Additional file 1 of Global patterns of asthma burden related to environmental risk factors during 1990–2019: an age-period-cohort analysis for global burden of disease study 2019

Additional file 1: Table S1. Quintiles of different SDI groups. Table S2. Countries and territories of different SDI groups in 1990 and 2019. Table S3. Full list of selected covariates for the CODEm models in the asthma estimation. Table S4. Lay description, disability weight and proportion of different levels of asthma severity. Table S5. 22 occupational asthmagens recorded in the International Labor Organization. Table S6. Change in age-standardized asthma deaths number related to different risk factors from 1990 to 2019. Table S7. Change in age-standardized asthma deaths percent related to different risk factors from 1990 to 2019. Table S8. Change in age-standardized asthma DALYs number related to different risk factors from 1990 to 2019. Table S9. Change in age-standardized asthma DALYs percent related to different risk factors from 1990 to 2019. Table S10. Net and local drifts for asthma deaths and DALYs rates attributed to smoking (%). Table S11. Net and local drifts for asthma deaths and DALYs rates attributed to occupational asthmagens (%). Figure S1. Age-standardized male asthma deaths and DALYs rates attributed to different risk factors in 2019 by countries. Figure S2. Age-standardized female asthma deaths and DALYs rates attributed to different risk factors in 2019 by countries. Figure S3. Age, period, and cohort effects on asthma deaths and DALYs rates attributed to smoking for male. Figure S4. Age, period, and cohort effects on asthma deaths and DALYs rates attributed to smoking for female. Figure S5. Age, period, and cohort effects on asthma deaths and DALYs rates attributed to occupational asthmagens for male. Figure S6. Age, period, and cohort effects on asthma deaths and DALYs rates attributed to occupational asthmagens for female

Facile synthesis and wide-band electromagnetic wave absorption properties of carbon-coated ZnO nanorods

<p>In this work, a facile and scalable acetylene decomposition method was employed to synthesize carbon-coated ZnO (ZnO@C) nanorods. The characterization of morphology and structure analysis demonstrate that ZnO nanorod was well coated by an amorphous carbon shell with a thickness of about 20 nm. Comparted with ZnO, ZnO@C exhibit significantly enhanced microwave absorption properties. The effective absorption bandwidth with RL values exceeding –10 dB can reach 5.3 GHz for ZnO@C with a matching thickness of 2.5 mm. The excellent microwave absorption arose from enhanced dielectric loss caused by interfacial polarization, dipole polarization and the formation of conductive network.</p

<i>N</i>‑Trimethyl Chitosan Chloride-Coated PLGA Nanoparticles Overcoming Multiple Barriers to Oral Insulin Absorption

Although several strategies have been applied for oral insulin delivery to improve insulin bioavailability, little success has been achieved. To overcome multiple barriers to oral insulin absorption simultaneously, insulin-loaded <i>N</i>-trimethyl chitosan chloride (TMC)-coated polylactide-<i>co</i>-glycoside (PLGA) nanoparticles (Ins TMC-PLGA NPs) were formulated in our study. The Ins TMC-PLGA NPs were prepared using the double-emulsion solvent evaporation method and were characterized to determine their size (247.6 ± 7.2 nm), ζ-potential (45.2 ± 4.6 mV), insulin-loading capacity (7.8 ± 0.5%) and encapsulation efficiency (47.0 ± 2.9%). The stability and insulin release of the nanoparticles in enzyme-containing simulated gastrointestinal fluids suggested that the TMC-PLGA NPs could partially protect insulin from enzymatic degradation. Compared with unmodified PLGA NPs, the positively charged TMC-PLGA NPs could improve the mucus penetration of insulin in mucus-secreting HT29-MTX cells, the cellular uptake of insulin via clathrin- or adsorption-mediated endocytosis in Caco-2 cells and the permeation of insulin across a Caco-2 cell monolayer through tight junction opening. After oral administration in mice, the TMC-PLGA NPs moved more slowly through the gastrointestinal tract compared with unmodified PLGA NPs, indicating the mucoadhesive property of the nanoparticles after TMC coating. Additionally, in pharmacological studies in diabetic rats, orally administered Ins TMC-PLGA NPs produced a stronger hypoglycemic effect, with 2-fold higher relative pharmacological availability compared with unmodified NPs. In conclusion, oral insulin absorption is improved by TMC-PLGA NPs with the multiple absorption barriers overcome simultaneously. TMC-PLGA NPs may be a promising drug delivery system for oral administration of macromolecular therapeutics

DataSheet_1_Integrated transcriptomic and metabolomic analysis reveals the metabolic programming of GM-CSF- and M-CSF- differentiated mouse macrophages.docx

Macrophages play a critical role in the inflammatory response and tumor development. Macrophages are primarily divided into pro-inflammatory M1-like and anti-inflammatory M2-like macrophages based on their activation status and functions. In vitro macrophage models could be derived from mouse bone marrow cells stimulated with two types of differentiation factors: GM-CSF (GM-BMDMs) and M-CSF (M-BMDMs), to represent M1- and M2-like macrophages, respectively. Since macrophage differentiation requires coordinated metabolic reprogramming and transcriptional rewiring in order to fulfill their distinct roles, we combined both transcriptome and metabolome analysis, coupled with experimental validation, to gain insight into the metabolic status of GM- and M-BMDMs. The data revealed higher levels of the tricarboxylic acid cycle (TCA cycle), oxidative phosphorylation (OXPHOS), fatty acid oxidation (FAO), and urea and ornithine production from arginine in GM-BMDMs, and a preference for glycolysis, fatty acid storage, bile acid metabolism, and citrulline and nitric oxide (NO) production from arginine in M-BMDMs. Correlation analysis with the proteomic data showed high consistency in the mRNA and protein levels of metabolic genes. Similar results were also obtained when compared to RNA-seq data of human monocyte derived macrophages from the GEO database. Furthermore, canonical macrophage functions such as inflammatory response and phagocytosis were tightly associated with the representative metabolic pathways. In the current study, we identified the core metabolites, metabolic genes, and functional terms of the two distinct mouse macrophage populations. We also distinguished the metabolic influences of the differentiation factors GM-CSF and M-CSF, and wish to provide valuable information for in vitro macrophage studies.</p

DataSheet_1_Key candidate genes and pathways in T lymphoblastic leukemia/lymphoma identified by bioinformatics and serological analyses.docx

T-cell acute lymphoblastic leukemia (T-ALL)/T-cell lymphoblastic lymphoma (T-LBL) is an uncommon but highly aggressive hematological malignancy. It has high recurrence and mortality rates and is challenging to treat. This study conducted bioinformatics analyses, compared genetic expression profiles of healthy controls with patients having T-ALL/T-LBL, and verified the results through serological indicators. Data were acquired from the GSE48558 dataset from Gene Expression Omnibus (GEO). T-ALL patients and normal T cells-related differentially expressed genes (DEGs) were investigated using the online analysis tool GEO2R in GEO, identifying 78 upregulated and 130 downregulated genes. Gene Ontology (GO) and protein-protein interaction (PPI) network analyses of the top 10 DEGs showed enrichment in pathways linked to abnormal mitotic cell cycles, chromosomal instability, dysfunction of inflammatory mediators, and functional defects in T-cells, natural killer (NK) cells, and immune checkpoints. The DEGs were then validated by examining blood indices in samples obtained from patients, comparing the T-ALL/T-LBL group with the control group. Significant differences were observed in the levels of various blood components between T-ALL and T-LBL patients. These components include neutrophils, lymphocyte percentage, hemoglobin (HGB), total protein, globulin, erythropoietin (EPO) levels, thrombin time (TT), D-dimer (DD), and C-reactive protein (CRP). Additionally, there were significant differences in peripheral blood leukocyte count, absolute lymphocyte count, creatinine, cholesterol, low-density lipoprotein, folate, and thrombin times. The genes and pathways associated with T-LBL/T-ALL were identified, and peripheral blood HGB, EPO, TT, DD, and CRP were key molecular markers. This will assist the diagnosis of T-ALL/T-LBL, with applications for differential diagnosis, treatment, and prognosis.</p

MiR-155 Enhances Insulin Sensitivity by Coordinated Regulation of Multiple Genes in Mice

<div><p>miR-155 plays critical roles in numerous physiological and pathological processes, however, its function in the regulation of blood glucose homeostasis and insulin sensitivity and underlying mechanisms remain unknown. Here, we reveal that miR-155 levels are downregulated in serum from type 2 diabetes (T2D) patients, suggesting that miR-155 might be involved in blood glucose control and diabetes. Gain-of-function and loss-of-function studies in mice demonstrate that miR-155 has no effects on the pancreatic β-cell proliferation and function. Global transgenic overexpression of miR-155 in mice leads to hypoglycaemia, improved glucose tolerance and insulin sensitivity. Conversely, miR-155 deficiency in mice causes hyperglycemia, impaired glucose tolerance and insulin resistance. In addition, consistent with a positive regulatory role of miR-155 in glucose metabolism, miR-155 positively modulates glucose uptake in all cell types examined, while mice overexpressing miR-155 transgene show enhanced glycolysis, and insulin-stimulated AKT and IRS-1 phosphorylation in liver, adipose tissue or skeletal muscle. Furthermore, we reveal these aforementioned phenomena occur, at least partially, through miR-155-mediated repression of important negative regulators (i.e. C/EBPβ, HDAC4 and SOCS1) of insulin signaling. Taken together, these findings demonstrate, for the first time, that miR-155 is a positive regulator of insulin sensitivity with potential applications for diabetes treatment.</p></div

A proposed model on the positive roles of miR-155 in glucose metabolism by coordinated regulation of multiple genes.

<p>A proposed model on the positive roles of miR-155 in glucose metabolism by coordinated regulation of multiple genes.</p

Regulation of gene expression and insulin signalling by miR-155.

<p><b>(A)</b> qRT-PCR analysis of the indicated gene expression in liver, WAT, BAT and SM of RL-m155 mice (4m). n = 5–10 mice per indicated genes. Values are statistically significant at *<i>P</i><0.05; **<i>P</i><0.01 and ^#<i>P</i><0.001. <b>(B)</b> Western blot analysis of the expression of the indicated proteins in liver, adipose tissue and SM of RL-m155 mice (4m; n = 4). <b>(C)</b> Western blot analysis for SOCS1, SOCS3 and HDAC4 expression in miR-155-expressing 7402 cells, 7402 cells transfected with miR-155 inhibitor, and hepa1-6 cells transfected with miR-155 mimics or miR-155 inhibitor. <b>(D)</b> Representative Western-blot analysis of insulin-stimulated AKT and IRS-1 (Insulin receptor substrate 1) phosphorylation in liver, adipose tissue or SM of control and RL-m155 mice (5m). <b>(E)</b> Representative immunoblot analysis of insulin-stimulated AKT phosphorylation versus total AKT protein levels in hepa1-6 cells transfected with miR-155 mimics or miR-155 inhibitor. <b>(F)</b> In vitro evaluation of cellular ¹⁸F-FDG uptake in miR-155-expressing 7402 cells, and hepa1-6 and C2C12 cells transiently transfected with miR-155 mimics by MicroPET/CT. The data on the fold changes in ¹⁸F-FDG uptake between miR-155-expressing indicated cells and the corresponding control cells were shown in <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1006308#pgen.1006308.s009" target="_blank">S9 Fig</a>. UC: untransfected cells.</p

Dysregulated miR-155 levels in serum from T2D patients.

<p><b>(A-B)</b> Basal levels of miR-107(A), miR-155 (B) and miR-146a (B) in healthy subjects (HS) (n = 30) and T2D patients (n = 30) detected by qRT-PCR. Values are statistically significant at **<i>P</i><0.01. <b>(C-D)</b> miR155 levels and homeostasis model indicators (HOMA-IR and HOMA-β). HOMA-IR: homeostasis model assessment of insulin resistance; HOMA-β: homeostasis model assessment of β-cell function.</p

Improved glucose tolerance and insulin sensitivity in RL-m155 mice.

<p><b>(A-C)</b> Blood glucose concentrations in fed-state (A), 12-hour–fasted (B) and 24-hour–fasted (C) mice. Control mice: n = 9 (3m) and n = 8 (5m); RL-m155 mice: n = 7 (3m) and n = 9 (5m). <b>(D)</b> Serum insulin concentrations in fed-state and 12-hour–fasted mice (5m). <b>(E-F)</b> Glucose tolerance test (GTT) in 12-hour–fasted mice (E) and area under the curve (AUC) (F) for this GTT (E). <b>(G)</b> Serum insulin measurements performed in 12-hour–fasted mice (3m) during a GTT (E). <b>(H)</b> GTT in 12-hour–fasted control (Con) and RL-m155 mice. <b>(I)</b> AUC analysis for this GTT (H). <b>(J)</b> Insulin tolerance test (ITT) of 12-hour–fasted control and RL-m155 mice. <b>(K)</b> AUC analysis for this ITT (J). <b>(L)</b> ITT performed on 12-hour–fasted 5-month-old control and RL-m155 mice. <b>(M)</b> AUC calculated from mice in (L). Values are statistically significant at *<i>P</i><0.05; **<i>P</i><0.01 and ^#<i>P</i><0.001.</p