Journal: Advanced Science

Article Title: Fc‐Dependent Targeting of the GAS6–MERTK Axis With Monoclonal and Bispecific Antibodies Overcomes Drug Resistance Across EGFR Mutations in Exons 19, 20, and 21

doi: 10.1002/advs.78290

Figure Lengend Snippet: GAS6 supports survival of TKI‐treated cells; blocking it delays resistance to osimertinib in an animal model. (A) Data were taken from a clinical trial, NCT03433469 (EGFR‐positive NSCLC patients). Patients were treated with osimertinib, and the cohort was segregated into Treatment Naïve (TN), Residual Disease (RD), and Progressive Disease (PD). The volcano plot presents delayed early genes that differ between patients with RD (4 samples) and PD (3 samples). MERTK, AXL, GAS6, and EGFR are highlighted in red. The average log2 of the fold change (FC) and the p ‐values are presented in a table. (B) GAS6 knockout (KO) and GAS6‐overexpressing (OX) PC9 cells were generated. Cells (500/well) were seeded in 96‐well plates and grown for 9 days. The cells were then fixed and stained with crystal violet to estimate cell numbers on specific days. *** , p < 0.001; **** , p < 0.0001. (C) The indicated derivatives of PC9 cells (1 × 10 3 , per well) were seeded in 96‐well plates. Next, cells were treated for 72 h with different concentrations of osimertinib. Cell viability was determined using a colorimetric assay. The histogram depicts cell viability under 10 n m osimertinib. (D‐F) PC9 cells (2.5 × 10 6 ) were injected subcutaneously in the flanks of CD1‐nu/nu mice. Once the tumor became palpable, 5–7 mice were randomized into the indicated 4 groups and treated for five weeks with either osimertinib (10 mg/kg) or/and a mAb197 against GAS6 (0.2 mg per injection; twice weekly). Individual tumor volumes (D) average tumor volumes per group, along with the average recorded on day 47 (E), and Kaplan‐Meier survival plots (F) are shown. Survival analysis was performed using Holm–Šídák's multiple comparisons test to assess statistical significance between treatment groups. The adjusted p ‐value for the comparison between osimertinib alone and osimertinib combined with mAb197 is 0.0044. All experiments were repeated at least twice.

Article Snippet: Balb/c mice were immunized with the extracellular domain of MERTK (SinoBiological, Cat: 10298‐H03H; 25 μg per injection).

Techniques: Blocking Assay, Animal Model, Knock-Out, Generated, 96 Well Plates, Staining, Colorimetric Assay, Injection, Analysis, Comparison

Journal: Advanced Science

Article Title: Fc‐Dependent Targeting of the GAS6–MERTK Axis With Monoclonal and Bispecific Antibodies Overcomes Drug Resistance Across EGFR Mutations in Exons 19, 20, and 21

doi: 10.1002/advs.78290

Figure Lengend Snippet: Dual blockade of EGFR and MERTK using antibodies delays tumor relapses, likely due to the ability of EGFR to interact with MERTK within membrane microdomains. (A, B) CD1‐nu/nu mice were subcutaneously implanted with PC9 cells (2.5 × 10 6 ). Once tumors became palpable, animals (5–7 per group) were randomized and treated twice weekly for 4 weeks with the indicated mAbs (200 µg/injection, intraperitoneally), and/or daily with osimertinib (5 mg/kg; orally). Tumor volumes were measured twice weekly. Tumor volumes on day 47 are shown as mean ± SEM. Statistical significance was determined using an unpaired t ‐test; * , p < 0.05. Tumor volumes and animal survival are shown. The grey‐shaded area indicates the treatment period. Data are presented as tumor volume (mean ± SEM; A) and the corresponding Kaplan–Meier survival curves (B). (C and D) PC9 and H1975 cells (3 × 10 3 ) were seeded in 96‐well plates. The next day, cells were treated for 3 days with different concentrations of osimertinib and MRX‐2843 in pairwise combinations. Following fixation, cells were stained with crystal violet to identify viable cells. The synergy scores of the drugs were calculated based on the Bliss reference model, using SynergyFinder. The red color indicates high synergy scores, implying cooperative EGFR‐MERTK interactions. (E) PC9 cells (1 × 10 4 ) were seeded on coverslips and allowed to adhere overnight. The next day, cells were serum starved for 6 h and treated with either EGF (100 ng/mL) or GAS6 (250 ng/mL) in serum‐free medium. Thereafter, the cells were fixed, permeabilized, and then stained with a rabbit anti‐MERTK antibody, as well as with a murine anti‐human EGFR antibody. Subsequently, a proximity ligation assay was performed using anti‐Rabbit Plus and anti‐Mouse Minus. The amplified product of the PLA test was labeled using a red dye, and nuclei were stained with DAPI. Images were obtained using a Zeiss Spinning Disk confocal microscope, and the analysis was performed using ImageJ. MERTK knockout PC9 cells were used as a negative control. Scale bar, 10 µm. All experiments were repeated twice. (F) PC9 cells were seeded on glass coverslips and serum‐starved for 8 h, followed by stimulation for 60 min with either EGF (100 ng/mL) or Gas6 (250 ng/mL). Cells were then fixed and immunostained for EGFR (green) and nuclear DNA (DAPI; blue) and caveolin‐1 (red). Colocalization of EGFR with caveolin‐1 is indicated by white arrows. Scale bar, 5 µm.

Article Snippet: Balb/c mice were immunized with the extracellular domain of MERTK (SinoBiological, Cat: 10298‐H03H; 25 μg per injection).

Techniques: Membrane, Injection, 96 Well Plates, Staining, Proximity Ligation Assay, Amplification, Labeling, Spinning Disk, Confocal, Microscopy, Analysis, Knock-Out, Negative Control, Glass

Journal: bioRxiv

Article Title: Efferocytosis Remodels Osteoclast Metabolism and Enhances Antibacterial Defense

doi: 10.64898/2026.10.13.759003

Figure Lengend Snippet: a , Heatmap showing expression of osteoclast-associated genes, TAM receptor family genes, and macrophage-associated genes during murine osteoclast differentiation (GSE147174). BMM, bone marrow-derived macrophages (M-CSF, 2 days); pOC, pre-osteoclasts (BMM + RANKL for 1 day); mOC, mature osteoclasts (BMM + RANKL for 3 days). n = 3 bulk RNA-seq samples per differentiation stage; each heatmap column represents one sample. b , Representative gel electrophoresis images of PCR products for Tyro3 , Axl , Mertk , and Actb in BMMs, pOCs, and mOCs. c , Quantitative PCR analysis of Tyro3 , Axl , and Mertk transcript levels in BMMs, pOCs and mOCs. d,e , Immunoblot analysis of AXL, MERTK, and β-actin expression in BMM, pOC, and mOC ( d ), with densitometric quantification ( e ). f,g , Immunofluorescence images of mouse femoral sections showing MERTK ( f ) and AXL ( g ) expression in bone-resident osteoclasts. MERTK and AXL are shown in red in f and g , respectively; CTSK is shown in green, and nuclei are shown in blue (DAPI). Quantification shows the number of receptor-positive multinucleated osteoclasts per bone perimeter and the percentage of osteoclasts positive for MERTK or AXL. Scale bars, 20 µm. h , Flow cytometric quantification of apoptotic neutrophil (aN) efferocytosis by BMMs and osteoclasts. i , Representative immunofluorescence images of BMMs and osteoclasts incubated with apoptotic neutrophils (aN). Phagocytes are shown in green, apoptotic neutrophils in red, and nuclei stained with DAPI (blue). White arrows indicate apoptotic cells with pyknotic nuclei, and yellow arrows indicate aN. Scale bars, 50 µm. j , Quantification of apoptotic neutrophil uptake by BMMs and osteoclasts following siRNA-mediated depletion of Axl or Mertk . The phagocytosis index was calculated as experimental engulfment (%) divided by control engulfment (%). Data are presented as mean ± s.d. Statistical significance was assessed using two-tailed unpaired t -tests ( h ) and one-way ANOVA followed by Tukey’s multiple comparisons test ( c,e,j ). n = 3 independent biological samples per group ( c,e,h,j ) and n = 5 mice ( f,g ). Each point represents one biological sample or one mouse, respectively; linked points in f,g denote measurements from the same mouse.

Article Snippet: C57BL/6J mice were obtained from the Southwest Hospital Animal Center (Chongqing, China), whereas Ly6G-tdTomato mice and Ctsk -Cre; Mertk flox/flox mice were obtained from Cyagen Biotechnology Co., Ltd. (Suzhou, China).

Techniques: Expressing, Derivative Assay, RNA Sequencing, Gel Electrophoresis, Real-time Polymerase Chain Reaction, Analysis, Western Blot, Immunofluorescence, Incubation, Staining, Control, Two Tailed Test

Journal: bioRxiv

Article Title: Efferocytosis Remodels Osteoclast Metabolism and Enhances Antibacterial Defense

doi: 10.64898/2026.10.13.759003

Figure Lengend Snippet: a , Overview of glucose metabolism and associated metabolic pathways, with a heatmap summarizing transcriptional signatures of glycolysis, the tricarboxylic acid cycle, and oxidative phosphorylation across BMMs, osteoclasts, and efferocytic osteoclasts. Bulk RNA-seq analyses used n = 3 biological replicates per group. b , Immunoblot analysis of HIF-1α, GLUT1, and proteins detected using an OXPHOS antibody cocktail in BMMs and osteoclasts before and after apoptotic neutrophil efferocytosis, with densitometric quantification. c , Immunoblot analysis of MERTK expression in BMMs and osteoclasts derived from OC(ΔMertk) mice and control littermates, with densitometric quantification normalized to β-actin. d , Immunofluorescence analysis of apoptotic neutrophil uptake by BMMs and osteoclasts derived from OC(ΔMertk) mice and control littermates. Engulfed apoptotic neutrophils were quantified per 100 µm². Scale bars, 20 µm (BMMs) and 50 µm (osteoclasts). e,f , Extracellular flux analysis of glycolytic activity and mitochondrial respiration following apoptotic neutrophil efferocytosis. Glycolytic activity was assessed by extracellular acidification rate (ECAR, mpH/min) ( e ), and mitochondrial respiration was assessed by oxygen consumption rate (OCR, pmol/min) ( f ). The oligomycin-sensitive component of OCR represents ATP-linked respiration. Data are presented as mean ± s.d. Statistical significance was assessed using two-tailed unpaired t -tests ( d ) and one-way ANOVA followed by Tukey’s multiple comparisons test ( b,c,e,f ). n = 3 independent biological samples per group ( b–d ); each point represents one biological sample. n = 7–9 measured wells per group ( e,f ); each point in the summary plots represents one well.

Article Snippet: C57BL/6J mice were obtained from the Southwest Hospital Animal Center (Chongqing, China), whereas Ly6G-tdTomato mice and Ctsk -Cre; Mertk flox/flox mice were obtained from Cyagen Biotechnology Co., Ltd. (Suzhou, China).

Techniques: Phospho-proteomics, RNA Sequencing, Western Blot, Analysis, Expressing, Derivative Assay, Control, Immunofluorescence, Activity Assay, Two Tailed Test

Journal: bioRxiv

Article Title: Efferocytosis Remodels Osteoclast Metabolism and Enhances Antibacterial Defense

doi: 10.64898/2026.10.13.759003

Figure Lengend Snippet: a , Schematic illustrating osteoclast metabolic rewiring toward increased glycolytic activity after efferocytosis. b , Lactate concentration in the culture media of BMMs and osteoclasts derived from OC(ΔMertk) mice and control littermates before and after efferocytosis. c,d , Functional assessment of sodium lactate supplementation. Osteoclast differentiation was evaluated by TRAP staining ( c ). Scale bars, 100 µm. Antibacterial activity was assessed by CFU quantification after Staphylococcus aureus challenge ( d ). e–g , LDH isoenzyme profiling of BMMs and osteoclasts before and after efferocytosis. Representative agarose gel electrophoresis images showing LDH isoenzyme patterns detected by in-gel NAD⁺/NBT-PMS activity staining ( e ), densitometric quantification of individual isoenzymes ( f ), and activity-derived estimates of LDHA/LDHB ratios ( g ). h , RT–qPCR analysis of Slc2a1 , Slc16a1 , and Slc16a3 expression before and after apoptotic neutrophil efferocytosis. Expression levels were normalized to Actb . i,j , Effects of pharmacological inhibition of MCT1, MCT4, and LDHA on viable bacterial counts in the presence or absence of apoptotic neutrophils in osteoclasts ( i ) and macrophages ( j ), assessed using CFU quantification after Staphylococcus aureus challenge. k , Proposed model of distinct lactate-handling programs in macrophages and osteoclasts after efferocytosis. The depicted transport directions and metabolic fates represent mechanistic hypotheses informed by the expression and isoenzyme profiles. Data are presented as mean ± s.d. Statistical significance was assessed using two-tailed unpaired t -tests ( c,i,j ) and one-way ANOVA followed by Tukey’s multiple comparisons test ( b,d,g,h ). n = 8 samples per group (b); n = 3 ( c,g,h ); n = 6–7 per group ( d ); n = 5–6 per group ( i ); n = 6 per group ( j ). Each point represents one independent biological sample.

Article Snippet: C57BL/6J mice were obtained from the Southwest Hospital Animal Center (Chongqing, China), whereas Ly6G-tdTomato mice and Ctsk -Cre; Mertk flox/flox mice were obtained from Cyagen Biotechnology Co., Ltd. (Suzhou, China).

Techniques: Activity Assay, Concentration Assay, Derivative Assay, Control, Functional Assay, Staining, Profiling, Agarose Gel Electrophoresis, Quantitative RT-PCR, Analysis, Expressing, Inhibition, Two Tailed Test

Journal: bioRxiv

Article Title: Efferocytosis Remodels Osteoclast Metabolism and Enhances Antibacterial Defense

doi: 10.64898/2026.10.13.759003

Figure Lengend Snippet: a–c , Phenotypic analysis of OC(ΔMertk) and littermate controls following Staphylococcus aureus bone infection. Body weight over 14 days (a), femoral micro-CT analysis at 14 dpi (b), and femoral bone marrow bacterial burden at 14 dpi (c). BV/TV, bone volume fraction; MMI (polar), mean polar moment of inertia. d , Schematic illustrating the bone marrow transplantation strategy. OC(ΔMertk) recipients were reconstituted with Cre + or Cre − bone marrow to generate Cre + BM→Cre + and Cre − BM→Cre + chimeric mice, respectively. e , TRAP staining and quantification of osteoclast-associated efferocytosis in femoral sections after BMT and S. aureus infection (14 dpi). Arrows indicate osteoclasts undergoing efferocytosis. Scale bars, 20 µm. f , Histological analysis of bone tissues from BMT-reconstituted mice at 14 dpi, with quantification of the S. aureus -positive areas (%) and osteoclast abundance. Scale bars, 100 µm. g , Micro-CT analysis of femurs from BMT-reconstituted mice at 14 dpi, with quantification of trabecular BV/TV and cortical MMI (polar). Data are presented as mean ± s.d. Statistical significance was assessed using two-tailed unpaired t -tests ( a,b,c,e,f,g ). n = 14 mice per genotype ( a,c ); n = 25 Cre− and 30 Cre+ mice ( b ); n = 6 mice per BMT group ( e ); n = 7 per group for S. aureus-positive area and n = 6 for osteoclast abundance ( f ); n = 12 Cre+ BM→Cre+ and 8 Cre− BM→Cre+ mice ( g ). Each point represents one mouse; measurements in a were repeated in the same animals.

Article Snippet: C57BL/6J mice were obtained from the Southwest Hospital Animal Center (Chongqing, China), whereas Ly6G-tdTomato mice and Ctsk -Cre; Mertk flox/flox mice were obtained from Cyagen Biotechnology Co., Ltd. (Suzhou, China).

Techniques: Analysis, Infection, Micro-CT, Transplantation Assay, Staining, Two Tailed Test

Journal: Advanced Science

Article Title: Fc‐Dependent Targeting of the GAS6–MERTK Axis With Monoclonal and Bispecific Antibodies Overcomes Drug Resistance Across EGFR Mutations in Exons 19, 20, and 21

doi: 10.1002/advs.78290

Figure Lengend Snippet:

Article Snippet: MERTK , 4319S , Cell Signaling Technology (CST) , AB_10614528.

Techniques: Cell-Signaling

Journal: Nature Communications

Article Title: Bioinspired porous metal-amino acid nanozymes enable multi-pathway treatment of atherosclerosis through anti-oxidation and pro-efferocytosis

doi: 10.1038/s41467-026-75509-4

Figure Lengend Snippet: a Schematic illustration of the pro-efferocytosis property of MMAzyme-S. (Created in BioRender. Huang, H. (2026) https://BioRender.com/7l5dwq4 ). b CLSM images depicting phagocytosis of CD47-overexpressed ACs in proinflammatory-phenotype macrophages pretreated with different samples. FCM results ( c ) and the corresponding quantitative analysis ( d ) of efferocytosis towards CD47-overexpressed ACs by proinflammatory phenotype macrophages pretreated with different samples ( n = 3 independent biological samples). e The quantitative results of the Western blotting of Mertk in macrophages under different treatments ( n = 3 independent biological samples. Samples in different blots were derived from the same experiment. All gels/blots were processed in parallel. f Schematics illustration for the mechanism of promoting cholesterol efflux mediated by MMAzyme-S (created in BioRender. Huang, H. (2026) https://BioRender.com/o3x56t5 ). g Optical microscopy images of induced foamy cell formation in macrophages under different treatments. h Cholesterol content in the supernatant of foamy cells under different treatments ( n = 4 independent biological samples). i Western blotting analysis of Mertk, PPARγ, LXRα, ABCA1, and ABCG1 in macrophages under different treatments. Corresponding quantitative results of the Western blotting of PPARγ ( j ), LXRα ( k ), ABCA1 ( l ), and ABCG1 ( m ) in macrophages under different treatments ( n = 3 independent biological samples. Samples in different blots were derived from the same experiment. All gels/blots were processed in parallel). Data in ( d , e , h , j – m ) were expressed as mean ± S.D. Significance in ( d , e , h , j – m ) was calculated using one-way ANOVA followed by Tukey’s post hoc test for multiple comparisons. Although the individual values of Group ii and Group iii in ( l ) do not overlap, the statistical analysis does not indicate a significant difference, possibly due to the limited sample size. Source data are provided as a file.

Article Snippet: The following primary antibodies were used in this study: CD47 Rabbit pAb (A1838, ABclonal,1:750), CD36/SR-B3 Rabbit pAb (A5792, ABclonal,1:2500), CCR2 Rabbit pAb (A2855, ABclonal,1:750), Na-K-ATP Rabbit pAb (GB11400, Servicebio,1:2000), MERTK Rabbit pAb (A5443, ABclonal,1:750), LXRα Rabbit mAb (A3974, ABclonal,1:3000), ABCG1 Rabbit mAb (A17907, ABclonal,1:1500), PPARγ Rabbit pAb (WL01800, Wanleibio,1:1000), Anti-ABCA1 antibody ( AB307536 , Abcam,1:1000), GAPDH Rabbit pAb (AC001, ABclonal,1:20000), p-SHP1 (8849, Cell Signaling Technology, 1:1000), HRP-conjugated Goat anti-Rabbit IgG (H+L) (AS014, ABclonal,1:5000).

Techniques: Western Blot, Derivative Assay, Microscopy

Journal: Scientific Reports

Article Title: Glucocorticoids induce a phagocytic C1Q+ macrophage phenotype primed for IFNγ-dependent CXCL9 secretion

doi: 10.1038/s41598-026-52733-y

Figure Lengend Snippet: GC-induced MΦ are highly efficient in C1q-mediated phagocytosis. ( A ) Gene set enrichment analysis (GSEA) of DEGs in MΦ exposed to CM of steroidogenic NCI-H295R cells in comparison to controls. ( B ) Visualization of the enrichment results on phagocytosis ( p < 2.2e-16; FDR: 0.011718). ( C ) Representative flow cytometry plots and ( D ) quantification of phagocytosis by MΦ exposed to CM of steroidogenic NCI-H295R cells or control. CD64 + CFSE+ double-positive cells were considered phagocytic macrophages. Groups were compared using one-way ANOVA with Tukey’s multiple comparisons test. N = 4 biological replicates from independent healthy blood donors ( E ) Percentages of phagocytic MΦ exposed to dexamethasone (100 nM) or control. N = 3 biological replicates from independent healthy blood donors are shown in mean +/- SD. Differences were compared using unpaired t-test. ( F ) Phagocytosis of M1-polarized MΦ after exposure to 10 µg/ml or 20 µg/ml purified human C1q. N = 3 biological replicates from independent healthy blood donors are shown in mean +/- SD. Groups were compared using one-way ANOVA with Tukey’s multiple comparisons test. ( G ) Phagocytosis of dexamethasone (100 nM) -polarized MΦ after exposure to 1 µg/ml, 10 µg/ml or 50 µg/ml anti-C1QA antibody. N = 3 biological replicates from independent healthy blood donors are shown in mean +/- SD. Groups were compared using one-way ANOVA with Tukey’s multiple comparisons test. ( H ) Phagocytosis of dexamethasone (100 nM)-polarized MΦ after exposure to the MerTK inhibitor UNC1062 (100 nM), anti-Gas6 antibody (20 µg/ml) or goat control IgG (20 µg/ml). N = 3 biological replicates from independent healthy blood donors are shown in mean +/- SD. Groups were compared using one-way ANOVA with Tukey’s multiple comparisons test. ( I ) Kaplan-Meier plots of PFS and OS according to tumoral CSF1 and C1QA expression. Higher gene expression was significantly associated with favorable PFS and OS. RNA expression and survival data was extracted from the TCGA dataset ( n = 76). NCI-R = NCI-H295R; mety=metyrapone.

Article Snippet: For inhibition studies, MФ were pre-incubated with the selective MerTK inhibitor UNC1062 (100 nM; MCE: Cat# HY-117548), anti-Gas6 antibody (20 μg/ml; R&D Systems, Cat# AB885, RRID: AB_354376), a goat isotype IgG control (20 μg/ml; Thermo Fisher Scientific, Cat# 02–6202, RRID: AB_2532946), purified C1q (Merck; Cat# C1740) or anti-C1QA antibody (LS-Bio; Cat# LS‐C100911; RRID: AB_2067267) for 30 min before they were added to early ferroptotic tumor cells.

Techniques: Comparison, Flow Cytometry, Control, Purification, Expressing, Gene Expression, RNA Expression