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Abstract Modulation of electronic spin states in cobalt-based catalysts is an effective strategy for molecule activations. Crystalline-amorphous interfaces often exhibit unique catalytic properties due to disruptions of long-range order and alterations in electronic structure. However, the mechanisms of molecule activation and spin states at interfaces remain elusive. Herein, we present a Co3O4 spinel-based catalyst featuring crystalline-amorphous interfaces. Characterization analyses confirm that tetrahedral Co2+ is selectively etched from bulk spinel, forming amorphous CoO islands on the surface. The resultant symmetry breaking in the coordination field induces a reconstruction of the Co3+ 3 d orbitals, leading to high-spin states. In CO oxidation, the interface serves as novel active sites with a lower energy barrier, facilitated by lattice oxygen activation. In N2O decomposition, the interface promotes reassociation of dissociated oxygen through quantum spin exchange interactions. This work provides a straightforward approach to modulating the spin state of interfaces and elucidates their role in molecule activations.

Abstract Graph data is essential for modeling complex relationships among entities. Graph Neural Networks (GNNs) have demonstrated effectiveness in processing low-order undirected graph data; however, in complex directed graphs, relationships between nodes extend beyond first-order connections and encompass higher-order relationships. Additionally, the asymmetry introduced by edge directionality further complicates node interactions, presenting greater challenges for extracting node information. In this paper, We propose TWC-GNN, a novel graph neural network design, as a solution to this problem. TWC-GNN uses node degrees to define higher-order topological structures, assess node importance, and capture mutual interactions between central nodes and their adjacent counterparts. This approach improves our understanding of complex relationships within the network. Furthermore, by integrating self-attention mechanisms, TWC-GNN effectively gathers higher-order node information in addition to focusing on first-order node information. Experimental results demonstrate that the integration of topological structures and higher-order node information is crucial for the learning process of graph neural networks, particularly in directed graphs, leading to improved classification accuracy.

Abstract Understanding Pd effects on NOx storage and release is crucial for designing passive NOx adsorber (PNA) to control NOx emissions during diesel cold-starts. Herein, we report two oxidation states of Pd species on CexZr1-xO2 regulated by metal-support interaction. Pdδ+ (0

Abstract Traffic density is a crucial indicator for evaluating the level of service, as it directly reflects the degree of road congestion and driving comfort. However, accurately predicting real-time traffic density has been a significant challenge in Intelligent Transportation Systems (ITS) due to the nonlinear and spatial-temporal dynamic complexity of traffic density. In this paper, we propose a novel Model-enhanced Spatial-Temporal Attention Network (MSTAN), which constructs a spatial-temporal traffic kernel density model using the Kernel Density Estimation (KDE) method to process the spatiotemporal data and calculate the probabilities of various spatiotemporal events. These probabilities are input into the attention mechanism, enabling the model to recognize the inherent connection between dynamic and distant events. Through this fusion, the network can deeply learn and analyze the spatial-temporal properties of traffic features. Furthermore, this paper utilizes the attention mechanism to dynamically model spatial-temporal dependencies, capturing real-time traffic conditions and density, and constructs a spatial-temporal attention module for learning. To validate the performance of the proposed MSTAN model, experiments are conducted on two public datasets of California highways (PeMS04 and PeMS08). The experimental results demonstrate that the MSTAN model outperforms existing state-of-the-art baseline models in terms of prediction accuracy, thus proving the effectiveness of the model both theoretically and practically.

Abstract Neoadjuvant immunochemotherapy (nICT) has dramatically changed the treatment landscape of operable esophageal squamous cell carcinoma (ESCC), but factors influencing tumor response to nICT are not well understood. Here, using single-cell RNA sequencing paired with T cell receptor sequencing, we profile tissues from ESCC patients accepting nICT treatment and characterize the tumor microenvironment context. CXCL13+CD8+ Tex cells, a subset of exhausted CD8+ T cells, are revealed to highly infiltrate in pre-treatment tumors and show prominent progenitor exhaustion phenotype in post-treatment samples from responders. We validate CXCL13+CD8+ Tex cells as a predictor of improved response to nICT and reveal CXCL13 to potentiate anti-PD-1 efficacy in vivo. Post-treatment tumors from non-responders are enriched for CXCL13+CD8+ Tex cells with notably remarkable exhaustion phenotype and TNFRSF4+CD4+ Tregs with activated immunosuppressive function and a significant clone expansion. Several critical markers for therapeutic resistance are also identified, including LRRC15+ fibroblasts and SPP1+ macrophages, which may recruit Tregs to form an immunosuppressive landscape. Overall, our findings unravel immune features of distinct therapeutic response to nICT treatment, providing a rationale for optimizing individualized neoadjuvant strategy in ESCC.

Abstract Lattice oxygen in metal oxides plays an important role in the reaction of diesel oxidation catalysts, but the atomic-level understanding of structural evolution during the catalytic process remains elusive. Here, we develop a Mn2O3/SmMn2O5 catalyst using a non-stoichiometric exsolution method to explore the roles of lattice oxygen in NO oxidation. The enhanced covalency of Mn–O bond and increased electron density at Mn3+ sites, induced by the interface between exsolved Mn2O3 and mullite, lead to the formation of highly active lattice oxygen adjacent to Mn3+ sites. Near-ambient pressure X-ray photoelectron and absorption spectroscopies show that the activated lattice oxygen enables reversible changes in Mn valence states and Mn-O bond covalency during redox cycles, reducing energy barriers for NO oxidation and promoting NO2 desorption via the cooperative Mars-van Krevelen mechanism. Therefore, the Mn2O3/SmMn2O5 exhibits higher NO oxidation activity and better resistance to hydrothermal aging compared to a commercial Pt/Al2O3 catalyst.

Objective: To investigate the relationship between 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) related parameters and the prognosis of multiple myeloma and to establish and validate a prediction model regarding the progression-free survival (PFS) of multiple myeloma.Methods: A retrospective analysis of 126 newly diagnosed multiple myeloma patients who attended Nanjing Drum Tower Hospital from 2014–2021. All patients underwent PET/CT before treatment and were divided into a training cohort (n = 75) and a validation cohort (n = 51). Multivariate Cox proportional hazard regression analysis incorporated PET/CT-related parameters and clinical indicators. A nomogram was established to individually predict PFS in MM patients. The model was evaluated by calculating the C-index and calibration curve.Results: Here, 4.2 was used as the cut-off value of SUVmax to divide patients into high and low groups. PFS significantly differed between patients in the high-SUVmax group and low-SUVmax group, and SUVmax was an independent predictor of PFS in newly diagnosed multiple myeloma (NDMM) patients. Univariate and multivariate cox regression analysis suggested that lactate dehydrogenase (LDH), bone marrow plasma cell (BMPC), and SUVmax affected PFS. These factors were incorporated to construct a nomogram model for predicting PFS at 1 and 2 years in NDMM patients. The C-index and calibration curves of the nomogram exhibited good accuracy and consistency, and the DCA curves suggested that the model had good clinical utility.Conclusion: The PET/CT parameter SUVmax is closely related to the prognosis of myeloma patients. The nomogram constructed in this study based on PET/CT-related parameters and clinical indicators individually predicts the PFS rate of NDMM patients and enables further risk stratification of NDMM patients.

Abstract Autoimmune related kidney diseases (ARKDs), including minimal change nephropathy (MCN), membranous nephropathy (MN), IgA nephropathy (IgAN), and lupus nephritis (LN), significantly affect renal function. These diseases are characterized by the formation of local immune complexes and the subsequent activation of the complement system, leading to kidney damage and proteinuria. Despite the known patterns of glomerular injury, the specific molecular mechanisms that contribute to renal tubular damage across ARKDs remain underexplored. Laser capture microdissection and liquid chromatography–tandem mass spectrometry (LC–MS/MS) were used to conduct a comparative proteomic analysis of renal tubular tissues from formalin-fixed paraffin-embedded samples. The cohort comprised of 10 normal controls (NC), 5 MCN, 4 MN, 17 IgAN, and 21 LN patients. Clinical parameters and histopathological assessments were integrated with proteomic findings to comprehensively investigate underlying pathogenic processes. Clinical evaluation indicated significant glomerular damage, as reflected by elevated urinary protein levels and reduced plasma albumin levels in patients with ARKD. Histological analyses confirmed varying degrees of tubular damage and deposition of immune complexes. Proteomic analyses identified significant changes in protein expression, particularly in complement components (C3, C4A, C4B, C8G, CFB, and SERPINA1) and mitochondrial proteins (ATP5F1E and ATP5PD), highlighting the common alterations in the complement system and mitochondrial proteins across ARKDs. These alterations suggest a novel complement–mitochondrial–epithelial–mesenchymal transition (EMT) pathway axis that contributes to tubular damage in ARKDs. Notably, significant alterations in CFB in tubular ARKD patients were revealed, implicating it as a therapeutic target. This study underscores the importance of complement activation and mitochondrial dysfunction in the pathogenesis of ARKDs, and proposes CFB as a potential therapeutic target to inhibit complement activation and mitigate tubular damage. Future research should validate the complement-mitochondrial-EMT pathway axis and explore the effects and mechanisms of CFB inhibitors in alleviating ARKD progression.

High-resolution digital elevation models (DEMs) of the lunar surface are crucial for lunar exploration missions and scientific research. The emergence of advanced technologies, such as Shape-from-Shading (SfS), has enabled the generation of pixel-wise high-resolution DEMs from monocular images of the lunar surface. However, SfS encounters significant challenges in locations with limited illumination, such as the lunar south pole, where the surface is largely covered by shadows. Therefore, this paper presents a novel shadow-constrained SfS approach for pixel-wise 3D surface reconstruction at the lunar south pole. The proposed approach uses multiple high-resolution images captured under different illumination conditions and an existing low-resolution DEM as the inputs and generates a high-resolution DEM with the same resolution as that of the input image through hierarchical SfS processing incorporating shadow constraints. Experiments were conducted using actual images collected by the Lunar Reconnaissance Orbiter (LRO) Narrow Angle Camera (NAC) at the lunar south pole. Comparisons with respect to photogrammetric DEMs generated from stereo NAC images show that the DEMs generated using the proposed approach exhibit the smallest root mean square error (RMSE). Moreover, shaded relief images rendered from the DEMs generated using the proposed approach demonstrate the highest similarity to the actual NAC images. Detailed profile comparisons further validate the effectiveness of the shadow constraint in optimizing 3D reconstruction in regions in proximity to shadows and within shadowed regions. The proposed shadow-constrained SfS approach can be used to generate high-resolution DEMs to support future missions to explore the lunar south pole, with applications including landing site evaluation and route planning for lunar probes or astronauts.

Abstract As the largest organ in the human body, skeletal muscle is essential for breathing support, movement initiation, and maintenance homeostasis. It has been shown that programmed cell death (PCD), which includes autophagy, apoptosis, and necrosis, is essential for the development of skeletal muscle. A novel form of PCD called ferroptosis is still poorly understood in relation to skeletal muscle. In this study, we observed that the activation of ferroptosis significantly impeded the differentiation of C2C12 myoblasts into myotubes and concurrently suppressed the expression of OTUB1, a crucial deubiquitinating enzyme. OTUB1-silenced C2C12 mouse myoblasts were used to investigate the function of OTUB1 in ferroptosis. The results show that OTUB1 knockdown in vitro significantly increased C2C12 ferroptosis and inhibited myogenesis. Interestingly, the induction of ferroptosis resulting from OTUB1 knockdown was concomitant with the activation of autophagy. Furthermore, OTUB1 interacted with the P62 protein and stabilized its expression by deubiquitinating it, thereby inhibiting autophagy-dependent ferroptosis and promoting myogenesis. All of these findings demonstrate the critical role that OTUB1 plays in controlling ferroptosis, and we suggest that focusing on the OTUB1-P62 axis may be a useful tactic in the treatment and prevention of disorders involving the skeletal muscle.

IntroductionThis research explores the role of critical thinking and cultural intelligence in psychological well-being through the lens of cultural identity development. It aims to understand how individuals think critically and navigate different cultural challenges that influence their psychological wellbeing.MethodsThe quantitative analysis utilizes various scales to elucidate the correlation between critical thinking beliefs, cultural intelligence, and well-being. The qualitative exploration employing NVivo 20.0 uncovers the interplay between critical thinking, cultural intelligence, and well-being in the construction of cultural identity and psychological selfhood.ResultsThe research results show a significant positive correlation between critical thinking, cultural intelligence, and psychological well-being. Themes such as well-being, cultural intelligence, critical thinking, and facing challenges illustrate how individuals navigate obstacles to achieve a meaningful and purposeful life. The findings from both the quantitative and qualitative analyses provide a comprehensive understanding of how critical thinking, cultural intelligence, and well-being intersect and influence individuals’ perceptions of themselves and their cultural identities.DiscussionThe research results suggest that developing critical thinking and cultural intelligence positively impacts individuals’ psychological well-being in cultural identity development. This can lead to greater belonging and acceptance in diverse cultural settings.

IntroductionThis study presented an end-to-end 3D deep learning model for the automatic segmentation of brain tumors.MethodsThe MRI data used in this study were obtained from a cohort of 630 GBM patients from the University of Pennsylvania Health System (UPENN-GBM). Data augmentation techniques such as flip and rotations were employed to further increase the sample size of the training set. The segmentation performance of models was evaluated by recall, precision, dice score, Lesion False Positive Rate (LFPR), Average Volume Difference (AVD) and Average Symmetric Surface Distance (ASSD).ResultsWhen applying FLAIR, T1, ceT1, and T2 MRI modalities, FusionNet-A and FusionNet-C the best-performing model overall, with FusionNet-A particularly excelling in the enhancing tumor areas, while FusionNet-C demonstrates strong performance in the necrotic core and peritumoral edema regions. FusionNet-A excels in the enhancing tumor areas across all metrics (0.75 for recall, 0.83 for precision and 0.74 for dice scores) and also performs well in the peritumoral edema regions (0.77 for recall, 0.77 for precision and 0.75 for dice scores). Combinations including FLAIR and ceT1 tend to have better segmentation performance, especially for necrotic core regions. Using only FLAIR achieves a recall of 0.73 for peritumoral edema regions. Visualization results also indicate that our model generally achieves segmentation results similar to the ground truth.DiscussionFusionNet combines the benefits of U-Net and SegNet, outperforming the tumor segmentation performance of both. Although our model effectively segments brain tumors with competitive accuracy, we plan to extend the framework to achieve even better segmentation performance.

Background: An association between increased aortic root dimensions (ARD) and elevated risk of cardiovascular mortality has been reported in the general population. However, evidence regarding the association between ARD and mortality in patients with acute heart failure (AHF) is limited. Methods: In a nationwide prospective cohort of the China Patient-Centered Evaluative Assessment of Cardiac Events Prospective Heart Failure Study, ARD was measured during diastole using echocardiography and indexed to body mass index (BMI). Cox proportional hazard models were used to validate the association between BMI-indexed ARD and mortality. Additionally, the relationship between BMI-indexed ARD and mortality was presented using restricted cubic spline in all populations, and both sexes. Results: A total of 2125 participants with ARD were included in the final analysis, among of 38.4 % were women, with a median age of 67 years. Over a median follow-up period of 54.4 (interquartile range: 30.1 to 59.7) months, 895 deaths occurred, with 750 attributed to cardiovascular causes and 145 to non-cardiovascular causes. Compared to the highest tertile group of BMI-indexed ARD, the lowest tertile group had a lower risk of cardiovascular mortality (hazard ratio [HR], 0.71; 95 % confidence interval [CI], 0.58 to 0.87; P

Abstract Background In China, real‐world data on surgical challenges and postoperative complications after neoadjuvant immunotherapy of lung cancer are limited. Methods Patients were retrospectively enrolled from January 2018 to January 2023, and their clinical and pathological characters were subsequently analyzed. Surgical difficulty was categorized into a binary classification according to surgical duration: challenging or routine. Postoperative complications were graded using Clavien–Dindo grades. Logistic regression was used to identify risk factors affecting the duration of surgery and postoperative complications greater than Clavien–Dindo grade 2. Results In total, 261 patients were included. Of these, stage III patients accounted for 62.5% (163/261) at initial diagnosis, with 25.3% (66/261) at stage IIIB. Central‐type non‐small‐cell lung cancer accounted for 61.7% (161/261). One hundred and forty patients underwent video‐assisted thoracoscopic surgery and lobectomy accounted for 53.3% (139/261) of patients. Surgical time over average duration was defined as challenging surgeries, accounting for 43.7%. The postoperative complications rate of 261 patients was only 22.2%. Smoking history (odds ratio [OR] = 9.96, 95% [CI] 1.15–86.01, p = 0.03), chemoimmunotherapy (OR = 2.89, 95% CI 1.22–6.86, p = 0.02), and conversion to open surgery (OR = 11.3, 95% CI 1.38–92.9, p = 0.02) were identified as independent risk factors for challenging surgeries, while pneumonectomy (OR = 0.36, 95% CI 0.15–0.86, p= 0.02) was a protective factor. Meanwhile, pneumonectomy (OR = 7.51, 95% CI 2.40–23.51, p

Abstract Background Studies have shown that chemotherapy and radiotherapy can cause premature ovarian failure and loss of fertility in female cancer patients. Ovarian cortex cryopreservation is a good choice to preserve female fertility before cancer treatment. Following the remission of the disease, the thawed ovarian tissue can be transplanted back and restore fertility of the patient. However, there is a risk to reintroduce cancer cells in the body and leads to the recurrence of cancer. Given the low success rate of current in vitro culture techniques for obtaining mature oocytes from primordial follicles, an artificial ovary with primordial follicles may be a good way to solve this problem. Methods In the study, we established an artificial ovary model based on the participation of mesenchymal stem cells (MSCs) to evaluate the effect of MSCs on follicular development and oocyte maturation. P2.5 mouse ovaries were digested into single cell suspensions and mixed with bone marrow derived mesenchymal stem cells (BM-MSCs) at a 1:1 ratio. The reconstituted ovarian model was then generated by using phytohemagglutinin. The phenotype and mechanism studies were explored by follicle counting, immunohistochemistry, immunofluorescence, in vitro maturation (IVM), in vitro fertilization (IVF), real-time quantitative polymerase chain reaction (RT-PCR), and Terminal-deoxynucleotidyl transferase mediated nick end labeling(TUNEL) assay. Results Our study found that the addition of BM-MSCs to the reconstituted ovary can enhance the survival of oocytes and promote the growth and development of follicles. After transplanting the reconstituted ovaries under kidney capsules of the recipient mice, we observed normal folliculogenesis and oocyte maturation. Interestingly, we found that BM-MSCs did not contribute to the formation of follicles in ovarian aggregation, nor did they undergo proliferation during follicle growth. Instead, the cells were found to be located around growing follicles in the reconstituted ovary. When theca cells were labeled with CYP17a1, we found some overlapped staining with green fluorescent protein(GFP)-labeled BM-MSCs. The results suggest that BM-MSCs may participate in directing the differentiation of theca layer in the reconstituted ovary. Conclusions The presence of BM-MSCs in the artificial ovary was found to promote the survival of ovarian cells, as well as facilitate follicle formation and development. Since the cells didn’t proliferate in the reconstituted ovary, this discovery suggests a potential new and safe method for the application of MSCs in clinical fertility preservation by enhancing the success rate of cryo-thawed ovarian tissues after transplantation.

Abstract Surface visibility (SV), a key indicator of atmospheric transparency, is used widely in the fields of environmental monitoring, transportation, and aviation. However, the sparse distribution and limited number of SV monitoring sites make it difficult to fulfill the urgent need for spatiotemporally seamless fine-scale monitoring. Here, we developed the operational real-time SV retrieval (RT-SVR) framework for China that incorporates information from multiple data sources, including Chinese Land Data Assimilation System meteorological data, in situ observations, and other ancillary data. Seamless hourly SV data with 6.25-km spatial resolution are available in real time via the operational RT-SVR model, which was built using a two-layer stacked ensemble approach that combines multiple machine learning algorithms and a deep learning module. Sample-based cross-validation of the RT-SVR model on approximately 41.3 million data pairs revealed strong robustness and high accuracy, with a Pearson correlation coefficient (R) value of 0.95 and a root mean square error (RMSE) of 3.17 km. An additional hindcast-validation experiment, performed with continuous observations obtained over one year (approximately 20.8 million data pairs), demonstrated the powerful generalization capabilities of the RT-SVR model, albeit with slight degradation in performance (R = 0.85, RMSE = 5.28 km). The seamless hourly SV data with real-time update capability enable tracking of the generation, development, and dissipation of various low-SV events (e.g., fog, haze, and dust storms) in China. The developed framework might also prove useful for quantitative retrieval of aerosol-related parameters (e.g., PM2.5, PM10, and aerosol optical depth).

Objective:. Home blood pressure monitoring (HBPM) is viewed as a facilitating factor in the initial diagnosis and long-term management of treated hypertension. However, evidence remains scarce about the effectiveness of HBPM use in the real world. This study aimed to examine the associations of HBPM use with blood pressure (BP) control and medication adherence. Methods:. This prospective cohort study included hypertensive patients with high cardiovascular risk who were aged ≥50 years. At baseline, information about types of BP monitor, frequency of HBPM, perception of anti-hypertensive treatment, and measured office BP were collected. During the 1-year follow-up (visits at 1, 2, 3, 6, and 12 months), information on medication adherence was collected at each visit. The 2 major outcomes were BP control at baseline and medication adherence during the 1-year follow-up. A log-binomial regression model was used to examine the association between frequency of HBPM and outcomes, stratified by the perceptions of anti-hypertensive treatment. Results:. A total of 5,363 hypertensive patients were included in the analysis. The age was (64.6 ± 7.2) years, and 41.2% (2,208) were female. Of the total patients, 85.9% (4,606) had a home BP monitor and 47.8% (2,564) had an incorrect perception of anti-hypertensive treatment. Overall, 24.2% (1,299) of patients monitored their BP daily, 37.6% (2,015) weekly, 17.3% (926) monthly, and 20.9% (1,123) less than monthly. At baseline, the systolic BP and diastolic BP were (146.6 ± 10.8) mmHg and (81.9 ± 10.6) mmHg, respectively, and 28.5% (1,527) of patients had their BP controlled. Regardless of whether the patients had correct or incorrect perceptions of anti-hypertensive treatment, there is no significant association between HBPM frequency and BP control at baseline. During the 1-year follow-up, 23.9% (1,280) of patients had non-adherence to medications at least once. In patients with an incorrect perception of anti-hypertensive treatment, those monitoring BP most frequently (daily) had the highest non-adherence rate (29.9%, 175/585). Compared with those monitoring their BP less than monthly, patients who monitored their BP daily were more likely not to adhere to anti-hypertensive medications (adjusted relative risk = 1.38, 95% confidence interval: 1.11–1.72, P = 0.004). Conclusions:. HBPM performance among hypertensive patients in China is, in general, sub-optimal. No association was observed between using HBPM alone and hypertension control, indicating that the effects of HBPM could be conditional. Patients’ misconceptions about anti-hypertensive treatment may impair the role of BP monitoring in achieving medication adherence. Fully incorporating the correct perception of hypertension into the management of hypertensive patients is needed.

Background Poor cardiovascular‐kidney‐metabolic (CKM) health is associated with premature mortality and excess morbidity in the United States. Adverse social conditions have a prominent impact on cardiometabolic diseases during the life course. We aim to examine the association between social risk profile (SRP) and CKM multimorbidity among US adults. Methods and Results We used data from the National Health and Nutrition Examination Survey from 1999 to 2018. The definition of CKM syndrome is the coexistence of subclinical or clinical cardiovascular disease, chronic kidney disease, and metabolic disorders. We classified participants by 4 CKM stages according to the different clinical severity of different forms of CKM syndrome. We calculated the summed number of positive SRP measures, including employed, high‐income level, food secure, high education attainment, private insurance, owning a house, and married, as SRP scores and classified them into 4 levels by quartiles: low (0–2), lower‐middle (3–4), upper‐middle (5–6), and high (7–8). A total of 18 373 US adults, aged 20 to 79 years, were included in our analyses. There were 2567 (9.4%) participants with low SRP score level. Most individual SRP measures and a combined SRP score were associated with CKM stages. Compared with high SRP score level, low SRP level was associated with higher odds of having CKM stage 1 (odds ratio [OR], 1.34 [95% CI, 1.06–1.70]), CKM stage 2 (OR, 2.03 [95% CI, 1.59–2.58]), CKM stage 3 (OR, 5.28 [95% CI, 3.29–8.47]), and CKM stage 4 (OR, 5.97 [95% CI, 4.20–8.49]). Conclusions Cumulative social disadvantage, denoted by higher SRP burden, was associated with higher odds of CKM multimorbidity, independent of demographic and lifestyle factors.

Addressing the threats of climate change, pollution, and overfishing to marine ecosystems necessitates a deeper understanding of coastal and oceanic fluid dynamics. Within this context, Lagrangian Coherent Structures (LCS) emerge as essential tools for elucidating the complexities of marine fluid dynamics. Methods used to detect LCS include geometric, probabilistic, cluster-based and braid-based approaches. Advancements have been made to employ Finite-time Lyapunov Exponents (FTLE) to detect LCS due to its high efficacy, reliability and simplicity. It has been proven that the FTLE approach has provided invaluable insights into complex oceanic phenomena like shear, confluence, eddy formations, and oceanic fronts, which also enhanced the understanding of tidal-/wind-driven processes. Additionally, FTLE-based LCS were crucial in identifying barriers to contaminant dispersion and assessing pollutant distribution, aiding environmental protection and marine pollution management. FTLE-based LCS has also contributed significantly to understanding ecological interactions and biodiversity in response to environmental issues. This review identifies pressing challenges and future directions of FTLE-based LCS. Among these are the influences of external factors such as river discharges, ice formations, and human activities on ocean currents, which complicate the analysis of ocean fluid dynamics. While 2D FTLE methods have proven effective, their limitations in capturing the full scope of oceanic phenomena, especially in 3D environments, are evident. The advent of 3D LCS analysis has marked progress, yet computational demands and data quality requirements pose significant hurdles. Moreover, LCS extracted from FTLE fields involves establishing an empirical threshold that introduces considerable variability due to human judgement. Future efforts should focus on enhancing computational techniques for 3D analyses, integrating FTLE and LCS into broader environmental models, and leveraging machine learning to standardize LCS detection.

ObjectiveThis study synthesized the highest level of evidence to analyse the effectiveness and safety of using extracorporeal shock wave therapy (ESWT) to treat upper limb tendonitis, which was unknown.DesignWe conducted a systematic review and meta-analysis of 18 randomized controlled trials (RCTs) in PubMed, Embase, Web of Science, Medline, and the Cochrane Library.MethodsTwo researchers performed the screening, data extraction, literature quality assessment, and heterogeneity analysis of the searched RCTs.ResultsThe main types of morbidity included rotator cuff tendonitis, lateral epicondylitis, finger tendonitis, and long bicipital tendonitis. The results of the meta-analysis showed that ESWT was effective in relieving pain in all four types of tendonitis. In addition, ESWT was more effective in relieving pain in patients with upper limb tendonitis than placebo at the 3- and 6-month follow-ups, especially with radial ESWT (RESWT). Data analysis of the forest plot showed that the experimental group with ESWT as an intervention had a significant improvement in function in patients with rotator cuff tendonitis at the 3-month follow-up. However, subgroup analysis showed that low-energy ESWT was effective in improving function in patients with calcified and non-calcified rotator cuff tendonitis, whereas it was not effective in relieving pain.ConclusionESWT can effectively improve the functional activity in patients with rotator cuff tendonitis and may produce positive analgesic effects in patients with upper limb tendonitis. The incidence of adverse effects is low.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023403594, identifier: PROSPERO, CRD42023403594.

Abstract Ficus carica L. (FC) is rich in phenolic compounds such as phenolic acids, flavonoids, and anthocyanins. Phenolic compounds in FC show remarkable health benefits and applications. The composition of phenolic compounds in FC can vary with some factors, such as variety, ripeness, geographical location, extraction methods and processing methods. New techniques such as supercritical fluid extraction, subcritical water extraction and ionic liquid extraction should be further developed and combined with traditional techniques to obtain higher quality sources of phenolic compounds. Numerous in vivo and in vitro studies reported healthy benefits of phenolic compounds in FC, such as anti‐oxidant, anti‐inflammatory, anti‐diabetic, anti‐obesity, anti‐cancer and anti‐Alzheimer's. Further works are required to reveal mechanisms and structure‐activity relationships, such as targeted metabolomics and pharmacological studies. In terms of applications, phenolic compounds in FC as prebiotics on the intestinal flora need to be further studied to expand their applicability in food fermentation. In a word, this review highlights the remarkable health benefits and application value of phenolic compounds in FC.

Abstract Background Radiomics is increasingly utilized to distinguish pulmonary nodules between lung adenocarcinoma (LUAD) and tuberculosis (TB). However, it remains unclear whether different segmentation criteria, such as the inclusion or exclusion of the cavity region within nodules, affect the results. Methods A total of 525 patients from two medical centers were retrospectively enrolled. The radiomics features were extracted according to two regions of interest (ROI) segmentation criteria. Multiple logistic regression models were trained to predict the pathology: (1) The clinical model relied on clinical‐radiological semantic features; (2) The radiomics models (radiomics+ and radiomics−) utilized radiomics features from different ROIs (including or excluding cavities); (3) the composite models (composite+ and composite−) incorporated both above. Results In the testing set, the radiomics+/− models and the composite+/− models still possessed efficient prediction performance (AUC ≥ 0.94), while the AUC of the clinical model was 0.881. In the validation set, the AUC of the clinical model was only 0.717, while that of the radiomics+/− models and the composite+/− models ranged from 0.801 to 0.825. The prediction performance of all the radiomics+/− and composite+/− models were significantly superior to that of the clinical model (p 0.05). Conclusions The present study established a machine learning‐based radiomics strategy for differentiating LUAD from TB lesions. The ROI segmentation including or excluding the cavity region may exert no significant effect on the predictive ability.

Abstract Objective To investigate the effectiveness of focused extracorporeal shock wave therapy (FESWT) in treating postpartum sacroiliac joint (SIJ) dysfunction. Methods A total of 90 patients with SIJ dysfunction were included and randomly assigned to FESWT, manual therapy (MT), or combination therapy (CT) groups. Pain intensity and Oswestry Disability Index (ODI) score were measured upon admission, after 1 and 2 weeks of treatments. The treatment efficacy and adverse events of each group were also assessed. Results There were no significant differences among three groups regarding clinical data, pain intensity, and ODI score on admission (all P > 0.05). After 1 week of treatment, FESWT exhibited similar pain intensity and lower ODI score (P

Abstract Background Previous studies have examined anesthetics to improve postoperative prognosis after knee arthroscopic surgery. However, it is currently unknown whether perioperative anesthetics can influence postoperative hospital stay. We investigated the impact of esketamine after knee arthroscopic surgery on post-operative length of stay, fever and surgical site infection. Methods This study included 455 patients who underwent knee surgery between January2020 and August 2021at a tertiary hospital in China. Patient characteristics, preoperative laboratory values, intra-operative anesthetic data, and postoperative outcomes were collected. Univariate and multivariate logistic regression analyses with or without propensity score matching were performed to identify factors related to post-operative discharge within 3 days(PD3). Results A total of 297 cases met our inclusion criteria. The mean age of patients was 42 ± 14 years, mean body mass index, 24.1 ± 3.5 kg/m2, 157(53%) patients were male. Meniscus-related procedures accounted for the most part of all the procedures with a percentage of 40.4%, followed by combined procedures of 35.4%. After we adjusted for demographic and intraoperative characteristics with propensity score matching, esketamine use was significantly associated with PD3 with the highest odds ratio of 2.28 (95% confidence interval (CI): 1.18–4.41, p = 0.014). Conclusion Esketamine use was associated with PD3 in patients underwent knee arthroscopic surgery. The findings of this study will be useful to anesthesiologists in making informed decisions regarding the choice of anesthetics for knee joint diseases. Trial registration This study was approved by the Ethics Committee (Approval No.:2023-041-01) of the Eighth Affiliated Hospital, Sun Yat-sen University and retrospectively registered.

Abstract Objectives Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by chronic hyperglycemia and metabolic stress, involved in the stepwise development of cardiovascular complications. Fibroblast growth factor 21 (FGF21) is a novel hepatokine involved in regulating glucose and lipid metabolism, and has been linked to the prediction, treatment, and improvement of prognosis in multiple cardiovascular diseases (CVDs). The aim of this study is to explore the relationship between FGF21 levels and vascular diseases (VDs) including carotid atherosclerosis (CAS) and hypertension (HP) in patients with T2DM. Methods Baseline serum FGF21 was determined in a cross-sectional study of 701 patients with T2DM and 258 healthy control. Results The morbidity of CAS was increased in T2DM patients with HP as compared with those without (p

Sea surface temperature (SST) prediction has received increasing attention in recent years due to its paramount importance in the various fields of oceanography. Existing studies have shown that neural networks are particularly effective in making accurate SST predictions by efficiently capturing spatiotemporal dependencies in SST data. Among various models, the ConvLSTM framework is notably prominent. This model skillfully combines convolutional neural networks (CNNs) with recurrent neural networks (RNNs), enabling it to simultaneously capture spatiotemporal dependencies within a single computational framework. To overcome the limitation that CNNs primarily capture local spatial information, in this paper we propose a novel model named DatLSTM that integrates a deformable attention transformer (DAT) module into the ConvLSTM framework, thereby enhancing its ability to process more complex spatial relationships effectively. Specifically, the DAT module adaptively focuses on salient features in space, while ConvLSTM further captures the temporal dependencies of spatial correlations in the SST data. In this way, DatLSTM can adaptively capture complex spatiotemporal dependencies between the preceding and current states within ConvLSTM. To evaluate the performance of the DatLSTM model, we conducted short-term SST forecasts in the Bohai Sea region with forecast lead times ranging from 1 to 10 days and compared its efficacy against several benchmark models, including ConvLSTM, PredRNN, TCTN, and SwinLSTM. Our experimental results show that the proposed model outperforms all of these models in terms of multiple evaluation metrics short-term SST prediction. The proposed model offers a new predictive learning method for improving the accuracy of spatiotemporal predictions in various domains, including meteorology, oceanography, and climate science.

Numerical weather prediction of sea surface temperature (SST) is crucial for regional operational forecasts. Deep learning offers an alternative approach to traditional numerical general circulation models for numerical weather prediction. In our previous work, we developed a sophisticated deep learning model known as the Attention-based Context Fusion Network (ACFN). This model integrates an attention mechanism with a convolutional neural network framework. In this study, we applied the ACFN model to the South China Sea to evaluate its performance in predicting SST. The results indicate that for a 1-day lead time, the ACFN model achieves a Mean Absolute Error of 0.215 °C and a coefficient of determination (R2) of 0.972. In addition, in situ buoy data were utilized to validate the forecast results. The Mean Absolute Error for forecasts using these data increased to 0.500 °C for a 1-day lead time, with a corresponding R2 of 0.590. Comparative analyses show that the ACFN model surpasses traditional models such as ConvLSTM and PredRNN in terms of accuracy and reliability.

(1) Background: Discarded young fig fruits (DYFFs) result in a waste of resources, such as sparse fruits and residual fruits, and there has been no research on the relationship between phenolic compounds and biological activity in DYFFs (2) Methods: Different deep eutectic solvents (DESs) and 80% ethanol were used to prepare DYFF extracts, and polyphenol extraction efficiency and bioactivities in the DYFFs extracts were compared. (3) Results: More than 1700 phytochemicals were identified in DYFFs, and thirteen of these typical phenolic compounds were analyzed quantitatively; chlorogenic acid, rutin, luteolin 8-C-glucoside, and epicatechin are the main polyphenols in DYFFs, especially chlorogenic acid with 2720–7980 mg/kg. Ferulic acid, caffeic acid, epicatechin, (+)-catechin, luteolin 8-C-glucoside, rutin, hesperetin, and chlorogenic acid showed different degrees of correlation with in vitro antioxidant activity. Moreover, the highest total phenol content found in the extracts of ChCl-Ethylene glycol (Choline chloride:Ethylene glycol = 1:2) was 8.88 mg GAE/g DW, and all quantitatively analyzed phenolic compounds had high levels in various DESs and 80% ethanol. The 80% ethanol and Choline chloride (ChCl) solvent system showed the greatest antioxidant properties, and the Choline chloride-Urea (Choline chloride: Urea = 1:2) extract of DYFFs exhibited the highest inhibitory activity. (4) Conclusions: DESs have demonstrated potential as promising green solvents, especially the ChCl solvent system, which facilitates the extraction of polyphenols.

Summary: Background: In recent years, a growing number of patients with multiple primary lung cancer (MPLC) are being diagnosed, and a subset of these patients is found to have a large number of lesions at the time of diagnosis, which are referred to as ‘super MPLC’. Methods: Here, we perform whole exome sequencing (WES) and immunohistochemistry (IHC) analysis of PD-L1 and CD8 on 212 tumor samples from 42 patients with super MPLC. Findings: We report the genomic alteration landscape of super MPLC. EGFR, RBM10 and TP53 mutation and TERT amplification are important molecular events in the evolution of super MPLC. We propose the conception of early intrapulmonary metastasis, which exhibits different clinical features from conventional metastasis. The IHC analyses of PD-L1 and CD8 reveal a less inflamed microenvironment of super MPLC than that of traditional non-small cell lung cancer (NSCLC). We identify the potentially susceptible germline mutations for super MPLC. Interpretation: Our study depicts the genomic characteristics and immune landscape, providing insights into the pathogenesis and possible therapeutic guidance of super MPLC. Funding: A full list of funding bodies that supported this study can be found in the Acknowledgements section.

A novel MXene/cadmium azide nanocomposite with a low input energy and high output power is designed by self-assembly of Cd ions on the MXene layers and subsequent in situ azidation in a solution reaction. The research result shows that cadmium azide nanoparticles with a uniform size of ∼50 nm are well dispersed on the MXene nanosheet’s surface, which is benefited from the rich functional groups on the MXene surface that can effectively immobilize and prevent the aggregation of the nanoparticles through electrostatic interaction. The thermal decomposition temperature (378.42 °C) and crystal structure of cadmium azide show no noticeable change after hybridizing with the MXene; more positively, the required input energy of the MXene/cadmium azide nanocomposite is significantly reduced, which is verified by its electric initiation input voltage of just 4.65 V. In addition, detonation can be realized by loading a less amount of the MXene/cadmium azide nanocomposite. These results demonstrate that the MXene/cadmium azide nanocomposite has the potential to be used as detonators in high-temperature environments.

Bone health encompasses not only bone mineral density but also bone architecture and mechanical properties that can impact bone strength. While specific dietary interventions have been proposed to treat various diseases such as obesity and diabetes, their effects on bone health remain unclear. The aim of this review is to examine literature published in the past decade, summarize the effects of currently popular diets on bone health, elucidate underlying mechanisms, and provide solutions to neutralize the side effects. The diets discussed in this review include a ketogenic diet (KD), a Mediterranean diet (MD), caloric restriction (CR), a high-protein diet (HP), and intermittent fasting (IF). Although detrimental effects on bone health have been noticed in the KD and CR diets, it is still controversial, while the MD and HP diets have shown protective effects, and the effects of IF diets are still uncertain. The mechanism of these effects and the attenuation methods have gained attention and have been discussed in recent years: the KD diet interrupts energy balance and calcium metabolism, which reduces bone quality. Ginsenoside-Rb2, metformin, and simvastatin have been shown to attenuate bone loss during KD. The CR diet influences energy imbalance, glucocorticoid levels, and adipose tissue, causing bone loss. Adequate vitamin D and calcium supplementation and exercise training can attenuate these effects. The olive oil in the MD may be an effective component that protects bone health. HP diets also have components that protect bone health, but their mechanism requires further investigation. In IF, animal studies have shown detrimental effects on bone health, while human studies have not. Therefore, the effects of diets on bone health vary accordingly.

With major signal analytical elements situated away from the measurement environment, extended gate (EG) ion-sensitive field-effect transistors (ISFETs) offer prospects for whole chip circuit design and system integration of chemical sensors. In this work, a highly sensitive and power-efficient ISFET was proposed based on a metal–ferroelectric–insulator gate stack with negative capacitance–induced super-steep subthreshold swing and ferroelectric memory function. Along with a remotely connected EG electrode, the architecture facilitates diverse sensing functions for future establishment of smart biochemical sensor platforms.

Introduction: Oesophageal cancer is a prevalent and deadly cancer around the world. Objectives: We aimed to present a comprehensive analysis of the global geographic patterns and temporal trends in the mortality and incidence of oesophageal cancer. Methods: The mortality and incidence data of oesophageal cancer in 2020 were obtained from the GLOBOCAN database. Based on World Health Organization (WHO) mortality database and the Cancer Incidence in Five Continents (CI5), we also retrieved the mortality and incidence age-standardized rates (ASRs) of oesophageal cancer. The average annual percentage changes (AAPCs) of mortality and incidence were calculated using the joinpoint regression analysis. Results: Globally, 0.54 million deaths and 0.6 million new cases were identified in 2020. In the majority of countries of South America and Asia, the mortality and incidence trends have substantially decreased, but trends in European countries have varied. The prevalence in European nations varied, but the incidence in most other continents decreased dramatically. In terms of mortality, the global average rate was 5.6 per 100000, ranging from 16.7 (Malawi) to 0.28 (Belize). European countries varied in mortality, such as Norway (AAPC, male: 0.68; female: 0.89) and Ireland (AAPC, male: −0.96; female: −1.52). Most non-European countries saw large decreases in mortality, such as Singapore (AAPC, male: −4.78; female: −6.89). The elderly had more noticeable trends in mortality and incidence in most countries. Conclusions: We have identified different trends in mortality and incidence among European countries, whereas declining trends were identified in most non-European countries. However, increasing trends were identified in specific subgroups of some countries, such as men in Thailand. For populations with rising mortality and incidence trends, more preventative efforts are required.

Abstract Aims This study aimed to evaluate the cumulative high‐sensitivity cardiac troponin T (hs‐cTNT) from admission to 12 months after discharge and its association with mortality after 12 months among patients with acute heart failure (HF). Methods We used data from the China Patient‐Centered Evaluative Assessment of Cardiac Events Prospective Heart Failure Study (China PEACE 5p‐HF Study), which enrolled patients hospitalized primarily for HF from 52 hospitals between 2016 and 2018. We included patients who survived within 12 months and had hs‐cTNT data at admission (within 48 h of admission) and 1 and 12 months after discharge. To evaluate the long‐term cumulative hs‐cTNT, we calculated cumulative hs‐cTNT levels and cumulative times of high hs‐cTNT level. Patients were divided into groups according to the quartiles of cumulative hs‐cTNT levels (Quartiles 1–4) and cumulative times of high hs‐cTNT levels (0–3 times). Multivariable Cox models were constructed to examine the association of cumulative hs‐cTNT with mortality during the follow‐up period. Results We included 1137 patients with a median age of 64 [interquartile range (IQR), 54–73] years; 406 (35.7%) were female. The median cumulative hs‐cTNT level was 150 (IQR, 91–241) ng/L*month. Based on the cumulative times of high hs‐cTNT levels, 404 (35.5%) patients were with zero time, 203 (17.9%) with one time, 174 (15.3%) with two times, and 356 (31.3%) with three times. During a median follow‐up of 4.76 (IQR, 4.25–5.07) years, 303 (26.6%) all‐cause deaths occurred. The increasing cumulative hs‐cTNT level and cumulative times of high hs‐cTNT level were independently associated with excess all‐cause mortality. Compared with Quartile 1 group, Quartile 4 had the highest hazard ratio (HR) of all‐cause mortality [4.14; 95% confidence interval (CI): 2.51–6.85], followed by Quartile 3 (HR: 3.35; 95% CI: 2.05–5.48) and Quartile 2 (HR: 2.47; 95% CI: 1.49–4.08) groups. Similarly, taking the patients with zero time of high hs‐cTNT level as the reference, the HRs were 1.60 (95% CI: 1.05–2.45), 2.61 (95% CI: 1.76–3.87), and 2.86 (95% CI: 1.98–4.14) in patients who had one, two, and three times of high hs‐cTNT level, respectively. Conclusions Elevated cumulative hs‐cTNT from admission to 12 months after discharge was independently associated with mortality after 12 months among patients with acute HF. Repeated measurements of hs‐cTNT after discharge may help monitor the cardiac damage and identify patients with high risk of death.

Background: Patients with acute heart failure (HF) are at high risk of 30-day readmission. Little is known about the characteristics and associated factors of 30-day readmissions among patients with acute HF in China. Methods: We enrolled consecutive patients hospitalized for acute HF and discharged from 52 hospitals in China from August 2016 to May 2018. We describe the rate of 30-day readmission, the time interval from discharge to readmission, and the causes of readmission. We also analyzed the factors associated with readmission risk by fitting multivariate Cox proportional hazards models. Results: We included 4875 patients with a median age of 67 years (interquartile range, 57–75), 3045 (62.5%) of whom were male. Within 30 days after discharge, 613 (12.6%) patients were readmitted for all causes, with a median from discharge to readmission of 12 (6–21) days. Most readmissions were attributed to cardiovascular causes (71.1%) and 60.0% to HF-related causes. Readmission occurred within 14 days of discharge in more than half of the patients (56.4%). Diabetes (hazard ratio [HR]: 1.25, 95% confidence interval [95% CI]: 1.06–1.50), anemia (HR: 1.26, 95% CI: 1.03–1.53), high New York Heart Association classification (HR: 1.48, 95% CI: 1.08–2.01), elevated N-terminal pro-B type natriuretic peptide (HR: 1.67, 95% CI: 1.24–2.25), and high-sensitivity cardiac troponin T (HR: 1.26, 95% CI: 1.01–1.58) were associated with increased risks of readmission. High systolic blood pressure (HR: 0.56, 95% CI: 0.38–0.81) and Kansas City Cardiomyopathy Questionnaire-12 scores (HR: 0.64, 95% CI: 0.44–0.94) were associated with decreased risk of readmission. Conclusions: In China, almost one in eight patients with acute HF were readmitted within 30 days after discharge, mainly due to cardiovascular reasons, and approximately three-fifths of the readmissions occurred in the first 14 days. Both clinical and patient-centered characteristics were associated with readmission.

Abstract Chemotherapy is widely used to treat colorectal cancer (CRC). Despite its substantial benefits, the development of drug resistance and adverse effects remain challenging. This study aimed to elucidate a novel role of glucagon in anti‐cancer therapy. In a series of in vitro experiments, glucagon inhibited cell migration and tube formation in both endothelial and tumor cells. In vivo studies demonstrated decreased tumor blood vessels and fewer pseudo‐vessels in mice treated with glucagon. The combination of glucagon and chemotherapy exhibited enhanced tumor inhibition. Mechanistic studies demonstrated that glucagon increased the permeability of blood vessels, leading to a pronounced disruption of vessel morphology. Signaling pathway analysis identified a VEGF/VEGFR‐dependent mechanism whereby glucagon attenuated angiogenesis through its receptor. Clinical data analysis revealed a positive correlation between elevated glucagon expression and chemotherapy response. This is the first study to reveal a role for glucagon in inhibiting angiogenesis and vascular mimicry. Additionally, the delivery of glucagon‐encapsulated PEGylated liposomes to tumor‐bearing mice amplified the inhibition of angiogenesis and vascular mimicry, consequently reinforcing chemotherapy efficacy. Collectively, the findings demonstrate the role of glucagon in inhibiting tumor vessel network and suggest the potential utility of glucagon as a promising predictive marker for patients with CRC receiving chemotherapy.

ObjectiveInflammatory-erosive arthritis is exacerbated by dysfunction of joint-draining popliteal lymphatic vessels (PLVs). Synovial mast cells are known to be pro-inflammatory in rheumatoid arthritis (RA). In other settings they have anti-inflammatory and tissue reparative effects. Herein, we elucidate the role of mast cells on PLV function and inflammatory-erosive arthritis in tumor necrosis factor transgenic (TNF-tg) mice that exhibit defects in PLVs commensurate with disease progression.MethodsWhole mount immunofluorescent microscopy, toluidine blue stained histology, scanning electron microscopy, and in silico bioinformatics were performed to phenotype and quantify PLV mast cells. Ankle bone volumes were assessed by μCT, while corresponding histology quantified synovitis and osteoclasts. Near-infrared indocyanine green imaging measured lymphatic clearance as an outcome of PLV draining function. Effects of genetic MC depletion were assessed via comparison of 4.5-month-old WT, TNF-tg, MC deficient KitW-sh/W-sh (cKit-/-), and TNF-tg x cKit-/- mice. Pharmacological inhibition of mast cells was assessed by treating TNF-tg mice with placebo or cromolyn sodium (3.15mg/kg/day) for 3-weeks.ResultsPLVs are surrounded by MCT+/MCPT1+/MCPT4+ mast cells whose numbers are increased 2.8-fold in TNF-tg mice. The percentage of peri-vascular degranulating mast cells was inversely correlated with ICG clearance. A population of MCT+/MCPT1-/MCPT4- mast cells were embedded within the PLV structure. In silico single-cell RNA-seq (scRNAseq) analyses identified a population of PLV-associated mast cells (marker genes: Mcpt4, Cma1, Cpa3, Tpsb2, Kit, Fcer1a & Gata2) with enhanced TGFβ-related signaling that are phenotypically distinct from known MC subsets in the Mouse Cell Atlas. cKit-/- mice have greater lymphatic defects than TNF-tg mice with exacerbation of lymphatic dysfunction and inflammatory-erosive arthritis in TNF-tg x cKit-/- vs. TNF-Tg mice. Cromolyn sodium therapy stabilized PLV mast cells, increased TNF-induced bone loss, synovitis, and osteoclasts, and decreased ICG clearance.ConclusionsMast cells are required for normal lymphatic function. Genetic ablation and pharmacological inhibition of mast cells exacerbates TNF-induced inflammatory-erosive arthritis with decreased lymphatic clearance. Together, these findings support an inflammatory role of activated/degranulated peri-PLV mast cells during arthritic progression, and a homeostatic role of intra-PLV mast cells, in which loss of the latter dominantly exacerbates arthritis secondary to defects in joint-draining lymphatics, warranting investigation into specific cellular mechanisms.

Abstract Iron deficiencies are the most common nonenteric syndromes observed in patients with inflammatory bowel disease, but little is known about their impacts on immune tolerance. Here we show that homeostasis of regulatory T cells in the intestine was dependent on high cellular iron levels, which were fostered by pentanoate, a short-chain fatty acid produced by intestinal microbiota. Iron deficiencies in Treg caused by the depletion of Transferrin receptor 1, a major iron transporter, result in the abrogation of Treg in the intestine and lethal autoimmune disease. Transferrin receptor 1 is required for differentiation of c-Maf+ Treg, major constituents of intestinal Treg. Mechanistically, iron enhances the translation of HIF-2α mRNA, and HIF-2α in turn induces c-Maf expression. Importantly, microbiota-produced pentanoate promotes iron uptake and Treg differentiation in the intestine. This subsequently restores immune tolerance and ameliorated iron deficiencies in mice with colitis. Our results thus reveal an association between nutrient uptake and immune tolerance in the intestine.

Abstract Background End-stage renal disease (ESRD) is the final stage of chronic kidney disease (CKD). In addition to the structurally intact chromosome genomic DNA, there is a double-stranded circular DNA called extrachromosomal circular DNA (eccDNA), which is thought to be involved in the epigenetic regulation of human disease. However, the features of eccDNA in ESRD patients are barely known. In this study, we identified eccDNA from ESRD patients and healthy people, as well as revealed the characteristics of eccDNA in patients with ESRD. Methods Using the high-throughput Circle-Sequencing technique, we examined the eccDNA in peripheral blood mononuclear cells (PBMCs) from healthy people (NC) (n = 12) and ESRD patients (n = 16). We analyzed the length distribution, genome elements, and motifs feature of eccDNA in ESRD patients. Then, after identifying the specific eccDNA in ESRD patients, we explored the potential functions of the target genes of the specific eccDNA. Finally, we investigated the probable hub eccDNA using algorithms. Results In total, 14,431 and 11,324 eccDNAs were found in the ESRD and NC groups, respectively, with sizes ranging from 0.01 kb to 60 kb at most. Additionally, the ESRD group had a greater distribution of eccDNA on chromosomes 4, 11, 13, and 20. In two groups, we also discovered several motifs of specific eccDNAs. Furthermore, we identified 13,715 specific eccDNAs in the ESRD group and 10,585 specific eccDNAs in the NC group, both of which were largely annotated as mRNA catalog. Pathway studies using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) showed that the specific eccDNA in ESRD was markedly enriched in cell junction and communication pathways. Furthermore, we identified potentially 20 hub eccDNA-targeting genes from all ESRD-specific eccDNA-targeting genes. Also, we found that 39 eccDNA-targeting genes were associated with ESRD, and some of these eccDNAs may be related to the pathogenesis of ESRD. Conclusions Our findings revealed the characteristics of eccDNA in ESRD patients and discovered potentially hub and ESRD-relevant eccDNA-targeting genes, suggesting a novel probable mechanism of ESRD.

Activated red mud (RM) has been proved to be a promising base material for the selective catalysis reduction (SCR) of NOx. The inherent low reducibility and acidity limited its low–temperature activity. In this work, molybdenum oxide, tungsten oxide, and cerium oxide were used to reconfigure the redox sites and acid sites of red mud based catalyst. When activated red mud was reconfigured by cerium-tungsten oxide (Ce–W@RM), the NOx conversion kept above 90% at 219–480 °C. The existence of Ce3+/Ce4+ redox electron pairs provided more surface adsorbed oxygen (Oα) and served as a redox cycle. Positive interactions between Ce, W species and Fe oxide in red mud occurred, which led to the formation of unsaturated chemical bond and promoted the activation of adsorbed NH3 species. WO3 and Ce2(WO4)3 (formed by solid–state reaction between Ce and W species) could provide more Brønsted acid sites (W–O modes of WO3, WO or W–O–W modes of Ce2(WO4)3). CeO2 species could provide more Lewis acid sites. The Langmuir–Hinshelwood (L-H) routes and Eley-Rideal (E-R) routes occurred in the low-temperature SCR reaction on the Ce–W@RM surface. NH4+ species on Brønsted acid sites, NH3 species on Lewis acid sites, bidentate nitrate and bridging nitrate species were key active intermediates species.

Abstract Introduction The number of patients with synchronous multiple primary lung cancer (sMPLC) has increased recently. However, diagnosing and selecting the appropriate therapeutic strategy for this type of disease is not simple. Case presentation This report presented a case of sMPLC with lymph node metastasis. With no smoking and cancer history, this patient had seven nodules in the right lung and underwent single-portal video-assisted thoracoscopic surgery (VATS). In addition, she received four cycles of chemotherapy after the operation. Whole exon sequencing (WES) was performed in five resected tissue samples (four tumors and one lymph node). We conducted genomic profiling and clone evolution analysis of the five samples. Gene detection helped to confirm that the metastasis lymph node was transferred from one nodule. There was apparent heterogeneity of gene mutations among the five samples of the patient, with only one shared “neurofilament heavy polypeptide” (NEFH) mutation. A dominant substitution of C > T/G > A was found in all the samples. Pyclone model was used to calculate all tissues' cellular prevalence (CP) values, and NEFH mutations were thought to be the ancestral clones. During the follow-up period, residual lesions showed no apparent changes and limited response to chemotherapy. Conclusions This report showed an essential role in genomic detection and selecting the appropriate treatment of sMPLC. Surgery remains the primary treatment strategy for this type of disease, and the occurrence and development of sMPLC need more in-depth research.

Artificial synapses are key elements in building bioinspired, neuromorphic computing systems. Ferroelectric field‐effect transistors (FeFETs) with excellent controllability and complementary metal oxide semiconductor (CMOS) compatibility are favorable to achieving synaptic functions with low power consumption and high scalability. However, because of the only nonvolatile ferroelectric (Fe) characteristics in the FeFET, it is difficult to develop bioplausible short‐term synaptic elements for spatiotemporal information processing. By judiciously combining defects (DE) and Fe domains in gate stacks, a compact artificial synapse featuring spatiotemporal information processing on a single Fe–DE fin FET (FinFET) is proposed. The devices are designed to work in a separate DE mode to induce short‐term plasticity by spontaneous charge detrapping, and a hybrid Fe–DE mode to trigger long‐term plasticity through the coupling of defects and Fe domains. The capability of the compact synapse is demonstrated by differentiating 16 temporal inputs. Moreover, the highly controllable static electricity of advanced FinFETs leads to an ultralow power of 2 fJ spike−1. An all Fe–DE FinFET reservoir computing (RC) system is then constructed that achieves a recognition accuracy of 97.53% in digit classification. This work enables constructing RC systems with fully advanced CMOS‐compatible devices featuring highly energy‐efficient and low‐hardware systems.

The identity development process has individual and societal components and is inherently intertwined with one’s broader sociocultural milieu. The correlation between the personal and social aspects of an individual’s identity considerably influences their behavior within their environment. This study examines cultural identity changes among English as a Foreign Language (EFL) students by conducting a questionnaire survey based on the anxiety/uncertainty management theory by Gudykunst (1995, 1998). The questionnaire was distributed twice: Study 1 used data from 483 students and Study 2 used data from 359 students. After each study, 20 students’ descriptions of Chinese and Western cultures were analyzed in NVivo. Guided by the ecological research paradigm, this study examines the impact of individual differences on cultural identity at the macro-, meso-, exo-, and micro- levels. The findings suggest that social context can influence an individual’s cultural identity, and cultural identity development accompanies being “oneself.”

Background Elevated hsCRP (high‐sensitivity C‐reactive protein) level is associated with worse prognosis among patients hospitalized for heart failure. However, the prognostic value of the long‐term cumulative hsCRP remains unknown. Methods and Results We consecutively enrolled patients hospitalized for heart failure and collected their hsCRP data at admission and 1 and 12 months after discharge. Long‐term cumulative hsCRP was evaluated using 2 approaches, cumulative hsCRP level quartiles and cumulative times of high hsCRP levels. Patients were classified into 4 groups by cumulative hsCRP level quartiles and cumulative times of high hsCRP levels (0‐ to 3‐times: number of times that hsCRP levels were higher than cutoff values at admission or 1 or 12 months), respectively. Multivariable Cox models were used to assess the association of mortality with cumulative hsCRP. A total of 1281 patients were included; the median age was 64 (interquartile range, 54–73) years, and 35.4% were women. Over a 4.8‐year (interquartile range, 4.2–5.1) follow‐up, 374 (29.2%) patients died. Elevated long‐term cumulative hsCRP level was related to higher mortality. Specifically, taking the quartile 1 as the reference, the hazard ratios (HRs) were 1.29 (95% CI, 0.92–1.81) for quartile 2, 1.62 (95% CI, 1.16–2.25) for quartile 3, and 2.38 (95% CI, 1.75–3.23) for quartile 4. Similarly, compared with the patients with 0‐times (hsCRP level lower than the cutoff values in all 3 time points) of high hsCRP level, the HRs were 1.36 for 1‐time (hsCRP level higher than the cutoff value in one of the 3 time points) (95% CI, 0.92–2.01), 1.95 for 2‐times (hsCRP levels higher than the cutoff values in 2 of the 3 time points) (95% CI, 1.34–2.82), and 2.80 for 3‐times (hsCRP levels higher than the cutoff values in the 3 time points) (95% CI, 1.97–4.00). Conclusions Increasing long‐term cumulative hsCRP level was associated with worse outcomes in patients hospitalized for acute heart failure. Repeated hsCRP measurements could assist physicians in identifying patients with a high risk of death. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT 02878811.

Salt-affected soil has become one of the major threats to soil health. However, the evaluation of biochar amendment effects and the underlying mechanisms on the physical, chemical, and biological indicators used for assessing the health of salt-affected soils is lacking. This review summarized biochar performance and mechanisms in improving the health of salt-affected soils. Biochar addition significantly improved soil physico-chemical properties by enhancing aggregate stability (15.0–34.9%), porosity (8.9%), and water retention capacity (7.8–18.2%), increasing cation exchange capacity (21.1%), soil organic carbon (63.1%), and nutrient availability (31.3–39.9%), as well as decreasing bulk density (6.0%) and alleviating salt stress (4.1–40.0%). Following biochar incorporation, soil biological health can also be improved, particularly enhancing microbial biomass (7.1–25.8%), facilitating enzyme activity (20.2–68.9%), and ultimately increasing plant growth. To properly assess the health of salt-affected soils, it is important to select indicators related to ecological service functions including plant production, water quality, climate change, and human health. This will improve the evaluation of soil multifunctionality and enhance current soil health assessment methods. Finally, limitations and future needs of biochar research and biochar-based technologies for soil health assessment in salt-affected soils are discussed. Based on a global meta-analysis to illustrate biochar effects on salt-affected soil health indicators, this review offers valuable insights for developing sustainable biochar-based tools for remediating salt-affected soil.

Abstract Grey-box fuzzing techniques have been widely used in software bug finding. In general, there are many decisions to make in the fuzzing process, including which code block in the target program should be explored first, which bytes of an input seed should be mutated to reach the target code block, and how to mutate the chosen input bytes. However, existing solutions usually rely on random exploration or certain heuristics to choose where and how to fuzz, which limits the efficiency of fuzzing. In this paper, we propose a novel solution CAMFuzz to guide the fuzzing process with explainable decisions in explainable artificial intelligence (XAI). First, we propose a dynamic weight adjustment algorithm, which considers both the difficulty of reaching a block and the number of unvisited blocks nearby, to find code blocks worthy to explore first. Second, we utilize a widely used local interpretation technique, i.e., class activation mapping (CAM), to recognize which part of an input seed should be mutated to reach a given target code block. Therefore, CAMFuzz can distinguish which part of code in the program is more important and which positions in the input file should be mutated first, in order to achieve a better code coverage and bug finding efficiency. Third, to further help the fuzzer increase fuzzing efficiency, we leverage a lightweight static program analysis to help the fuzzer identify magic values. We implement a prototype of CAMFuzz and evaluate it on 13 real-world programs (including 11 open source targets, 2 closed-source commercial products including a Microsoft component and Hancom Office) Results show that CAMFuzz outperforms state-of-the-art fuzzers in both code coverage and bug finding. To detail, CAMFuzz on average achieves 2.07 $$\times$$ × more bugs and 1.17 $$\times$$ × coverage improvements. In total, it found 19 previously unknown vulnerabilities, of which 6 have been assigned by CVE so far.

IntroductionDefective lymphatic drainage and translocation of B-cells in inflamed (Bin) joint-draining lymph node sinuses are pathogenic phenomena in patients with severe rheumatoid arthritis (RA). However, the molecular mechanisms underlying this lymphatic dysfunction remain poorly understood. Herein, we utilized multi-omic spatial and single-cell transcriptomics to evaluate altered cellular composition (including lymphatic endothelial cells, macrophages, B-cells, and T-cells) in the joint-draining lymph node sinuses and their associated phenotypic changes and cell-cell interactions during RA development using the tumor necrosis factor transgenic (TNF-Tg) mouse model.MethodsPopliteal lymph nodes (PLNs) from wild-type (n=10) and TNF-Tg male mice with “Early” (5 to 6-months of age; n=6) and “Advanced” (>8-months of age; n=12) arthritis were harvested and processed for spatial transcriptomics. Single-cell RNA sequencing (scRNAseq) was performed in PLNs from the TNF-Tg cohorts (n=6 PLNs pooled/cohort). PLN histopathology and ELISPOT along with ankle histology and micro-CT were evaluated. Histopathology of human lymph nodes and synovia was performed for clinical correlation.ResultsAdvanced PLN sinuses exhibited an increased Ighg2b/Ighm expression ratio (Early 0.5 ± 0.1 vs Advanced 1.4 ± 0.5 counts/counts; p

Ectomycorrhizal (ECM) fungi play fundamental roles in host plant growth and terrestrial ecosystems. Cedrus deodara is cultivated in several regions in China, has high ecological, economic and medicinal value, for its afforestation and providing timber and wood oil. Here, we investigated ECM colonization status of four urban C. deodara forests in Nantong, East China. We also characterized soil spore banks by conducting bioassay experiments using soils collected from these forests. In total, we identified 19 ECM fungal species, of which 13 species were found in mature forests and 9 species were identified in bioassay experiments, with only 3 species shared. Soil pH and available P content had significant effects on species occurrence in both mature trees and bioassay seedlings on local scales. ECM communities clearly (A = 0.391, p = 0.006) separated mature forests from spore banks. Thelephoracae was the richest family we detected associated with C. deodara, while Trichophaea sp. was the most dominant in mature forests, and Wilcoxina sp. was dominant in spore banks. ECM richness affected the growth of bioassay seedlings, especially after inoculation with 2 ECM species, promoting root growth, significantly (F = 3.028, p = 0.050), but it had no effects on shoots (F = 1.778, p = 0.177). No effect of inoculation rate was found on seedlings growth. To conserve this important tree species, the ECM fungi that are associated with it should be considered.