Dupilumab therapy improves gut microbiome dysbiosis and tryptophan metabolism in Chinese patients with atopic dermatitis.

BACKGROUND: Dupilumab has demonstrate its potential to orchestrate inflammatory skin microenvironment, enhance skin barrier and shift skin microbiome dysbiosis, collectively contributing to clinical improvement in patients with atopic dermatitis (AD). As the second genome of human body, growing evidence suggests that the gut microbiome might relate to the host response to treatments. Little is known about the association between dupilumab treatment and gut microbiome in AD patients. OBJECTIVE: We aimed to characterize the gut microbiome among Chinese subjects with or without AD and determine the potential effect of dupilumab on the gut microbiome. RESULTS: The 16 s rRNA gene sequencing was conducted on 48 healthy controls (HC), 44 AD patients and 27 AD patients who received dupilumab for 16 weeks. Prior to treatment, we identified the changed beta-diversity, increased Firmicutes/Bacteroidetes ratio, decreased Bifidobacterium and expanded Faecalibacterium among the AD patients compared to HC. After 16 weeks of dupilumab treatment, gut microbiome dysbiosis of the AD patients improved with reversed beta-diversity, closer bacterial connections, increased colonization of Bifidobacterium, Ruminococcus gnavus, and Coprococcus, which were negatively correlated with disease severity indicators. This shift was largely independent of the degree of clinical improvement. Bacterial function analysis revealed further metabolic alterations following dupilumab treatment, including up-regulated expression of genes involved in the indole pathway of tryptophan metabolism, corroborated by quantitative UHPLC-MS/MS analysis. CONCLUSION: Dupilumab treatment tends to help shift the gut microbial dysbiosis in AD patients to a healthier state, along with improved intestinal tryptophan metabolism, suggesting the gut flora and its metabolites may mediate part of the synergistic therapeutic effects on the host.

p53 accelerates endothelial cell senescence in diabetic retinopathy by enhancing FoxO3a ubiquitylation and degradation via UBE2L6.

Diabetic retinopathy (DR) is the most common ocular fundus disease in diabetic patients. Chronic hyperglycemia not only promotes the development of diabetes and its complications, but also aggravates the occurrence of senescence. Previous studies have shown that DR is associated with senescence, but the specific mechanism has not been fully elucidated. Here, we first detected the differentially expressed genes (DEGs) and cellular senescence level of db/db mouse retinas by bulk RNA sequencing. Then, we used single-cell sequencing (scRNA-seq) to identify the main cell types in the retina and analyzed the DEGs in each cluster. We demonstrated that p53 expression was significantly increased in retinal endothelial cell cluster of db/db mice. Inhibition of p53 can reduce the expression of SA-ß-Gal and the senescence-associated secretory phenotype (SASP) in HRMECs. Finally, we found that p53 can promote FoxO3a ubiquitination and degradation by increasing the expression of the ubiquitin-conjugating enzyme UBE2L6. Overall, our results demonstrate that p53 can accelerate the senescence process of endothelial cells and aggravate the development of DR. These data reveal new targets and insights that may be used to treat DR.

Development and validation of machine learning-augmented algorithm for insulin sensitivity assessment in the community and primary care settings: a population-based study in China.

Objective: Insulin plays a central role in the regulation of energy and glucose homeostasis, and insulin resistance (IR) is widely considered as the "common soil" of a cluster of cardiometabolic disorders. Assessment of insulin sensitivity is very important in preventing and treating IR-related disease. This study aims to develop and validate machine learning (ML)-augmented algorithms for insulin sensitivity assessment in the community and primary care settings. Methods: We analyzed the data of 9358 participants over 40 years old who participated in the population-based cohort of the Hubei center of the REACTION study (Risk Evaluation of Cancers in Chinese Diabetic Individuals). Three non-ensemble algorithms and four ensemble algorithms were used to develop the models with 70 non-laboratory variables for the community and 87 (70 non-laboratory and 17 laboratory) variables for the primary care settings to screen the classifier of the state-of-the-art. The models with the best performance were further streamlined using top-ranked 5, 8, 10, 13, 15, and 20 features. Performances of these ML models were evaluated using the area under the receiver operating characteristic curve (AUROC), the area under the precision-recall curve (AUPR), and the Brier score. The Shapley additive explanation (SHAP) analysis was employed to evaluate the importance of features and interpret the models. Results: The LightGBM models developed for the community (AUROC 0.794, AUPR 0.575, Brier score 0.145) and primary care settings (AUROC 0.867, AUPR 0.705, Brier score 0.119) achieved higher performance than the models constructed by the other six algorithms. The streamlined LightGBM models for the community (AUROC 0.791, AUPR 0.563, Brier score 0.146) and primary care settings (AUROC 0.863, AUPR 0.692, Brier score 0.124) using the 20 top-ranked variables also showed excellent performance. SHAP analysis indicated that the top-ranked features included fasting plasma glucose (FPG), waist circumference (WC), body mass index (BMI), triglycerides (TG), gender, waist-to-height ratio (WHtR), the number of daughters born, resting pulse rate (RPR), etc. Conclusion: The ML models using the LightGBM algorithm are efficient to predict insulin sensitivity in the community and primary care settings accurately and might potentially become an efficient and practical tool for insulin sensitivity assessment in these settings.

Central nervous system complications in SARS-CoV-2-infected patients.

OBJECTIVE: To investigate the clinical manifestations, treatment and prognosis of COVID-19-associated central nervous system (CNS) complications. METHODS: In this single-centre observation study, we recruited patients with COVID-19-associated CNS complications at the neurology inpatient department of the Eighth Affiliated Hospital, Sun Yat-Sen University (Futian, Shenzhen) from Dec 2022 to Feb 2023. Patients were analysed for demographics, clinical manifestations, cerebrospinal fluid properties, electroencephalographic features, neuroimaging characteristics, and treatment outcome. All patients were followed-up at 1 and 2 months after discharge until Apr 2023. RESULTS: Of the 12 patients with COVID-19-associated CNS complications, the CNS symptoms occur between 0 days and 4 weeks after SARS-CoV-2 infection. The most common CNS symptoms were memory deficits (4/12, 33%), Unresponsiveness (4/12, 33%), mental and behavioural disorders (4/12, 33%). Seven of 12 cases can be categorized as probable SARS-CoV-2 encephalitis, and 5 cases can be described as brainstem encephalitis, acute disseminated encephalomyelitis, optic neuritis, multiple sclerosis or tremor probably associated with SARS-CoV-2 infection. Six patients received antiviral therapy, and 11 patients received glucocorticoid therapy, of which 3 patients received human immunoglobulin synchronously. Nine patients recovered well, two patients had residual neurological dysfunction, and one patient passed away from complications associated with tumor. CONCLUSION: In this observational study, we found that the inflammatory or immune-related complications were relatively common manifestations of COVID-19-associated CNS complications, including different phenotypes of encephalitis and CNS inflammatory demyelinating diseases. Most patients recovered well, but a few patients had significant neurological dysfunctions remaining.

Peptide/glycyrrhizic acid supramolecular polymer: An emerging medical adhesive for dural sealing and repairing.

Medical adhesives have emerged as potential materials for sealing, hemostasis and wound repairing in modern clinical surgery. However, most of existing medical adhesives are still far away from the clinical requirements for simultaneously meeting desirable tissue adhesion, safety, biodegradability, anti-swelling property, and convenient operability. Here, we present an entirely new kind of peptide-based underwater adhesives, which are constructed via cross-linked supramolecular copolymerization between cationic short peptides and glycyrrhizic acid (GA) in an aqueous solution. We revealed the unique molecular mechanism of the peptide/GA supramolecular polymers and underlined the importance of arginine residues in the enhancement of the bulk cohesion of the peptide/GA adhesive. We thus concluded a design guideline that the peptide sequence has to be encoded with multiple arginine termini and hydrophobic residues. The resulting adhesives exhibited effective tissue adhesion, robust cohesion, low cell cytotoxicity, acceptable hemocompatibility, inappreciable inflammation response, appropriate biodegradability, and excellent anti-swelling property. More attractively, the dried peptide/GA powder was able to rapidly self-gel into adhesives by absorbing water, suggesting conveniently clinical operability. Animal experiments showed that the peptide/GA supramolecular polymers could be utilized as reliable medical adhesives for dural sealing and repairing.

Cyclophilin D Contributes to Airway Epithelial Mitochondrial Damage in Chronic Obstructive Pulmonary Disease.

INTRODUCTION: Airway epithelial mitochondrial injury is an important pathogenesis of chronic obstructive pulmonary disease (COPD). Cyclophilin D (CypD) is a component of mitochondrial permeability transition pore and related to mitochondrial damage. However, the role of CypD in airway epithelial mitochondrial injury and COPD pathogenesis remains unclear. METHODS: CypD expression in human airway epithelium was determined by immunohistochemistry, and mitochondrial structure of airway epithelial cell was observed under the transmission electron microscopy. The expression of CypD signaling pathway in cigarette smoke extract (CSE)-treated airway epithelial cells was measured by real-time PCR and Western-blot. CSE-induced damage of airway epithelial cell and mitochondria was further studied. RESULTS: Immunohistochemistry and transmission electron microscopy analysis revealed that CypD expression in airway epithelium was significantly increased associated with notable airway epithelial mitochondrial structure damage in the patients with COPD. The mRNA and protein expression of CypD was significantly increased in concentration- and time-dependent manners when airway epithelial cells were treated with CSE. CypD siRNA pretreatment significantly suppressed the increases of CypD and Bax expression, and reduced the decline of Bcl-2 expression in 7.5% CSE-treated airway epithelial cells. Furthermore, CypD silencing significantly attenuated mitochondrial damage and cell apoptosis, and increased cell viability when airway epithelial cells were stimulated with 7.5% CSE. CONCLUSION: These data suggest that CypD signaling pathway is involved in the pathogenesis of COPD and provide a potential therapeutic target for COPD.

Engineered Biosynthesis through the Adenylation Domains from Nonribosomal Peptide Synthetases.

Nonribosomal peptide synthetases, consisted of multiple catalytic domains, are involved in the biosynthesis of an important family of bioactive natural products in a coordinated manner. Among the functional domains, adenylation domains are specifically responsible for recognizing carboxylic acid building blocks and synthesizing aminoacyl adenylates. Given their critical roles in the biosynthesis of the growing peptide, A-domains are also referred to as the "gatekeeper". In this review, very recent developments on the A-domains from NRPSs are reviewed to expand the fundamental knowledge of the A domain, including knowledge on the structures, functions, and molecular interactions. Several recent examples were also discussed to highlight the great potential of A-domain engineering. This study should provide a framework for the combinatorial biosynthesis or synthetic biology-driven microbial production of novel nonribosomal peptides.

Framingham risk score conventional risk factors are potent to predict all-cause mortality using machine learning algorithms: a population-based prospective cohort study over 40 years in China.

Predicting all-cause mortality using available or conveniently modifiable risk factors is potentially crucial in reducing deaths precisely and efficiently. Framingham risk score (FRS) is widely used in predicting cardiovascular diseases, and its conventional risk factors are closely pertinent to deaths. Machine learning is increasingly considered to improve the predicting performances by developing predictive models. We aimed to develop the all-cause mortality predictive models using five machine learning (ML) algorithms (decision trees, random forest, support vector machine (SVM), XgBoost, and logistic regression) and determine whether FRS conventional risk factors are sufficient for predicting all-cause mortality in individuals over 40 years. Our data were obtained from a 10-year population-based prospective cohort study in China, including 9143 individuals over 40 years in 2011, and 6879 individuals followed-up in 2021. The all-cause mortality prediction models were developed using five ML algorithms by introducing all features available (182 items) or FRS conventional risk factors. The area under the receiver operating characteristic curve (AUC) was used to evaluate the performance of the predictive models. The AUC and 95% confidence interval of the all-cause mortality prediction models developed by FRS conventional risk factors using five ML algorithms were 0.75 (0.726-0.772), 0.78 (0.755-0.799), 0.75 (0.731-0.777), 0.77 (0.747-0.792), and 0.78 (0.754-0.798), respectively, which is close to the AUC values of models established by all features (0.79 (0.769-0.812), 0.83 (0.807-0.848), 0.78 (0.753-0.798), 0.82 (0.796-0.838), and 0.85 (0.826-0.866), respectively). Therefore, we tentatively put forward that FRS conventional risk factors were potent to predict all-cause mortality using machine learning algorithms in the population over 40 years.

Evolution of the 14-3-3 gene family in monocotyledons and dicotyledons and validation of MdGRF13 function in transgenic Arabidopsis thaliana.

KEY MESSAGE: The 14-3-3 family is more highly conserved among monocotyledons, and overexpression of MdGRF13 improved drought and salt tolerance in transgenic Arabidopsis thaliana. The 14-3-3 are highly conserved regulatory proteins found in eukaryotes and play an essential role in plant growth, development and stress response. However, the 14-3-3 gene family evolution in monocotyledons and dicotyledons and the biological functions of the MdGRF13 under abiotic stress remain unknown. In our study, 195 members of the 14-3-3 family were identified from 12 species and divided into ε group and the Non-ε group. Synteny analysis within the 14-3-3 family indicated that segmental duplication events contributed to the expansion of the family. Selective pressure analysis indicated that purifying selection was a vital force in the 14-3-3 genes evolution, and monocotyledons had a lower million years ago (Mya) mean values than dicotyledons. Meanwhile, the codon adaptation index (CAI) and frequency of optical codons (FOP) are higher and the effective number of codons (Nc) is lower in monocotyledons 14-3-3 genes compared to dicotyledons. Moreover, the yeast two-hybrid (Y2H) demonstrated that MdGRF13 interacts with MdRD22, MdLHP1a and MdMORF1. Significantly, the malondialdehyde (MDA) content and relative conductivity were decreased, while the superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) activities were increased in transgenic Arabidopsis compared to the wild type (WT) under drought and salt stress. These results suggest that overexpression of MdGRF13 significantly improved the tolerance to drought and salt stress in transgenic Arabidopsis. Thus, our results provide a theoretical basis for exploring the evolution and function of the 14-3-3 gene family in monocotyledons and dicotyledons.

Titanium dioxide nanoparticles functionalized chitosan toward bio-based antibacterial adsorbent for enhanced phosphate capture.

Developing an eco-friendly, sustainable and antibacterial adsorbent is significant for actual water treatment. Herein, a bio-based antibacterial adsorbent based on titanium dioxide (TiO2) nanoparticles functionalized chitosan (CS) was prepared through an in-situ hydrolysis strategy using titanium oxysulfate as the source of TiO2. The as-obtained CS/TiO2 nanocomposite was characterized by a variety of analytical techniques. According to the Langmuir mode, the adsorption capacity of CS/TiO2 reached 23.64 mg P g-1, almost 8 times higher than that of CS. In addition, the normalized adsorption capacity (adsorption value per Ti) of CS/TiO2 was calculated to be 102.68 mg P g-1 Ti-1, much higher than pure TiO2 (60.11 mg P g-1 Ti-1). Moreover, CS/TiO2 exhibited a highly selective capacity for phosphate removal in the presence of competing anions, and showed high stability in a wide pH range of 3.0-8.0. When the phosphate concentration was 2.0 mg P L-1, the removal efficiency of phosphate reached 99.5 % and the residual concentration was only 10 µg P L-1, which meets the USEPA standards for eutrophication prevention and control. In addition, after treatment by CS/TiO2, the phosphate concentration of two sewage water samples decreased from 1.50 and 1.0 mg P L-1 to <0.10 mg P L-1, meeting the standard of level II water based on the Environmental Quality Standard of China (GB3838-2002). Ligand exchange and electrostatic interactions are mainly responsible for phosphate adsorption by CS/TiO2. Furthermore, the CS/TiO2 nanocomposites exhibited excellent antibacterial activity, which could avoid biofouling contamination caused by microorganisms. Benefiting from the above advantages, the as-designed CS/TiO2 nanocomposite has great potential as a bio-based antibacterial adsorbent for phosphate capture or removal from wastewater.

Preparation and Characterization of an Invasive Plant-Derived Biochar-Supported Nano-Sized Lanthanum Composite and Its Application in Phosphate Capture from Aqueous Media.

Invasive plants pose a great threat to natural ecosystems owing to their rapid propagation and spreading ability in nature. Herein, a typical invasive plant, Solidago canadensis, was chosen as a novel feedstock for the preparation of nano-sized lanthanum-loaded S. canadensis-derived biochar (SCBC-La), and its adsorption performance for phosphate removal was evaluated by batch adsorption experiment. The composite was characterized by multiple techniques. Effects of parameters, such as the initial concentration of phosphate, time, pH, coexisting ions, and ionic strength, were studied on the phosphate removal. Adsorption kinetics and isotherms showed that SCBC-La shows a faster adsorption rate at a low concentration and SCBC-La exhibits good La utilization efficiency than some of the reported La-modified adsorbents. Phosphate can be effectively removed over a relatively wide pH of 3-9 because of the high pH pzc of SCBC-La. Furthermore, the SCBC-La shows a strong anti-interference capability in terms of pH value, coexisting ions, and ionic strength, exhibiting a highly selective capacity for phosphate removal. Additionally, Fourier transform infrared spectroscopy (FT-IR) and X-ray photoelectron spectroscopy (XPS) measurements reveal that hydroxyl groups on the surface of SCBC-La were replaced by phosphate and manifest the reversible transformation between La(OH)3 and LaPO4. Considering its high adsorption capacity and excellent selectivity, SCBC-La is a promising material for preventing eutrophication. This work gives a new method of pollution control with waste treatment since the invasive plant (S. canadensis) is converted into biochar-based nanocomposite for effective removal of phosphate to mitigate eutrophication.

A Recyclable Magnetic Aminated Lignin Supported Zr-La Dual-Metal Hydroxide for Rapid Separation and Highly Efficient Sequestration of Phosphate.

The application of lignin-based adsorbents in the efficient removal of phosphate from wastewater has attracted much attention and been intensively studied in recent years. However, most currently reported lignin-based adsorbents are difficult to recover and recycle. Herein, we have developed a recyclable, nanostructured bio-adsorbent, poly(ethyleneimine) (PEI)-modified lignin (LG) integrated with Fe3O4 and Zr-La dual-metal hydroxide (LG-NH2@Fe3O4@Zr-La), by the Mannich reaction followed by the chemical coprecipitation method. Multilayer adsorption existed on the surface of LG-NH2@Fe3O4@Zr-La based on the isotherm fitting curve, and its adsorption capacity reached 57.8 mg P g-1, exhibiting a higher phosphate uptake than most reported metallic oxide-based composites. The adsorption process was dominated by inner-sphere complexation of ligand-exchange and electrostatic interactions. Moreover, LG-NH2@Fe3O4@Zr-La exhibited excellent selectivity against coexisting anions, and the adsorption was more efficient under acidic conditions. When the phosphate concentration was 2.0 mg P L-1, the removal efficiency of phosphate reached 99.5% and the residual concentration was only 10 µg P L-1, which meets the United States Environmental Protection Agency (USEPA) standard for eutrophication prevention. In addition, the LG-NH2@Fe3O4@Zr-La displayed excellent reusability, maintaining 91.8% of removal efficiency after five cycles. Importantly, owing to the magnetic properties of the loaded Fe3O4, the resulting composite could be separated within 30 s under an external magnetic field. Thus, the separable and recyclable biobased magnetic adsorbent developed in this work exhibited promising application in phosphate capture from real sewage. This research study provides a new perspective for lignin valorization in lignocellulose biorefineries and establishes an approach for developing an economical and efficient bio-adsorbent for phosphate removal from wastewater.

[Immobilizing engineered Escherichia coli cells into zeolitic imidazolate framework 8 for efficient biosynthesis of Ala-Gln].

The α-amino acid ester acyltransferase (SAET) from Sphingobacterium siyangensis is one of the enzymes with the highest catalytic ability for the biosynthesis of l-alanyl-l-glutamine (Ala-Gln) with unprotected l-alanine methylester and l-glutamine. To improve the catalytic performance of SAET, a one-step method was used to rapidly prepare the immobilized cells (SAET@ZIF-8) in the aqueous system. The engineered Escherichia coli (E. coli) expressing SAET was encapsulated into the imidazole framework structure of metal organic zeolite (ZIF-8). Subsequently, the obtained SAET@ZIF-8 was characterized, and the catalytic activity, reusability and storage stability were also investigated. Results showed that the morphology of the prepared SAET@ZIF-8 nanoparticles was basically the same as that of the standard ZIF-8 materials reported in literature, and the introduction of cells did not significantly change the morphology of ZIF-8. After repeated use for 7 times, SAET@ZIF-8 could still retain 67% of the initial catalytic activity. Maintained at room temperature for 4 days, 50% of the original catalytic activity of SAET@ZIF-8 could be retained, indicating that SAET@ZIF-8 has good stability for reuse and storage. When used in the biosynthesis of Ala-Gln, the final concentration of Ala-Gln reached 62.83 mmol/L (13.65 g/L) after 30 min, the yield reached 0.455 g/(L·min), and the conversion rate relative to glutamine was 62.83%. All these results suggested that the preparation of SAET@ZIF-8 is an efficient strategy for the biosynthesis of Ala-Gln.

Plant Protein-Peptide Supramolecular Polymers with Reliable Tissue Adhesion for Surgical Sealing.

The fusion of protein science and peptide science opens up new frontiers in creating innovative biomaterials. Herein, a new kind of adhesive soft materials based on a natural occurring plant protein and short peptides via a simple co-assembly route are explored. The hydrophobic zein is supercharged by sodium dodecyl sulfate to form a stable protein colloid, which is intended to interact with charge-complementary short peptides via multivalent ionic and hydrogen bonds, forming adhesive materials at macroscopic level. The adhesion performance of the resulting soft materials can be fine-manipulated by customizing the peptide sequences. The adhesive materials can resist over 78 cmH2 O of bursting pressure, which is high enough to meet the sealing requirements of dural defect. Dural sealing and repairing capability of the protein-peptide biomaterials are further identified in rat and rabbit models. In vitro and in vivo assays demonstrate that the protein-peptide adhesive shows excellent anti-swelling property, low cell cytotoxicity, hemocompatibility, and inflammation response. In particular, the protein-peptide supramolecular biomaterials can in vivo dissociate and degrade within two weeks, which can well match with the time-window of the dural repairing. This work underscores the versatility and availability of the supramolecular toolbox in the easy-to-implement fabrication of protein-peptide biomaterials.

Atmospheric dry deposition fluxes of trace metals over the Eastern China Marginal Seas: Impact of emission controls.

Atmospheric deposition is an important exogenous input of trace metals to Eastern China Marginal Seas (ECMS), which is strongly affected by human activities. With emission control practices implemented in China, it still remains unknown what changes have taken place in the atmospheric dry depositions of the trace metals over ECMS. This study aimed to estimate the atmospheric dry depositions of Zn, Pb, Cu, and Cd over ECMS via Weather Research and Forecasting Model-Community Multiscale Air Quality Modeling System (WRF-CMAQ) in the two winter periods of January 2012 and January 2019 as well as to explore the impacts of emission control on the depositions. The anthropogenic metal emissions from China, the Korean Peninsula, Japan, and marine ships were investigated in this study. In 2012, the dry deposition fluxes of Zn, Pb, Cu, and Cd over ECMS were in the ranges of 0.50-3.4 µg m-2 d-1, 0.22-1.9 µg m-2 d-1, 0.14-0.90 µg m-2 d-1, and 12-88 ng m-2 d-1, respectively. The deposition fluxes of the four metals over Bohai Sea (BS) and Yellow Sea (YS) were 2-3 times those over East China Sea (ECS). Outflow of polluted air masses from East Asia increased the metal depositions by 3- 5-fold relative to clear days. Compared with 2012, a 5-85 % reduction in the metal depositions over ECMS were estimated in 2019, largest reductions were found over YS and BS. Meteorological variation was able to decrease or increase the metal depositions. However, the emission control only caused a reduction in the entire study region. The metal inputs to the sea were significantly lower from the ship emissions than from the continental anthropogenic emissions, although the proportion of the ship emissions in the total metal depositions rose slightly from 2012 to 2019.

Apolipoprotein A-IV restrains fat accumulation in skeletal and myocardial muscles by inhibiting lipogenesis and activating PI3K-AKT signalling.

BACKGROUND: One of the pathological characteristics of obesity is fat accumulation of skeletal muscles (SKM) and the myocardium, involving mechanisms of insulin resistance and abnormal lipid metabolism. Apolipoprotein A-IV (ApoA-IV) is an essential gene in both glucose and lipid metabolisms. MATERIALS AND METHODS: Using high-fat diet (HFD) induced obese apoA-IV-knockout mice and subsequent introduction of exogenous recombinant-ApoA-IV protein and adeno-associated virus (AAV)-transformed apoA-IV, we examined lipid metabolism indicators of SKM and the myocardium, which include triglyceride (TG) content, RT-PCR for lipogenic indicators and western blotting for AKT phosphorylation. Similarly, we used high-glucose-fed or palmitate (Pal)-induced C2C12 cells co-cultured with ApoA-IV protein to evaluate glucose uptake, the phosphoinositide 3-kinase (PI3K)-AKT pathway, and lipid metabolisms. RESULTS: In stable obese animal models, we find ApoA-IV-knockout mice show elevated TG content, enhanced expression of lipogenic enzymes and diminished phosphorylated AKT in SKM and the myocardium, but both stable hepatic expression of AAV-apoA-IV and brief ApoA-IV protein administration suppress lipogenesis and promote AKT phosphorylation. In a myoblast cell line C2C12, ApoA-IV protein suppresses Pal-induced lipid accumulation and lipogenesis but enhances AKT activation and glucose uptake, and the effect is abolished by a PI3K inhibitor. CONCLUSION: We find that ApoA-IV reduces fat accumulation by suppressing lipogenesis and improves glucose uptake in SKM and the myocardium by regulating the PI3K-AKT pathway.

Atmospheric input of silicon to the China adjacent seas: Non-negligible contributions from anthropogenic sources.

Atmospheric deposition is an important source of exogenous Si in the oceans. As a typical crustal element, Si in the atmosphere emitted from anthropogenic sources is ignored. In this study, the atmospheric dry deposition of anthropogenic Si to China adjacent seas was calculated using WRF-CMAQ in January and July 2019 to investigate the contribution of anthropogenic Si to the oceans. Si emitted from 13 anthropogenic sources in China, the Korean Peninsula, Japan, and marine ships was considered. Emissions of anthropogenic Si in January and July 2019 were 30.2 and 22.0 Gg, respectively. The highest Si emissions were concentrated over eastern China, e.g. Beijing-Tianjin-Hebei region, Shandong province, Yangtze river delta area (0.2-21.3 ng m-2 s-1), while the lowest emissions were in northwestern China (< 5.2 ng m-2 s-1). Among the Bohai (BS), Yellow (YS), and East China seas (ECS), dry deposition fluxes over the southern YS were highest (4.6-16.8 µg m-2 d-1), and those over the ECS were lowest (0.2-7.7 µg m-2 d-1). During pollution episodes, the outflow of polluted air masses from the continent caused a 10-fold increase in Si deposition compared with clear days. The relative contribution of continental anthropogenic emissions and ship combustion varied significantly in two seasons. In winter, deposition from continental anthropogenic emissions to total anthropogenic Si deposition was higher than 96 %. While in summer, the contributions from ship combustion increased obviously, accounting for 10-38 %. Deposition flux of dissolved Si from anthropogenic sources over China adjacent seas was about 4-38 % of that of dissolved mineral dust Si. The annual Si depositions from atmospheric anthropogenic sources to the Si fluxes from rivers to the China adjacent seas were 0.03 %-2.8 %. The marine primary productivity in the BS, YS, and ECS caused by atmospheric anthropogenic dissolved Si deposition were 1.3, 1.2, and 0.7 mg C m-2 a-1, respectively.

Hyperinsulinemic-Euglycemic Clamp in Conscious Rats Based on the Tail Artery and Vein Catheterization.

Insulin sensitivity evaluation is very important in the management and investigation of type 1 diabetes. Hyperinsulinemic-euglycemic clamp (HEC) is considered to be the "gold standard" method for the assessment of insulin sensitivity in vivo. Here, we describe the method of performing the hyperinsulinemic-glycemic clamp based on the tail artery and vein catheterization after administration of local anesthesia to the tail root in conscious rats. Insulin and glucose were infused via the tail vein, and blood samples for further determination were collected from the tail artery. This procedure makes the hyperinsulinemic-euglycemic clamp easier and more convenient to perform.

A magnetically recyclable lignin-based bio-adsorbent for efficient removal of Congo red from aqueous solution.

It has been always attractive to design a sustainable bio-derived adsorbent based on industrial waste lignin for removing organic dyes from water. However, existing adsorbent strategies often lead to the difficulties in adsorbent separation and recycling. Herein, we report a novel magnetically recyclable bio-adsorbent of Mg(OH)2/Fe3O4/PEI functionalized enzymatic lignin (EL) composite (EL-PEI@Fe3O4-Mg) for removing Congo red (CR) by Mannish reaction and hydrolysis-precipitation. The Mg(OH)2 and PEI functionalized EL on the surface act as active sites for the removal of CR, while the Fe3O4 allows for the easy separation under the help of a magnet. As-obtained EL-PEI@Fe3O4-Mg forms flower-like spheres and has a relatively lager surface area of 24.8 m2 g-1 which is 6 times that of EL. The EL-PEI@Fe3O4-Mg exhibits a relatively high CR adsorption capacity of 74.7 mg g-1 which is 15 times that of EL when initial concentration is around 100 mg L-1. And it can be easily separated from water by applying an external magnetic field. Moreover, EL-PEI@Fe3O4-Mg shows an excellent anti-interference capability according to the results of pH values and salt ions influences. Importantly, EL-PEI@Fe3O4-Mg possesses a good reusability and a removal efficiency of 92 % for CR remains after five consecutive cycles. It is illustrated that electrostatic attraction, π-π interaction and hydrogen binding are primary mechanisms for the removal of CR onto EL-PEI@Fe3O4-Mg. This work provides a novel sustainable strategy for the development of highly efficient, easy separable, recyclability bio-derived adsorbents for removing organic dyes, boosting the efficient utilization of industrial waste lignin.

Apolipoprotein A-IV reduced metabolic inflammation in white adipose tissue by inhibiting IKK and JNK signaling in adipocytes.

Apolipoprotein A-IV (ApoA-IV) plays a role in satiation and serum lipid transport. In diet-induced obesity (DIO) C57BL/6J mice, ApoA-IV deficiency induced in ApoA-IV-/-knock-out (KO mice) resulted in increased bodyweight, insulin resistance (IR) and plasma free fatty acid (FFA), which was partially reversed by stable ApoA-IV-green fluorescent protein (KO-A4-GFP) transfection in KO mice. DIO KO mice exhibited increased M1 macrophages in epididymal white adipose tissue (eWAT) as well as in the blood. Based on RNA-sequencing analyses, cytokine-cytokine receptor interactions, T cell and B cell receptors, and especially IL-17 and TNF-α, were up-regulated in eWAT of DIO ApoA-IV KO compared with WT mice. Supplemented ApoA-IV suppressed lipopolysaccharide (LPS)-induced IKK and JNK phosphorylation in Raw264.7 macrophage cell culture assays. When the culture medium was supplemented to 3T3-L1 adipocytes they exhibited an increased sensitivity to insulin. ApoA-IV protects against obesity-associated metabolic inflammation mainly through suppression in M1 macrophages of eWAT, IL17-IKK and IL17-JNK activity.