Journal: Nature Metabolism

Article Title: A catecholamine-independent pathway controlling adaptive adipocyte lipolysis

doi: 10.1038/s42255-025-01424-5

Figure Lengend Snippet: a , Microarray-based gene expression of lipolytic inhibitors from Fig. in purified mouse adipocytes (C57BL/6J male; GSE27017 , PMID: 23967297) from gWAT (WAT Ad, N = 3) and femur–tibia (rBMAT and cBMAT mix—BMAd, N = 3) and human adipocytes (mixed male and female, aged 53–87 years; PMID: 28574591) from subcutaneous adipose tissue (WAT Ad, N = 3) and femoral head (rBMAT and cBMAT mix—BMAd, N = 3). Arrows indicate expression of candidate lipolysis inhibitor G0s2 . b , Ratio of ATGL-inhibitor G0s2 to ATGL ( Pnpla2 ) in purified mouse adipocytes as in a fed chow (6, 14, and 18 months, N = 3 per group) or a high-fat diet (HFD; 6 and 14 months, N = 3/group). c , Ratio in human purified bone marrow stromal cells (BMSCs) from femoral head and adipocytes as in a ( N = 3 per group). d , Ratio in mouse cBMAT-filled CV with males and females combined ( N = 10 ICV PBS, N = 12 ICV leptin, N = 6 ICV leptin + subcutaneous insulin pellet). Dotted line, average value for iWAT. ins, insulin; Lep, leptin. e – h , Female 11–12-week-old WT control littermates and adipocyte-specific G0s2 KO mice (WT fed N = 6, WT 24-h fast N = 5, cKO fed N = 7, cKO fast N = 5). BMAT quantification ( e ) with representative images; bone is shown in light grey with BMAT in dark grey ( f ). Whole CV were rapidly extracted and quartered with immediate placement in lipolysis stimulation buffer containing 5 µM FSK, 10 mM 8-bromo or vehicle control (2 × CV per mouse per treatment condition in 150 µl in a 96-well plate). Plates were incubated at 37°C in 5% CO 2 with samples taken for glycerol measurement after 1.5 and 4.0 h ( g ). Percentage change in glycerol release over time relative to vehicle control for cBMAT-filled CV ( h ). i , We treated 10 mg of iWAT per 150 µl in a 96-well plate from the same animals as described in g as a positive control. j , k , Body mass ( j ) and iWAT mass ( k ) are from the same animals. Mean ± standard deviation ( a – e , j and k ). Mean ± s.e.m. ( h and i ). Individual data points represent biological replicates. Two-tailed t -tests ( b ). One-way ANOVA with Tukey’s multiple comparisons test ( c and d ). Two-way ANOVA genotype × fast with Šidák’s multiple comparisons test ( e and k ). Three-way ANOVA genotype × fast × time ( h – j ). *P < 0.05, ** P < 0.005, *** P < 0.001, **** P < 0.0001. g created with BioRender.com .

Article Snippet: Wells contained 150 μl solution as follows: first well, vehicle treatment (Hank’s Balanced Salt Solution + 2% fatty acid-free BSA + 1:500 dimethylsulfoxide vehicle control); second well, the same as the first well with 5 μM FSK (Cayman Chemical, 66575-29-9); and the third well, the same as the first well with 10 mM 8-bromo cAMP (MedChemExpress, HY-101379A).

Techniques: Microarray, Gene Expression, Purification, Expressing, Control, Incubation, Positive Control, Standard Deviation, Two Tailed Test

Journal: Bioactive Materials

Article Title: Shape memory bone screws loading L-arginine and Ca 2+ propagate mechanical stimulation, energize bone cells and augment bone regeneration

doi: 10.1016/j.bioactmat.2025.07.007

Figure Lengend Snippet: Schematics showing the design and application of SMP bone screw. (A) Fabrication and shape memory function of SMP bone screw; (B) Schematic illustration of preparation process of SMP-Ca/ArgX (X = 0.5, 1, 2) bone screw; (C) Dopamine-assisted coating of Ca 2+ and Arg's SMP-Ca/Arg screw and subsequent implantation into the bone defect site; (D) SMP-Ca/Arg-P bone screw (an SMP bone screw coated with PDA, Ca 2+ , and 2.0 mg/mL of Arg, and then compressed) can release mechanical force and Arg/Ca 2+ for coupled osteogenesis–angiogenesis in bone repair; (E) Schematic illustration of the forces activate the mechanosensitive transient receptor potential vanilloid 4 (TRPV4) protein and piezo type mechanosensitive ion channel component 2 (PIEZO2). This activation boosts adenosine triphosphate (ATP) generation and enhancing cellular metabolism, facilitating the influx of Ca 2+ and Arg released by the SMP-Ca/Arg bone screws through activated calcium channels (e.g., TRPV4 and PIEZO2) and cell membrane proteins (e.g., cationic amino acid transporter (CAT)). The elevated Ca 2+ level further upregulates calmodulin (CaM) and increase the activity of nitric oxide synthase (NOS) for Arg decomposition to regenerate nitric oxide (NO). This subsequently activates the NO-cGMP pathway, promoting coupled osteogenesis and angiogenesis. The calcium signaling pathway is visually represented by blue arrows, the NO-cGMP pathway is represented by red arrows, and the forces exerted by the SMP-Ca/Arg-P bone screw is indicated by orange arrows.

Article Snippet: Similarly, on day 3, the cGMP ELISA kit (Bioss, China) was used to measure the amount of cGMP.

Techniques: Activation Assay, Membrane, Activity Assay

Journal: Bioactive Materials

Article Title: Shape memory bone screws loading L-arginine and Ca 2+ propagate mechanical stimulation, energize bone cells and augment bone regeneration

doi: 10.1016/j.bioactmat.2025.07.007

Figure Lengend Snippet: In vitro osteogenesis and angiogenesis potential of SMP bone screw. (A) Schematic illustration showing the released Ca 2+ and Arg synergistically activate the NO-cGMP pathway, ultimately promoting both osteogenesis and angiogenesis. Release profiles of (B) Ca 2+ and (C) Arg from different SMP bone screws. (D) Representative ALP staining images (with enlarged images inserted) and (E) quantitative analysis of ALP activity of rBMSCs on day 3 and day 7. (F) Representative ARS images and (G) quantitative analysis of calcium deposition of rBMSCs on day 7 and day 14. (H) Representative fluorescence images showing the endothelial network formation in HUVECs after co-culture for 6 and 12 h. (I-K) Relative expression of angiogenic-related gene expression including eNOS, nitrite levels, and cGMP concentration of rBMSCs and HUVECs on day 3. Data were presented as mean ± SD and analyzed by one-way ANOVA (n = 3 for each sample, ∗ p < 0.05, ∗∗ p < 0.01, and ∗∗∗ p < 0.001). These results suggest that Ca 2+ and Arg synergistically activate the NO-cGMP signaling pathway to promote osteogenesis and angiogenesis.

Article Snippet: Similarly, on day 3, the cGMP ELISA kit (Bioss, China) was used to measure the amount of cGMP.

Techniques: In Vitro, Staining, Activity Assay, Fluorescence, Co-Culture Assay, Expressing, Gene Expression, Concentration Assay

Journal: Bioactive Materials

Article Title: Shape memory bone screws loading L-arginine and Ca 2+ propagate mechanical stimulation, energize bone cells and augment bone regeneration

doi: 10.1016/j.bioactmat.2025.07.007

Figure Lengend Snippet: Bioinformatic analysis of gene expression of rMSCs on different bone screws. (A) Principal component analysis of gene expression profile of rMSCs grown in the presence of cSMP screw or SMP-Ca/Arg2-P screw; (B) Venn diagram illustration of the significant DEGs between the SMP-Ca/Arg2-P group and the cSMP group; (C) Volcano plots of transcriptomic analysis of DEGs in cSMP versus SMP-Ca/Arg2-P; (D) Up-regulated enriched Kyoto Encyclopedia of Genes and Genomes pathways of cSMP versus SMP-Ca/Arg2-P; (E) Heatmap evaluation of up-regulated DEGs involved in mechanosensitive calcium, PI3K-Akt and cGMP-PKG signaling pathways; (F-G) Relative messenger RNA expression evaluation of targeted genes via qRT-PCR; (H) Schematic illustration of potential SMP-Ca/Arg2-P-mediated activation of the mechanosensitive and NO-cGMP signaling pathway for coupling osteogenesis-angiogenesis. Sample size n = 3 for all experiments. Data were presented as mean ± SD and analyzed by one-way ANOVA ( n = 6 for each sample, ∗ p < 0.05, ∗∗ p < 0.01, and ∗∗∗ p < 0.001).

Article Snippet: Similarly, on day 3, the cGMP ELISA kit (Bioss, China) was used to measure the amount of cGMP.

Techniques: Gene Expression, Protein-Protein interactions, RNA Expression, Quantitative RT-PCR, Activation Assay