial therapeutics have proven highly effective in preventing tumor spread and recurrence, used alone or in combination with traditional therapies. In recent years, a growing number of researchers have significantly improved the targeting and penetration of bacteria by using genetic engineering technology, which has received widespread attention in the field of tumor therapy. In this paper, we provide an overview and assessment of the advancements made in the field of tumor therapy using genetically engineered bacteria. We cover three major aspects: the development of engineered bacteria, their integration with other therapeutic techniques, and the current state of clinical trials. Lastly, we discuss the limitations and challenges that are currently being faced in the utilization of engineered bacteria for tumor therapy.

Photoredox-catalyzed unsymmetrical diamination of alkenes for access to vicinal diamines.

A photoredox-catalyzed unsymmetrical diamination of alkenes by using N-aminopyridinium salts and nitriles as the amination reagents has been developed. Various vicinal diamines were obtained in moderate to excellent yields under mild reaction conditions. Furthermore, this protocol could be applied in the late-stage modification of pharmaceuticals and natural products. Preliminary mechanistic studies suggested that this methodology may undergo a radical pathway followed by a Ritter-type reaction.

Comparison of the cachexia index based on hand-grip strength (H-CXI) with the original CXI for the prediction of cancer cachexia and prognosis in patients who underwent radical colectomy for colorectal cancer.

Background and aims: The cachexia index (CXI) is a novel biomarker for estimating cancer cachexia. The cachexia index based on hand-grip strength (H-CXI) has been recently developed as a simple proxy for CXI. The present study aims to compare both the H-CXI and CXI for the prediction of cancer cachexia and postoperative outcomes in patients who underwent radical colectomy for colorectal cancer. Methods: Patients who underwent radical operations for colorectal cancer were included in this study. Cancer cachexia was diagnosed according to the international consensus outlined by Fearon et al. The cachexia index (CXI) was calculated as [skeletal muscle index (SMI) × serum albumin/neutrophil-to-lymphocyte ratio (NLR)]. The H-CXI was calculated as [hand-grip strength (HGS)/height2 × serum albumin/NLR]. The SMI was measured based on the preoperative CT images at the third lumbar vertebra (L3) level. HGS was measured before surgery. Results: From July 2014 to May 2021, a total of 1,411 patients were included in the present study, of whom 361 (25.6%) were identified as having cancer cachexia. Patients with cachexia had a lower CXI (p < 0.001) and lower H-CXI (p < 0.001) than those without cachexia. A low CXI but not low H-CXI independently predicted cancer cachexia in the multivariate analysis (OR 1.448, p = 0.024). Both a low CXI (HR 1.476, p < 0.001 for OS; HR 1.611, p < 0.001 for DFS) and low H-CXI (HR 1.369, p = 0.007 for OS; HR 1.642, p < 0.001 for DFS) were independent predictors for overall survival (OS) and disease-free survival (DFS) after adjusting for the same covariates. A low H-CXI but not low CXI was an independent risk factor for postoperative complications (OR 1.337, p = 0.044). No significant association was found between cancer cachexia and postoperative complications. Conclusion: The CXI and H-CXI exhibited better prognostic value than cancer cachexia for the prediction of postoperative outcomes in patients who underwent radical colectomy for colorectal cancer. The H-CXI was a superior index over the CXI in predicting short-term clinical outcomes, whereas the CXI demonstrated a closer correlation with Fearon's criteria for cancer cachexia. Ideal tools for the assessment of cancer cachexia should incorporate not only weight loss but also muscle mass, physical function, and inflammatory state.

Immunoassay System Based on the Technology of Time-Resolved Fluorescence Resonance Energy Transfer.

To enhance the specificity and sensitivity, cut the cost, and realize joint detection of multiple indicators, an immunoassay system based on the technology of time-resolved fluorescence resonance energy transfer (TR-FRET) was studied. Due to the FRET of the reagent, the donor probe and acceptor probe emitted specific fluorescence to enhance specificity. Long-lifetime specific fluorescence from the acceptor probe was combined with time-resolved technology to enhance sensitivity. A xenon flash lamp and a photomultiplier tube (PMT) were selected as the light source and detector, respectively. A filter-switching mechanism was placed in the light path, so the fluorescence signal from the donor and acceptor was measured alternately. The instrument's design is given, and some specificI parts are described in detail. Key technical specifications of the instrument and procalcitonin (PCT), C-reactive protein (CRP), and interleukin-6(IL-6) were tested, and the test results were presented subsequently. The CV value of the self-designed counting module is better than 0.01%, and the instrument noises for 620 nm and 665 nm are 41.44 and 10.59, respectively. When set at 37 °C, the temperature bias (B) is 0.06 °C, and the temperature fluctuation is 0.10 °C. The CV and bias are between ±3% and 5%, respectively, when pipetting volumes are between 10 µL and 100 µL. Within the concentration range of 0.01 nM to 10 nM, the luminescence values exhibit linear regression correlation coefficients greater than 0.999. For PCT detection, when the concentration ranges from 0.02 ng/mL to 50 ng/mL, the correlation coefficient of linear fitting exceeds 0.999, and the limit of quantification is 0.096 ng/mL. For CRP and IL-6, the detection concentration ranges from 0 ng/mL to 500 ng/mL and 0 ng/mL to 20 ng/mL, respectively, with limits of quantification of 2.70 ng/mL and 2.82 ng/mL, respectively. The experimental results confirm the feasibility of the technical and instrumental solutions.

The ultrasound-based radiomics-clinical machine learning model to predict papillary thyroid microcarcinoma in TI-RADS 3 nodules.

Background: Conventional ultrasound (CUS) technology has proven to be successful in the identification of thyroid nodules. Moreover, the American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS) was developed for the purpose of evaluating the risk of thyroid nodules based on ultrasound imaging. Nevertheless, identifying papillary thyroid microcarcinoma (PTMC) from TI-RADS 3 nodules using this system can be difficult due to overlapping morphological features. The main objective of this study was to investigate the efficacy of a machine learning model that utilizes ultrasound-based radiomics features and clinical information in accurately predicting the presence of PTMC in TI-RADS 3 nodules. Methods: A total of 221 patients with TI-RADS 3 nodules were included, consisting of 91 cases of PTMC and 130 benign thyroid nodules. They were randomly divided into training and test cohort in an 8:2 ratio. Radiomics features were extracted from CUS images by manually outlining the targets, while clinical parameters were obtained from electronic medical records. The radiomics model, clinical model, and combined model were constructed and validated to distinguish between PTMC and benign thyroid nodules. Radiomics variables were extracted via the Pyradiomics package (V1.3.0). Moreover, least absolute shrinkage and selection operator (LASSO) regression was used for feature selection. Light Gradient Boosting Machine (LightGBM) was employed to build both radiomics and clinical models. Ultimately, a radiomics-clinical model, which fused radiomics features with clinical information, was developed. Results: Among a total of 1,477 radiomics features, fifteen features that were found to be associated with PTMC through univariate analysis and LASSO regression were selected for the development of the radiomics model. The combined "radiomics-clinical" model demonstrated superior diagnostic accuracy compared to the clinical model for distinguishing PTMC in both the training dataset [area under receiver operating curve (AUC): 0.975 vs. 0.845] and the validation dataset (AUC: 0.898 vs. 0.811). We constructed a radiomics-clinical nomogram, and the clinical applicability was confirmed through decision curve analysis. Conclusions: Utilizing an ultrasound-based radiomics approach has proven to be effective in predicting PTMC in patients with TI-RADS 3 nodules.

Vascular plant communities and biocrusts act as controlling factors in mitigating soil erosion on the Great Wall in a semi-humid area of Northwestern China.

The Great Wall, a World Heritage Site and a vertical wall habitat, is under threat of soil erosion. The role of vascular plants and biocrust in controlling soil erosion has attracted attention, yet our knowledge of the underlying mechanism is limited, and there is a lack of systematic strategies for erosion prevention and control. In this study, we quantified the vascular plant community functional composition (including species diversity, functional diversity, and community-weighted mean), biocrust coverage, and soil erosion levels associated with seven different zones (lower, middle, and upper zones on East and West faces, plus wall crest) of the Great Wall. We then employed a combination of linear regression analysis, random forest model, and structural equation model to evaluate the individual and combined effects, as well as the direction and relative importance of these factors in reducing soil erosion. The results indicated that the vascular plant species richness, species diversity, functional richness, community-weighted mean, and moss crust coverage decreased significantly from the crest to the lower zone of the Great Wall (P < 0.05), and were negatively correlated with the soil erosion area and depth on both sides of the Great Wall (P < 0.05). This suggests that higher zones on the wall favored the colonization and growth of biocrusts and vascular plants and that biocrusts and vascular plants reduced soil erosion on the wall. Based on these findings, we propose a "restoration framework" for managing soil erosion on walls, based on biocrust and vascular plant communities (namely target species selection, plant community construction, biocrust inoculation, and maintenance of community stability), which aims to address the urgent need for more effective soil erosion prevention and control strategies on the Great Wall and provide practical methods that practitioners can utilize.

MEK1/2-PKM2 Pathway Modulates the Immunometabolic Reprogramming of Proinflammatory Allograft-infiltrating Macrophages During Heart Transplant Rejection.

BACKGROUND: Emerging evidence has highlighted the role of macrophages in heart transplant rejection (HTR). However, the molecular signals modulating the immunometabolic phenotype of allograft-infiltrating macrophages (AIMs) during HTR remain unknown. METHODS: We analyzed single-cell RNA sequencing data from cardiac graft-infiltrating immunocytes to characterize the activation patterns and metabolic features of AIMs. We used flow cytometry to determine iNOS and PKM2 expression and MEK/ERK signaling activation levels in AIMs. We then generated macrophage-specific Mek1/2 knockout mice to determine the role of the MEK1/2-PKM2 pathway in the proinflammatory phenotype and glycolytic capacity of AIMs during HTR. RESULTS: Single-cell RNA sequencing analysis showed that AIMs had a significantly elevated proinflammatory and glycolytic phenotype. Flow cytometry analysis verified that iNOS and PKM2 expressions were significantly upregulated in AIMs. Moreover, MEK/ERK signaling was activated in AIMs and positively correlated with proinflammatory and glycolytic signatures. Macrophage-specific Mek1/2 deletion significantly protected chronic cardiac allograft rejection and inhibited the proinflammatory phenotype and glycolytic capacity of AIMs. Mek1/2 ablation also reduced the proinflammatory phenotype and glycolytic capacity of lipopolysaccharides + interferon-γ-stimulated macrophages. Mek1/2 ablation impaired nuclear translocation and PKM2 expression in macrophages. PKM2 overexpression partially restored the proinflammatory phenotype and glycolytic capacity of Mek1/2 -deficient macrophages. Moreover, trametinib, an Food and Drug Administration-approved MEK1/2 inhibitor, ameliorated chronic cardiac allograft rejection. CONCLUSIONS: These findings suggest that the MEK1/2-PKM2 pathway is essential for immunometabolic reprogramming of proinflammatory AIMs, implying that it may be a promising therapeutic target in clinical heart transplantation.

Polarimetric Helmholtz Stereopsis.

Helmholtz stereopsis (HS) exploits the reciprocity principle of light propagation (i.e., the Helmholtz reciprocity) for 3D reconstruction of surfaces with arbitrary reflectance. In this paper, we present the polarimetric Helmholtz stereopsis (polar-HS), which extends the classical HS by considering the polarization state of light in the reciprocal paths. With the additional phase information from polarization, polar-HS requires only one reciprocal image pair. We derive the reciprocity relationship of Mueller matrix and formulate new reciprocity constraint that takes polarization state into account. We also utilize polarimetric constraints and extend them to the case of perspective projection. For the recovery of surface depths and normals, we incorporate reciprocity constraint with diffuse/specular polarimetric constraints in a unified optimization framework. For depth estimation, we further propose to utilize the consistency of diffuse angle of polarization. For normal estimation, we develop a normal refinement strategy based on degree of linear polarization. Using a hardware prototype, we show that our approach produces high-quality 3D reconstruction for different types of surfaces, ranging from diffuse to highly specular.

Anti-obesity effects of mulberry leaf extracts on female high-fat diet-induced obesity: Modulation of white adipose tissue, gut microbiota, and metabolic markers.

Mulberry leaves (MLs) are reported to have beneficial effects in modulating obesity in male models. However, the impact of different types of mulberry leaf extracts (MLEs) on female models, specifically their influence on adipocytes, gut microbiota, and related metabolic markers, remains poorly understood. In this study, we observed a strong correlation between the total phenolic content (TPC), antioxidant and adipocyte modulation effects of water extracted MLEs. HB-W (water-extracted baiyuwang) and HY-W (water-extracted Yueshen) demonstrated remarkable inhibition effects on adipocytes in 3 T3-L1 adipocytes model. Moreover, MLEs effectively reduced the levels of triglycerides (TG), non-esterified fatty acids (NEFA), and total cholesterol (T-CHO) in adipocytes in vitro. In vivo experiments conducted on female mice with high fat diet (HFD)-induced obesity revealed the anti-obesity effects of HB-W and HY-W, leading to a significant decrease in weight gain rates and notable influence on the ratios of adipose tissue, particularly white adipose tissue (WAT). Gene expression analysis demonstrated the up-regulation of WAT-related genes (Pla2g2a and Plac8) by HB-W, while HY-W supplementation showed beneficial effects on the regulation of blood sugar-related genes. Furthermore, both HB-W and HY-W exhibited modulatory effects on obesity-related gut microbiota (Firmicutes-to-Bacteroidetes ratio) and short chain fatty acid (SCFA) contents. Importantly, they also mitigated abnormalities in liver function and uncoupling protein 1 (UPC1) expression. Overall, our findings underscore the anti-obesity effects of MLEs in female rats with high-fat diet-induced obesity.

Interplays between plants and environmental factors determine pullout resistance on different revegetated slopes in mining areas.

Plant roots play a crucial role in enhancing soil stability and protecting slopes during ecological restoration, particularly in mining areas where external-soil spray seeding is employed. However, the relationship between plant root pullout resistance and environmental factors on different types of slopes remains unclear. In this study, we investigated the interactions between the pullout resistance of a dominant species, Artemisia gmelinii, and environmental factors on three slope types (rocky, geotechnical, and soil) using multi-group structural equation modeling. Our findings reveal that the pullout resistance of plant roots was strongly influenced by various factors, including but not limited to biological factors such as plant height and biomass. It showed a positive correlation between soil silt content and soil nutrient levels. Notably, the pullout resistance on soil slopes was significantly higher than on rocky slopes. Furthermore, the impact of soil nutrients and texture on pullout resistance was more pronounced on geotechnical and soil slopes compared to rocky slopes. Multi-group structural equation modeling highlighted that among all environmental factors, slope gradient and underground biomass had the most significant influence on pullout resistance across all slope types. Specifically, slope gradient had a greater effect on soil slopes, whereas underground biomass played a more prominent role on rocky and geotechnical slopes. Overall, our study suggests that when implementing external-soil spray seeding in mining areas, it is crucial to consider the interplay between plant roots and environmental factors, including slope properties. This holistic approach is crucial for maximizing the effectiveness of plants in slope protection during eco-engineering projects.

Am I Winning or Losing? Probing the Appraisal of Partial Wins via Response Vigor.

Attempts to obtain rewards are not always successful. Despite investing much time, effort, or money, sometimes individuals may not obtain any reward. Other times they may obtain some reward, but the obtained reward may be smaller than their initial investment, such as partial wins in gambling. It remains unclear how such ambiguous outcomes are appraised. To address this question, we systematically varied the payoffs for different outcomes in a computerized scratch card task across three experiments. To test outcome appraisal, we used response vigor as a novel proxy. In the scratch card task, participants turned three cards one by one. Depending on the turned cards, they either received an amount that was higher than the wager (win), an amount lower than the wager (partial win), or nothing (loss). Overall, participants responded to partial wins more slowly than losses, but more quickly than wins. Partial wins were therefore appraised to be better than losses, but worse than wins. Importantly, further analyses showed that outcome appraisal was not based on the net win or loss amount. Instead, participants primarily used the configuration of turned cards as a cue for the relative rank of an outcome within a specific game. Outcome appraisals thus utilize simple heuristic rules, rely on salient information (such as outcome-related cues in gambling), and are specific to a local context. Together, these factors may contribute to the misperception of partial wins as real wins in gambling. Future work may examine how outcome appraisal may be modulated by the salience of certain information, and investigate the appraisal process in contexts beyond gambling.

Sarcopenia predicts postoperative complications and survival in colorectal cancer patients with GLIM-defined malnutrition: Analysis from a prospective cohort study.

OBJECTIVE: To investigate whether sarcopenia could predict postoperative outcomes in patients with colorectal cancer with Global Leadership Initiative on Malnutrition (GLIM)-defined malnutrition. METHODS: Clinical data of patients who underwent radical resection for colorectal cancer were prospectively collected. Sarcopenia was diagnosed by the combination of low handgrip strength and low muscle quantity or quality as measured by abdominal computed tomography (CT) images. Logistic regression analysis and Cox proportional hazards regression analysis were performed to identify independent predictors for postoperative complications and survival, respectively. RESULTS: A total of 310 patients with colorectal cancer with GLIM-defined malnutrition were included, of which 145 (46.77%) were identified with sarcopenia. Malnutritional patients with sarcopenia had significantly higher incidences of total complications (34.5% versus 15.8%), severe complications (9.7% versus 1.8%), longer lengths of postoperative hospital stay (median, 14 days versus 12 days), and more costs (median, 56,257 RMB versus 49,024 RMB) than those without sarcopenia. Sarcopenia was an independent predictive factor for postoperative complications (OR 2.531, 95% CI 1.451-4.415), overall survival (HR 1.519, 95% CI 1.026-2.248), and disease-free survival (HR 1.847, 95% CI 1.324-2.576). Patients with severe sarcopenia had a higher incidence of severe complications but not total complications or survival than those with not-severe sarcopenia. Moreover, the predictive value of sarcopenia for postoperative complications was attributed to muscle strength and quality but not muscle quantity. CONCLUSION: Sarcopenia predicts postoperative complications and survival in patients with colorectal cancer with GLIM-defined malnutrition. Preoperative assessment of sarcopenia is still necessary when nutritional assessment has been well performed.

A deep learning model, NAFNet, predicts adverse pathology and recurrence in prostate cancer using MRIs.

We aimed to apply a potent deep learning network, NAFNet, to predict adverse pathology events and biochemical recurrence-free survival (bRFS) based on pre-treatment MRI imaging. 514 prostate cancer patients from six tertiary hospitals throughout China from 2017 and 2021 were included. A total of 367 patients from Fudan University Shanghai Cancer Center with whole-mount histopathology of radical prostatectomy specimens were assigned to the internal set, and cancer lesions were delineated with whole-mount pathology as the reference. The external test set included 147 patients with BCR data from five other institutes. The prediction model (NAFNet-classifier) and integrated nomogram (DL-nomogram) were constructed based on NAFNet. We then compared DL-nomogram with radiology score (PI-RADS), and clinical score (Cancer of the Prostate Risk Assessment score (CAPRA)). After training and validation in the internal set, ROC curves in the external test set showed that NAFNet-classifier alone outperformed ResNet50 in predicting adverse pathology. The DL-nomogram, including the NAFNet-classifier, clinical T stage and biopsy results, showed the highest AUC (0.915, 95% CI: 0.871-0.959) and accuracy (0.850) compared with the PI-RADS and CAPRA scores. Additionally, the DL-nomogram outperformed the CAPRA score with a higher C-index (0.732, P < 0.001) in predicting bRFS. Based on this newly-developed deep learning network, NAFNet, our DL-nomogram could accurately predict adverse pathology and poor prognosis, providing a potential AI tools in medical imaging risk stratification.

Interorgan communication with the liver: novel mechanisms and therapeutic targets.

The liver is a multifunctional organ that plays crucial roles in numerous physiological processes, such as production of bile and proteins for blood plasma, regulation of blood levels of amino acids, processing of hemoglobin, clearance of metabolic waste, maintenance of glucose, etc. Therefore, the liver is essential for the homeostasis of organisms. With the development of research on the liver, there is growing concern about its effect on immune cells of innate and adaptive immunity. For example, the liver regulates the proliferation, differentiation, and effector functions of immune cells through various secreted proteins (also known as "hepatokines"). As a result, the liver is identified as an important regulator of the immune system. Furthermore, many diseases resulting from immune disorders are thought to be related to the dysfunction of the liver, including systemic lupus erythematosus, multiple sclerosis, and heart failure. Thus, the liver plays a role in remote immune regulation and is intricately linked with systemic immunity. This review provides a comprehensive overview of the liver remote regulation of the body's innate and adaptive immunity regarding to main areas: immune-related molecules secreted by the liver and the liver-resident cells. Additionally, we assessed the influence of the liver on various facets of systemic immune-related diseases, offering insights into the clinical application of target therapies for liver immune regulation, as well as future developmental trends.

Awareness and use of five imaging decision rules for musculoskeletal injuries: a systematic review.

BACKGROUND: Several validated decision rules are available for clinicians to guide the appropriate use of imaging for patients with musculoskeletal injuries, including the Canadian CT Head Rule, Canadian C-Spine Rule, National Emergency X-Radiography Utilization Study (NEXUS) guideline, Ottawa Ankle Rules and Ottawa Knee Rules. However, it is unclear to what extent clinicians are aware of the rules and are using these five rules in practice. OBJECTIVE: To determine the proportion of clinicians that are aware of five imaging decision rules and the proportion that use them in practice. DESIGN: Systematic review. METHODS: This was a systematic review conducted in accordance with the 'Preferred reporting items for systematic reviews and meta-analyses' (PRISMA) statement. We performed searches in MEDLINE (via Ovid), CINAHL (via EBSCO), EMBASE (via Ovid), Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science and Scopus databases to identify observational and experimental studies with data on the following outcomes among clinicians related to five validated imaging decision rules: awareness, use, attitudes, knowledge, and barriers and facilitators to implementation. Where possible, we pooled data using medians to summarise these outcomes. RESULTS: We included 39 studies. Studies were conducted in 15 countries (e.g. the USA, Canada, the UK, Australasia, New Zealand) and included various clinician types (e.g. emergency physicians, emergency nurses and nurse practitioners). Among the five decision rules, clinicians' awareness was highest for the Canadian C-Spine Rule (84%, n = 3 studies) and lowest for the Ottawa Knee Rules (18%, n = 2). Clinicians' use was highest for NEXUS (median percentage ranging from 7 to 77%, n = 4) followed by Canadian C-Spine Rule (56-71%, n = 7 studies) and lowest for the Ottawa Knee Rules which ranged from 18 to 58% (n = 4). CONCLUSION: Our results suggest that awareness of the five imaging decision rules is low. Changing clinicians' attitudes and knowledge towards these decision rules and addressing barriers to their implementation could increase use.

The OX40-TRAF6 axis promotes CTLA-4 degradation to augment antitumor CD8+ T-cell immunity.

Immune checkpoint blockade (ICB), including anti-cytotoxic T-lymphocyte associated protein 4 (CTLA-4), benefits only a limited number of patients with cancer. Understanding the in-depth regulatory mechanism of CTLA-4 protein stability and its functional significance may help identify ICB resistance mechanisms and assist in the development of novel immunotherapeutic modalities to improve ICB efficacy. Here, we identified that TNF receptor-associated factor 6 (TRAF6) mediates Lys63-linked ubiquitination and subsequent lysosomal degradation of CTLA-4. Moreover, by using TRAF6-deficient mice and retroviral overexpression experiments, we demonstrated that TRAF6 promotes CTLA-4 degradation in a T-cell-intrinsic manner, which is dependent on the RING domain of TRAF6. This intrinsic regulatory mechanism contributes to CD8+ T-cell-mediated antitumor immunity in vivo. Additionally, by using an OX40 agonist, we demonstrated that the OX40-TRAF6 axis is responsible for CTLA-4 degradation, thereby controlling antitumor immunity in both tumor-bearing mice and patients with cancer. Overall, our findings demonstrate that the OX40-TRAF6 axis promotes CTLA-4 degradation and is a potential therapeutic target for the improvement of T-cell-based immunotherapies.