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Angiogenesis is vital for tumor growth and metastasis. Emerging evidence suggests that metabolic reprogramming in endothelial cells (EC) may affect angiogenesis. Here, we showed that multiple regulators in the fructose metabolism pathway, especially fructose transporter SLC2A5 and fructose-metabolizing enzyme ketohexokinase (KHK), were upregulated in tumor endothelial cells from hepatocellular carcinoma (HCC). In mouse models with hepatoma xenografts or with Myc/sgp53-induced liver cancer, dietary fructose enhanced tumor angiogenesis, tumor growth, and metastasis, which could be attenuated by treatment with an inhibitor of SLC2A5. Furthermore, vessel growth was substantially increased in fructose-containing Matrigel compared with PBS-Matrigel. Inhibiting fructose metabolism in EC cells in vivo using EC-targeted nanoparticles loaded with siRNA against KHK significantly abolished fructose-induced tumor angiogenesis. Fructose treatment promoted the proliferation, migration, and tube formation of ECs and stimulated mitochondrial respiration and ATP production. Elevated fructose metabolism activated AMPK to fuel mitochondrial respiration, resulting in enhanced EC migration. Fructose metabolism was increased under hypoxic conditions as a result of HIF1α-mediated upregulation of multiple genes in the fructose metabolism pathway. These findings highlight the significance of fructose metabolism in ECs for promoting tumor angiogenesis. Restricting fructose intake or targeting fructose metabolism is a potential strategy to reduce angiogenesis and suppress tumor growth. Significance: Fructose metabolism in endothelial cells fuels mitochondrial respiration to stimulate tumor angiogenesis, revealing fructose metabolism as a therapeutic target and fructose restriction as a dietary intervention for treating cancer.

A single-atomic sulfur anode, constructed by ∼32 wt% single-atomic sulfur uniformly incorporated into the carbon lattice of hollow carbon nanospheres, demonstrates an outstanding combination of capacity, cyclability, and rate for potassium storage.

Quantitative activity and species source data of natural products (NPs) are important for drug discovery, medicinal plant research, and microbial investigations. Activity values of NPs against specific targets are useful for discovering targeted therapeutic agents and investigating the mechanism of medicinal plants. Composition/concentration values of NPs in individual species facilitate the assessments and investigations of the therapeutic quality of herbs and phenotypes of microbes. Here, we describe an update of the NPASS natural product activity and species source database previously featured in NAR. This update includes: (i) new data of ∼95 000 records of the composition/concentration values of ∼1 490 NPs/NP clusters in ∼390 species, (ii) extended data of activity values of ∼43 200 NPs against ∼7 700 targets (∼40% and ∼32% increase, respectively), (iii) extended data of ∼31 600 species sources of ∼94 400 NPs (∼26% and ∼32% increase, respectively), (iv) new species types of ∼440 co-cultured microbes and ∼420 engineered microbes, (v) new data of ∼66 600 NPs without experimental activity values but with estimated activity profiles from the established chemical similarity tool Chemical Checker, (vi) new data of the computed drug-likeness properties and the absorption, distribution, metabolism, excretion and toxicity (ADMET) properties for all NPs. NPASS update version is freely accessible at http://bidd.group/NPASS.

Optic nerve sheath diameter (ONSD) measurement is one of the non-invasive methods recommended for increased intracranial pressure (ICP) monitoring.This study aimed to evaluate the roles of optic nerve sheath diameter (ONSD) and ONSD/eyeball transverse diameter (ETD) ratio in predicting prognosis of death in comatose patients with acute stroke during their hospitalization.A total of 67 comatose patients with acute stroke were retrospectively recruited. The ONSD and ETD were measured by cranial computed tomography (CT) scan. All patients underwent cranial CT scan within 24 h after coma onset. Patients were divided into death group and survival group according to their survival status at discharge. The differences of the ONSD and ONSD/ETD ratio between the two groups and their prognostic values were compared.The ONSD and ONSD/ETD ratio were 6.07 ± 0.72 mm and 0.27 ± 0.03 in the comatose patients, respectively. The ONSD was significantly greater in the death group than that in the survival group (6.32 ± 0.67 mmThe mortality increased in comatose patients with acute stroke when the ONSD was5.7 mm or the ONSD/ETD ratio was0.25. Both indexes could be used as prognostic tools for comatose patients with acute stroke. The ONSD/ETD ratio was more stable than the ONSD alone, which would be preferred in clinical practice.

Emotion can be influenced during self-isolation, and to avoid severe mood swings, emotional regulation is meaningful. To achieve this, efficiently recognizing emotion is a vital step, which can be realized by electroencephalography signals. Previously, inspired by the knowledge of sequencing in bioinformatics, a method termed brain rhythm sequencing that analyzes electroencephalography as the sequence consisting of the dominant rhythm has been proposed for seizure detection. In this work, with the help of similarity measure methods, the asymmetric features are extracted from the sequences generated by different channel data. After evaluating all asymmetric features for emotion recognition, the optimal feature that yields remarkable accuracy is identified. Therefore, the classification task can be accomplished through a small amount of channel data. From a music emotion recognition experiment and a public DEAP dataset, the classification accuracies of various test sets are approximately 80-85% when employing an optimal feature extracted from one pair of symmetrical channels. Such performances are impressive when using fewer resources is a concern. Further investigation revealed that emotion recognition shows strongly individual characteristics, so an appropriate solution is to include the subject-dependent properties. Compared to the existing works, this method benefits from the design of a portable emotion-aware device used during self-isolation, as fewer scalp sensors are needed. Hence, it would provide a novel way to realize emotional applications in the future.

This PDF file includes:Supplementary Figures S1 to S11Supplementary Table S1

Angiogenesis is vital for tumor growth and metastasis. Emerging evidence suggests that metabolic reprogramming in endothelial cells (EC) may affect angiogenesis. Here, we showed that multiple regulators in the fructose metabolism pathway, especially fructose transporter SLC2A5 and fructose-metabolizing enzyme ketohexokinase (KHK), were upregulated in tumor endothelial cells from hepatocellular carcinoma (HCC). In mouse models with hepatoma xenografts or with Myc/sgp53-induced liver cancer, dietary fructose enhanced tumor angiogenesis, tumor growth, and metastasis, which could be attenuated by treatment with an inhibitor of SLC2A5. Furthermore, vessel growth was substantially increased in fructose-containing Matrigel compared with PBS-Matrigel. Inhibiting fructose metabolism in EC cells in vivo using EC-targeted nanoparticles loaded with siRNA against KHK significantly abolished fructose-induced tumor angiogenesis. Fructose treatment promoted the proliferation, migration, and tube formation of ECs and stimulated mitochondrial respiration and ATP production. Elevated fructose metabolism activated AMPK to fuel mitochondrial respiration, resulting in enhanced EC migration. Fructose metabolism was increased under hypoxic conditions as a result of HIF1α-mediated upregulation of multiple genes in the fructose metabolism pathway. These findings highlight the significance of fructose metabolism in ECs for promoting tumor angiogenesis. Restricting fructose intake or targeting fructose metabolism is a potential strategy to reduce angiogenesis and suppress tumor growth.Significance:Fructose metabolism in endothelial cells fuels mitochondrial respiration to stimulate tumor angiogenesis, revealing fructose metabolism as a therapeutic target and fructose restriction as a dietary intervention for treating cancer.

To investigate how the National Health Commission of China (NHCC)-recommended Chinese medicines (CMs) modulate the major maladjustments of coronavirus disease 2019 (COVID-19), particularly the clinically observed complications and comorbidities.By focusing on the potent targets in common with the conventional medicines, we investigated the mechanisms of 11 NHCC-recommended CMs in the modulation of the major COVID-19 pathophysiology (hyperinflammations, viral replication), complications (pain, headache) and comorbidities (hypertension, obesity, diabetes). The constituent herbs of these CMs and their chemical ingredients were from the Traditional Chinese Medicine Information Database. The experimentally-determined targets and the activity values of the chemical ingredients of these CMs were from the Natural Product Activity and Species Source Database. The approved and clinical trial drugs against these targets were searched from the Therapeutic Target Database and DrugBank Database. Pathways of the targets was obtained from Kyoto Encyclopedia of Genes and Genomes and additional literature search.Overall, 9 CMs modulated 6 targets discovered by the COVID-19 target discovery studies, 8 and 11 CMs modulated 8 and 6 targets of the approved or clinical trial drugs for the treatment of the major COVID-19 complications and comorbidities, respectively.The coordinated actions of each NHCC-recommended CM against a few targets of the major COVID-19 pathophysiology, complications and comorbidities, partly have common mechanisms with the conventional medicines.

BACKGROUND: Arrhythmia is not uncommon among pulmonary hypertension (PH) population, and may be associated with disease severity. HYPOTHESIS: To investigate different spectrums and prevalence of arrhythmias in different clinical PH groups in Chinese population. METHODS: Patients diagnosed with PH between April 15, 2019, and August 2, 2021, were enrolled prospectively. The prevalence of different types of arrhythmias in PH patients were calculated. Logistic regression analyses were conducted to determine independent predictors for arrhythmia. RESULTS: One thousand patients were enrolled. The prevalence of any arrhythmia, sinus node dysfunction, sinus tachycardia, atrial fibrillation, atrial flutter, other types of atrial tachycardia, atrioventricular block, and ventricular tachycardia is 44.4%, 12.2%, 15.2%, 8.1%, 4.1%, 10.2%, 7.1%, and 2.5%. Logistic regression analyses revealed that older age and larger right ventricle (odds ratio: 1.111 and 1.095, p

In this study, NiCr2O4 coatings co-doped with metal borides MBx (M = V, Mo and Fe) and MnO2 were synthesized by atmospheric plasma spraying. The phase composition, microstructure, infrared radiation performances as well as the thermal resistance of the coatings were investigated. All coatings possessed typically layer stacked microstructure, and the thickness and roughness (Ra) of the ceramic coatings ranging about 50-60 μm and 3.51-3.65 μm, correspondingly. Besides, the doped coatings still had a spinel structure. Since the metal ions and boron ions entered into the spinel lattice, which induced lattice distortion and enhanced the infrared activity of lattice vibrational absorption, the infrared emissivity of the coatings at 5-25 μm was increased effectively. The highest emissivity at 5-25 μm was obtained by V-doped coating, which was 0.8836 about 0.0175 higher than that of pure NiCr2O4 coating. However, the emissivity at 3∼5 μm was declined owing to compensating effect of high-valence ion doping, which reduced the hole's concentration and the intersub-band transition absorption. The lowest emissivity of 0.8664 was obtained with Mo-doped coating at 3-5 μm, which was 0.017 lower than that of pure NiCr2O4 coating. Attributed to the donor levels introduced through high-valance doping, the free electron's concentration increased, which promoted the transition absorption of free electrons from the impurity levels to the conduction band, resulting in higher emissivity at 0.75-2.5 μm. The highest emissivity of 0.935 at 0.75-2.5 μm was obtained with the Mo-doped coating, which was 0.02 higher than that of pure NiCr2O4 coating. As for high temperature performance, the VB2–MnO2 co-doped coating possessed the highest emissivity of 0.92 in 2.5∼25 μm at 1000 °C, and also showed good thermal resistance after 30 thermal cycles with water-cooling from 750 °C to 25 °C.

BackgroundThe impact of hospital volume on the long-term survival of esophageal squamous cell carcinoma (ESCC) has not been well assessed in China, especially for stage I–III stage ESCC. We performed a large sample size study to assess the relationships between hospital volume and the effectiveness of ESCC treatment and the hospital volume value at the lowest risk of all-cause mortality after esophagectomy in China.AimTo investigate the prognostic value of hospital volume for assessing postoperative long-term survival of ESCC patients in China.MethodsThe date of 158,618 patients with ESCC were collected from a database (1973–2020) established by the State Key Laboratory for Esophageal Cancer Prevention and Treatment, the database includes 500,000 patients with detailed clinical information of pathological diagnosis and staging, treatment approaches and survival follow-up for esophageal and gastric cardia cancers. Intergroup comparisons of patient and treatment characteristics were conducted with the X2 test and analysis of variance. The Kaplan-Meier method with the log-rank test was used to draw the survival curves for the variables tested. A Multivariate Cox proportional hazards regression model was used to analyze the independent prognostic factors for overall survival. The relationship between hospital volume and all-cause mortality was assessed using restricted cubic splines from Cox proportional hazards models. The primary outcome was all-cause mortality.ResultsIn both 1973-1996 and 1997-2020, patients with stage I-III stage ESCC who underwent surgery in high volume hospitals had better survival than those who underwent surgery in low volume hospitals (both PConclusionHospital volume can be used as an indicator to predict the postoperative survival of ESCC patients. Our results suggest that the centralized management of esophageal cancer surgery is meaningful to improve the survival of ESCC patients in China, but the hospital volume should preferably not be higher than 1027 cases/year.Core tipHospital volume is considered to be a prognostic factor for many complex diseases. However, the impact of hospital volume on long-term survival after esophagectomy has not been well evaluated in China. Based on a large sample size of 158,618 ESCC patients in China spanning 47 years (1973-2020), We found that hospital volume can be used as a predictor of postoperative survival in patients with ESCC, and identified hospital volume thresholds with the lowest risk of death from all causes. This may provide an important basis for patients to choose hospitals and have a significant impact on the centralized management of hospital surgery.

Exploring the governance mechanisms of industrial carbon emissions in heavy industrial zones under the background of ecological civilization construction is of great significance to achieve the goal of 'double carbon' and environmental justice. With Liaoning heavy industrial zones as an example, we constructed a tripartite evolutionary game model of local government, industrial enterprises and third-party verification institutions. We examined the key factors affecting the strategic choice of industrial carbon emission tripartite stakeholders. The strategic choices of three stakeholders under different equilibrium points were simulated, and the industrial carbon emission governance mechanisms were constructed. The results showed that the stakeholder strategy choices of industrial carbon emissions under different equilibrium circumstances in the study area were in line with the reality and ideal respectively. In different equilibrium situations of tripartite stakeholder game, local governments, and third-party verification institutions played a leading role in the strategic choices of carbon emissions in different stable equilibrium circumstances. Policy subsidies, fines for violations, emission reduction costs, verification costs and regulatory costs were the key factors influencing the evolutionary game among the three stakeholders of industrial carbon emissions in the study area. Combined with the key influencing factors of industrial carbon emissions, the governance mechanisms of industrial carbon emissions in the study area were constructed from four aspects: innovation mechanism, constraint mechanism, market mechanism, and reverse forcing mechanism. Improving the balanced distribution of industrial carbon emission benefits in the study area amd promoting cooperation among the three parties would help realize environmental justice under the game of industrial carbon emission stakeholders.探寻生态文明建设背景下重工业区工业碳排放治理机制,对于实现“双碳”目标和环境正义具有重要意义。本研究以辽宁重工业区为例,构建地方政府、工业企业和第三方核查机构三方演化博弈模型,探讨影响工业碳排放策略选择的关键因素,对不同均衡点下三方利益主体的策略选择进行仿真,进而构建工业碳排放治理机制。结果表明: 不同均衡情景下,研究区工业碳排放利益主体策略选择分别符合现实和理想两种情景。在三方利益主体博弈的不同均衡情景中,地方政府和第三方核查机构在不同稳定性均衡情景碳排放策略选择中分别起主导作用。政策补贴、违规行为罚款、减排成本、核查成本和监管成本是研究区工业碳排放三方利益主体演化博弈的关键影响因素。结合工业碳排放的关键影响因素,从创新机制、约束机制、市场机制和倒逼机制4个方面构建研究区工业碳排放治理机制。完善研究区工业碳排放利益均衡分配,促进三方利益主体合作,可实现工业碳排放利益主体博弈下的环境正义。.

Keratin pearls (KP) is an important indicator of the degree of tumor cell differentiation of esophageal squamous cell carcinomas (ESCC). However, the independent prognostic value of KP in ESCC patients remains unclear. The hematoxylin-eosin (H&E) stained tissue microarrays (TMAs) or whole slides of the patients were prepared to identify the existence of KP. Kaplan-Meier (KM) survival analysis as well as univariate and multivariate Cox regression analyses were used to evaluate the prognostic value of KP. A nomogram based on KP and other clinicopathologic characteristics was constructed. The C-index, calibration curve, Receiver Operating Characteristic (ROC) curve, and Decision Curve Analysis (DCA) were used to evaluate the nomogram. The results indicated KP is a protective factor against lymph node metastasis and is closely associated with the differentiation degree in ESCC patients. KM survival analysis showed that the overall survival (OS) of patients with KP was significantly better than for patients without KP. In addition, multivariate Cox regression analysis revealed that KP was an independent predictor of OS. Furthermore, ROC curve demonstrated that KP combined with differentiation degree could more accurately predict the 5-year survival rate than differentiation degree alone. Importantly, the nomogram showed good discrimination and calibration abilities in both training and validation groups, which could more accurately predict the 3-, 5-, and 10-year survival rates of ESCC patients and adds to the predictive value of TNM stage alone. In conclusion, KP is an independent predictor of prognosis in patients with ESCC and provides incremental prognostic value to degree of differentiation.

An open-frame aluminophosphate, K[(Zn0.5Al0.5)2P2O8] (KZAPO), was rationally designed by a substitution design strategy and synthesized by a high-temperature molten salt method. Compared with the parent crystal of K[ZnBP2O8], KZAPO was characterized by similar 4 × 8 × 8 networks, a comparable short-wave ultraviolet transparency and a more regular tetrahedral frame with the mixing of (ZnO4)6- and (AlO4)5- anionic groups, highlighting the multifunctional roles that anionic group mixing played in structural and property modulations. In particular, KZAPO was characterized by a high thermal stability (over 850 °C) and a congruent-melting behavior, being conducive to practical applications.