N-p-coumaroyloctopamine ameliorates hepatic glucose metabolism and oxidative stress involved in a PI3K/AKT/GSK3ß pathway.

Type 2 diabetes mellitus is regarded as a chronic metabolic disease characterized by hyperglycemia. Long-term hyperglycemia may result in oxidative stress, damage pancreatic ß-cell function and induce insulin resistance. Herein we explored the anti-hypoglycemic effects and mechanisms of action of N-p-coumaroyloctopamine (N-p-CO) in vitro and in vivo. N-p-CO exhibited high antioxidant activity, as indicated by the increased activity of SOD, GSH and GSH-Px in HL-7702 cells induced by both high glucose (HG) and palmitic acid (PA). N-p-CO treatment significantly augmented glucose uptake and glycogen synthesis in HG/PA-treated HL-7702 cells. Moreover, administration of N-p-CO in diabetic mice induced by both high-fat diet (HFD) and streptozotocin (STZ) not only significantly increased the antioxidant levels of GSH-PX, SOD and GSH, but also dramatically alleviated hyperglycemia and hepatic glucose metabolism in a dose-dependent manner. More importantly, N-p-CO upregulated the expressions of PI3K, AKT and GSK3ß proteins in both HG/PA-induced HL-7702 cells and HFD/STZ-induced mice. These findings clearly suggest that N-p-CO exerts anti-hypoglycemic and anti-oxidant effects, most probably via the regulation of a PI3K/AKT/GSK3ß signaling pathway. Thus, N-p-CO may have high potentials as a new candidate for the prevention and treatment of diabetes.

Textured Asymmetric Membrane Electrode Assemblies of Piezoelectric Phosphorene and Ti3C2Tx MXene Heterostructures for Enhanced Electrochemical Stability and Kinetics in LIBs.

Black phosphorus with a superior theoretical capacity (2596 mAh g-1) and high conductivity is regarded as one of the powerful candidates for lithium-ion battery (LIB) anode materials, whereas the severe volume expansion and sluggish kinetics still impede its applications in LIBs. By contrast, the exfoliated two-dimensional phosphorene owns negligible volume variation, and its intrinsic piezoelectricity is considered to be beneficial to the Li-ion transfer kinetics, while its positive influence has not been discussed yet. Herein, a phosphorene/MXene heterostructure-textured nanopiezocomposite is proposed with even phosphorene distribution and enhanced piezo-electrochemical coupling as an applicable free-standing asymmetric membrane electrode beyond the skin effect for enhanced Li-ion storage. The experimental and simulation analysis reveals that the embedded phosphorene nanosheets not only provide abundant active sites for Li-ions, but also endow the nanocomposite with favorable piezoelectricity, thus promoting the Li-ion transfer kinetics by generating the piezoelectric field serving as an extra accelerator. By waltzing with the MXene framework, the optimized electrode exhibits enhanced kinetics and stability, achieving stable cycling performances for 1,000 cycles at 2 A g-1, and delivering a high reversible capacity of 524 mAh g-1 at - 20 â„ƒ, indicating the positive influence of the structural merits of self-assembled nanopiezocomposites on promoting stability and kinetics.

Construction of nano-silica particle clusters and their effects on the shear thickening properties of liquids.

It is of great research significance to prepare a new shear thickening fluid (STF) with a simple process, remarkable thickening effect and excellent impact resistance from the properties of the particles. Inspired by the shear thickening mechanism, nano-silica particle clusters (SPC) with different morphological structures were prepared by the reaction of amino-modified silica with polyethylene glycol diglycidyl ether (PEGDGE), and the structure models of particle clusters were designed through theoretical analysis. The structure of SPC was affected by the degree of amination modification and the molecular weight of PEGDGE, which was analyzed by DLS and TEM. The shear thickening behavior of the fluid was evaluated by steady-state rheology and dynamic-state rheology analysis. The shear thickening behavior of the fluid composed of SPC also changed greatly with the influence of the degree of amination modification and the molecular weight of PEGDGE. In addition, compared with the STF contained original silica, the STF contained SPC could produce a faster and stronger shear thickening response. Therefore, silica particle clusters are not only a promising candidate for the preparation of high-performance shear thickening fluids, but can also be better applied to industrial and scientific fields such as impact protection and shock absorption.

The Medical Action Ontology: A tool for annotating and analyzing treatments and clinical management of human disease.

BACKGROUND: Navigating the clinical literature to determine the optimal clinical management for rare diseases presents significant challenges. We introduce the Medical Action Ontology (MAxO), an ontology specifically designed to organize medical procedures, therapies, and interventions. METHODS: MAxO incorporates logical structures that link MAxO terms to numerous other ontologies within the OBO Foundry. Term development involves a blend of manual and semi-automated processes. Additionally, we have generated annotations detailing diagnostic modalities for specific phenotypic abnormalities defined by the Human Phenotype Ontology (HPO). We introduce a web application, POET, that facilitates MAxO annotations for specific medical actions for diseases using the Mondo Disease Ontology. FINDINGS: MAxO encompasses 1,757 terms spanning a wide range of biomedical domains, from human anatomy and investigations to the chemical and protein entities involved in biological processes. These terms annotate phenotypic features associated with specific disease (using HPO and Mondo). Presently, there are over 16,000 MAxO diagnostic annotations that target HPO terms. Through POET, we have created 413 MAxO annotations specifying treatments for 189 rare diseases. CONCLUSIONS: MAxO offers a computational representation of treatments and other actions taken for the clinical management of patients. Its development is closely coupled to Mondo and HPO, broadening the scope of our computational modeling of diseases and phenotypic features. We invite the community to contribute disease annotations using POET (https://poet.jax.org/). MAxO is available under the open-source CC-BY 4.0 license (https://github.com/monarch-initiative/MAxO). FUNDING: NHGRI 1U24HG011449-01A1 and NHGRI 5RM1HG010860-04.

Hydrated alginate polysaccharide fabrics grafted with sliver nanocrystals for wearable thermal and health management.

The creation of functional components with precise chemistries on carbohydrate polymers is of great significance for future wearable biomedicine and health management. Among various carbohydrate polymers, marine polysaccharide featured with antimicrobial, biodegradable and biocompatible properties is an ideal platform while the water-swelling nature makes it difficult to form stable interface. Here, well-dispersed silver nanoparticles have been in-situ assembled on hydrated alginate fabric (AF), involving chemical absorption of Ag ions and in-situ reduction of conductive Ag layer. Owing to the stable complex formed between Ag ions and carboxyl groups, the Ag-grafted AF exhibits superior Joule heating capability, including low operating voltage (1-3 V), high saturation temperature (63 °C), rapid response time (25 s) and outstanding durability against harsh conditions. Furthermore, the Ag-grafted AF demonstrates noticeable inhibition against E. coli and S. aureus as compared with the pristine AF. This work provides a rational strategy for the functionalization of hydrated polysaccharide and enables wearable thermotherapy devices for human health management.

Latest advances: Improving the anti-inflammatory and immunomodulatory properties of PEEK materials.

Excellent biocompatibility, mechanical properties, chemical stability, and elastic modulus close to bone tissue make polyetheretherketone (PEEK) a promising orthopedic implant material. However, biological inertness has hindered the clinical applications of PEEK. The immune responses and inflammatory reactions after implantation would interfere with the osteogenic process. Eventually, the proliferation of fibrous tissue and the formation of fibrous capsules would result in a loose connection between PEEK and bone, leading to implantation failure. Previous studies focused on improving the osteogenic properties and antibacterial ability of PEEK with various modification techniques. However, few studies have been conducted on the immunomodulatory capacity of PEEK. New clinical applications and advances in processing technology, research, and reports on the immunomodulatory capacity of PEEK have received increasing attention in recent years. Researchers have designed numerous modification techniques, including drug delivery systems, surface chemical modifications, and surface porous treatments, to modulate the post-implantation immune response to address the regulatory factors of the mechanism. These studies provide essential ideas and technical preconditions for the development and research of the next generation of PEEK biological implant materials. This paper summarizes the mechanism by which the immune response after PEEK implantation leads to fibrous capsule formation; it also focuses on modification techniques to improve the anti-inflammatory and immunomodulatory abilities of PEEK. We also discuss the limitations of the existing modification techniques and present the corresponding future perspectives.

The Medical Action Ontology: A Tool for Annotating and Analyzing Treatments and Clinical Management of Human Disease.

Navigating the vast landscape of clinical literature to find optimal treatments and management strategies can be a challenging task, especially for rare diseases. To address this task, we introduce the Medical Action Ontology (MAxO), the first ontology specifically designed to organize medical procedures, therapies, and interventions in a structured way. Currently, MAxO contains 1757 medical action terms added through a combination of manual and semi-automated processes. MAxO was developed with logical structures that make it compatible with several other ontologies within the Open Biological and Biomedical Ontologies (OBO) Foundry. These cover a wide range of biomedical domains, from human anatomy and investigations to the chemical and protein entities involved in biological processes. We have created a database of over 16000 annotations that describe diagnostic modalities for specific phenotypic abnormalities as defined by the Human Phenotype Ontology (HPO). Additionally, 413 annotations are provided for medical actions for 189 rare diseases. We have developed a web application called POET (https://poet.jax.org/) for the community to use to contribute MAxO annotations. MAxO provides a computational representation of treatments and other actions taken for the clinical management of patients. The development of MAxO is closely coupled to the Mondo Disease Ontology (Mondo) and the Human Phenotype Ontology (HPO) and expands the scope of our computational modeling of diseases and phenotypic features to include diagnostics and therapeutic actions. MAxO is available under the open-source CC-BY 4.0 license (https://github.com/monarch-initiative/MAxO).

Pathogenesis and therapeutic implications of matrix metalloproteinases in intervertebral disc degeneration: A comprehensive review.

Intervertebral disc (IVD) degeneration (IDD) is a common disorder that affects the spine and is a major cause of lower back pain (LBP). The extracellular matrix (ECM) is the structural foundation of the biomechanical properties of IVD, and its degradation is the main pathological characteristic of IDD. Matrix metalloproteinases (MMPs) are a group of endopeptidases that play an important role in the degradation and remodeling of the ECM. Several recent studies have shown that the expression and activity of many MMP subgroups are significantly upregulated in degenerated IVD tissue. This upregulation of MMPs results in an imbalance of ECM anabolism and catabolism, leading to the degradation of the ECM and the development of IDD. Therefore, the regulation of MMP expression is a potential therapeutic target for the treatment of IDD. Recent research has focused on identifying the mechanisms by which MMPs cause ECM degradation and promote IDD, as well as on developing therapies that target MMPs. In summary, MMP dysregulation is a crucial factor in the development of IDD, and a deeper understanding of the mechanisms involved is needed to develop effective biological therapies that target MMPs to treat IDD.

Carbon trading and COVID-19: a hybrid machine learning approach for international carbon price forecasting.

Accurate carbon price forecasting can better allocate carbon emissions and thus ensure a balance between economic development and potential climate impacts. In this paper, we propose a new two-stage framework based on processes of decomposition and re-estimation to forecast prices across international carbon markets. We focus on the Emissions Trading System (ETS) in the EU, as well as the five main pilot schemes in China, spanning the period from May 2014 to January 2022. In this way, the raw carbon prices are first separated into multiple sub-factors and then reconstructed into factors of 'trend' and 'period' with the use of Singular Spectrum Analysis (SSA). Once the subsequences have been thus decomposed, we further apply six machine learning and deep learning methods, allowing the data to be assembled and thus facilitating the prediction of the final carbon price values. We find that from amongst these machine learning models, the Support vector regression (SSA-SVR) and Least squares support vector regression (SSA-LSSVR) stand out in terms of performance for the prediction of carbon prices in both the European ETS and equivalent models in China. Another interesting finding to come out of our experiments is that the sophisticated algorithms are far from being the best performing models in the prediction of carbon prices. Even after accounting for the impacts of the COVID-19 pandemic and other macro-economic variables, as well as the prices of other energy sources, our framework still works effectively.

Ontologizing health systems data at scale: making translational discovery a reality.

Common data models solve many challenges of standardizing electronic health record (EHR) data but are unable to semantically integrate all of the resources needed for deep phenotyping. Open Biological and Biomedical Ontology (OBO) Foundry ontologies provide computable representations of biological knowledge and enable the integration of heterogeneous data. However, mapping EHR data to OBO ontologies requires significant manual curation and domain expertise. We introduce OMOP2OBO, an algorithm for mapping Observational Medical Outcomes Partnership (OMOP) vocabularies to OBO ontologies. Using OMOP2OBO, we produced mappings for 92,367 conditions, 8611 drug ingredients, and 10,673 measurement results, which covered 68-99% of concepts used in clinical practice when examined across 24 hospitals. When used to phenotype rare disease patients, the mappings helped systematically identify undiagnosed patients who might benefit from genetic testing. By aligning OMOP vocabularies to OBO ontologies our algorithm presents new opportunities to advance EHR-based deep phenotyping.

The effect of low-carbon transportation pilot policy on carbon performance: evidence from China.

In 2011, aiming to achieve sustainable development in the transportation sector, the Chinese government started a pilot policy of low-carbon transportation system (LCTS). Based on the panel data for 280 prefecture-level cities in China from 2006 to 2017, we first measure carbon efficiency by using the SBM-DEA model, and identify the direct and spatial spillover effects of LCTS on carbon efficiency and carbon intensity by adopting a spatial difference-in-differences approach (SDID). The results indicate that LCTS construction not only enhances local carbon performance but also has a significant spatial spillover effect in neighboring cities. The results are still valid after a series of robustness tests. The mechanism analysis reveals that LCTS can elevate carbon performance by improving energy efficiency, green innovation, and developing public transit. The direct and indirect effects of LCTS on carbon performance show more pronounced effects in megalopolis and eastern region. This paper provides reliable empirical evidence for the effect of LCTS on carbon performance, which is conducive to deepening the understanding of carbon emissions and has a high reference value for the rational formulation of carbon reduction policies.

Analysis of factors influencing the job satisfaction of medical staff in tertiary public hospitals, China: A cross-sectional study.

Introduction: Since the outbreak of the novel coronavirus pneumonia (COVID-19), China has entered normalization phase of its epidemic prevention and control measures that emphasizes 'precise prevention and control,' 'dynamic zeroing', and 'universal vaccination'. However, medical staff continue to face physical and mental stress. The present study aimed to investigate the job satisfaction of medical staff in China, as well as any associated factors. Methods: 2,258 medical staff completed a questionnaire specially designed for this study. Independent samples t-tests, one-way analysis of variance, and binary logistic regression were used to analyze associated factors. Results: Overall, 48.4% of the participants expressed satisfaction with their job; the highest-scoring dimension was interpersonal relationships (3.83 ± 0.73), while the lowest scoring dimension was salary and benefits (3.13 ± 0.94). The logistic regression model indicated that job satisfaction among medical staff is associated with being aged 40-49 years [odds ratio (OR) = 2.416] or > 50 years (OR = 2.440), having an above-undergraduate education level (OR = 1.857), holding a position other than doctor [i.e., nurse (OR = 3.696) or 'other' (OR = 2.423)], having a higher income (OR = 1.369), and having fewer monthly overtime shifts (OR = 0.735-0.543). Less than half of the medical staff expressed satisfaction with their job, indicating that the overall level is not high. Discussion: This research enriches the study of medical workers' job satisfaction during periods when epidemic prevention and control has become familiar and routine. To improve medical workers' job satisfaction, administrators should seek to enhance medical staff's remuneration, reduce their work pressure, and meet their needs (where reasonable).

Ethnic disparities in ambient air and traffic-related pollution exposure and ethnic-specific impacts on clinical biomarker levels.

BACKGROUND: Although characterizing the inequality in pollution exposure burden across ethnic groups and the ethnic-specific exposure associations is of great social and public health importance, it has not been systematically investigated in large population studies. METHODS: The UK Biobank data (N = 485, 806) of individual-level air ambient and traffic-related pollution exposure, biomarkers routinely used in clinical practice, genotype, life-style factors, and socioeconomic status were analyzed. Air pollution exposure estimates were compared among six genetically inferred ethnic groups. We also quantified the association between exposure and biomarkers within and across ethnicities. RESULTS: Non-European participants (defined by genetics) disproportionately bear a higher burden of exposure than their European counterparts even after adjusting for covariables including socioeconomic status. For example, exposure to NO2 in people with African ancestry was 30.7 % higher (p = 1.5E-786) than European subjects. Within the genetically defined African group, larger African genetic ancestry proportion (AGAP) was linked to higher ambient air pollutant exposure. Trans-Ethnic analysis identified 32 clinical biomarkers associated with environmental exposure. For 13 biomarkers, the association with exposure was significantly different or even in opposing directions across ethnic groups. CONCLUSIONS: Substantial disparities in air pollution exposure was observed among genetically-defined ethnic groups. Most importantly, we show that the impact of exposure on biomarkers varies by ethnicity. Reducing the disproportionally high exposure burden on non-European populations and alleviating the adverse consequences in an ethnic-specific manner are of great urgency and significance.

ROS-responsive magnesium-containing microspheres for antioxidative treatment of intervertebral disc degeneration.

Intervertebral disc degeneration (IVDD) is a degenerative disease characterized by lower-back pain, causing disability globally. Antioxidant therapy is currently considered one of the most promising strategies for IVDD treatment, given the crucial role of reactive oxygen species (ROS) in IVDD pathogenesis. Herein, a ROS-responsive magnesium-containing microsphere (Mg@PLPE MS) was constructed for the antioxidative treatment of IVDD. The Mg@PLPE MS has a core-shell structure comprising poly(lactic-co-glycolic acid) (PLGA) and ROS-responsive polymer poly(PBT-co-EGDM) as the shell and a magnesium microparticle as the core. The poly(PBT-co-EGDM) can be destroyed by H2O2 through the H2O2-triggered hydrophobic-to-hydrophilic transition, subsequently promoting an Mg-water reaction to produce H2. Thus, Mg@PLPE MS provides a valuable platform for H2O2 elimination and controlled H2 release. The generated H2 scavenge for ROS by reacting with noxious •OH. Notably, the Mg@PLPE MS exerted significant antioxidative and anti-inflammatory effects in a disc degeneration rat model and alleviated extracellular matrix degradation and disc cells apoptosis, thereby underlining its efficacy in IVDD treatment. The Mg@PLPE MS also exhibited robust biocompatibility and negligible toxicity, presenting the promise for the antioxidative treatment of IVDD in vivo. STATEMENT OF SIGNIFICANCE: Antioxidant therapy is currently considered one of the most promising strategies for intervertebral disc degeneration (IVDD) treatment, given the crucial role of reactive oxygen species (ROS) in IVDD pathogenesis. Here, ROS-responsive magnesium-containing microspheres (Mg@PLPE MSs) were constructed to alleviate IVDD through controlled release of hydrogen gas. The Mg@PLPE MSs can effectively scavenge overproduced ROS by simultaneously reacting with H2O2 and •OH, thus creating a suitable microenvironment for inhibition of ECM degradation. As a result, Mg@PLPE MSs treated IVDD rats exhibit minimal nucleus pulposus decrease, less extracellular matrix degradation, minimal radial fissure of fibrous rings, and higher disc height index. Therefore, the as-prepared Mg@PLPE MSs may shed a new light on clinical treatment of IVDD.

The status and influencing factors of adolescents' mental health in a province of China: A cross-sectional study.

OBJECTIVE: To understand the mental health status of adolescents in China and its influencing factors. METHODS: The stratified cluster sampling method was used to evaluate the mental health status of 5633 adolescents using the Symptom Checklist (SCL-90). RESULTS: There were statistically significant differences in the overall mean score of SCL-90 and the mean score of each subscale among adolescents in gender, grade, family, and region. The mean score of the interpersonal sensitivity and phobic anxiety subscales of the adolescents with rural household registration was higher than that of the urban household registration. Except for hostility and phobic anxiety subscales, there was a significant difference between junior high school and senior high school students in the remaining subscales. There were significant differences between only children and non-only children in the obsessive-compulsive symptoms and phobic anxiety subscales. The mean scores of depression, phobic anxiety, and other subscales of left-behind adolescents were significantly different from those of non-left-behind adolescents. Female gender (OR = 1.789), different-grade (junior high school sophomore: OR = 2.201; junior high school third grade: OR = 2.004; high school freshman: OR = 2.279; high school sophomore: OR = 2.947; high school senior: OR = 2.112), different-region (central region: OR = 1.302; southern region: OR = 1.925) and high school (OR = 1.281) adolescents had a higher risk of mental health problems, while those from two-parent families (OR = 0.68) had a lower risk. LIMITATIONS: This study is a cross-sectional study and not widely representative. CONCLUSION: Gender, grade, region, and academic period are risk factors, and a two-parent family is a protective factor for adolescents' mental health.

Piezoelectric 1T Phase MoSe2 Nanoflowers and Crystallographically Textured Electrodes for Enhanced Low-Temperature Zinc-Ion Storage.

Transition metal dichalcogenides (TMDs) are regarded as promising cathode materials for zinc-ion storage owing to their large interlayer spacings. However, their capabilities are still limited by sluggish kinetics and inferior conductivities. In this study, a facile one-pot solvothermal method is exploited to vertically plant piezoelectric 1T MoSe2  nanoflowers on carbon cloth (CC) to fabricate crystallographically textured electrodes. The self-built-in electric field owing to the intrinsic piezoelectricity during the intercalation/deintercalation processes can serve as an additional piezo-electrochemical coupling accelerator to enhance the migration of Zn2+ . Moreover, the expanded interlayer distance (9-10 Å), overall high hydrophilicity, and conductivity of the 1T phase MoSe2  also promoted the kinetics. These advantages endow the tailored 1T MoSe2 /CC nanopiezocomposite with feasible Zn2+ diffusion and desirable electrochemical performances at room and low temperatures. Moreover, 1T MoSe2 /CC-based quasi-solid-state zinc-ion batteries are constructed to evaluate the potential of the proposed material in low-temperature flexible energy storage devices. This work expounds the positive effect of intrinsic piezoelectricity of TMDs on Zn2+ migration and further explores the availabilities of TMDs in low-temperature wearable energy-storage devices.

Unraveling the mechanisms of intervertebral disc degeneration: an exploration of the p38 MAPK signaling pathway.

Intervertebral disc (IVD) degeneration (IDD) is a worldwide spinal degenerative disease. Low back pain (LBP) is frequently caused by a variety of conditions brought on by IDD, including IVD herniation and spinal stenosis, etc. These conditions bring substantial physical and psychological pressure and economic burden to patients. IDD is closely tied with the structural or functional changes of the IVD tissue and can be caused by various complex factors like senescence, genetics, and trauma. The IVD dysfunction and structural changes can result from extracellular matrix (ECM) degradation, differentiation, inflammation, oxidative stress, mechanical stress, and senescence of IVD cells. At present, the treatment of IDD is basically to alleviate the symptoms, but not from the pathophysiological changes of IVD. Interestingly, the p38 mitogen-activated protein kinase (p38 MAPK) signaling pathway is involved in many processes of IDD, including inflammation, ECM degradation, apoptosis, senescence, proliferation, oxidative stress, and autophagy. These activities in degenerated IVD tissue are closely relevant to the development trend of IDD. Hence, the p38 MAPK signaling pathway may be a fitting curative target for IDD. In order to better understand the pathophysiological alterations of the intervertebral disc tissue during IDD and offer potential paths for targeted treatments for intervertebral disc degeneration, this article reviews the purpose of the p38 MAPK signaling pathway in IDD.

Deciphering the atomic-scale structural origin for large dynamic electromechanical response in lead-free Bi0.5Na0.5TiO3-based relaxor ferroelectrics.

Despite the extraordinary electromechanical properties of relaxor ferroelectrics, correlating their properties to underlying atomic-scale structures remains a decisive challenge for these "mess" systems. Here, taking the lead-free relaxor ferroelectric Bi0.5Na0.5TiO3-based system as an example, we decipher the atomic-scale structure and its relationship to the polar structure evolution and large dynamic electromechanical response, using the direct atomic-scale point-by-point correlation analysis. With judicious chemical modification, we demonstrate the increased defect concentration is the main driving force for deviating polarizations with high-angle walls, leading to the increased random field. Meanwhile, the main driving force for deviating polarizations with low-angle walls changes from the anti-phase oxygen octahedral tilting to the multidirectional A-O displacement, leading to the decreased anisotropy field. Benefiting from the competitive and synergetic equilibrium of anisotropic field versus random field, the facilitated polarization rotation and extension versus facilitated domain switching are identified to be responsible for the giant electromechanical response. These observations lay a foundation for understanding the "composition-structure-property" relationships in relaxor ferroelectric systems, guiding the design of functional materials for electromechanical applications.