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Abstract Background Hemoglobin-to-red blood cell distribution width ratio (HRR) had great predictive value for the prognosis of malignant tumors and cardiovascular disease. However, its predictive value for the occurrence of acute kidney injury (AKI) in elderly intertrochanteric fracture patients remains unclear. This study aims to analyze the correlation between the early postoperative HRR and the risk of postoperative AKI in elderly intertrochanteric fracture patients. Methods We reviewed the medical records of 307 elderly intertrochanteric fracture patients in this single-center retrospective cohort study. We performed univariate analysis on the relevant parameters, and parameters with significant differences were included in the following logistic regression model for multivariate analysis. Then, we used a receiver operating characteristic (ROC) curve to evaluate the predictive value of the early postoperative HRR level for AKI in elderly intertrochanteric fracture patients. Patients were divided into a high HRR group and a low HRR group according to the cutoff point determined by ROC curve analysis. Subsequently, the relevance between postoperative HRR and AKI was further determined using propensity score matching (PSM) and inverse probability of treatment weighting (IPTW). Results The area under the curve of the early postoperative HRR for predicting postoperative AKI was 0.714 (95% CI: 0.618–0.809). The cutoff value was 5.44. The sensitivity was 72.7%, and the specificity was 70.8%. Patients were divided into low HRR (⩽ 5.44) and high HRR (> 5.44) groups according to the cutoff value. PSM and IPTW analysis indicated that the risk of AKI in the low HRR group was significantly higher than that in the high HRR group in both the matched cohort (OR = 6.914, 95% CI: 1.714–46.603, p = 0.016) and the weighted group (OR = 2.784, 95% CI: 1.415–5.811, p = 0.040). Conclusions Early postoperative HRR is an accurate, accessible, and economical blood test parameter that can predict the risk of postoperative AKI in elderly patients with femoral intertrochanteric fracture.

Abstract Background Proper control of the lineage bias of megakaryocytic and erythroid progenitor cells (MEPs) is of significant importance, the disorder of which will lead to abnormalities in the number and function of platelets and erythrocytes. Unfortunately, the signaling pathways regulating MEP differentiation largely remain to be elucidated. This study aimed to analyze the role and the underlying molecular mechanism of miR-1915-3p in megakaryocytic and erythroid differentiation. Methods We utilized miRNA mimics and miRNA sponge to alter the expression of miR-1915-3p in megakaryocytic and/or erythroid potential cells; siRNA and overexpression plasmid to change the expression of SOCS4, a potential target of miR-1915-3p. The expression of relevant surface markers was detected by flow cytometry. We scanned for miR-1915-3p target genes by mRNA expression profiling and bioinformatic analysis, and confirmed the targeting by dual-luciferase reporter assay, western blot and gain- and lost-of-function studies. One-way ANOVA and t-test were used to analyze the statistical significance. Results In this study, overexpression or knockdown of miR-1915-3p inhibited or promoted erythroid differentiation, respectively. Accordingly, we scanned for miR-1915-3p target genes and confirmed that SOCS4 is one of the direct targets of miR-1915-3p. An attentive examination of the endogenous expression of SOCS4 during megakaryocytic and erythroid differentiation suggested the involvement of SOCS4 in erythroid/megakaryocytic lineage determination. SOCS4 knockdown lessened erythroid surface markers expression, as well as improved megakaryocytic differentiation, similar to the effects of miR-1915-3p overexpression. While SOCS4 overexpression resulted in reversed effects. SOCS4 overexpression in miR-1915-3p upregulated cells rescued the effect of miR-1915-3p. Conclusions miR-1915-3p acts as a negative regulator of erythropoiesis, and positively in thrombopoiesis. SOCS4 is one of the key mediators of miR-1915-3p during the differentiation of MEPs.

Abstract Identifying spatially variable genes (SVGs) is crucial for understanding the spatiotemporal characteristics of diseases and tissue structures, posing a distinctive challenge in spatial transcriptomics research. We propose HEARTSVG, a distribution-free, test-based method for fast and accurately identifying spatially variable genes in large-scale spatial transcriptomic data. Extensive simulations demonstrate that HEARTSVG outperforms state-of-the-art methods with higher $${F}_{1}$$ F 1 scores (average $${F}_{1}$$ F 1 Score=0.948), improved computational efficiency, scalability, and reduced false positives (FPs). Through analysis of twelve real datasets from various spatial transcriptomic technologies, HEARTSVG identifies a greater number of biologically significant SVGs (average AUC = 0.792) than other comparative methods without prespecifying spatial patterns. Furthermore, by clustering SVGs, we uncover two distinct tumor spatial domains characterized by unique spatial expression patterns, spatial-temporal locations, and biological functions in human colorectal cancer data, unraveling the complexity of tumors.

Abstract Objective The objective of this study was to conduct a comprehensive analysis of the molecular transmission networks and transmitted drug resistance (TDR) patterns among individuals newly diagnosed with HIV-1 in Nanjing. Methods Plasma samples were collected from newly diagnosed HIV patients in Nanjing between 2019 and 2021. The HIV pol gene was amplified, and the resulting sequences were utilized for determining TDR, identifying viral subtypes, and constructing molecular transmission network. Logistic regression analyses were employed to investigate the epidemiological characteristics associated with molecular transmission clusters. Results A total of 1161 HIV pol sequences were successfully extracted from newly diagnosed individuals, each accompanied by reliable epidemiologic information. The analysis revealed the presence of multiple HIV-1 subtypes, with CRF 07_BC (40.57%) and CRF01_AE (38.42%) being the most prevalent. Additionally, six other subtypes and unique recombinant forms (URFs) were identified. The prevalence of TDR among the newly diagnosed cases was 7.84% during the study period. Employing a genetic distance threshold of 1.50%, the construction of the molecular transmission network resulted in the identification of 137 clusters, encompassing 613 nodes, which accounted for approximately 52.80% of the cases. Multivariate analysis indicated that individuals within these clusters were more likely to be aged ≥ 60, unemployed, baseline CD4 cell count ≥ 200 cells/mm3, and infected with the CRF119_0107 (P

Over the last few decades, ultrafast laser processing has become a widely used tool for manufacturing microstructures and nanostructures. The real-time monitoring of laser material processing provides opportunities to inspect processes and provide feedback. To date, in-situ and real-time monitoring of laser material processing has rarely been performed. To this end, we propose dual-path snapshot compressive microscopy (DP-SCM) for high-speed, large field-of-view, and high-resolution imaging for in-situ and real-time ultrafast laser processing. In the evaluation of DP-SCM, the field of view, lateral resolution, and imaging speed were measured to be 2 mm, 775 nm, and 500 fps, respectively. In ultrafast laser processing, the laser scanning process is observed using a DP-SCM system when translating the sample stage and scanning the focused femtosecond laser. Finally, we monitored the development of a self-organized nanograting structure to validate the potential of our system for unveiling new material mechanisms. The proposed method serves as an add-up (plug-and-play) module for any imaging setup and has vast potential for opening new avenues for high-throughput imaging in laser material processing.

Abstract Notch signaling, renowned for its role in regulating cell fate, organ development, and tissue homeostasis across metazoans, is highly conserved throughout evolution. The Notch receptor and its ligands are transmembrane proteins containing epidermal growth factor-like repeat sequences, typically necessitating receptor-ligand interaction to initiate classical Notch signaling transduction. Accumulating evidence indicates that the Notch signaling pathway serves as both an oncogenic factor and a tumor suppressor in various cancer types. Dysregulation of this pathway promotes epithelial-mesenchymal transition and angiogenesis in malignancies, closely linked to cancer proliferation, invasion, and metastasis. Furthermore, the Notch signaling pathway contributes to maintaining stem-like properties in cancer cells, thereby enhancing cancer invasiveness. The regulatory role of the Notch signaling pathway in cancer metabolic reprogramming and the tumor microenvironment suggests its pivotal involvement in balancing oncogenic and tumor suppressive effects. Moreover, the Notch signaling pathway is implicated in conferring chemoresistance to tumor cells. Therefore, a comprehensive understanding of these biological processes is crucial for developing innovative therapeutic strategies targeting Notch signaling. This review focuses on the research progress of the Notch signaling pathway in cancers, providing in-depth insights into the potential mechanisms of Notch signaling regulation in the occurrence and progression of cancer. Additionally, the review summarizes pharmaceutical clinical trials targeting Notch signaling for cancer therapy, aiming to offer new insights into therapeutic strategies for human malignancies.

Photocatalyzed alkylsulfonylation of unactivated alkenes using DABCO. (SO2)2 and thianthrenium salts via a distal heteroaryl migration process has been developed, which provides a new means of synthesizing a variety of valuable alkylsulfonyl-substituted compounds. These alkylsulfonyl radicals couple with unactivated alkenes to undergo efficient intermolecular reactions, followed by distal heteroaryl migration. This mild catalytic method is tolerant of functional groups and affords medicinally relevant alkylsulfonylated heterocycles.

As artificial intelligence-based automatic generation technology advances, the emergence of misinformation in more sophisticated guises has become a significant threat to the economy and social order. Among its forms, out-of-context misinformation stands out as particularly deceptive and readily executable. This type of misinformation involves malicious actors enhancing the credibility of false narratives by misrepresenting contextual details such as individuals, events, and locations within real images. To address the shortcomings of current detection algorithms, which heavily depend on knowledge bases and often overlook the stance relationship between the information under scrutiny and online evidence, a stance analysis-based out-of-context misinformation detection method was developed. This method involved several steps for the detection of an image-caption pair along with the corresponding textual and visual evidence retrieved from the Internet. Initially, a stance gain score for each piece of textual evidence was calculated based on the co-occurrence of named entities. Subsequently, independent stance analysis networks were utilized to perform hierarchical clustering on both the image and visual evidence, as well as on the caption and textual evidence. This process involved the extraction of semantic stance representations, facilitated by multiple attention mechanisms and a stance analysis module. The authenticity of the image-caption pair was subsequently predicted based on the outcomes of semantic comparison and stance analysis. Experimental results indicate that the incorporation of stance analysis significantly enhances the method's detection capabilities. Specifically, the accuracy of this method outperforms the state-of-the-art algorithm that employs Internet evidence for detection by 2.3%.

Abstract Background The association between osteoarthritis (OA) and hypertension is a subject of ongoing debate in observational research, and the underlying causal relationship between them remains elusive. Methods This study retrospectively included 24,871 participants in the National Health and Nutrition Examination Survey (NHANES) from 2013 to 2020. Weighted logistic regression was performed to investigate the connection between OA and hypertension. Additionally, Mendelian randomization (MR) analysis was conducted to explore the potential causal relationship between OA and hypertension. Results In the NHANES data, after adjusting for multiple confounding factors, there was no significant relationship between OA and hypertension (OR 1.30, 95% CI, 0.97–1.73, P = 0.089). However, among males, OA appeared to be associated with a higher risk of hypertension (OR 2.25, 95% CI, 1.17–4.32, P = 0.019). Furthermore, MR results indicate no relationship between multiple OA phenotypes and hypertension: knee OA (IVW, OR 1.024, 95% CI: 0.931–1.126, P = 0.626), hip OA (IVW, OR 0.990, 95% CI: 0.941–1.042, P = 0.704), knee or hip OA (IVW, OR 1.005, 95% CI: 0.915–1.105, P = 0.911), and OA from UK Biobank (IVW, OR 0.796, 95% CI: 0.233–2.714, P = 0.715). Importantly, these findings remained consistent across different genders and in reverse MR. Conclusions Our study found that OA patients had a higher risk of hypertension only among males in the observational study. However, MR analysis did not uncover any causal relationship between OA and hypertension.

Abstract Oxidative stress-induced lipid accumulation is mediated by lipid droplets (LDs) homeostasis, which sequester vulnerable unsaturated triglycerides into LDs to prevent further peroxidation. Here we identify the upregulation of lipopolysaccharide-binding protein (LBP) and its trafficking through LDs as a mechanism for modulating LD homeostasis in response to oxidative stress. Our results suggest that LBP induces lipid accumulation by controlling lipid-redox homeostasis through its lipid-capture activity, sorting unsaturated triglycerides into LDs. N-acetyl-L-cysteine treatment reduces LBP-mediated triglycerides accumulation by phospholipid/triglycerides competition and Peroxiredoxin 4, a redox state sensor of LBP that regulates the shuttle of LBP from LDs. Furthermore, chronic stress upregulates LBP expression, leading to insulin resistance and obesity. Our findings contribute to the understanding of the role of LBP in regulating LD homeostasis and against cellular peroxidative injury. These insights could inform the development of redox-based therapies for alleviating oxidative stress-induced metabolic dysfunction.

Abstract The circadian clock regulates animal physiological activities. How temperature reorganizes circadian-dependent physiological activities remains elusive. Here, using in-vivo two-photon imaging with the temperature control device, we investigated the response of the Drosophila central circadian circuit to temperature variation and identified that DN1as serves as the most sensitive temperature-sensing neurons. The circadian clock gate DN1a’s diurnal temperature response. Trans-synaptic tracing, connectome analysis, and functional imaging data reveal that DN1as bidirectionally targets two circadian neuronal subsets: activity-related E cells and sleep-promoting DN3s. Specifically, behavioral data demonstrate that the DN1a-E cell circuit modulates the evening locomotion peak in response to cold temperature, while the DN1a-DN3 circuit controls the warm temperature-induced nocturnal sleep reduction. Our findings systematically and comprehensively illustrate how the central circadian circuit dynamically integrates temperature and light signals to effectively coordinate wakefulness and sleep at different times of the day, shedding light on the conserved neural mechanisms underlying temperature-regulated circadian physiology in animals.

Abstract Background The comparison between sedation and general anesthesia (GA) in terms of all-cause mortality remains a subject of ongoing debate. The primary objective of our study was to investigate the impact of GA and sedation on all-cause mortality in order to provide clarity on this controversial topic. Methods A systematic review and meta-analysis were conducted, incorporating cohort studies and RCTs about postoperative all-cause mortality. Comprehensive searches were performed in the PubMed, EMBASE, and Cochrane Library databases, with the search period extending until February 28, 2023. Two independent reviewers extracted the relevant information, including the number of deaths, survivals, and risk effect values at various time points following surgery, and these data were subsequently pooled and analyzed using a random effects model. Results A total of 58 studies were included in the analysis, with a majority focusing on endovascular surgery. The findings of our analysis indicated that, overall, and in most subgroup analyses, sedation exhibited superiority over GA in terms of in-hospital and 30-day mortality. However, no significant difference was observed in subgroup analyses specific to cerebrovascular surgery. About 90-day mortality, the majority of studies centered around cerebrovascular surgery. Although the overall pooled results showed a difference between sedation and GA, no distinction was observed between the pooled ORs and the subgroup analyses based on RCTs and matched cohort studies. For one-year all-cause mortality, all included studies focused on cardiac and macrovascular surgery. No difference was found between the HRs and the results derived from RCTs and matched cohort studies. Conclusions The results suggested a potential superiority of sedation over GA, particularly in the context of cardiac and macrovascular surgery, mitigating the risk of in-hospital and 30-day death. However, for the longer postoperative periods, this difference remains uncertain. Trial registration PROSPERO CRD42023399151; registered 24 February 2023.

PurposeTo investigate the predictive value of leukocyte subsets and C-reactive protein (CRP) in coronary artery disease (CAD).MethodsWe conducted a Mendelian randomization analysis (MR) on leukocyte subsets, C-reactive protein (CRP) and CAD, incorporating data from 68,624 patients who underwent coronary angiography from 2010 to 2022. After initial screening, clinical data from 46,664 patients were analyzed. Techniques employed included propensity score matching (PSM), logistic regression, lasso regression, and random forest algorithms (RF). Risk factors were assessed, and the sensitivity and specificity of the models were evaluated using receiver operating characteristic (ROC) curves. Additionally, survival analysis was conducted based on a 36-month follow-up period.ResultsThe inverse variance weight (IVW) analysis showed that basophil count (OR 0.92, 95% CI: 0.84–1.00, P = 0.048), CRP levels (OR 0.87, 95% CI: 0.73–1.00, P = 0.040), and lymphocyte count (OR 1.10, 95% CI: 1.04–1.16, P = 0.001) are significant risk factors for CAD. Using LASSO regression, logistic regression, and RF analysis, both CRP and lymphocyte counts were consistently identified as risk factors for CAD, prior to and following PSM. The ROC curve analysis indicated that the combination of lymphocyte and CRP levels after PSM achieves a higher diagnostic value (0.85). Survival analysis revealed that high lymphocyte counts and low CRP levels are associated with a decreased risk of Major Adverse Cardiovascular Events (MACE) (P

Background: The efficacy and adeptness of ChatGPT 3.5 and ChatGPT 4.0 in the precise diagnosis and management of conditions like atopic dermatitis and Autoimmune blistering skin diseases (AIBD) remain to be elucidated. So this study examined the accuracy and effectiveness of the ChatGPT responses related to understanding, therapies, and specific cases of these two conditions. Method: Firstly, the responses provided by ChatGPTs to a set of 50 questionnaires underwent evaluation by five distinct dermatologists, with complete adjudication of the third-party reviewer. The comparative analysis included the evaluative efficacy of both ChatGPT3.5 and ChatGPT4.0 against the diagnostic abilities exhibited by three distinct cohorts of qualified clinical professionals. And then, an examination was conducted to assess the diagnostic proficiency of ChatGPT3.5 and ChatGPT4.0 in the context of diagnosing specific instances of skin blistering autoimmune diseases. Results: In assessing the proficiency of ChatGPTs in generating responses related to fundamental knowledge about AD it is noteworthy that both versions of ChatGPTs, despite their lack of specialized training on medical databases, exhibited a commendable capacity to yield solutions that exhibited a substantial degree of concurrence with evidence-based medical information. Accordingly we observed that the performance of ChatGPT-4.0 beyond that of the ChatGPT-3.5. However, it it crucial to emphasize that ChatGPT-4.0 did not show the ability to offer answers surpassing those provided by associate senior, and senior medical professionals. In the assessment designed to determine the proficiency of ChatGPTs in recognizing particular type of AIBD, it is evident that both ChatGPT-4 and ChatGPT-3.5 demonstrated inadequacy in providing responses that are both precise and accurate for each individual occurrence of this skin condition. Conclusion: Both ChatGPT-3.5 and ChatGPT-4.0 satisfactory for addressing fundamental inquiries related to atopic dermatitis, however they prove insufficient for diagnosing AIBD. The progress of ChatGPT in achieving utility within the professional medical domain remains a considerable journey ahead.

The intrinsic magnetization compensation behaviors of rare-earth iron garnets (REIGs) make the material promising for applications in ultrafast spin storage devices. REIG/heavy metal heterostructures such as TbIG/Pt often display two sign crossovers of anomalous Hall effect resistance with varying temperatures. One of these crossovers is attributed to the magnetization compensation of REIG, and the other to the competition between the magnetic proximity effect and the spin Hall effect. Here, we design trilayer REIG heterostructures based on two rare-earth species (Tb and Eu). We modulate the layer stacking of the TbIG/EuIG/TbIG sandwich with a fixed total thickness and explore the contributions of REIG bulk and REIG/Pt interfaces on these two crossover points. As TbIG gradually moves away from Pt, the compensation temperature shows some fluctuations. However, when TbIG is entirely out of contact with Pt, the second crossover point undergoes a change that shows REIG/Pt interface dependency. The results highlight the dominance of REIG bulk on the compensation behavior and the interface sensitivity of the second crossover point. This study provides a reference for designing controllable spintronics devices, such as magnon valve applications.

Hyperlipidemia-induced osteoporosis is marked by increased bone marrow adiposity, and treatment with statins for hyperlipidemia often leads to new-onset osteoporosis. Endosome-associated trafficking regulator 1 (ENTR1) has been found to interact with different proteins in pathophysiology, but its exact role in adipogenesis is not yet understood. This research aimed to explore the role of ENTR1 in adipogenesis and to discover a new small molecule that targets ENTR1 for evaluating its effectiveness in treating hyperlipidemia-induced osteoporosis. We found that ENTR1 expression increased during the adipogenesis of bone marrow mesenchymal cells (BMSCs). ENTR1 gain- and loss-of-function assays significantly enhanced lipid droplets formation. Mechanistically, ENTR1 binds peroxisome proliferator-activated receptor γ (PPARγ) and enhances its expression, thereby elevating adipogenic markers including C/EBPα and LDLR. Therapeutically, AN698/40746067 attenuated adipogenesis by targeting ENTR1 to suppress PPARγ. In vivo, AN698/40746067 reduced bone marrow adiposity and bone loss, as well as prevented lipogenesis-related obesity, inflammation, steatohepatitis, and abnormal serum lipid levels during hyperlipidemia. Together, these findings suggest that ENTR1 facilitates adipogenesis by PPARγ involved in BMSCs’ differentiation, and targeted inhibition of ENTR1 by AN698/40746067 may offer a promising therapy for addressing lipogenesis-related challenges and alleviating osteoporosis following hyperlipidemia.

Abstract Background Chronic cough is a common symptom in patients post the coronavirus disease 2019 (COVID-19). In this study, we aimed to investigate the efficacy of inhaled corticosteroids (ICS) and the clinical characteristics of patients with post-COVID-19 chronic cough during the Omicron era. Methods An ambispective, longitudinal cohort study was conducted that included patients with post-COVID-19 who attended the respiratory clinic at our hospital between January 1, 2023, and March 31, 2023 with a complaint of persistent cough lasting more than 8 weeks. At 30 and 60 days after the first clinic visit for post-COVID-19 chronic cough, enrolled patients were prospectively followed up. We compared the changes in symptoms and pulmonary function between patients receiving ICS treatment (ICS group) and those not receiving ICS treatment (NICS group) at the two visits. Results A total of 104 patients with post-COVID-19 chronic cough were enrolled in this study (ICS group, n = 51; NICS group, n = 53). The most common symptoms accompanying post-COVID-19 chronic cough were sputum (58.7%, 61/104) and dyspnea (48.1%, 50/104). Seventy-one (82.6%, 71/86) patients had airway hyperresponsiveness, and 49 patients (47.1%, 49/104) were newly diagnosed with asthma. Most patients (95.2%, 99/104) exhibited improvement at 60 days after the first visit. The pulmonary function parameters of the patients in the ICS group were significantly improved compared to the baseline values (P

Abstract Metal-halide perovskite thin monocrystals featuring efficient carrier collection and transport capabilities are well suited for radiation detectors, yet their growth in a generic, well-controlled manner remains challenging. Here, we reveal that mass transfer is one major limiting factor during solution growth of perovskite thin monocrystals. A general approach is developed to overcome synthetic limitation by using a high solute flux system, in which mass diffusion coefficient is improved from 1.7×10–10 to 5.4×10–10 m2 s–1 by suppressing monomer aggregation. The generality of this approach is validated by the synthesis of 29 types of perovskite thin monocrystals at 40–90 °C with the growth velocity up to 27.2 μm min–1. The as-grown perovskite monocrystals deliver a high X-ray sensitivity of 1.74×105 µC Gy−1 cm−2 without applied bias. The findings regarding limited mass transfer and high-flux crystallization are crucial towards advancing the preparation and application of perovskite thin monocrystals.

Abstract Background Identifying individuals with mild cognitive impairment (MCI) at risk of progressing to Alzheimer’s disease (AD) provides a unique opportunity for early interventions. Therefore, accurate and long-term prediction of the conversion from MCI to AD is desired but, to date, remains challenging. Here, we developed an interpretable deep learning model featuring a novel design that incorporates interaction effects and multimodality to improve the prediction accuracy and horizon for MCI-to-AD progression. Methods This multi-center, multi-cohort retrospective study collected structural magnetic resonance imaging (sMRI), clinical assessments, and genetic polymorphism data of 252 patients with MCI at baseline from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. Our deep learning model was cross-validated on the ADNI-1 and ADNI-2/GO cohorts and further generalized in the ongoing ADNI-3 cohort. We evaluated the model performance using the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, specificity, and F1 score. Results On the cross-validation set, our model achieved superior results for predicting MCI conversion within 4 years (AUC, 0.962; accuracy, 92.92%; sensitivity, 88.89%; specificity, 95.33%) compared to all existing studies. In the independent test, our model exhibited consistent performance with an AUC of 0.939 and an accuracy of 92.86%. Integrating interaction effects and multimodal data into the model significantly increased prediction accuracy by 4.76% (P = 0.01) and 4.29% (P = 0.03), respectively. Furthermore, our model demonstrated robustness to inter-center and inter-scanner variability, while generating interpretable predictions by quantifying the contribution of multimodal biomarkers. Conclusions The proposed deep learning model presents a novel perspective by combining interaction effects and multimodality, leading to more accurate and longer-term predictions of AD progression, which promises to improve pre-dementia patient care.

Abstract The peroxisome proliferator-activated receptor (PPAR) signaling pathway plays a crucial role in systemic cell metabolism, energy homeostasis and immune response inhibition. However, its significance in hepatocellular carcinoma (HCC) has not been well documented. In our study, based on the RNA sequencing data of HCC, consensus clustering analyses were performed to identify PPAR signaling pathway-related molecular subtypes, each of which displaying varying survival probabilities and immune infiltration status. Following, a prognostic prediction model of HCC was developed by using the random survival forest method and Cox regression analysis. Significant difference in survival outcome, immune landscape, drug sensitivity and pathological features were observed between patients with different prognosis. Additionally, decision tree and nomogram models were adopted to optimize the prognostic prediction model. Furthermore, the robustness of the model was verified through single-cell RNA-sequencing data. Collectively, this study systematically elucidated that the PPAR signaling pathway-related prognostic model has good predictive efficacy for patients with HCC. These findings provide valuable insights for further research on personalized treatment approaches for HCC.

Abstract Objective This study is designed to investigate the impact of body mass index (BMI) on the short-term outcomes of patients undergoing off-pump coronary artery bypass graft (OPCAB) surgery. Methods Data was obtained from 1006 Chinese patients who underwent isolated, primary OPCAB at a high-traffic cardiovascular center during 2020. Subjects were categorized, by BMI, into a low & normal weight (LN) group (BMI

Abstract Background Diabetic foot ulcer (DFU) is one of the most common and severe complications of diabetes, with vascular changes, neuropathy, and infections being the primary pathological mechanisms. Glutamine (Gln) metabolism has been found to play a crucial role in diabetes complications. This study aims to identify and validate potential Gln metabolism biomarkers associated with DFU through bioinformatics and machine learning analysis. Methods We downloaded two microarray datasets related to DFU patients from the Gene Expression Omnibus (GEO) database, namely GSE134431, GSE68183, and GSE80178. From the GSE134431 dataset, we obtained differentially expressed Gln-metabolism related genes (deGlnMRGs) between DFU and normal controls. We analyzed the correlation between deGlnMRGs and immune cell infiltration status. We also explored the relationship between GlnMRGs molecular clusters and immune cell infiltration status. Notably, WGCNA to identify differentially expressed genes (DEGs) within specific clusters. Additionally, we conducted GSVA to annotate enriched genes. Subsequently, we constructed and screened the best machine learning model. Finally, we validated the predictions' accuracy using a nomogram, calibration curves, decision curve analysis (DCA), and the GSE134431, GSE68183, and GSE80178 dataset. Results In both the DFU and normal control groups, we confirmed the presence of deGlnMRGs and an activated immune response. From the GSE134431 dataset, we obtained 20 deGlnMRGs, including CTPS1, NAGS, SLC7A11, GGT1, GCLM, RIMKLA, ARG2, ASL, ASNS, ASNSD1, PPAT, GLS2, GLUD1, MECP2, ASS1, PRODH, CTPS2, ALDH5A1, DGLUCY, and SLC25A12. Furthermore, two clusters were identified in DFU. Immune infiltration analysis indicated the presence of immune heterogeneity in these two clusters. Additionally, we established a Support Vector Machine (SVM) model based on 5 genes (R3HCC1, ZNF562, MFN1, DRAM1, and PTGDS), which exhibited excellent performance on the external validation datasetGSE134431, GSE68183, and GSE80178 (AUC = 0.929). Conclusion This study has identified five Gln metabolism genes associated with DFU, revealing potential novel biomarkers and therapeutic targets for DFU. Additionally, the infiltration of immune-inflammatory cells plays a crucial role in the progression of DFU.

Abstract Background and aim Two oral antivirals (Nirmatrelvir- ritonavir and Azvudine) are widely used in China practice during the Omicron wave of the pandemic. However, little evidence regarding the real-world effectiveness of these two oral antivirals in in-hospital patients. We aimed to evaluate the clinical effectiveness of nirmatrelvir-ritonavir versus azvudine among adult hospitalized patients with COVID-19. Methods This retrospective cohort study used data from three Chinese PLA General Hospital medical centres. Hospitalized patients with COVID-19 treated with azvudine or nirmatrelvir-ritonavir from Dec 10, 2022, to February 20, 2023, and did not require invasive ventilation support on admission were eligible for inclusion. Results After exclusions and propensity-score matching, the final analysis included 486 azvudine recipients and 486 nirmatrelvir-ritonavir recipients. By 28 days of initiation of the antivirus treatment, the crude incidence rate of all-cause death was similar in both types of antivirus treatment (nirmatrelvir-ritonavir group 2.8 events 1000 person-days [95% CI, 2.1–3.6] vs azvudine group 3.4 events/1000 person-days [95% CI, 2.6–4.3], P = 0.38). Landmark analysis showed that all-cause death was lower in the nirmatrelvir-ritonavir (3.5%) group than the azvudine (6.8%, P = 0.029) within the initial 10-day admission period, while no significant difference was observed for results between 10 and 28 days follow-up. There was no significant difference between the nirmatrelvir-ritonavir group and the azvudine group in cumulative incidence of the composite disease progression event (8.6% with nirmatrelvir-ritonavir vs. 10.1% with azvudine, HR, 1.22; 95% CI 0.80–1.86, P = 0.43). Conclusion Among patients hospitalized with COVID-19 during the omicron wave in Beijing, similar in-hospital clinical outcomes on 28 days were observed between patients receiving nirmatrelvir-ritonavir and azvudine. However, it is worth noticing that nirmatrelvir-ritonavir appears to hold an advantage over azvudine in reducing early mortality. Further randomized controlled trials are needed to verify the efficacy of those two antivirus medications especially in early treatment.

Abstract Due to the limited transmission capabilities of terrestrial intelligent devices within the Internet of Remote Things (IoRT), this paper proposes an optimization scheme aimed at enhancing data transmission rate while ensuring communication reliability. This scheme focuses on multi-unmanned aerial vehicle (UAV)-assisted IoRT data communication within the satellite–aerial–terrestrial integrated network (SATIN), which is one of the key technologies for the sixth generation (6G) networks. To optimize the system’s data transmission rate, we introduce a multi-dimensional coverage and power optimization (CPO) algorithm, rooted in the block coordinate descent (BCD) method. This algorithm concurrently optimizes various parameters, including the number and deployment of UAVs, the correlation between IoRT devices and UAVs, and the transmission power of both devices and UAVs. To ensure comprehensive coverage of a large-scale randomly distributed array of terrestrial devices, combined with machine learning algorithm, we present the Dynamic Deployment based on K-means (DDK) algorithm. Additionally, we address the non-convexity challenge in resource allocation for transmission power through variable substitution and the successive convex approximation technique (SCA). Simulation results substantiate the remarkable efficacy of our CPO algorithm, showcasing a maximum 240% improvement in the uplink transmission rate of IoRT data compared to conventional methods.

Vancomycin-resistant Enterococcus faecium (E. faecium) infection is associated with higher mortality rates. Previous studies have emphasized the importance of innate immune cells and signalling pathways in clearing E. faecium, but a comprehensive analysis of host-pathogen interactions is lacking. Here, we investigated the interplay of host and E. faecium in a murine model of septic peritonitis. Following injection with a sublethal dose, we observed significantly increased murine sepsis score and histological score, decreased weight and bacterial burden, neutrophils and macrophages infiltration, and comprehensive activation of cytokine-mediated signalling pathway. In mice receiving a lethal dose, hypothermia significantly improved survival, reduced bacterial burden, cytokines, and CD86 expression of MHC-II+ recruited macrophages compared to the normothermia group. A mathematical model constructed by observational data from 80 animals, recapitulated the host-pathogen interplay, and further verified the benefits of hypothermia. These findings indicate that E. faecium triggers a severe activation of cytokine-mediated signalling pathway, and hypothermia can improve outcomes by reducing bacterial burden and inflammation.

AbstractBackground The effectiveness of nirmatrelvir–ritonavir has mainly been shown in non-hospitalized patients with mild-to-moderate coronavirus disease 2019 (COVID-19). The real-world effectiveness of nirmatrelvir-ritonavir urgently needs to be determined using representative in-hospital patients with COVID-19 during the Omicron wave of the pandemic.Methods We performed a multicentre, retrospective study in five Chinese PLA General Hospital medical centers in Beijing, China. Patients hospitalized with COVID-19 from 10 December 2022 to 20 February 2023 were eligible for inclusion. A 1:1 propensity score matching was performed between the nirmatrelvir-ritonavir group and the control group.Results 1010 recipients of nirmatrelvir-ritonavir and 1010 matched controls were finally analyzed after matching. Compared with matched controls, the nirmatrelvir-ritonavir group had a lower incidence rate of all-cause death (4.6/1000 vs. 6.3/1000 person-days, p = 0.013) and a higher incidence rate of clinical improvement (47.6/1000 vs. 45.8/1000 person-days, p = 0.012). Nirmatrelvir-ritonavir was associated with a 22% lower all-cause mortality and a 14% higher incidence of clinical improvement. Initiation of nirmatrelvir-ritonavir within 5 days after symptom onset was associated with a 50% lower mortality and a 26% higher clinical improvement rate. By contrast, no significant associations were identified among patients receiving nirmatrelvir-ritonavir treatment more than 5 days after symptom onset. Nirmatrelvir-ritonavir was also associated with a 50% increase in survival days and a 12% decrease in days to clinical improvement.Conclusion Among hospitalized patients with COVID-19 during the Omicron wave in Beijing, China, the early initiation of nirmatrelvir-ritonavir was associated with clinical benefits of lowering mortality and improving clinical recovery.

BackgroundThere have been conflicting reports about the proarrhythmic risk of p-synephrine (SYN). To address this, human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) combined with the microelectrode array (MEA) system have been utilized to assess arrhythmia risks, particularly in the context of adrenomimetic drugs.AimThis study aims to determine whether MEA recordings from hiPSC-CMs could predict the proarrhythmic risk of adrenomimetic drugs and to investigate the cardiovascular effects and mechanisms of SYN.Materials and methodsWe employed MEA recordings to assess the electrophysiological properties of hiPSC-CMs and conducted concentration-response analyses to evaluate the effects of SYN and Isoprenaline (ISO) on beating rate and contractility. A risk scoring system for proarrhythmic risks was established based on hiPSC-CMs in this study. ISO, a classic beta-adrenergic drug, was also evaluated. Furthermore, the study evaluated the risk of SYN and recorded the concentration-response of beating rate, contractility and the change in the presence or absence of selective β1, β2 and β3 adrenergic blockers.ResultsOur results suggested that ISO carries a high risk of inducing arrhythmias, aligning with existing literature. SYN caused a 30% prolongation of the field potential duration (FPD) at a concentration of 206.326 μM, a change significantly different from baseline measurements and control treatments. The half maximal effective concentration (EC50) of SYN (3.31 μM) to affect hiPSC-CM beating rate is much higher than that of ISO (18.00 nM). The effect of SYN at an EC50 of 3.31 μM is about ten times more potent in hiPSC-CMs compared to neonatal rat cardiomyocytes (34.12 μM). SYN increased the contractility of cardiomyocytes by 29.97 ± 11.65%, compared to ISO's increase of 50.56 ± 24.15%. β1 receptor blockers almost eliminated the beating rate increase induced by both ISO and SYN, while neither β2 nor β3 blockers had a complete inhibitory effect.ConclusionThe MEA and hiPSC-CM system could effectively predict the risk of adrenomimetic drugs. The study concludes that the proarrhythmia risk of SYN at conventional doses is low. SYN is more sensitive in increasing beating rate and contractility in human cardiomyocytes compared to rats, primarily activating β1 receptor.

Abstract Motor proteins, encoded by Kinesin superfamily (KIF) genes, are critical for brain development and plasticity. Increasing studies reported KIF’s roles in neurodevelopmental disorders. Here, a 6 years and 3 months‐old Chinese boy with markedly symptomatic epilepsy, intellectual disability, brain atrophy, and psychomotor retardation was investigated. His parents and younger sister were phenotypically normal and had no disease‐related family history. Whole exome sequencing identified a novel heterozygous in‐frame deletion (c.265_267delTCA) in exon 3 of the KIF5C in the proband, resulting in the removal of evolutionarily highly conserved p.Ser90, located in its ATP‐binding domain. Sanger sequencing excluded the proband's parents and family members from harboring this variant. The activity of ATP hydrolysis in vitro was significantly reduced as predicted. Immunofluorescence studies showed wild‐type KIF5C was widely distributed throughout the cytoplasm, while mutant KIF5C was colocalized with microtubules. The live‐cell imaging of the cargo‐trafficking assay revealed that mutant KIF5C lost the peroxisome‐transporting ability. Drosophila models also confirmed p.Ser90del's essential role in nervous system development. This study emphasized the importance of the KIF5C gene in intracellular cargo‐transport as well as germline variants that lead to neurodevelopmental disorders and might enable clinicians for timely and accurate diagnosis and disease management in the future.

Abstract RNA methylation modification plays a crucial role as an epigenetic regulator in the oncogenesis of hepatocellular carcinoma (HCC). Numerous studies have investigated the molecular mechanisms underlying the methylation of protein-coding RNAs in the progression of HCC. Beyond their impact on mRNA, methylation modifications also influence the biological functions of non-coding RNAs (ncRNAs). Here, we present an advanced and comprehensive overview of the interplay between methylation modifications and ncRNAs in HCC, with a specific focus on their potential implications for the tumor immune microenvironment. Moreover, we summarize promising therapeutic targets for HCC based on methylation-related proteins. In the future, a more profound investigation is warranted to elucidate the effects of ncRNA methylation modifications on HCC pathogenesis and devise valuable intervention strategies. Video Abstract

Abstract In existing remote sensing image retrieval (RSIR) datasets, the number of images among different classes varies dramatically, which leads to a severe class imbalance problem. Some studies propose to train the model with the ranking‐based metric (e.g., average precision [AP]), because AP is robust to class imbalance. However, current AP‐based methods overlook an important issue: only optimising samples ranking before each positive sample, which is limited by the definition of AP and is prone to local optimum. To achieve global optimisation of AP, a novel method, namely Optimising Samples after positive ones & AP loss (OSAP‐Loss) is proposed in this study. Specifically, a novel superior ranking function is designed to make the AP loss differentiable while providing a tighter upper bound. Then, a novel loss called Optimising Samples after Positive ones (OSP) loss is proposed to involve all positive and negative samples ranking after each positive one and to provide a more flexible optimisation strategy for each sample. Finally, a graphics processing unit memory‐free mechanism is developed to thoroughly address the non‐decomposability of AP optimisation. Extensive experimental results on RSIR as well as conventional image retrieval datasets show the superiority and competitive performance of OSAP‐Loss compared to the state‐of‐the‐art.

Beautiful Bay is the main task of marine eco-environmental protection during 2021-2025. In recent years, Jiangsu has fully implemented the deployment requirements of the CPC Central Committee and the State Council on promoting the construction of Beautiful Bay, and became the first one to establish a series of funding policies and whole-process supervision systems for Beautiful Bay in China. The construction of the first provincial demonstration projects of Beautiful Bay was organized and carried out, which has been a good example for the construction of Beautiful Bay in China. Based on the analysis of the progress, problems and challenges in the construction of Beautiful Bay in Jiangsu Province in recent years, this paper discusses the practical path for the construction of Beautiful Bay in Jiangsu Province and puts forward the following suggestions: improving water quality in coastal waters by coordinating land and sea areas, focusing on areas where water quality is not stable enough to meet standards and controlling rivers flowing into the sea; Improving coordination mechanisms and carrying out construction of Beautiful Bay in a coordinated manner; Expanding the space and improving the quality of marine services by restoring damaged shoals, strengthening the management of marine garbage, and improving supporting public facilities; Strengthening the assessment of the ecological environment of the bay and promoting the construction of Beautiful Bay in batches. The above suggestions will help the marine ecological environment improve fundamentally.

Abstract Gamma radiation is progressively emerging as an effective method to enhance the sterilization efficiency of medical plastics including Polyvinyl chloride (PVC). The parameters of the radiation facility will affect the efficiency of radiation sterilization. To investigate these effects, we simulate the gamma radiation sterilization performance of PVC material sample using Monte Carlo Method. The simulation results indicated that compared with the sterilization time of 20–90 min from high-temperature steam sterilization of medical waste, by optimizing the parameters of the model radiation facility, the radiation sterilization time can be reduced to 6.61 min. The optimized model facility parameters are as follows: the gamma photon energy is 1.25 MeV, the model space is 300 × 300 × 300 cm3, the reflective layer material is concrete and its thickness is 8 cm, the PVC sample layer area is 100 × 100 cm2, the distance between the radiation source and the PVC sample layer is 150 cm, the energy deposition in the bottom layer of the PVC sample layer is 1.31315 × 10–6 MeV/g. This study offers a potentially feasible way for PVC sterilization, while also providing a crucial reference for the further promotion and application of radiation sterilization technology.

Abstract Background China has a high mortality from nasopharyngeal carcinoma (NPC). The NPC mortality trends in China from 2006 to 2020 were described and analyzed to understand its epidemiological characteristics by region and sex and to explore age, period, and cohort effects. Methods This study utilized NPC mortality data from the China Health Statistical Yearbook. A joinpoint regression model was used to fit the standardized NPC mortality and age-specific mortality. The age-period-cohort model was applied to investigate age, period, and cohort effects on NPC mortality risk. Results The results showed that the NPC mortality rate in China has been declining steadily. From 2006 to 2020, the standardized NPC mortality rate in most age groups showed a significant downward trend. The annual percentage change was smaller in rural areas than in urban areas. The mortality risks of rural males and rural females from 2016 to 2020 were 1.139 times and 1.080 times those from 2011 to 2015, respectively. Both urban males born in 1984–1988 and rural males born in 1979–1983 exhibited an increasing trend in NPC mortality risk. Conclusions Our study confirmed the effectiveness of NPC prevention and treatment strategies in China from 2006 to 2020. However, it underscored the urgent need for targeted interventions in rural areas to further reduce NPC mortality rates.

Abstract Background The risk of extracolonic cancer is increased in inflammatory bowel disease (IBD) patients, but it is not clear whether there is a causal relationship. We aimed to systematically estimate the causal relationship between IBD and extracolonic cancers. Methods Independent genetic variants strongly associated with IBD were extracted as instrumental variables from genome-wide association study (GWAS) conducted by the International IBD Genetics Consortium including 12,882 IBD patients, 5956 Crohn’s disease (CD) patients, and 6968 ulcerative colitis (UC) patients. Three sources of cancer GWAS were selected as outcome data. Two-sample Mendelian randomization (MR) analysis was conducted to assess the causal effects of IBD on 32 extracolonic cancers. The meta-analysis was applied to assess the combined causal effect with multiple MR results. Results IBD, CD, and UC have potential causal associations with oral cavity cancer (IBD: OR = 1.180, 95% CI: 1.059 to 1.316, P = 0.003; CD: OR = 1.112, 95% CI: 1.008 to 1.227, P = 0.034; UC: OR = 1.158, 95% CI: 1.041 to 1.288, P = 0.007). Meta-analysis showed a significant positive causal relationship between IBD and breast cancer (OR = 1.059; 95% CI: 1.033 to 1.086; P

Atmospheric methane is one of the major greenhouse gases and has a great impact on climate change. To obtain the polluted levels of atmospheric methane in the ground-level range, this study used satellite observations and vertical profile features derived by atmospheric chemistry model to estimate the ground methane concentrations in first. Then, the improved daily ground-level atmospheric methane concentration dataset with full spatial coverage (100%) and 5-km resolution in mainland China from 2019 to 2021 were retrieved by station-based observations and gaussian regression model. The overall estimated deviation between the estimated ground methane concentrations and the WDCGG station-based measurements is less than 10 ppbv. The R by ten-fold cross-validation is 0.93, and the R2 is 0.87. The distribution of the ground-level methane concentrations in the Chinese region is characterized by high in the east and south, and low in the west and north. On the time scale, ground-level methane concentration in the Chinese region is higher in winter and lower in summer. Meanwhile, the spatial and temporal distribution and changes of ground-level methane in local areas have been analyzed using Shandong Province as an example. The results have a potential to detect changes in the distribution of methane concentration.

Purpose: To identify essential oils (EOs) active against non-growing stationary phase Mycobacterium abscessus and multidrug-resistant M. abscessus strains. Methods: The activity of EOs against both stationary and log phase M. abscessus was evaluated by colony forming unit (CFU) assay and minimum inhibitory concentration (MIC) testing. Results: We assessed the activity of 80 EOs against stationary phase M. abscessus and found 12 EOs (Cinnamon, Satureja montana, Palmarosa, Lemon eucalyptus, Honey myrtle, Combava, Health shield, Mandarin, Thyme, Rosewood, Valerian Root and Basil) at 0.5% concentration to be active against both growing and non-growing stationary phase M. abscessus. Among them, Satureja montana essential oil and Palmarosa essential oil could eliminate all stationary phase M. abscessus at 0.125% and Cinnamon essential oil could eliminate stationary phase bacteria at 0.063% after 1-day treatment. Interestingly, these EOs also exhibited promising activity against multidrug-resistant M. abscessus clinical strains. Conclusions: Our study indicates that some EOs display outstanding effectiveness against both drug susceptible M. abscessus and multidrug-resistant M. abscessus isolates. These findings may be significant for the treatment of persistent M. abscessus infections.

Abstract Background Cardiac myxoma (CM) is the most common (58%–80%) type of primary cardiac tumours. Currently, there is a need to develop medical therapies, especially for patients not physically suitable for surgeries. However, the mechanisms that shape the tumour microenvironment (TME) in CM remain largely unknown, which impedes the development of targeted therapies. Here, we aimed to dissect the TME in CM at single‐cell and spatial resolution. Methods We performed single‐cell transcriptomic sequencing and Visium CytAssist spatial transcriptomic (ST) assays on tumour samples from patients with CM. A comprehensive analysis was performed, including unsupervised clustering, RNA velocity, clonal substructure inference of tumour cells and cell–cell communication. Results Unsupervised clustering of 34 759 cells identified 12 clusters, which were assigned to endothelial cells (ECs), mesenchymal stroma cells (MSCs), and tumour‐infiltrating immune cells. Myxoma tumour cells were found to encompass two closely related phenotypic states, namely, EC‐like tumour cells (ETCs) and MSC‐like tumour cells (MTCs). According to RNA velocity, our findings suggest that ETCs may be directly differentiated from MTCs. The immune microenvironment of CM was found to contain multiple factors that promote immune suppression and evasion, underscoring the potential of using immunotherapies as a treatment option. Hyperactive signals sent primarily by tumour cells were identified, such as MDK, HGF, chemerin, and GDF15 signalling. Finally, the ST assay uncovered spatial features of the subclusters, proximal cell–cell communication, and clonal evolution of myxoma tumour cells. Conclusions Our study presents the first comprehensive characterisation of the TME in CM at both single‐cell and spatial resolution. Our study provides novel insight into the differentiation of myxoma tumour cells and advance our understanding of the TME in CM. Given the rarity of cardiac tumours, our study provides invaluable datasets and promotes the development of medical therapies for CM.

Due to the demands for both environmental protection and modernization of the goose industry in China, the traditional goose waterside rearing systems have been gradually transitioning to the modern intensive dryland rearing ones, such as the net-floor mixed rearing system (MRS) and cage rearing system (CRS). However, the goose immune responses to different dryland rearing systems remain poorly understood. This study aimed to investigate and compare the age-dependent effects of MRS and CRS on the splenic histomorphological characteristics and immune-related genes expression profiles among three economically important goose breeds, including Sichuan White goose (SW), Gang goose (GE), and Landes goose (LD). Morphological analysis revealed that the splenic weight and organ index of SW were higher under CRS than under MRS (p

Introduction Atrial fibrillation (AF) is a significant cause of perioperative stroke in aortic and mitral valve surgeries. Although several large studies have evaluated surgical left atrial appendage occlusion (SLAAO) during cardiac surgeries, their retrospective nature and an uncontrolled broad spectrum of conditions leave them subject to potential residual confounding. This trial aims to test the hypothesis that opportunistic SLAAO can prevent long-term stroke after cardiac surgery in patients receiving mitral or aortic valve surgeries without a history of AF and with a CHA2DS2-VASc score of 2 or higher.Methods and design This study is a single-blinded, multicentre, randomised controlled trial. A total of 2118 patients planning to undergo aortic or mitral surgery without AF will be recruited and equally randomised into intervention or control arms at a 1:1 ratio. In the intervention arm, suture excision of the left atrial appendage (LAA) will be performed during the operation in addition to the original surgery plan. In the control arm, the operation will be performed according to the surgery plan without any intervention on the LAA. The primary outcome is a composite of newly occurred ischaemic stroke or transient ischaemic attack and cardiovascular mortality during a 1-year follow-up. Secondary outcomes include postoperative AF, cardiovascular mortality, newly occurred ischaemic stroke, newly occurred transient ischaemic attack, newly occurred haemorrhagic stroke, bleeding events, and AF-associated health utilisation.Ethics and dissemination The Ethics Committee in Fuwai Hospital approved this study. Patients will give informed consent to the study. An information leaflet will be provided to participating patients to introduce the SLAAO procedure. Patients and the public will not get involved in developing the research hypothesis, study design or any other part of this protocol. We plan to publish several papers in peer-reviewed journals about the current research and these will include a description of the study’s development and the main findings of the study.Trial registration number ChiCTR2100042238.

We explored the nonlinear characteristics of energy resolution (ER) for the sealed NaI (Tl) scintillator detector by using a gamma-ray spectroscopy system and Monte Carlo simulation. Our research focused on the two primary factors of energy resolution including the photomultiplier tube (PMT) voltage and the distance between the gamma-ray sources (137Cs and 60Co) and the scintillator detector. The experimental results showed that energy resolution decreased when the PMT voltage increased, and the energy resolution of NaI (Tl) detectors reached a smaller value (6.92%, 6.76%, and 6.56%), especially with the PMT voltage in the range of 575–595 V. In addition, a suitable distance between the gamma-ray source and the scintillator (5 cm) can also effectively reduce the energy resolution. We established the simulation models of the experimental NaI (Tl) detectors and simulated their energy spectra. The simulation results in the peak area agreed with the experimental results. A possible better PMT voltage choice has been proposed to obtain a smaller energy resolution.

Abstract Enzymes achieve high catalytic activity with their elaborate arrangements of amino acid residues in confined optimized spaces. Nevertheless, when exposed to complicated environmental implementation scenarios, including high acidity, organic solvent and high ionic strength, enzymes exhibit low operational stability and poor activity. Here, we report a metal-organic frameworks (MOFs)-based artificial enzyme system via second coordination sphere engineering to achieve high hydrolytic activity under mild conditions. Experiments and theoretical calculations reveal that amide cleavage catalyzed by MOFs follows two distinct catalytic mechanisms, Lewis acid- and hydrogen bonding-mediated hydrolytic processes. The hydrogen bond formed in the secondary coordination sphere exhibits 11-fold higher hydrolytic activity than the Lewis acidic zinc ions. The MOFs exhibit satisfactory degradation performance of toxins and high stability under extreme working conditions, including complicated fermentation broth and high ethanol environments, and display broad substrate specificity. These findings hold great promise for designing artificial enzymes for environmental remediation.

Tbx18, Wt1, and Tcf21 have been identified as epicardial markers during the early embryonic stage. However, the gene markers of mature epicardial cells remain unclear. Single-cell transcriptomic analysis was performed with the Seurat, Monocle, and CellphoneDB packages in R software with standard procedures. Spatial transcriptomics was performed on chilled Visium Tissue Optimization Slides (10x Genomics) and Visium Spatial Gene Expression Slides (10x Genomics). Spatial transcriptomics analysis was performed with Space Ranger software and R software. Immunofluorescence, whole-mount RNA in situ hybridization and X-gal staining were performed to validate the analysis results. Spatial transcriptomics analysis revealed distinct transcriptional profiles and functions between epicardial tissue and non-epicardial tissue. Several gene markers specific to postnatal epicardial tissue were identified, including Msln, C3, Efemp1, and Upk3b. Single-cell transcriptomic analysis revealed that cardiac cells from wildtype mouse hearts (from embryonic day 9.5 to postnatal day 9) could be categorized into six major cell types, which included epicardial cells. Throughout epicardial development, Wt1, Tbx18, and Upk3b were consistently expressed, whereas genes including Msln, C3, and Efemp1 exhibited increased expression during the mature stages of development. Pseudotime analysis further revealed two epicardial cell fates during maturation. Moreover, Upk3b, Msln, Efemp1, and C3 positive epicardial cells were enriched in extracellular matrix signaling. Our results suggested Upk3b, Efemp1, Msln, C3, and other genes were mature epicardium markers. Extracellular matrix signaling was found to play a critical role in the mature epicardium, thus suggesting potential therapeutic targets for heart regeneration in future clinical practice.

Abstract Multi-spectral imaging is a fundamental tool characterizing the constituent energy of scene radiation. However, current multi-spectral video cameras cannot scale up beyond megapixel resolution due to optical constraints and the complexity of the reconstruction algorithms. To circumvent the above issues, we propose a tens-of-megapixel handheld multi-spectral videography approach (THETA), with a proof-of-concept camera achieving 65-megapixel videography of 12 wavebands within visible light range. The high performance is brought by multiple designs: We propose an imaging scheme to fabricate a thin mask for encoding spatio-spectral data using a conventional film camera. Afterwards, a fiber optic plate is introduced for building a compact prototype supporting pixel-wise encoding with a large space-bandwidth product. Finally, a deep-network-based algorithm is adopted for large-scale multi-spectral data decoding, with the coding pattern specially designed to facilitate efficient coarse-to-fine model training. Experimentally, we demonstrate THETA’s advantageous and wide applications in outdoor imaging of large macroscopic scenes.

Mycobacterium abscessus (M. abscessus) is a multidrug-resistant nontuberculous mycobacterium (NTM) that is responsible for a wide spectrum of infections in humans. The lack of effective bactericidal drugs and the formation of biofilm make its clinical treatment very difficult. The FDA-approved drug library containing 3048 marketed and pharmacopeial drugs or compounds was screened at 20 μM against M. abscessus type strain 19977 in 7H9 medium, and 62 hits with potential antimicrobial activity against M. abscessus were identified. Among them, bithionol, a clinically approved antiparasitic agent, showed excellent antibacterial activity and inhibited the growth of three different subtypes of M. abscessus from 0.625 μM to 2.5 μM. We confirmed the bactericidal activity of bithionol by the MBC/MIC ratio being ≤4 and the time–kill curve study and also electron microscopy study. Interestingly, it was found that at 128 μg/mL, bithionol could completely eliminate biofilms after 48h, demonstrating an outstanding antibiofilm capability compared to commonly used antibiotics. Additionally, bithionol could eliminate 99.9% of biofilm bacteria at 64 μg/mL, 99% at 32 μg/mL, and 90% at 16 μg/mL. Therefore, bithionol may be a potential candidate for the treatment of M. abscessus infections due to its significant antimicrobial and antibiofilm activities.

The low survival rate of transplanted plantlets, which has limited the utility of tissue-culture-based methods for the rapid propagation of tree peonies, is due to plantlet dormancy after rooting. We previously determined that the auxin response factor PsARF may be a key regulator of tree peony dormancy. To clarify the mechanism mediating tree peony plantlet dormancy, PsARF genes were systematically identified and analyzed. Additionally, PsARF16a was transiently expressed in the leaves of tree peony plantlets to examine its regulatory effects on a downstream gene network. Nineteen PsARF genes were identified and divided into four classes. All PsARF genes encoded proteins with conserved B3 and ARF domains. The number of motifs, exons, and introns varied between PsARF genes in different classes. The overexpression of PsARF16a altered the expression of NCED, ZEP, PYL, GA2ox1, GID1, and other key genes in abscisic acid (ABA) and gibberellin (GA) signal transduction pathways, thereby promoting ABA synthesis and decreasing GA synthesis. Significant changes to the expression of some key genes contributing to starch and sugar metabolism (e.g., AMY2A, BAM3, BGLU, STP, and SUS2) may be associated with the gradual conversion of sugar into starch. This study provides important insights into PsARF functions in tree peonies.

In the sixth generation (6G) era, intelligent machine network (IMN) applications, such as intelligent transportation, require collaborative machines with communication, sensing, and computation (CSC) capabilities. This article proposes an integrated communication, sensing, and computation (ICSAC) framework for 6G to achieve the reciprocity among CSC functions to enhance the reliability and latency of communication, accuracy and timeliness of sensing information acquisition, and privacy and security of computing to realize the IMN applications. Specifically, the sensing and communication functions can merge into unified platforms using the same transmit signals, and the acquired real-time sensing information can be exploited as prior information for intelligent algorithms to enhance the performance of communication networks. This is called the computing-empowered integrated sensing and communications (ISAC) reciprocity. Such reciprocity can further improve the performance of distributed computation with the assistance of networked sensing capability, which is named the sensing-empowered integrated communications and computation (ICAC) reciprocity. The above ISAC and ICAC reciprocities can enhance each other iteratively and finally lead to the ICSAC reciprocity. To achieve these reciprocities, we explore the potential enabling technologies for the ICSAC framework. Finally, we present the evaluation results of crucial enabling technologies to show the feasibility of the ICSAC framework.

The soil moisture (SM) influences tree growth with climate change. However, the spatial and temporal dynamics of tree water use strategies in climate-sensitive areas remain uncertain. Therefore, we collected the tree-ring oxygen isotope (δ18OTR) chronologies and divided the wet–dry gradients according to the precipitation on the Tibetan Plateau (TP). Further, the relationship between the δ18OTR and environmental factors was analyzed across different gradients. We found the following: (1) The SM during the growing season was the most important factor for δ18OTR. (2) The response of the δ18OTR to the SM had a lag in arid areas than in humid areas. (3) Trees absorbed the SM on the surface in humid areas (r = −0.49 to −0.41, p < 0.01), while trees absorbed the SM from deep in the soil in arid areas (r = −0.48 to −0.29, p < 0.01). The results demonstrated that trees were better able to cope with drought stress in arid regions because they used more stable deep soil water than in humid regions. Therefore, the findings will provide a scientific basis for water use of trees using the δ18OTR in complex environmental contexts. Trees with single water use strategies should be given more attention to keep ecosystems healthy.

Abstract The Janus kinase (JAK) signal transducer and activator of transcription (JAK-STAT) pathway is an evolutionarily conserved mechanism of transmembrane signal transduction that enables cells to communicate with the exterior environment. Various cytokines, interferons, growth factors, and other specific molecules activate JAK-STAT signaling to drive a series of physiological and pathological processes, including proliferation, metabolism, immune response, inflammation, and malignancy. Dysregulated JAK-STAT signaling and related genetic mutations are strongly associated with immune activation and cancer progression. Insights into the structures and functions of the JAK-STAT pathway have led to the development and approval of diverse drugs for the clinical treatment of diseases. Currently, drugs have been developed to mainly target the JAK-STAT pathway and are commonly divided into three subtypes: cytokine or receptor antibodies, JAK inhibitors, and STAT inhibitors. And novel agents also continue to be developed and tested in preclinical and clinical studies. The effectiveness and safety of each kind of drug also warrant further scientific trials before put into being clinical applications. Here, we review the current understanding of the fundamental composition and function of the JAK-STAT signaling pathway. We also discuss advancements in the understanding of JAK-STAT–related pathogenic mechanisms; targeted JAK-STAT therapies for various diseases, especially immune disorders, and cancers; newly developed JAK inhibitors; and current challenges and directions in the field.