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Abstract Metabolic studies at the single cell level can directly define the cellular phenotype closest to physiological or disease states. However, the current single cell metabolome (SCM) study using mass spectroscopy has difficulty giving a complete view of the metabolic activity in the cell, and the prediction of the metabolism‐phenotype relationship is limited by the potential inconsistency between transcriptomic and metabolic levels. Here, the single‐cell simultaneous metabolome and transcriptome profiling method (scMeT‐seq) is developed at one single cell, based on sub‐picoliter sampling from the cell for the initial metabolome profiling followed by single cell transcriptome sequencing. This design not only provides sufficient cytoplasm for SCM but also nicely keeps the cellular viability for the accurate transcriptomic analysis in the same cell. Integrative analysis of scMeT‐seq reveals both dynamical and cell state‐specific associations between metabolome and transcriptome in the macrophages with defined metabolic perturbations. Moreover, metabolite signatures are mapped to the single‐cell trajectory and gene correlation network of macrophage transition, which allows the unsupervised functional interpretation of metabolome. Thus, the established scMeT‐seq should lead to a new perspective in metabolic research by transforming metabolomics from a metabolite snapshot to a functional approach.

ABSTRACT Background Distinctive heterogeneity characterizes diffuse large B‐cell lymphoma (DLBCL), one of the most frequent types of non‐Hodgkin's lymphoma. Mitochondria have been demonstrated to be closely involved in tumorigenesis and progression, particularly in DLBCL. Objective The purposes of this study were to identify the prognostic mitochondria‐related genes (MRGs) in DLBCL, and to develop a risk model based on MRGs and machine learning algorithms. Methods Transcriptome profiles and clinical information were obtained from the Gene Expression Omnibus (GEO) database. The risk model was defined using Least Absolute Shrinkage and Selection Operator (Lasso) regression algorithm, and its prognostic value was further examined in independent datasets. Patients were stratified into two clusters based on the risk scores, additionally a nomogram was generated based on the risk score and clinical characteristics. Gene pathway level, microenvironment, expression of targeted therapy‐associated genes, response to immunotherapy, drug sensitivity, and somatic mutation status were compared between clusters. Results Eighteen prognostic MRGs (DNM1L, PUSL1, CHCHD4, COX7A1, CPT1A, CYP27A1, POLDIP2, PCK2, MRPL2, PDK3, PDK4, MARC2, ACSM3, COA7, THNSL1, ATAD3B, C15orf48, TOMM70A) were identified to construct the risk model. Remarkable discrepancies were observed between groups. The high‐risk group had shorter overall survival, less immune infiltration, lower CD20 and higher PD‐L1 expression than the low‐risk group. Distinct immune microenvironment, responses to immunotherapy and predictive drug IC50 values were found between groups. Conclusions We established a novel prognostic mitochondria‐related signature by machine learning algorithm, which also demonstrated outstanding predictive value in tumor microenvironment and responses to therapies.

Objective The accurate measurement of Cobb angles is crucial for the effective clinical management of patients with adolescent idiopathic scoliosis (AIS). The Lenke classification system plays a pivotal role in determining the appropriate fusion levels for treatment planning. However, the presence of interobserver variability and time‐intensive procedures presents challenges for clinicians. The purpose of this study is to compare the measurement accuracy of our developed artificial intelligence measurement system for Cobb angles and Lenke classification in AIS patients with manual measurements to validate its feasibility. Methods An artificial intelligence (AI) system measured the Cobb angle of AIS patients using convolutional neural networks, which identified the vertebral boundaries and sequences, recognized the upper and lower end vertebras, and estimated the Cobb angles of the proximal thoracic, main thoracic, and thoracolumbar/lumbar curves sequentially. Accordingly, the Lenke classifications of scoliosis were divided by oscillogram and defined by the AI system. Furthermore, a man–machine comparison (n = 300) was conducted for senior spine surgeons (n = 2), junior spine surgeons (n = 2), and the AI system for the image measurements of proximal thoracic (PT), main thoracic (MT), thoracolumbar/lumbar (TL/L), thoracic sagittal profile T5–T12, bending views PT, bending views MT, bending views TL/L, the Lenke classification system, the lumbar modifier, and sagittal thoracic alignment. Results In the AI system, the calculation time for each patient's data was 0.2 s, while the measurement time for each surgeon was 23.6 min. The AI system showed high accuracy in the recognition of the Lenke classification and had high reliability compared to senior doctors (ICC 0.962). Conclusion The AI system has high reliability for the Lenke classification and is a potential auxiliary tool for spinal surgeons.

Abstract Background Identifying the risk factors for distant metastasis in early‐onset colorectal cancer (EOCRC) is crucial for elucidating its etiology and facilitating preventive treatment. This study aims to characterize the variability in EOCRC incidence and discern both heterogeneous and homogeneous risk factors associated with synchronous liver, lung, and hepato‐lung metastases. Methods This study included patients with EOCRC enrolled in the SEER database between 2010 and 2015 and divided patients into three groups by synchronous liver, lung, and hepato‐lung metastases. Each group of patients with different metastasis types was randomly assigned to the development and validation cohort in a ratio of 7:3. Logistic regression was used to analyze the heterogeneous and homogenous risk factors for synchronous liver, lung, and hepato‐lung metastases in the development cohort of patients. Nomograms were built to calculate the risk of metastasis, and the receiver operating characteristic (ROC) curve and calibration curve were used to quantitatively evaluate their performance. Results A total of 16,336 eligible patients with EOCRC were included in this study, of which 17.90% (2924/16,336) had distant metastases. The overall incidences of synchronous liver, lung, and hepato‐lung metastases were 11.90% (1921/16,146), 2.42% (390/16,126), and 1.50% (241/16,108), respectively. Positive CEA values before treatment, increased lymphatic metastases, and deeper invasion of intestinal wall were positively correlated with three distant types of metastases. On the contrary, the correlation of age, ethnicity, location of primary tumor, and histologic grade among the three types was inconsistent. The ROC curve and calibration curve proved to have fine performance in predicting distant metastases of EOCRC. Conclusions There are significant differences in the incidence of distant metastases in EOCRC, and related risk factors are heterogeneous and homogenous. Although limited risk factors were incorporated in this study, the established nomograms indicated good predictive performance.

Abstract Galaxaura divaricata is a partially calcified macroalga that hampers coral recruitment, growth, and recovery via the excretion of allelopathic secondary metabolites. Herbivorous fishes are not major consumers of Galaxaura spp. and there is a need to understand feeding preferences for Galaxaura divaricata in other macroherbivores, like sea urchins and green sea turtles that could act as potential controlling agents. Under certain environmental conditions, G. divaricata can proliferate and overgrow degraded reefs for several years, as documented for several coral patch reefs in the lagoon of Dongsha Atoll, South China Sea. This study aimed to experimentally test the feeding preferences of five species of sea urchin and two individual green sea turtles, Chelonia mydas, for G. divaricata. Specifically, we quantified and compared the consumption rates of the allelopathic G. divaricata with Gracilaria edulis, a nonallelopathic, fleshy red alga, known to be highly favored by herbivores. Results showed that the five urchin species fed on both G. edulis and G. divaricata. However, urchins consumed 2–8 times less wet weight of G. divaricata (range 0.3–3.1 g urchin−1 24 h−1) compared to G. edulis (range 0.6–18 g urchin−1 24 h−1), suggesting that urchin grazing may exert some control on G. divaricata abundance but is likely ineffective for a large‐scale removal of the alga. Further, both green sea turtles avoided G. divaricata and selectively fed on G. edulis. More experiments are needed to test the potential role of herbivores in controlling the overgrowth of coral competitive and allelopathic macroalgae, like Galaxaura on coral reefs.

Conclusions: Computed tomography angiography is essential for assessing the condition of the remaining embolic coils. In cases with thrombosed parent arteries, a conservative approach, like the transection of exposed coils, can be employed as part of the management strategy.

Abstract Purpose The optimal practice regarding cervical lymph node biopsy (CLNB) remains to be defined to provide the best clinical management in nasopharyngeal carcinoma (NPC). This study aimed to investigate the effect of CLNB on the survival of NPC patients. Methods Patients diagnosed with NPC from 2004 to 2015 were identified using the Surveillance, Epidemiology, and End Results database. Multivariate logistic regression, Kaplan–Meier method, Cox proportional hazards regression analysis, and propensity score matching (PSM) were used to determine the factors associated with CLNB and prognostic effect of CLNB of NPC. Results We included 1903 patients in this study. There were 321 (16.9%) and 1582 (83.1%) patients with and without CLNB, respectively. The percentage of CLNB was 19.4% in 2004 and was decreased to 8.6% in 2015 (p = 0.044). Patients diagnosed in later years (p = 0.008), older age (p

Abstract In degraded coral reef ecosystems, allelopathic macroalgae have received increasing attention from marine ecologists because their secondary metabolites (also known as allelochemicals) kill corals that grow adjacent to them and weaken the recovery of degraded reefs. One well‐known coral‐killing macroalga is the calcareous red seaweed Galaxaura. However, our knowledge of how coral reef fishes interact with allelopathic algae like Galaxaura is very limited. Here, we documented novel observations of feeding interactions of 17 species of coral reef fishes (herbivorous and carnivorous) with the filamentous Galaxaura divaricata on degraded lagoon patch reefs in Dongsha Atoll (South China Sea). Video analyses showed that territorial farming damselfishes (i.e., Dischistodus perspicillatus, D. prosopotaenia, Hemiglyphidodon plagiometopon, Pomacentrus grammorhynchus, P. adelus, and Neoglyphidodon nigroris) and juvenile parrotfishes (Scarus schlegeli, S. ghobban, S. rivulatus, and Chlorurus spilurus) likely used G. divaricata as a feeding substratum. Further, microscopic analyses revealed that the filamentous surface of G. divaricata harbored a wealth of epiphytic microalgae, such as filamentous cyanobacteria (i.e., Leptolyngbya, Lyngbya, Rivularia, Oscillatoria, and Stigonema), diatoms (i.e., Synedra, Nitzschia, Mastogloia, and Pleurosigma), and filamentous red algae (i.e., Heterosiphonia), suggesting that these fishes targeted the nutrient‐rich microscopic epiphytes rather than the nutrient‐poor host. Juvenile benthic carnivores (i.e., Labridae, Parupeneus multifasciatus, and Meiacanthus grammistes) form feeding assemblages with roving parrotfishes to feed on small invertebrates (i.e., amphipods, copepods, isopods, gastropods, and polychaetes) associated with G. divaricata. Given that coral reef fishes appear to target the epiphytes associated with Galaxaura rather than the alga itself, these observations thus substantiate the threat posed by the overgrowth of G. divaricata to coral recovery in degraded reef systems due to the lack of natural grazers.

Abstract Nitrogen doping has readily emerged as an efficient solution to boost potassium‐ion storage of carbonaceous materials. Nevertheless, the capacity and lifespan enhancement of derived electrodes is still plagued by the incompetent in coordinating the dopant configurations. In the realm of emerging potassium‐ion hybrid capacitor (PIHC) device, dictating nitrogen doping to enhance pseudocapacitive behavior and improve K+ diffusion kinetics of carbonaceous anodes is scarcely demonstrated. Herein, we report the design of hierarchical N‐doped carbon nanopolyhedron@nanosheet composite via a salt‐confined synthetic strategy with tunable doping configurations toward advanced PIHC anode. A harmonized edge‐ to graphitic‐nitrogen ratio in such dual‐carbon materials enables outstanding rate capability (130 mAh g−1 at 10.0 A g−1) and cyclic performance (with a capacity retention of 80% after 2000 cycles at 5.0 A g−1) in half‐cell tests. As expected, the thus‐assembled PIHC full device with a working voltage of 4.2 V presents a high energy/power density (146 Wh kg−1/8000 W kg−1) and favorable cyclicability. This work is anticipated to offer an innovative insight into the coordination of nitrogen doping configurations in heteroatom‐doped carbon anode targeting high‐performance PIHC applications.

Abstract Background To investigate the potential molecular mechanism of ovarian cancer (OC) evolution and immunological correlation using the integrated bioinformatics analysis. Methods Data from the Gene Expression Omnibus was used to gain differentially expressed genes (DEGs). Gene Ontology and Kyoto Encyclopedia of Gene and Genome pathway analysis were completed by utilizing the Database for Annotation, Visualization, and Integrated Discovery. After multiple validations via The Cancer Genome Atlas (TCGA), Genotype‐Tissue Expression (GTEx) projects, the Human Protein Atlas, Kaplan–Meier (KM) plotter, and immune logical relationships of the key gene SOBP were evaluated based on Tumor Immune Estimation Resource, and Gene Set Enrichment Analysis (GSEA) software. Finally, the lncRNAs‐miRNAs‐mRNAs subnetwork was predicted by starBase, TargetScan, miRBD, and LncBase, individually. Correlation of expression and prognosis for mRNAs, miRNAs, and lncRNAs were confirmed by TCGA, Gene Expression Profiling Interactive Analysis 2 (GEPIA 2), starBase, and KM. Results A total of 192 shared DEGs were discovered from the four data sets, including 125 upregulated and 67 downregulated genes. Functional enrichment analysis presented that they were mainly enriched in cartilage development, pathway in PI3 K‐Akt signaling pathway. Lower expression of SOBP was the independent prognostic factor for inferior prognosis in OC patients. The downregulation of SOBP enhanced the infiltration levels of B cells, CD8+ T cells, Macrophage, Neutrophil, and Dendritic cells. GSEA also disclosed low SOBP showed a significantly associated with the activation of various immune‐related pathways. Finally, we first reported that the MEG8/miR‐378d/SOBP axis was linked to the development and prognosis of OC through regulating the cytokines pathway. Conclusions Our study establishes a novel MEG8/miR‐378d/SOBP axis in the development and prognosis of OC, and the triple subnetwork probably affects the progression of the OC by regulating the cytokines pathway.

Abstract Background We aim to assess the value of locoregional treatment (LRT) including breast‐conserving surgery (BCS), mastectomy (MAST), and radiotherapy (RT) in patients with de novo stage IV breast cancer. Methods Patients with de novo stage IV breast cancer were retrospectively identified from the Surveillance, Epidemiology, and End Results database between 2004 and 2014. Kaplan‐Meier analysis, log‐rank tests, propensity score matching (PSM), and the multivariate Cox proportional model were used for statistical analysis. Results A total of 5798 patients were identified including 849 (14.6%), 763 (13.2%), 2338 (40.3%), and 1848 (31.9%) who received BCS alone, BCS+RT, MAST alone, and MAST+RT, respectively. The proportions of receiving BCS decreased from 35.9% in 2004 to 26.2% in 2014 (p = 0.002), and the probability of patients receiving MAST increased from 64.1% in 2004 to 74.8% in 2014 (p = 0.002). Before PSM, there was a significant difference in breast cancer‐specific survival (BCSS) among the treatment arms. Patients who received RT had better BCSS, the 5‐year BCSS was 40.5%, 52.3%, 41.5%, and 47.7% in patients treated with BCS alone, BCS+RT, MAST alone, and MAST+RT, respectively (p

Abstract Background T3N0 breast cancer might be a distinct clinical and biological entity, with higher heterogeneity and presenting diverse responses to locoregional and systemic therapy. The aim of the current study was to validate the prognostic effect and assess the treatment decision‐making of the American Joint Committee on Cancer (AJCC) eighth pathological prognostic staging in T3N0 breast cancer after mastectomy. Methods We retrospectively included 2465 patients with stage T3N0 breast cancer who had undergone mastectomy between 2010 and 2014 using the data from Surveillance, Epidemiology, and End Results program. The primary endpoint of this study was breast cancer–specific survival (BCSS). Results Of the entire cohort, 76.0% of patients in the seventh AJCC staging system were restaged to the eighth AJCC pathological prognostic staging system. A total of 1431 (58.1%) and 1175 (47.7%) of them received chemotherapy and postmastectomy radiotherapy (PMRT), respectively. Pathological staging was an independent prognostic factor for BCSS. Using pathological prognostic stage IA as the reference, BCSS gradually became worse with increased hazard ratios. The 5‐years BCSS was 96.9%, 95.5%, 91.1%, 85.6%, and 75.5% in pathological prognostic stage IA, IB, IIA, IIB, and IIIA breast cancers, respectively (P

This paper reports the wind pressure characteristics on long-span roofs under fluctuating wind in a vertical direction based on a large eddy simulation (LES). Three types of roofs, i.e., saddle, wavy, and continuous arch roofs, are tested. First, the membrane structure canopy is measured, and the model is established for numerical simulation. The computational models and methods are verified by comparing the obtained wind pressure distributions on the roof with the measured results and numerical simulation results under other methods. Next, a numerical simulation is performed to understand not only the wind pressure and the wind speed time series but also the wind vibration responses and fluid-solid coupling. The effects of lateral fluctuating wind at different wind speeds on the wind-induced vibration response and wind pressure distribution of different membrane structures are studied. Based on the results, the wind pressure zones of the roofs are discussed. Furthermore, the original structures are optimized and numerically simulated considering the streamlined design concept to study the influence mechanism of fluctuating wind on the roof in more detail.

Objective. We evaluated the effects and mechanisms of GDC0623 on osteogenic differentiation of osteoblasts induced by IL-1β. Methodology. Osteoblasts were treated with 20 ng/ml IL-1β and 0.1 µM GDC0623. Cell proliferation levels were evaluated by the cell counting kit 8 (CCK8), EdU assay, and western blotting [proliferating cell nuclear antigen (PCNA) and Cyclin D1]. Osteoblasts were cultured in an osteogenic induction medium for 1–3 weeks after which their differentiations were assessed by alkaline phosphatase (ALP) staining, Alizarin Red staining, calcium concentration, immunocytochemistry staining, real-time quantitative PCR (RT-qPCR), and immunofluorescence staining. The osteogenesis-associated mechanisms were further evaluated by western blotting using appropriate antibodies. Results. Relative to the control group, IL-1β induced the rapid proliferation of osteoblasts and suppressed their osteogenic differentiations by upregulating the activities of MEK-Erk1/2 as well as Jak-Stat3 pathways and by elevating MMP13 and MMP9 levels. However, blocking of the MEK-Erk1/2 signaling pathway by GDC0623 treatment reversed these effects. Conclusion. Inhibition of Jak-Stat3 pathway by C188-9 downregulated the expression levels of MMP9 and MMP13, activated MEK-Erk1/2 pathway, and inhibited osteogenic differentiation.