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Abstract Background To explore the pulmonary-vascular-stump filling-defect on CT and investigate its association with cancer progression. Methods Records in our institutional database from 2018 to 2022 were retrospectively analyzed to identify filling-defects in the pulmonary-vascular-stump after lung cancer resection and collect imaging and clinical data of patients. Results Among the 1714 patients analyzed, 95 cases of filling-defects in the vascular stump after lung cancer resection were identified. After excluding lost-to-follow-up cases, a total of 77 cases were included in the final study. Morphologically, the filling-defects were dichotomized as 46 convex-shape and 31 concave-shape cases. Concave defects exhibited a higher incidence of increase compared to convex defects (51.7% v. 9.4%, P = 0.001). Among 61 filling defects in the pulmonary arterial stump, four (6.5%) increasing concave defects showed the nuclide concentration on PET and extravascular extension. The progression-free survival (PFS) time differed significantly among the concave, convex, and non-filling-defect groups (log-rank P

Abstract Background Stroke-associated pneumonia (SAP) and gastrointestinal bleeding (GIB) are common medical complications after stroke. The previous study suggested a strong association between SAP and GIB after stroke. However, little is known about the time sequence of SAP and GIB. In the present study, we aimed to verify the association and clarify the temporal sequence of SAP and GIB after ischemic stroke. Methods Patients with ischemic stroke from in-hospital Medical Complication after Acute Stroke study were analyzed. Data on occurrences of SAP and GIB during hospitalization and the intervals from stroke onset to diagnosis of SAP and GIB were collected. Multiple logistic regression was used to evaluate the association between SAP and GIB. Kruskal-Wallis test was used to compare the time intervals from stroke onset to diagnosis of SAP and GIB. Results A total of 1129 patients with ischemic stroke were included. The median length of hospitalization was 14 days. Overall, 86 patients (7.6%; 95% CI, 6.1-9.2%) developed SAP and 47 patients (4.3%; 95% CI, 3.0-5.3%) developed GIB during hospitalization. After adjusting potential confounders, SAP was significantly associated with the development of GIB after ischemic stroke (OR = 5.13; 95% CI, 2.02-13.00; P

Background and Purpose Non-high-density lipoprotein cholesterol (non-HDL-C), which represents the total cholesterol content of all pro-atherogenic lipoproteins, has recently been included as a new target for lipid-lowering therapy in high-risk atherosclerotic patients in multiple guidelines. Herein, we aimed to explore the relationship between non-HDL-C level and the efficacy and safety of ticagrelor-aspirin versus clopidogrel-aspirin in preventing stroke recurrence. Methods This study comprised a post hoc analysis of the CHANCE-2 (Ticagrelor or Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events II) trial, from which 5,901 patients with complete data on non-HDL-C were included and categorized by median non-HDL-C levels, using a cutoff of 3.5 mmol/L. The primary efficacy and safety outcomes were recurrent stroke and severe or moderate bleeding within 90 days. Results Ticagrelor-aspirin significantly reduced the risk of recurrent stroke in patients with low non-HDL-C (71 [4.8%] vs. 119 [7.7%]; adjusted hazard ratio [HR] 0.54; 95% confidence interval [CI], 0.40–0.74), but not in those with high non-HDL-C (107 [7.3%] vs. 108 [7.6%]; adjusted HR, 0.88; 95% CI, 0.67–1.16), compared with clopidogrel-aspirin (P for interaction=0.010). When analyzed as a continuous variable, the benefit of ticagrelor-aspirin for recurrent stroke decreased as non-HDL-C levels increased. No significant differences in the treatment assignments across the non-HDL-C groups were observed in terms of the rate of severe or moderate bleeding (5 [0.3%] vs. 8 [0.5%] in the low non-HDL-C group; 4 [0.3%] vs. 2 [0.1%] in the high non-HDL-C group; P for interaction=0.425). Conclusion CHANCE-2 participants with low non-HDL-C levels received more clinical benefit from ticagrelor-aspirin versus clopidogrel-aspirin compared to those with high non-HDL-C, following minor ischemic stroke or transient ischemic attack.

Abstract Background Taurine, a semi-essential micronutrient, could be utilized as a sulfur source for some bacteria; however, little is known about its effect on the accumulation of fermentation products. Here, it investigated the effect of taurine on co-production of bioethanol and Monascus azaphilone pigments (MonAzPs) for a fungus. Results A newly isolated fungus of 98.92% identity with Monascus purpureus co-produced 23.43 g/L bioethanol and 66.12, 78.01 and 62.37 U/mL red, yellow and orange MonAzPs for 3 d in synthetic medium (SM). Taurine enhanced bioethanol titer, ethanol productivity and ethanol yield at the maximum by 1.56, 1.58 and 1.60 times than those of the control in corn stover hydrolysates (CSH), and red, yellow and orange MonAzPs were raised by 1.24, 1.26 and 1.29 times, respectively. Taurine was consumed extremely small quantities for M. purpureus and its promotional effect was not universal for the other two biorefinery fermenting strains. Taurine intensified the gene transcription of glycolysis (glucokinase, phosphoglycerate mutase, enolase and alcohol dehydrogenase) and MonAzPs biosynthesis (serine hydrolases, C-11-ketoreductase, FAD-dependent monooxygenase, 4-O-acyltransferase, deacetylase, NAD(P)H-dependent oxidoredutase, FAD-dependent oxidoredutase, enoyl reductase and fatty acid synthase) through de novo RNA-Seq assays. Furthermore, taurine improved cell membrane permeability through changing cell membrane structure by microscopic imaging assays. Conclusions Taurine reinforced co-production of bioethanol and MonAzPs by increasing gene transcription level and cell membrane permeability for M. purpureus. This work would offer an innovative, efficient and taurine-based co-production system for mass accumulation of the value-added biofuels and biochemicals from lignocellulosic biomass.

ABSTRACTAccurate evaluation of terrestrial carbon balance is essential for designing climate change mitigation policies, and capabilities of remote sensing techniques in monitoring carbon fluxes are widely recognized for their great contributions to regional and global carbon budget accounting. In this review, we synthesized satellite-based data and methodologies to estimate the main flux components of terrestrial carbon balance and their uncertainties over the past two decades. The global gross primary production (GPP) during the period 2001–2022 is 134 ± 14 PgC yr−1, and nearly half of them occurs in tropical forest regions such as South America and Africa. Less than 2% of global GPP is converted into a net carbon sink of 2.28 ± 1.12 PgC yr−1 using satellite-based atmospheric inversion during 2015–2020, and this sink is comparable to the stock change-based estimate (2.49 PgC yr−1) but twice as large as model-based estimate (1.08 ± 0.78 PgC yr−1). By decomposing satellite-derived net carbon balance into different terms including satellite-derived carbon emissions from land-use change and wildfires (3.55 PgC yr−1), we inferred that ~ 43% of global GPP would be respired through soil microbes (57.1 PgC yr−1), but which is higher than the previous bottom-up estimate (39–46 PgC yr−1). We then propose that an accurate remote sensing of terrestrial carbon balance requires to enhance representations of photosynthetic responses to rising CO2 and disturbances, develop satellite-constrained belowground carbon dynamics and separate natural fluxes from anthropogenic CO2 emissions, by integrating multi-source satellite sensors in orbit, revolutionized remote sensing capabilities with focused field campaigns in data-scarce regions.

Abstract The cell cycle is a crucial biological process that is involved in cell growth, development, and reproduction. It can be divided into G1, S, G2, and M phases, and each period is closely regulated to ensure the production of two similar daughter cells with the same genetic material. However, many obstacles influence the cell cycle, including the R-loop that is formed throughout this process. R-loop is a triple-stranded structure, composed of an RNA: DNA hybrid and a single DNA strand, which is ubiquitous in organisms from bacteria to mammals. The existence of the R-loop has important significance for the regulation of various physiological processes. However, aberrant accumulation of R-loop due to its limited resolving ability will be detrimental for cells. For example, DNA damage and genomic instability, caused by the R-loop, can activate checkpoints in the cell cycle, which in turn induce cell cycle arrest and cell death. At present, a growing number of factors have been proven to prevent or eliminate the accumulation of R-loop thereby avoiding DNA damage and mutations. Therefore, we need to gain detailed insight into the R-loop resolution factors at different stages of the cell cycle. In this review, we review the current knowledge of factors that play a role in resolving the R-loop at different stages of the cell cycle, as well as how mutations of these factors lead to the onset and progression of diseases.

Abstract Somatic mutations related to clonal hematopoiesis of indeterminate potential (CHIP) are risk factors for stroke. The impact of DNMT3A, the most mutated gene in CHIP, on clinical functional outcomes of acute ischemic stroke (AIS) remains unclear. In a well‐characterized cohort of 8524 ischemic stroke patients, we demonstrated that DNMT3A‐driven CHIP was significantly associated with neurological disability in these patients. With a stroke mouse model of transient middle cerebral artery occlusion (tMCAO), we demonstrated that DNMT3A protein levels in the brain penumbra increased. The DNMT3A inhibitor RG108 administration amplified neutrophil proliferation in the blood, promoted neutrophil infiltration into the brain penumbra, and exaggerated proinflammatory activation in tMCAO male mice. DNMT3A inhibition also significantly increased infarct volume and worsened neurobehavioral function in tMCAO male mice. In conclusion, DNMT3A somatic mutations are associated with worsened neurological disability in some patients with AIS, potentially through increased neutrophil proliferation and infiltration in the ischemic brain region. These findings suggest a possible mechanism for proinflammatory activation and tissue damage in the affected brain tissue, highlighting the need for further research in this area.

Background We aim to identify the distinct lesion patterns and regions associated with functional outcome and inflammation in patients with acute ischemic stroke, and investigate whether the association between lesion patterns and functional outcome was mediated by inflammation. Methods and Results We performed nonnegative matrix factorization to derived low‐dimensional lesion patterns (atoms), and Bayesian linear regression models were applied to explore the associations of lesion patterns with inflammatory factors including high‐sensitivity C‐reactive protein and interleukin‐6, as well as functional outcome (defined as modified Rankin Scale score at 3 months). The difference distribution mean and 95% highest probability density interval (HPDI) were calculated. Mediation analysis was used to examine the mediating effects of inflammation on the relationships between lesion patterns and functional outcome. Seven lesion patterns were derived from 5914 patients with acute ischemic stroke. Lesion patterns distributed in the cortical regions were associated with inflammatory response, including atom 1 (interleukin‐6: mean, 0.113 [95% HPDI, 0.073–0.162]; high‐sensitivity C‐reactive protein: mean, 0.082 [95% HPDI, 0.038–0.123]) and atom 4 (interleukin‐6: mean, 0.113 [95% HPDI, 0.071–0.167]; high‐sensitivity C‐reactive protein: mean, 0.108 [95% HPDI, 0.058–0.165]). These lesion patterns were also significantly associated with functional outcome (atom 1: mean, 1.958 [95% HPDI, 1.538–2.383]; atom 4: mean, 2.245 [95% HPDI, 1.773–2.741]). Mediation analysis suggested that interleukin‐6 explained 15.34% and 7.47% in the association of atom 1 and atom 4 with functional outcome, respectively. Conclusions Certain lesion patterns that are associated with both inflammation and functional outcome of acute ischemic stroke, especially cortical infarction, may play a role in functional outcome through modulating inflammatory reactions.

Summary: Background: Endovascular therapy (EVT) was demonstrated effective in acute large vessel occlusion (LVO) with large infarction. Revealing subgroups of patients who would or would not benefit from EVT will further inform patient selection for EVT. Methods: This post-hoc analysis of the ANGEL-ASPECT trial, a randomised controlled trial of 456 adult patients with acute anterior-circulation LVO and large infarction, defined by ASPECTS 3–5 or infarct core volume 70–100 mL, enrolled from 46 centres across China, between October 2, 2020 and May 18, 2022. Patients were randomly assigned (1:1) to receiving EVT and medical management or medical management alone. One patient withdrew consent, 455 patients were included in this post-hoc analysis and categorised into 4 subgroups by lower or higher NIHSS (< or ≥16) and smaller or larger infarct core (< or ≥70 mL). Those with lower NIHSS & smaller core, and higher NIHSS & larger core were considered clinical-radiological matched subgroups; otherwise clinical-radiological mismatched subgroups. Primary outcome was 90-day modified Rankin Scale (mRS). ANGEL-ASPECT is registered with ClinicalTrials.gov, NCT04551664. Findings: Overall, 139 (30.5%) patients had lower NIHSS & smaller core, 106 (23.3%) higher NIHSS & larger core, 130 (28.6%) higher NIHSS & smaller core, and 80 (17.6%) lower NIHSS & larger core. There was significant ordinal shift in the 90-day mRS toward a better outcome with EVT in clinical-radiological matched subgroups: lower NIHSS & smaller core (generalised OR, 1.76; 95% CI, 1.18–2.62; p = 0.01) and higher NIHSS & larger core (1.64; 1.06–2.54; 0.01); but not in the two clinical-radiological mismatched subgroups. Interpretation: Our findings suggested that in patients with anterior-circulation LVO and large infarction, EVT was associated with improved 90-day functional outcomes in those with matched clinical and radiological severities, but not in those with mismatched clinical and radiological severities. Simultaneous consideration of stroke severity and infarct core volume may inform patient selection for EVT. Funding: Unrestricted grants from industry [Covidien Healthcare International Trading (Shanghai), Johnson & Johnson MedTech, Genesis MedTech (Shanghai), and Shanghai HeartCare Medical Technology].

In this paper, we introduce MP-GT, a novel Graph Neural Network model that leverages meta-path-guided optimization within the GCN-Transformer framework to enhance application (App) usage prediction accuracy. Our approach addresses issues such as suspended animation and over-smoothing by extracting both local subgraph structures and global graph structures using a combination of GCN and Transformer method. Furthermore, we enhance the capture of semantic information and App usage patterns by incorporating a meta path-guided objective function. Extensive experiments demonstrate that MP-GT outperforms the widely adopted baseline of semantic-aware representation learning via Graph Convolutional Network (SA-GCN) by 13.33% in terms of Accuracy@1. Additionally, MP-GT surpasses the popular baseline of context-aware App usage prediction with heterogeneous graph embedding (CAP) by 74.02% in the same metric. Moreover, MP-GT reduces training time by 79.47% compared to SA-GCN. These findings validate that our approach not only achieves higher prediction accuracy but also converges faster than the baseline models. Therefore, MP-GT proves to be an effective and superior solution for the App usage prediction task.

Objective The Gouli area is one of the important gold and polymetallic belt in the East Kunlun Orogen. There is no research on lineament identification and mineral exploration based on multisource remote sensing data in the area. Methods In this paper, various enhancement techniques were employed on Landsat 8 OLI, GF-2 and DEM data to delineate structural lineaments. Meanwhile, information on geological, mineral and geochemical anomalies was combined to define prospecting targets in the Gouli area. Results The results show that (1) The tectonic framework of the study area can be divided into two regions by the boundary of Kaketeer-Seride. The lineament in the northern region is most developed in the NNE direction, followed by the near-EW direction, and less distributed in the NW and NE directions. The lineament in the southern region is mainly developed in the near-EW direction, and the NW to NE directions are less distributed. (2) The gold ore is controlled by lineaments. (3) The areas of densely distributed and intersected lineaments, as well as the areas connected by different colors on remote sensing images, are favorable locations for gold mineralization. Finally, based on the comprehensive analysis of multiple geological information and remote sensing interpreted tectonic information, four prospecting targets were identified in the study area and verified in the field. Conclusion This study proves that multisource remote sensing data can better identify the spatial structure characteristics of surface tectonics, which can provide a reference and basis for prospecting new deposits in the Gouli area.

Abstract Adenosine-to-inosine (A-to-I) editing of RNA, catalyzed by adenosine deaminase acting on RNA (ADAR) enzymes, is a prevalent RNA modification in mammals. It has been shown that A-to-I editing plays a critical role in multiple diseases, such as cardiovascular disease, neurological disorder, and particularly cancer. ADARs are the family of enzymes, including ADAR1, ADAR2, and ADAR3, that catalyze the occurrence of A-to-I editing. Notably, A-to-I editing is mainly catalyzed by ADAR1. Given the significance of A-to-I editing in disease development, it is important to unravel the complex roles of ADAR1 in cancer for the development of novel therapeutic interventions. In this review, we briefly describe the progress of research on A-to-I editing and ADARs in cancer, mainly focusing on the role of ADAR1 in cancer from both editing-dependent and independent perspectives. In addition, we also summarized the factors affecting the expression and editing activity of ADAR1 in cancer.

Traditional aluminum alloys are unsuitable for structural use above 200 ℃ due to precipitate coarsening or dissolution. Laser powder bed fusion (LPBF) additive manufacturing technique enables fabricating novel aluminum alloys with enhanced high-temperature properties. This study focuses on investigating the mechanical properties and microstructural evolution of a novel LPBF-fabricated Al-Cu-Li-Sc-Zr alloy at elevated temperatures. The microstructure is characterized by nano-scale grains and precipitates. Excellent grain structure and precipitate stability result in superior high-temperature mechanical properties. This study advances additively manufactured aluminum alloy design for potential high-temperature applications, offering valuable insights into their behavior in extreme environments.

Abstract Background Grassroots medical institutions are the primary “battlefield” of hypertension management based on hierarchical diagnosis and treatment policies in China. There is a considerable difference in the insured population and reimbursement ratio between different medical insurance programs. The management of hypertension directly affects the development trend of cardiovascular and cerebrovascular diseases. Methods To understand the difference between different medical insurance programs regarding the management of older hypertensive patients, all outpatients aged 60 and above with hypertension in the basic medical insurance database of Beijing, China, from April 1, 2019, to January 31, 2020, were included. Medical behaviours included patients’ choice of hospital level, type of hospital, number of hospitals visited, grassroots medical institutions and cross-district visits. Medication adherence was evaluated by calculating the medication possession ratio of antihypertensive medications. First, we adopted a statistical description for medical behaviours and medication adherence. Then, multivariate logistic regression was used to analyse the influencing factors of medication adherence. Results This study included 1.29 million patients with Urban Employee Basic Medical Insurance (UEBMI) and 0.31 million patients with Urban‒Rural Resident Basic Medical Insurance (URRBMI). The proportions of patients with UEBMI who chose tertiary hospitals, comprehensive hospitals, grassroots medical institutions and cross-district visits were 25.84%, 56.09%, 57.34% and 39.32%, respectively, while those of patients with URRBMI were 11.14%, 60.59%, 81.28% and 6.07%, respectively. The medication adherence rates of men and women taking one medication were 61.04% and 55.86%, respectively. UEBMI patients who took their medication accounted for 62.36%, while only 40.27% of URRBMI patients adhered to their medication. The percentages of young-old, old-old and oldest-old patients who took their antihypertensive medications were 58.05%, 59.09% and 56.78%, respectively. The adherence to taking ≥ 2 medications (35.47%) was lower than that to taking one medication (58.33%). The medication adherence rates of patients with UEBMI and URRBMI for taking ≥ 2 medications were 37.21% and 27.45%, respectively. Conclusions Patients with UEBMI were more inclined to choose tertiary hospitals and cross-district visits than patients with URRBMI. The adherence of patients with UEBMI was better than that of patients with URRBMI in China.

Well 1 of Bailongshan Coal Mine is a coal and gas blow-out mine, the use of full-face tunnel boring machine (TBM) can better meet the needs of safe, efficient and environmentally friendly construction of coal mines. The cutterhead is a key component to determine the efficiency of TBM construction, and its reasonable design is essential to ensure the safety of coal mine production. Based on the analysis of the differences in engineering demands and geological characteristics between coal mine gas control roadway and non-coal mine tunnel, the design requirements of TBM cutterhead in coal mine gas control roadway are summarized, and the design process of TBM cutter head in gas control roadway is illustrated. The small diameter TBM cutterhead is designed for the gas control roadway in Well 1 of Bailongshan Coal Mine, and the initial scheme of the cutterhead is determined from three main aspects: the body structure, the layout of the cutters, and muck removal structure, then, the scheme of cutterhead is finally formed in combination with the verification of overturning moment, unbalanced force, strength and stiffness. The TBM cutterhead of gas control roadway in Well 1 Bailongshan Coal Mine adopts a planar two-part structure, the cutters are arranged in the form of single helix cutter layout, and the cutter spacing design is determined according to the discrete element simulation analysis. The scraper bucket is uniform distributed around the cutterhead, and its size is determined according to the volume of muck removal. The analysis of mechanical properties shows that the maximum overturning torque of the cutterhead is 946.53 kNm, and the overturning torque generated by the cutters is 523.28 kNm, accounting for 55.3%. The maximum horizontal and vertical unbalanced force generated by the cutters is 78.12 kN, which is only accounts for 17.2% of the vertical unbalanced force generated by the cutterhead gravity. The maximum stress of the cutterhead is 99 MPa and the maximum deformation is 0.4 mm, which is equivalent to that the overall thickness strain of the cutterhead is about 0.27‰, its performance meeting the design requirements. The cutterhead design process for gas control roadway in Well 1 of Bailongshan Coal Mine can provide reference for TBM cutterhead design of similar projects.

In the coal mine tunnel TBM excavation, in order to identify the broken surrounding rock state in time during the excavation process, a method based on tunnel excavation parameters for identifying the surrounding rock characteristics of coal mine tunnels is proposed. Firstly, according to the abnormal changes in the travel parameters of the support boot hydraulic cylinder during the excavation, it is judged that the TBM excavation has entered the broken surrounding rock section from the stable surrounding rock section, thus obtaining the data set of the stable surrounding rock section and the transitional section. Then, based on the data set, the correlation and recognition ability of the tunneling parameters are analyzed, the excavation parameters for identifying the broken rock characteristics are selected, and finally, a long short-term memory (LSTM) model is used for prediction. According to the prediction results of the excavation parameters, the identification index is obtained, and subsequent identification of the rock breaking state in the following sections is completed. This method is applied in a gas control tunnel of a coal mine, and the precision of the LSTM model in predicting the excavation parameters is higher than 98%. Based on the prediction results, the relative error percentage of the excavation parameters is calculated as an identification index. With a threshold of 5% relative error percentage, the identified rock breaking state exists in three data segments, which is consistent with the judgment of the support boot hydraulic cylinder travel. This shows that this method can effectively identify the broken rock characteristics of the surrounding rock, and has the advantages of high intelligence level and little interference in construction.

The high heterogeneity of lung squamous cell carcinomas (LUSC) and the complex tumor microenvironment lead to non-response to immunotherapy in many patients. Therefore, characterizing the heterogeneity of the tumor microenvironment in patients with LUSC and further exploring the immune features and molecular mechanisms that lead to immune resistance will help improve the efficacy of immunotherapy in such patients. Herein, we retrospectively analyzed the RNA sequencing (RNA-seq) data of 513 LUSC samples with other multiomics and single-cell RNA-seq data and validated key features using multiplex immunohistochemistry. We divided these samples into six subtypes (CS1–CS6) based on the RNA-seq data and found that CS3 activates the immune response with a high level of lymphocyte infiltration and gathers a large number of patients with advanced-stage disease but increases the expression of exhausted markers cytotoxic T-lymphocyte associated protein 4, lymphocyte-activation gene 3, and programmed death-1. The prediction of the response to immunotherapy showed that CS3 is potentially resistant to immune checkpoint blockade therapy, and multi-omic data analysis revealed that CS3 specifically expresses immunosuppression-related proteins B cell lymphoma 2, GRB2-associated binding protein, and dual-specificity phosphatase 4 and has a high mutation ratio of the driver gene ATP binding cassette subfamily A member 13. Furthermore, single-cell RNA-seq verified lymphocyte infiltration in the CS3 subtype and revealed a positive relationship between the expression of LAMC2-CD44 and immune resistance. LAMC2 and CD44 are epithelial-mesenchymal transition-associated genes that modulate tumor proliferation, and multicolor immunofluorescence validated the negative relationship between the expression of LAMC2-CD44 and immune infiltration. Thus, we identified a lymphocyte-infiltrated subtype (CS3) in patients with LUSC that exhibited resistance to immune checkpoint blockade therapy, and the co-hyperexpression of LAMC2-CD44 contributed to immune resistance, which could potentially improve immunological efficacy by targeting this molecule pair in combination with immunotherapy.

Background Elevated white blood cell count, fibrinogen levels, and lower levels of albumin signify higher systemic inflammatory response, hypercoagulable state, and poorer nutritional status, respectively. However, a consistent conclusion could not be drawn on whether the association between inflammatory markers and cardiovascular disease was affected by the presence of chronic kidney disease (CKD). We aimed to explore the association between inflammation and adverse outcomes in patients with acute ischemic stroke (AIS), as well as whether this association differs due to the presence of CKD. Methods and Results This research was based on the Third China National Stroke Registry. The main adverse outcomes were poor functional outcome, stroke recurrence, and combined vascular event after 1 year. Inflammation was defined as the worst quartile of at least 2 of the aforementioned 3 markers. Finally, 8493 patients with AIS were enrolled in this study. The adjusted odds ratios/hazard ratios and 95% CIs of inflammation were 1.58 (1.34–1.86) for poor functional outcomes, 1.25 (1.06–1.47) for stroke recurrence, and 1.25 (1.06–1.46) for combined vascular event. The association between inflammation and adverse outcomes existed only in patients with AIS without CKD, although the interaction between CKD and inflammation was not statistically significant. (P for interaction >0.05). Conclusions Inflammation, which was defined as a combination of fibrinogen, white blood cell count, and albumin, was associated with all 1‐year adverse outcomes among patients with AIS. Routine assessment of these biomarkers could become a potential part of the clinical evaluation for patients with AIS, especially those without CKD, aiding clinicians in risk stratification and treatment decision‐making.

Background Insulin resistance as a significant vascular risk factor has been studied in relation to cerebral small vessel disease (SVD). Evidence suggests that insulin resistance might trigger high blood pressure (BP). Therefore, we aimed to investigate whether insulin resistance impacts SVD with a mediating effect of BP in nondiabetic subjects. Methods and Results PRECISE (Polyvascular Evaluation for Cognitive Impairment and Vascular Events) study participants underwent brain and vascular imaging techniques and metabolomic risk factors measurements. Insulin resistance was evaluated by the insulin sensitivity index and the Homeostatic Model Assessment for Insulin Resistance based on the standard oral glucose tolerance test. On average, 2752 nondiabetic subjects (47.1% men) aged 60.9 years were included. The multivariable logistic regression model and linear regression model tested the association of insulin resistance with BP components (including systolic BP [SBP], diastolic BP (DBP), and pulse pressure [PP]) and SVD, and of BP components with SVD. In the mediation analysis, SBP, DBP, and PP were found to partially mediate the detrimental effect of insulin resistance (assessed by the insulin sensitivity index) on lacunes (mediation percentage: SBP, 31.15%; DBP, 34.21%; PP, 10.43%), white matter hyperintensity (mediation percentage: SBP, 37.34%; DBP, 44.15%; PP, 9.80%), and SVD total burden (mediation percentage: SBP, 42.07%; DBP, 49.29%; PP, 11.71%) (all P

Active vibration control is a critical issue of the wind turbine in the field of marine energy. First, based on a three-degree-of-freedom wind turbine, a state space model subject to wind and wave loads is obtained. Then, a delayed state feedback control scheme is illustrated to reduce the vibration of platform pitch angle and tower top foreaft displacement, where the control channel includes time-delay state signals. The designed controller’s existence conditions are investigated. The simulation results show that the delayed feedback H∞ controller can significantly suppress wind- and wave-induced vibration of the wind turbine. Furthermore, it presents potential advantages over the delay-free feedback H∞ controller and the classic linear quadratic regulator in two aspects: vibration control performance and control cost.

Radiation-induced lung injury is a common complication associated with radiotherapy. It is characterized by early-stage radiation pneumonia and subsequent radiation pulmonary fibrosis. However, there is currently a lack of effective therapeutic strategies for radiation-induced lung injury. Recent studies have shown that tolerogenic dendritic cells interact with regulatory T cells and/or regulatory B cells to stimulate the production of immunosuppressive molecules, control inflammation, and prevent overimmunity. This highlights a potential new therapeutic activity of tolerogenic dendritic cells in managing radiation-induced lung injury. In this review, we aim to provide a comprehensive overview of tolerogenic dendritic cells in the context of radiation-induced lung injury, which will be valuable for researchers in this field.

In recent years, various data-driven algorithms have been applied to the classification and staging of brain glioma MRI detection. However, the restricted availability of brain glioma MRI data in purely data-driven deep learning algorithms has presented challenges in extracting high-quality features and capturing their complex patterns. Moreover, the analysis methods designed for 2D data necessitate the selection of ideal tumor image slices, which does not align with practical clinical scenarios. Our research proposes an novel brain glioma staging model, Medical Cognition Embedded (MCE) model for 3D data. This model embeds knowledge characteristics into data-driven approaches to enhance the quality of feature extraction. Approach includes the following key components: (1) Deep feature extraction, drawing upon the imaging technical characteristics of different MRI sequences, has led to the design of two methods at both the algorithmic and strategic levels to mimic the learning process of real image interpretation by medical professionals during film reading; (2) We conduct an extensive Radiomics feature extraction, capturing relevant features such as texture, morphology, and grayscale distribution; (3) By referencing key points in radiological diagnosis, Radiomics feature experimental results, and the imaging characteristics of various MRI sequences, we manually create diagnostic features (Diag-Features). The efficacy of proposed methodology is rigorously evaluated on the publicly available BraTS2018 and BraTS2020 datasets. Comparing it to most well-known purely data-driven models, our method achieved higher accuracy, recall, and precision, reaching 96.14%, 93.4%, 97.06%, and 97.57%, 92.80%, 95.96%, respectively.

Summary: Background: The atherogenicity of remnant cholesterol (RC), a contributor to residual risk of cardiovascular events, has been underlined by recent guidelines. We aimed to evaluate the relationship between RC levels and the efficacy and safety of genotype-guided dual antiplatelet therapy in the CHANCE-2 trial. Methods: This post-hoc study used data from the CHANCE-2 trial, which was a randomised, double-blind, placebo-controlled trial of 6412 patients (aged >40 years) enrolled from 202 hospitals in China, between Sept 23, 2019, and March 22, 2021, who carried CYP2C19 loss-of-function alleles and had either an acute minor stroke or high-risk transient ischaemic attack (TIA), and could start treatment within 24 h of symptom onset. Participants received either (1:1) ticagrelor plus aspirin (control) or clopidogrel plus aspirin (intervention) and the effect of reducing the 3-month risk of any new stroke was assessed (ischemic or haemorrhagic, primary outcome). From the CHANCE-2 study population, we enrolled 5890 patients with complete data on RC. The cutoff point of RC for distinguishing patients with greater benefit from ticagrelor-aspirin versus clopidogrel-aspirin was determined with subpopulation treatment effect pattern plot. The primary efficacy and safety outcome was recurrent stroke and severe or moderate bleeding within 90 days, respectively. CHANCE-2 is registered with ClinicalTrials.gov, NCT04078737. Findings: The cutoff to define elevated RC was 0.91 mmol/L. Ticagrelor-aspirin versus clopidogrel-aspirin was associated with a reduced risk of recurrent stroke in patients with non-elevated RC levels (122 [5.3%] versus 179 [7.8%]; hazard ratio [HR], 0.68; 95% confidence interval [CI], 0.54–0.85), but this benefit was absent in those with elevated RC levels (58 [8.4%] versus 48 [7.3%]; HR, 1.10; 95% CI, 0.73–1.65; P-interaction = 0.03). When analyzed as a continuous variable, the benefit of ticagrelor-aspirin on recurrent stroke decreased as RC levels increased. The rates of severe or moderate bleeding between treatment groups were similar across RC categories (0.3% versus 0.3%, P-interaction = 0.95). Interpretation: Our post-hoc findings suggest that RC could be a potential biomarker to discriminate patients who received more benefits from ticagrelor-aspirin versus clopidogrel-aspirin therapy in CYP2C19 loss-of-function carriers with minor stroke or TIA. These findings need to be validated in an independent study. Funding: The National Key Research and Development Program of China, Beijing Natural Science Foundation Haidian original innovation joint fund, Fund for Young Talents of Beijing Medical Management Center, the high-level public health talents, Training Fund for Open Projects at Clinical Institutes and Departments of Capital Medical University; and Salubris.

Aims This study aimed to explore whether a relationship exists between dipping patterns and 1-year functional outcome in patients with acute ischemic stroke (IS) or transient ischemic attack (TIA). Methods Data from the Blood Pressure and Clinical Outcome in TIA or Ischemic Stroke Study (BOSS), a nationwide, hospital-based, longitudinal cohort study, was used for this study. Patients with acute IS or TIA were recruited within 7 days after onset and ambulatory blood pressure monitoring was performed during hospitalization. Patients were defined as dippers if nocturnal systolic blood pressure fell by ≥10%, non-dippers if 0–10%, and reverse dippers if < 0%. Poor functional outcome was defined as a modified Rankin Scale (mRS) score of 3–5. Logistic regression analysis was used to test the association between dipping patterns and 1-year functional outcome. Results Among the 1808 IS/TIA patients, 19.19% were dippers, 53.21% were non-dippers, and 27.60% were reverse dippers. Poor functional outcome occurred in 22.44% of reverse dippers, which was significantly higher than that of dippers (16.14%) and non-dippers (16.53%) (P = .014). A univariate analysis revealed that reverse dipping was a risk factor for poor functional outcome (Odds ratio 1.504, 95% confidence interval 1.055–2.145, P = .024). However, this significance disappeared after adjusting for confounders. Conclusions Reverse dipping was prevalent in patients with IS/TIA. The higher incidence of 1-year poor functional outcome in reverse dippers warrants further investigation.

Abstract Introduction Similar white matter hyperintensities (WMH) burden may have varied cognitive outcomes in patients with cerebral small vessel disease (CSVD). This study aimed to evaluate whether blood–brain barrier (BBB) permeability is associated with cognitive impairment (CI) heterogeneity in patients with WMH. Methods We recruited 51 participants with WMH. We evaluated WMH burden using the Fazekas scale and WMH volume on structural magnetic resonance imaging (MRI), and assessed BBB permeability using dynamic contrast-enhanced (DCE)-MRI. We used permeability–surface area product (PS) from the Patlak model to represent BBB permeability. All patients underwent Mini-Mental State Examination (MMSE), Boston Naming Test (BNT) and animal verbal fluency test (VFT) for cognitive assessment. We divided patients into CI and non-CI groups based on their MMSE scores (

Abstract Ischemic stroke is a leading cause of global mortality and long-term disability. However, there is a paucity of whole-genome sequencing studies on ischemic stroke, resulting in limited knowledge of the interplay between genomic and phenotypic variations among affected patients. Here, we outline the STROMICS design and present the first whole-genome analysis on ischemic stroke by deeply sequencing and analyzing 10,241 stroke patients from China. We identified 135.59 million variants, > 42% of which were novel. Notable disparities in allele frequency were observed between Chinese and other populations for 89 variants associated with stroke risk and 10 variants linked to response to stroke medications. We investigated the population structure of the participants, generating a map of genetic selection consisting of 31 adaptive signals. The adaption of the MTHFR rs1801133-G allele, which links to genetically evaluated VB9 (folate acid) in southern Chinese patients, suggests a gene-specific folate supplement strategy. Through genome-wide association analysis of 18 stroke-related traits, we discovered 10 novel genetic-phenotypic associations and extensive cross-trait pleiotropy at 6 lipid-trait loci of therapeutic relevance. Additionally, we found that the set of loss-of-function and cysteine-altering variants present in the causal gene NOTCH3 for the autosomal dominant stroke disorder CADASIL displayed a broad neuro-imaging spectrum. These findings deepen our understanding of the relationship between the population and individual genetic layout and clinical phenotype among stroke patients, and provide a foundation for future efforts to utilize human genetic knowledge to investigate mechanisms underlying ischemic stroke outcomes, discover novel therapeutic targets, and advance precision medicine.

To address the security risks associated with fixed offset mapping in self-embedded watermarking technology, as well as the limited recovery rate of single watermarking methods, an image double fragile watermarking algorithm based on block neighborhood was proposed.The image was divided into non-overlapping blocks of size 4×4 and block truncation coding was used to generate the recovery watermark based on the image block.For each image block, a neighborhood of a proper size was specified and two mapping blocks were randomly selected from the regions within and outside the neighborhood.Then the recovery watermark was embedded into the two mapping blocks simultaneously.The image block neighborhood setting mechanism of the algorithm ensured that the image block maintains a certain distance from its corresponding mapping block.Additionally, the selection mechanism of mapping blocks inside and outside the image block neighborhood ensured a certain distance between the two mapping blocks, thereby guaranteeing the security of the watermark.In the case of continuous region tampering, the relationship between the tampered region and the neighborhood of the image block was analyzed theoretically.The analysis showed that a suitable image block neighborhood can improve the average recovery rate of the tampered area compared with the random mapping embedding algorithm.Besides, the distribution trend of the average recovery rate of the tampered area and the recovery rate of each image block in the tampered area were given by numerical calculation.It was found that the tampered area image block can be recovered 100%, some image blocks in the center of the tampered area can be recovered 100%, and the recovery rate of image blocks in tampered area will be reduced.The experimental results verify the rationality and effectiveness of the theoretical analysis.Moreover, when the neighborhood parameters are large, the proposed algorithm achieves a higher average recovery rate of the tampered region than the random mapping embedding algorithm in the case of continuous region tampering.

Abstract Background In large-scale high-throughput sequencing projects and biobank construction, sample tagging is essential to prevent sample mix-ups. Despite the availability of fingerprint panels for DNA data, little research has been conducted on sample tagging of whole genome bisulfite sequencing (WGBS) data. This study aims to construct a pipeline and identify applicable fingerprint panels to address this problem. Results Using autosome-wide A/T polymorphic single nucleotide variants (SNVs) obtained from whole genome sequencing (WGS) and WGBS of individuals from the Third China National Stroke Registry, we designed a fingerprint panel and constructed an optimized pipeline for tagging WGBS data. This pipeline used Bis-SNP to call genotypes from the WGBS data, and optimized genotype comparison by eliminating wildtype homozygous and missing genotypes, and retaining variants with identical genomic coordinates and reference/alternative alleles. WGS-based and WGBS-based genotypes called from identical or different samples were extensively compared using hap.py. In the first batch of 94 samples, the genotype consistency rates were between 71.01%-84.23% and 51.43%-60.50% for the matched and mismatched WGS and WGBS data using the autosome-wide A/T polymorphic SNV panel. This capability to tag WGBS data was validated among the second batch of 240 samples, with genotype consistency rates ranging from 70.61%-84.65% to 49.58%-61.42% for the matched and mismatched data, respectively. We also determined that the number of genetic variants required to correctly tag WGBS data was on the order of thousands through testing six fingerprint panels with different orders for the number of variants. Additionally, we affirmed this result with two self-designed panels of 1351 and 1278 SNVs, respectively. Furthermore, this study confirmed that using the number of genetic variants with identical coordinates and ref/alt alleles, or identical genotypes could not correctly tag WGBS data. Conclusion This study proposed an optimized pipeline, applicable fingerprint panels, and a lower boundary for the number of fingerprint genetic variants needed for correct sample tagging of WGBS data, which are valuable for tagging WGBS data and integrating multi-omics data for biobanks.

Abstract Background Lignocellulose-derived aldehyde inhibitors seriously blocked the biorefinery of biofuels and biochemicals. To date, the economic production of lignocellulose-based products heavily relied on high productivities of fermenting strains. However, it was expensive and time-consuming for the achievable rational modification to strengthen stress tolerance robustness of aldehyde inhibitors. Here, it aimed to improve aldehyde inhibitors tolerance and cellulosic bioethanol fermentability for the chassis Zymomonas mobilis ZM4 pretreated using energy-efficient and eco-friendly cold plasma. Results It was found that bioethanol fermentability was weaker in CSH (corn stover hydrolysates) than that in synthetic medium for Z. mobilis, and thus was attributed to the inhibition of the lignocellulose-derived aldehyde inhibitors in CSH. Convincingly, it further confirmed that the mixed aldehydes severely decreased bioethanol accumulation through additional aldehydes supplementary assays in synthetic medium. After assayed under different processing time (10–30 s), discharge power (80–160 W), and working pressure (120–180 Pa) using cold atmosphere plasma (CAP), it achieved the increased bioethanol fermentability for Z. mobilis after pretreated at the optimized parameters (20 s, 140 W and 165 Pa). It showed that cold plasma brought about three mutation sites including ZMO0694 (E220V), ZMO0843 (L471L) and ZMO0843 (P505H) via Genome resequencing-based SNPs (single nucleotide polymorphisms). A serial of differentially expressed genes (DEGs) were further identified as the potential contributors for stress tolerance via RNA-Seq sequencing, including ZMO0253 and ZMO_RS09265 (type I secretion outer membrane protein), ZMO1941 (Type IV secretory pathway protease TraF-like protein), ZMOr003 and ZMOr006 (16S ribosomal RNA), ZMO0375 and ZMO0374 (levansucrase) and ZMO1705 (thioredoxins). It enriched cellular process, followed by metabolic process and single-organism process for biological process. For KEGG analysis, the mutant was also referred to starch and sucrose metabolism, galactose metabolism and two-component system. Finally, but interestingly, it simultaneously achieved the enhanced stress tolerance capacity of aldehyde inhibitors and bioethanol fermentability in CSH for the mutant Z. mobilis. Conclusions Of several candidate genetic changes, the mutant Z. mobilis treated with cold plasma was conferred upon the facilitated aldehyde inhibitors tolerance and bioethanol production. This work would provide a strain biocatalyst for the efficient production of lignocellulosic biofuels and biochemicals.

Abstract With the urgent need to implement the EU countries pledges and to monitor the effectiveness of Green Deal plan, Monitoring Reporting and Verification tools are needed to track how emissions are changing for all the sectors. Current official inventories only provide annual estimates of national CO2 emissions with a lag of 1+ year which do not capture the variations of emissions due to recent shocks including COVID lockdowns and economic rebounds, war in Ukraine. Here we present a near-real-time country-level dataset of daily fossil fuel and cement emissions from January 2019 through December 2021 for 27 EU countries and UK, which called Carbon Monitor Europe. The data are calculated separately for six sectors: power, industry, ground transportation, domestic aviation, international aviation and residential. Daily CO2 emissions are estimated from a large set of activity data compiled from different sources. The goal of this dataset is to improve the timeliness and temporal resolution of emissions for European countries, to inform the public and decision makers about current emissions changes in Europe.

Abstract Denitrification and leaching nitrogen (N) losses are poorly constrained in Earth System Models (ESMs). Here, we produce a global map of natural soil 15N abundance and quantify soil denitrification N loss for global natural ecosystems using an isotope-benchmarking method. We show an overestimation of denitrification by almost two times in the 13 ESMs of the Sixth Phase Coupled Model Intercomparison Project (CMIP6, 73 ± 31 Tg N yr−1), compared with our estimate of 38 ± 11 Tg N yr−1, which is rooted in isotope mass balance. Moreover, we find a negative correlation between the sensitivity of plant production to rising carbon dioxide (CO2) concentration and denitrification in boreal regions, revealing that overestimated denitrification in ESMs would translate to an exaggeration of N limitation on the responses of plant growth to elevated CO2. Our study highlights the need of improving the representation of the denitrification in ESMs and better assessing the effects of terrestrial ecosystems on CO2 mitigation.

Abstract Oncolytic viruses have recently been proven to be an effective and promising cancer therapeutic strategy, but there is rare data about oncolytic therapy in esophageal squamous cell carcinoma (ESCC), especially oncolytic measles virotherapy. Therefore, this study aimed to explore whether the recombinant measles virus vaccine strain rMV-Hu191 has an oncolytic effect against ESCC cells in vitro and in vivo and elucidate the underlying mechanisms. Our results showed that rMV-Hu191 could efficiently replicate in and kill ESCC cells through caspase-3/GSDME-mediated pyroptosis. Mechanistically, rMV-Hu191 triggers mitochondrial dysfunction to induce pyroptosis, which is mediated by BAK (BCL2 antagonist/killer 1) or BAX (BCL2 associated X). Further analysis revealed that rMV-Hu191 activates inflammatory signaling in ESCC cells, which may enhance the oncolytic efficiency. Moreover, intratumoral injection of rMV-Hu191 induced dramatic tumor regression in an ESCC xenograft model. Collectively, these findings imply that rMV-Hu191 exhibits an antitumor effect through BAK/BAX-dependent caspase-3/GSDME-mediated pyroptosis and provides a potentially promising new therapy for ESCC treatment.

While neuroblastoma accounts for 15% of childhood tumor-related deaths, treatments against neuroblastoma remain scarce and mainly consist of cytotoxic chemotherapeutic drugs. Currently, maintenance therapy of differentiation induction is the standard of care for neuroblastoma patients in clinical, especially high-risk patients. However, differentiation therapy is not used as a first-line treatment for neuroblastoma due to low efficacy, unclear mechanism, and few drug options. Through compound library screening, we accidently found the potential differentiation-inducing effect of AKT inhibitor Hu7691. The protein kinase B (AKT) pathway is an important signaling pathway for regulating tumorigenesis and neural differentiation, yet the relation between the AKT pathway and neuroblastoma differentiation remains unclear. Here, we reveal the anti-proliferation and neurogenesis effect of Hu7691 on multiple neuroblastoma cell lines. Further evidence including neurites outgrowth, cell cycle arrest, and differentiation mRNA marker clarified the differentiation-inducing effect of Hu7691. Meanwhile, with the introduction of other AKT inhibitors, it is now clear that multiple AKT inhibitors can induce neuroblastoma differentiation. Furthermore, silencing AKT was found to have the effect of inducing neuroblastoma differentiation. Finally, confirmation of the therapeutic effects of Hu7691 is dependent on inducing differentiation in vivo, suggesting that Hu7691 is a potential molecule against neuroblastoma. Through this study, we not only define the key role of AKT in the progression of neuroblastoma differentiation but also provide potential drugs and key targets for the application of differentiation therapies for neuroblastoma clinically.

Background This study aimed to investigate the efficacy and safety of ticagrelor–aspirin versus clopidogrel–aspirin in Chinese patients by the presence and clinical presentation of intracranial artery stenosis (ICAS) using randomized trial data from the CHANCE‐2 (Clopidogrel in High‐Risk Patients With Acute Nondisabling Cerebrovascular Events‐II) trial. Methods and Results A total of 6412 patients with minor stroke or transient ischemic attack who carried CYP2C19 loss‐of‐function alleles were randomized to either the ticagrelor–aspirin or clopidogrel–aspirin group. Patients without imaging of the intracranial artery were excluded from the nonprespecified subgroup analysis of CHANCE‐2. All patients included were classified into the following groups: without ICAS, symptomatic ICAS, or asymptomatic ICAS. The primary efficacy outcome was new strokes within 90 days. There were 5893 patients (median age, 64.8 years; 33.9% women) included, and 172 (4.9%), 171 (10.5%), and 57 (7.7%) cases of new strokes occurred within 90 days in the without ICAS, with symptomatic ICAS, and with asymptomatic ICAS groups, respectively. Ticagrelor–aspirin was associated with reduced risk of new stroke in patients without ICAS (62 [3.5%] versus 110 [6.3%]; hazard ratio [HR], 0.57 [95% CI, 0.41–0.78]) but not in those with symptomatic ICAS (HR, 0.77 [95% CI, 0.56–1.05]) or in those with asymptomatic ICAS (HR, 0.77 [95% CI, 0.43–1.38]) compared with clopidogrel–aspirin (P for interaction=0.14). There were no significant differences in the proportion of severe or moderate bleeding events among different ICAS groups. Conclusions Patients without ICAS received a significantly greater benefit from ticagrelor–aspirin than clopidogrel–aspirin after minor ischemic stroke or transient ischemic attack, and there was no statistically significant difference between treatments in patients with symptomatic ICAS or asymptomatic ICAS. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04078737.

Carbon nanotubes (CNTs) had potential applications in energy conversion and storage devices, and it could be prepared by expanded graphite loaded with catalyst at high temperature, however, the mechanism of carbon nanotube growth in expanded graphite need further confirmation. In this work, carbon nanotubes’ in situ growth in expanded graphite (EG) were prepared via catalytic pyrolysis reaction using carbores P as a carbon source and Co(NO3)3•6H2O as a catalyst. The results of X-ray diffraction (XRD), scanning electron microscope (SEM) and energy dispersive X-ray spectroscope (EDS) indicated the carbon nanotubes could generate in, EG with the presence of carbores P as a carbon source and cobalt nitrate as a catalyst. More interestingly, the growth mechanism of carbon nanotubes could be concluded by the results of differential thermal analysis-thermogravimetry-mass spectrometry (DTA-TG-MS) and X-ray photoelectron spectroscopy (XPS) analysis. The pyrolysis products of carbores P were mainly hydrocarbon gas such as CH4 gas, which reacts with Co(NO3)3·6H2O catalyst to reduces CoOx to Co particles, then the carbon form pyrolysis was deposited the on the surface catalyst Co particles and, after continuous solid dissolution and precipitation, carbon nanotubes were at last generated in EG at last.

Summary: Septic acute kidney injury (S-AKI), the most common type of acute kidney injury (AKI), is intimately related to pyroptosis and oxidative stress in its pathogenesis. Carboxy-terminus of Hsc70-interacting protein (CHIP), a U-box E3 ligase, modulates oxidative stress by degrading its targeted proteins. The role of CHIP in S-AKI and its relevance with pyroptosis have not been investigated. In this study, we showed that CHIP was downregulated in renal proximal tubular cells in lipopolysaccharide (LPS)-induced S-AKI. Besides, the extent of redox injuries in S-AKI was attenuated by CHIP overexpression or activation but accentuated by CHIP gene disruption. Mechanistically, our work demonstrated that CHIP interacted with and ubiquitinated NLRP3 to promote its proteasomal degradation, leading to the inhibition of NLRP3/ACS inflammasome-mediated pyroptosis. In summary, this study revealed that CHIP ubiquitinated NLRP3 to alleviate pyroptosis in septic renal injuries, suggesting that CHIP might be a potential therapeutic target for S-AKI.

Abstract An effective systemic mechanism regulates tumor development and progression; thus, a rational design in a one‐stone‐two‐birds strategy is meant for cancer treatment. Herein, a hollow Fe3O4 catalytic nanozyme carrier co‐loading lactate oxidase (LOD) and a clinically‐used hypotensor syrosingopine (Syr) are developed and delivered for synergetic cancer treatment by augmented self‐replenishing nanocatalytic reaction, integrated starvation therapy, and reactivating anti‐tumor immune microenvironment. The synergetic bio‐effects of this nanoplatform stemmed from the effective inhibition of lactate efflux through blocking the monocarboxylate transporters MCT1/MCT4 functions by the loaded Syr as a trigger. Sustainable production of hydrogen peroxide by catalyzation of the increasingly residual intracellular lactic acid by the co‐delivered LOD and intracellular acidification enabled the augmented self‐replenishing nanocatalytic reaction. Large amounts of produced reactive oxygen species (ROS) damaged mitochondria to inhibit oxidative phosphorylation as the substituted energy supply upon the hampered glycolysis pathway of tumor cells. Meanwhile, remodeling anti‐tumor immune microenvironment is implemented by pH gradient reversal, promoting the release of proinflammatory cytokines, restored effector T and NK cells, increased M1‐polarize tumor‐associated macrophages, and restriction of regulatory T cells. Thus, the biocompatible nanozyme platform achieved the synergy of chemodynamic/immuno/starvation therapies. This proof‐of‐concept study represents a promising candidate nanoplatform for synergetic cancer treatment.

Cisplatin is one of the major causes of acute kidney injury (AKI) in clinical practice, and ferroptosis is an essential form of cell death in cisplatin-induced AKI (CP-AKI). WW domain binding protein-2 (WBP2), a molecular chaperon, is involved in the progression of various malignancies, but its role in renal injuries has not been investigated. Our present study employed bioinformatics analysis to identify WBP2 as a potential modulator of AKI and ferroptosis. Preliminary laboratory investigations showed that WBP2, highly expressed in renal proximal tubular cells, was downregulated in CP-AKI. Further studies demonstrated that WBP2 decelerated ferroptosis to alleviate CP-AKI. Mechanistically, WBP2 interacted with glutathione peroxidase 4 (GPX4, a key detoxicating enzyme for ferroptosis) via its PPXY1 motif to inhibit ferroptosis. Furthermore, the in-depth investigations revealed that WBP2 competed with heat shock cognate protein 70 (HSC70) for the binding with the KEFRQ-like motifs of GPX4, leading to the deceleration of chaperon-mediated autophagy of GPX4. All in all, this study indicated the beneficial effect of WBP2 in CP-AKI and its relevance with ferroptosis, thus providing a novel insight into the modulation of ferroptosis in cisplatin-related nephropathy.

Abstract We present a near-real-time global gridded daily CO2 emissions dataset (GRACED) throughout 2021. GRACED provides gridded CO2 emissions at a 0.1° × 0.1° spatial resolution and 1-day temporal resolution from cement production and fossil fuel combustion over seven sectors, including industry, power, residential consumption, ground transportation, international aviation, domestic aviation, and international shipping. GRACED is prepared from the near-real-time daily national CO2 emissions estimates (Carbon Monitor), multi-source spatial activity data emissions and satellite NO2 data for time variations of those spatial activity data. GRACED provides the most timely overview of emissions distribution changes, which enables more accurate and timely identification of when and where fossil CO2 emissions have rebounded and decreased. Uncertainty analysis of GRACED gives a grid-level two-sigma uncertainty of value of ±19.9% in 2021, indicating the reliability of GRACED was not sacrificed for the sake of higher spatiotemporal resolution that GRACED provides. Continuing to update GRACED in a timely manner could help policymakers monitor energy and climate policies’ effectiveness and make adjustments quickly.

Abstract Objective Minor stroke or transient ischemic attack (TIA) usually have mild and nondisabling symptoms, and these functional deficits may recover fully e.g., TIA, however, part of them still suffer from cognitive impairment and poor outcomes. We conducted a study to determine the relationship between cognition evaluated by Montreal Cognitive Assessment (MoCA) and poor functional outcomes assessed by the Modified Rankin Scale (mRS) (mRS ≥ 2) and Stroke Impact Scale (SIS)-16(SIS-1622 and MoCA-3 m>22; improved PSCI group: with MoCA-2w ≤ 2 and MoCA-3 m>22;delayed PSCI group: MoCA-2w>22 and MoCA-3 m ≤ 22; persisting PSCI group: with MoCA-2w ≤ 22 and MoCA-3 m ≤ 22. Results A total of 1675 stroke patients were recruited in this study. There were 818 patients (48.84%) who had PSCI at baseline. Of these, 123 patients (15%) had mRS ≥2 at 3 months. The persisting PSCI group was a significant predictor of functional dependence at 3 months and 1 year after stroke and when adjusted for covariates such as gender, age, history of stroke, depression and intracranial atherosclerotic stenosis, stroke subtype and acute infarction type. Conclusion Persisting PSCI increased the risk of poor functional outcome after 3 months and 1 year follow-up. These high-risk individuals should be identified for targeted rehabilitation and counseling to improve longer-term post-stroke outcome.

Abstract Background The triglyceride-glucose (TyG) index was significantly related to clinical outcome in patients with cardiovascular disease (CAD) and cerebrovascular disease (CVD). We aim to investigate the association between TyG index and clinical prognosis of acute ischemic stroke (IS) patients with type-2 diabetes mellitus (T2DM). Methods Among 19,604 patients with acute IS admitted to the China National Stroke Registry II (CNSRII), 3359 IS patients with T2DM were included in the cross-sectional analysis. The TyG index (calculated by ln [fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]) was split into four quartiles. The outcomes included recurrent IS, all-cause death and poor outcome at 1 year were analyzed. The association between the TyG index and adverse cerebrovascular outcomes was assessed by proportional hazards regression analysis. Results During 1 year follow-up, recurrent IS, all-cause death and poor outcome occurred in 305 (9.08%), 229 (6.82%) and 443 (47.9%) cases, respectively. Multivariable Cox proportional hazards analyses showed that the risk of incident primary endpoints was associated with a higher TyG quartile. After adjustment for confounding factors, patients with a higher TyG index had an association with IS recurrence (adjusted hazard ratio, 1.41; 95% confidence interval, 0.97–2.03; P = 0.048) and all-cause death (adjusted hazard ratio, 1.70; 95% confidence interval, 1.062–2.74; P = 0.028), compared with those in the first quartile at 1 year time follow-up. In addition, there were interactions between TyG index and age (≥ 65), female, hypertensive agents, anticoagulant agents, statins and antidiabetic agents in subgroup analyses, especially patients without taken anticoagulant drugs were significantly related to IS recurrence, all-cause death and poor outcome (P = 0.003, P = 0.006 and P = 0.001, respectively). Conclusions TyG index is strongly related to the IS recurrence and all-cause death in acute IS patients with T2DM. This finding indicates that the TyG index might be a potential predictor of clinical outcome for acute IS patients with T2DM.

Background Smoking is a well‐established risk factor for the development of acute ischemic stroke (AIS). However, the “smoker's paradox” suggests that it is associated with favorable clinical outcomes following stroke. We aimed to reevaluate the association between smoking and in‐hospital outcomes in patients with AIS in contemporary practice. Methods and Results A total of 649 610 inpatients with AIS from 1476 participating hospitals in the Chinese Stroke Center Alliance were included. In‐hospital outcomes measurement included all‐cause mortality, discharge against medical advice, and complications. Multivariable logistic regression models adjusting for baseline characteristics, clinical profiles at presentation, and in‐hospital management were used to evaluate the association between smoking and in‐hospital outcomes. A propensity score–matched analysis was also conducted. Of these patients with AIS, 36.8% (n=238 912) were smokers. Smokers were younger, had fewer comorbidities, and had slightly lower rates of adverse in‐hospital outcomes than nonsmokers (all‐cause death or discharge against medical advice: 6.0% versus 6.1%; in‐hospital complications: 14.5% versus 15.1%). Multivariable analysis revealed that smoking was associated with higher risk of adverse in‐hospital outcomes (all‐cause death or discharge against medical advice: odds ratio [OR], 1.05 [95% CI, 1.02–1.08]; P

ObjectiveTo analyze the clinical characteristics and follow-up data of children with different clinical phenotypes of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD).MethodsThe basic demographic and clinical features, laboratory and imaging examination results, and follow-up data of 74 Chinese children with different phenotypes of MOGAD were retrospectively reviewed and analyzed.ResultsThe male-to-female ratio in this cohort was 1:1.39. The clinical phenotypes of MOGAD included acute disseminated encephalomyelitis (ADEM; n = 37), encephalitis (n = 11), optic neuritis (ON, n = 9), neuromyelitis optica spectrum disorder (NMOSD; n = 9), transverse myelitis (TM; n = 6), leukodystrophy-like manifestations (n = 1), and meningitis (n = 1). The mean age of disease onset was 86 months. The number of leukocytes in the cerebrospinal fluid of patients with ADEM was significantly higher than that in patients with ON but lower than that in patients with TM (p

Lattice structures are crucial for weight reduction, and laser powder bed fusion (LPBF) is an efficient fabrication method. However, there's a notable research gap in understanding the residual deformation of LPBF-fabricated lattice structures. This study investigates the residual deformation of three basic lattice structures, body centre cell (BCC), face centre cell (FCC), and diamond cell (DC), fabricated via LPBF to reveal their deformation mechanisms. Analysis covers horizontal direction, building direction, and total deformations, unveiling complex structural responses. Lower relative densities exhibit a prevalent structural deformation mode (SDM) causing significant deformations, while higher densities shift to an intrinsic deformation mode (IDM) dominated by contraction during fabrication. The FCC structure shows optimal stability with minimal residual deformation across most densities. This study offers insightful findings and a detailed mechanistic analysis of residual deformation in LPBF-fabricated lattice structures, applicable across various configurations, ensuring design process uniformity and reliability.

Abstract Little is known about the relationship between baseline systolic blood pressure (SBP) and subsequent clinical events in patients with different lesion patterns on diffusion weighted imaging (DWI). We analyzed the Acute Non‐disabling Cerebrovascular Events (CHANCE) trial dataset. Patients were categorized into negative DW imaging (no detectable lesions), lacunar infarction (single lesion ≤15 mm) and non‐lacunar infarction (single lesion >15 mm or multiple lesions) based on lesion patterns on DWI. The primary outcome was recurrent stroke within 90 days. Cox proportional hazards models were used to assess the association between SBP levels and stroke outcomes in patients with different lesion patterns. A total of 1089 patients were analyzed. We found 258 cases (23.7%) with negative DW imaging, 392 (36.0%) with lacunar infarction and 439 (40.3%) with non‐lacunar infarction. Patients with non‐lacunar infarction had the highest incidence of stroke at 90‐day (P

Abstract Hypertriglyceridemia-induced acute pancreatitis (HTGP) is characterized by the acute and excessive release of FFA produced by pancreatic lipases. However, the underlying mechanisms of this disease remain poorly understood. In this study, we describe the involvement of the RNA binding protein hnRNPA2B1 in the development of HTGP. We used palmitic acid (PA) and AR42J cells to create a model of HTGP in vitro. RT-PCR and western blot analyses revealed a decrease in the level of hnRNPA2B1 protein but not mRNA expression in PA-treated cells. Further analyses revealed that hnRNPA2B1 expression was regulated at the post-translational level by neddylation. Restoration of hnRNPA2B1 expression using the neddylation inhibitor MLN4924 protected AR42J cells from PA-induced inflammatory injury by preventing NF-κB activation and restoring fatty acid oxidation and cell proliferation. Furthermore, RNA immunoprecipitation studies demonstrated that hnRNPA2B1 orchestrates fatty acid oxidation by regulating the expression of the mitochondrial trifunctional protein-α (MTPα). Administration of MLN4924 in vivo restored hnRNPA2B1 protein expression in the pancreas of hyperlipidemic mice and ameliorated HTGP-associated inflammation and pancreatic tissue injury. In conclusion, we show that hnRNPA2B1 has a central regulatory role in preventing HTGP-induced effects on cell metabolism and viability. Furthermore, our findings indicate that pharmacological inhibitors that target neddylation may provide therapeutic benefits to HTGP patients.

Abstract Triple-negative breast cancer (TNBC) is a heterogeneous subtype of breast cancer that displays highly aggressive with poor prognosis. Owing to the limited targets and drugs for TNBC clinical therapy, it is necessary to investigate the factors regulating cancer progression and develop novel therapies for cancer treatment. Ferroptosis, a nonapoptotic form of programmed cell death characterized by accumulation of iron-dependent peroxidation of phospholipids, is regulated by cellular metabolism, redox homeostasis, and various cancer-related signaling pathways. Recently, considerable progress has been made in demonstrating the critical role of lipid metabolism in regulating ferroptosis, indicating potential combinational therapeutic strategies for cancer treatment. In this study, by drug combination screen of lipid metabolism compounds with ferroptosis inducers in decreasing TNBC cell viability, we found potent synergy of the CB1 antagonist rimonabant with erastin/(1 S, 3 R)-RSL3 (RSL3) in inhibiting TNBC cell growth both in vitro and in vivo via promoting the levels of lipid peroxides, malondialdehyde (MDA), 4-hydroxynonenal (4-HNE) and cytosolic reactive oxygen species (ROS) production, enhancing intracellular glutathione (GSH) depletion and inducing G1 cell cycle arrest. We identified that inhibition of CB1 promoted the effect of erastin/RSL3 on inducing ferroptosis and enhanced their inhibitory effect on tumor growth. Using RNA-Seq, fatty acid analyses and functional assays, we found that CB1 regulated stearoyl-CoA desaturase 1 (SCD1)- and fatty acyl desaturase 2 (FADS2)-dependent fatty acid metabolism via phosphatidylinositol 3 kinase (PI3K)-AKT and mitogen-activated protein kinase (MAPK) signaling pathways to modulate ferroptosis sensitivity in TNBC cells. These data demonstrate that dual targeting of CB1 and ferroptosis could be a promising therapeutic strategy for TNBC.

Measurement(s) carbon dioxide emissions Technology Type(s) carbon monitor Sample Characteristic - Environment city Sample Characteristic - Location worldwide

Abstract To address the security risk caused by fixed offset mapping and the limited recoverability of random mapping used in image watermarking, a self‐embedding fragile image watermarking algorithm based on deneighbourhood mapping are proposed. First, the image is divided into several 2 × 2 blocks, and authentication watermark and recovery watermark are generated based on the average value of the image blocks. Then, the denighbourhood mapping is implemented as, for each image block, its mapping block is randomly selected outside its neighbourhood. Finally, the authentication watermark and the recovery watermark are embedded into the image block itself and its mapping block. Theoretical analysis indicates that in the case of continuous area tampering, the proposed watermarking algorithm can achieve a better recovery rate than that of the method based on the random mapping. The experimental results verify the rationality and effectiveness of the theoretical analysis. Moreover, compared with the existing embedding algorithms based on random mapping, chaos mapping, and Arnold mapping, in the case of continuous area tampering, the proposed algorithm also achieves a higher average recovery rate.