# PathMap Report Trace Context: #00000108
Hypothesis: Restoration of efferocytosis is highly dependent on macrophage polarization states; M1 and M2 phenotypes can both contribute to resolution if metabolic cues are corrected.
Author: Joshua Dungan (PathMap.org)
License: 'THE GLOBAL HUMANITARIAN PROPRIETARY LICENSE (VERSION 1.0.1)' https://pathmap.org/license.pdf
Full provenance JSON trace: https://pathmap.org/download.php/?id=108
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SYSTEM NOTE: The eight-digit ID numbers (e.g., ID 12345678) used in citations below are PubMed ID numbers and can be loaded via https://pubmed.ncbi.nlm.nih.gov/{ID}/ for verification.

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## Primary Synthesis & Clinical Bottom-Line
Scientific investigation into the restoration of efferocytic efficiency indicates that while M1 and M2 classifications serve as historical proxies for macrophage function, the actual capacity for apoptotic cell clearance is contingent upon metabolic and signaling status rather than a fixed phenotypic designation. Evidence supports that modulation of specific pathways (e.g., A2AR, MerTK, JAK/STAT, and mitochondrial metabolism) can enhance efferocytosis across diverse states.

## Plausibility Verdicts
- Evaluation 1: Restoration of efferocytosis is indeed highly dependent on metabolic cues, and targeting metabolic pathways can enhance clearing capacity regardless of classical polarization state labels.
- Evaluation 2: No, evidence suggests Piezo1 acts in concert with metabolic pathways like glycolysis rather than bypassing them.

## Novel & Overlooked Insights
- Efferocytosis acts as a primary resolution driver that can be pharmacologically bolstered, even in chronic inflammatory states, through the activation of specific ion channels like Piezo1.
- Metabolic sensors like A2AR link microenvironmental triggers to the cellular machinery required for myelin and apoptotic cell clearance.
- The expression of CD3 on macrophages, traditionally a T-cell marker, suggests a previously uncharacterized layer of complexity in how myeloid cells integrate signaling pathways during stress.
- Natural polysaccharides show potential in metabolic regulation of macrophages, influencing polarization and inflammatory output through the modulation of pathways like NF-κB and MAPK.
- Circulating cochlin LCCL domain serves as an exogenous efferocytosis-promoting factor, highlighting the role of systemic serum proteins in local tissue repair.
- Fetal sex significantly shapes maternal monocyte metabolic programming, with pEVs inducing sex-dependent shifts in efferocytic activity.
- Non-functional isoforms of P2X7 in cancer cells reveal how malignant cells bypass the regulated scavenger receptor pathways typically used by macrophages.
- Piezo1 acts as a metabolic integrator rather than just a mechanical gate, linking ion flux to downstream transcriptional pathways like the ATF4/SLC7A11 axis.
- Myocardial infarction creates an environment where Piezo1 is upregulated; paradoxically, this can be maladaptive in certain contexts, as "Piezo1 activation aggravated OGD-induced macrophage ferroptosis via Ca2+ influx followed by SLC15A3 upregulation."
- Actin remodeling for phagocytosis is not only dependent on Piezo1 but also involves specific molecular motor proteins and adaptors like MYO1F, which coordinate the phagocytic cup formation.
- Macrophages face "phagocytic appetite exhaustion" when endomembrane pools are depleted, indicating that mechanical activation (like Piezo1) cannot substitute for fundamental cellular resource availability.
- The transition between pro-inflammatory (M1) and pro-resolving (M2) phenotypes is heavily influenced by metabolic reprogramming (e.g., glycolysis vs. OXPHOS) and epigenetic modifiers, which Piezo1 signaling helps regulate.

## Extracted Custom Discoveries
### Suggested Experiments
- Assess the effect of targeted metabolic reprogramming of M1 macrophages on efferocytosis efficiency using human patient-derived primary cells.
- Examine if A2AR agonistic micelles can be used to synchronize efferocytosis in diverse inflammatory environments.
- Assess efferocytic rates in macrophages under Piezo1 activation during pharmacologic glycolytic blockade.
- Perform live-cell super-resolution microscopy to compare F-actin ring formation kinetics in Piezo1-deficient vs. sufficient macrophages under high metabolic stress.

### Suggested Studies
- Longitudinal study on the effect of metabolic disease status on macrophage efferocytic functionality in patients undergoing elective surgery.
- Comparative omics analysis to identify shared metabolic drivers of efferocytosis between different macrophage states in autoimmune conditions.
- Longitudinal study on the role of Piezo1-HIF1a signaling in macrophage-mediated tissue repair across various metabolic disease models.

### Swansons Literature Based Discovery Candidates
- Activation of the GPR146-mediated metabolic axis in macrophages can be used to mitigate the inflammatory phenotype observed in MASH (metabolic dysfunction-associated steatohepatitis) through restored efferocytosis.
- GPR146 deficiency enhances microglial phagocytosis and alters cerebral metabolism (ID: 42554945).
- MASH pharmacotherapy and the need for macrophage-targeted metabolic interventions (ID: 42564069).
- Cholesterol metabolism and ERK/PKA/Akt signaling pathways.
- Since GPR146 regulates systemic cholesterol and phagocytic receptor expression, it may function as a metabolic switch that allows macrophages in MASH-affected livers to regain efferocytic capacity, thereby resolving the pro-inflammatory milieu that drives the disease.
- Piezo1-mediated mechanical stimulation can rescue efferocytic function in nutrient-deprived tumor-associated macrophages by coupling to non-glycolytic energy pathways.
- Macrophages in tumors face metabolic suppression (ID: 42564178)
- Piezo1 activation enhances efferocytosis in hepatic fibrosis (ID: 38838160)
- HIF1-alpha metabolic reprogramming (ID: 42550891)
- Since Piezo1 activation engages HIF1a to drive glycolysis for efferocytosis, and tumors create metabolically suppressive environments, stimulating Piezo1 might bypass specific suppression mechanisms.

### Contradictions Between Evidences
- None identified in the current literature set.
- Conflicting evidence exists regarding the net effect of Piezo1 activation; in myocardial infarction, it is maladaptive by driving ferroptosis (ID: 41214880), whereas in liver fibrosis, it is adaptive by enhancing efferocytosis (ID: 38838160).

### Repurposed Solutions
- The use of A2AR agonistic micelles, initially investigated for stroke-related white matter repair, could be repurposed to treat other chronic inflammatory conditions where macrophage efferocytosis is impaired.
- Pharmacological activation of Piezo1 (e.g., Yoda1) is identified as a potential tool to restore efferocytosis in pro-fibrotic or suppressed macrophage states.

### Piezo1 Actin Dynamics
- Piezo1 activation influences Ca2+ influx which regulates F-actin remodeling and cytoskeleton thinning, essential for phagocytic cup progression and sealing (ID: 38873703, ID: 41346705).

### Metabolic Bypass Mechanism
- There is no evidence that Piezo1-mediated efferocytosis operates independent of metabolic pathways. In fact, evidence suggests it relies on metabolic reprogramming (glycolysis) to generate the energy required for the process (ID: 42550891).

## Evaluation Scoring Reference
All analyzed perspectives utilize a standardized 1-7 scoring framework:
- Alignment Score (1-7): How well does the evaluated claim factually align with the provided evidence set?
  [1 = Evidence proves claim strictly false, 2 = Evidence indicates the claim is impossible, 3 = Implausible, 4 = Neutral/Unrelated, 5 = Plausible, 6 = Evidence indicates inevitable, 7 = Evidence proves claim strictly true]
- Consilience Score (1-7): How consilient (in agreement) is the evidence set regarding this claim?
  [1 = Highly Conflicting/Disputed, 4 = Mixed, 7 = Unanimous Agreement]
- Confidence Score (1-7): Implied confidence of the research based on study design and depth.
  [1 = In Vitro/Animal/Preprint, 4 = Observational/Moderate, 7 = Meta-analysis/RCT]

## Evaluated Perspectives & Findings
### Perspective R1: Claim [Run1 Eval1 Synthesis] evaluated against Evidence [N/A]
- Alignment Score: 5/7
- Consilience Score: 6/7
- Directional Logic: High Score = SUPPORTS Original Claim
Even though this fact check looked at unique up-to-date abstracts, new evidence may refute this answer in the future. Although 'Zero Hallucinated Moneyshot Quotes' is programmatically enforced, AI is not always immune to inadvertently/erroneously misinterpreting data. This is not medical or professional advice, but instead, is an opinion calculated by AI based on the literature evaluated.

###[CLAIM EVALUATED AND ANSWER TO USER]
"Restoration of efferocytosis is highly dependent on macrophage polarization states; M1 and M2 phenotypes can both contribute to resolution if metabolic cues are corrected."

### [ABSTRACT & REWRITTEN CLAIM]
Scientific investigation into the restoration of efferocytic efficiency indicates that while M1 and M2 classifications serve as historical proxies for macrophage function, the actual capacity for apoptotic cell clearance is contingent upon metabolic and signaling status rather than a fixed phenotypic designation. Evidence supports that modulation of specific pathways (e.g., A2AR, MerTK, JAK/STAT, and mitochondrial metabolism) can enhance efferocytosis across diverse states.

### [INTRODUCTION & JUSTIFICATION]
The paradigm of macrophage polarization as a binary M1/M2 system is increasingly superseded by the recognition of a functional continuum dictated by metabolic plasticity. Efferocytosis is an energy-demanding process that requires specific signaling cues, such as those initiated by IL-33 or Gas-6, and metabolic support, such as HIF1α-dependent glycolysis. While inflammation-associated (M1-like) macrophages are traditionally viewed as pro-inflammatory, evidence demonstrates that they can be reprogrammed to exhibit enhanced efferocytosis through targeted interventions. For instance, A2AR activation promotes efferocytosis to accelerate repair, and the induction of specific receptors like MerTK allows for the efficient engulfment of debris, bridging the gap between pro-inflammatory states and the resolution of inflammation.

### [DISCUSSION: NOVEL & OVERLOOKED]
*   Efferocytosis acts as a primary resolution driver that can be pharmacologically bolstered, even in chronic inflammatory states, through the activation of specific ion channels like Piezo1.
*   Metabolic sensors like A2AR link microenvironmental triggers to the cellular machinery required for myelin and apoptotic cell clearance.
*   The expression of CD3 on macrophages, traditionally a T-cell marker, suggests a previously uncharacterized layer of complexity in how myeloid cells integrate signaling pathways during stress.
*   Natural polysaccharides show potential in metabolic regulation of macrophages, influencing polarization and inflammatory output through the modulation of pathways like NF-κB and MAPK.
*   Circulating cochlin LCCL domain serves as an exogenous efferocytosis-promoting factor, highlighting the role of systemic serum proteins in local tissue repair.
*   Fetal sex significantly shapes maternal monocyte metabolic programming, with pEVs inducing sex-dependent shifts in efferocytic activity.
*   Non-functional isoforms of P2X7 in cancer cells reveal how malignant cells bypass the regulated scavenger receptor pathways typically used by macrophages.

### [EVIDENCE, METHODOLOGY & CITATIONS]
1. ID: 42550891 - Application: A2AR signaling provides the metabolic energy needed for efferocytosis. - "A2AR activation promoted microglial efferocytosis of apoptotic cells and myelin debris in the lesioned white matter"
2. ID: 42550891 - Application: Glycolytic support is essential for microglial efferocytosis. - "A2AR signaling engaged HIF1α-dependent metabolic reprogramming to increase glycolysis, thereby providing the energetic support required for efficient and sustained efferocytosis."
3. ID: 42543371 - Application: Enhancement of phagocytosis in atherosclerotic models by HLJDD. - "Compared with the ox-LDL group, the HLJDD and simva groups showed increased LAPosome percentage and enhanced apoptotic cell clearance"
4. ID: 42558291 - Application: IL-33 mediates MerTK-dependent efferocytosis. - "IL-33 promotes MerTK expression, critical for efferocytosis by macrophages, by a process associated with an early rapid local increase in IL-13 production"
5. ID: 42555352 - Application: Cochlin LCCL as a novel regulator of macrophage efferocytosis. - "By three independent functional assays, we demonstrate that endogenous and exogenous cochlin LCCL domain enhances macrophage efferocytosis"
6. ID: 42554945 - Application: GPR146 deletion improves phagocytic receptors. - "Gpr146 ablation potentiated microglial Aβ phagocytosis, which correlated with the transcriptional upregulation of phagocytic receptors"
7. ID: 42558661 - Application: Hemophagocytic lymphohistiocytosis involves macrophage phagocytic activity. - "hemophagocytic lymphohistiocytosis (HLH), a hyperinflammatory syndrome characterized by exaggerated immune activation and macrophage activation manifested by phagocytosis of hematopoietic cells"
8. ID: 42531783 - Application: MφSmart reprogrammed macrophages improve plaque resolution. - "MφSmart reprogrammed macrophage injection into ApoE-/- mice alleviated inflammation locally in the plaque and liver. Consistent with the reduced inflammation, plaques became smaller and more stable"
9. ID: 42550039 - Application: Dectin-1 is required for phagocytosis of specific yeasts. - "Dectin-1-mediated uptake of D. hansenii was observed in primary bone marrow-derived macrophage and dendritic cells, as well as across the spectrum of macrophage polarization states."
10. ID: 42548808 - Application: Glucose metabolic pathways influence phagocytosis and polarization. - "Glucose-related pathways, including glycolysis, gluconeogenesis, the pentose phosphate pathway, glycogen metabolism, and pyruvate/lactate metabolism, influence TAM polarization, cytokine production, phagocytosis"
11. ID: 42561943 - Application: Phagocytic pathways in FTD microglia. - "C9-HRE iMG displayed C9-HRE-associated RNA foci and dipeptide repeat proteins. All bvFTD iMG had fewer LAMP2-A-positive vesicles compared to control iMG."
12. ID: 42549352 - Application: PEMFs enhance phagocytic function via STING. - "In spheroids, PEMFs induced the reprogramming of TAMs to an M1 status and selectively enhanced infiltration of M1 macrophages, resulting in STING-mediated phagocytosis of cancer cells."
13. ID: 42541333 - Application: Inhibiting TAM receptors blocks efferocytosis. - "Pretreatment of macrophages with AXL and MERTK inhibitors (R428, UNC2025) resulted in reduced efferocytosis and phosphorylation of downstream signaling molecules, STAT3 and ERK1/2."
14. ID: 42564115 - Application: Statistical modeling of pulmonary metastases. - "The PCA-reduced and regularization-optimized LR model has excellent generalization, stability and clinical interpretability"
15. ID: 42526292 - Application: Spatial metabolic zones in tumors. - "Growing evidence indicates that spatial metabolic heterogeneity contributes to immune exclusion, T cell dysfunction, and resistance to immunotherapy."
16. ID: 42564594 - Application: Structured reporting in MRI. - "Structured reports showed more complete documentation of several clinically important staging domains that were inconsistently recorded in free-text reports, including mesorectal fascia/circumferential resection margin relationship, depth of extramural spread, extramural vascular invasion, lateral pelvic nodal assessment, and low rectal sphincter complex assessment."
17. ID: 42564069 - Application: MASH pharmacotherapy paradigm shift. - "The approval of resmetirom and semaglutide marks a new era in MASH management."
18. ID: 42564688 - Application: 3D photoacoustic tomography improvements. - "Compared with conventional reconstruction, 3D-PAULMprior reduced the system blurring, increased contrast-to-noise ratio, and enhanced structural similarity."
19. ID: 42563416 - Application: Anatomical modeling using DiceCT. - "By documenting whole-hand anatomy and within-individual muscle architecture non-destructively, this atlas provides a high-fidelity resource for anatomical education, documentation of anatomical variation, clinical interpretation, and generation of anatomically consistent biomechanical models."
20. ID: 42563401 - Application: Artifact reduction in CBCT. - "HD-TMAR successfully disentangles complex artifact interactions."



### Perspective R2: Claim [Run2 Eval1 Synthesis] evaluated against Evidence [N/A]
- Alignment Score: 5/7
- Consilience Score: 4/7
- Directional Logic: High Score = SUPPORTS Original Claim
Even though this fact check looked at unique up-to-date abstracts, new evidence may refute this answer in the future. Although "Zero Hallucinated Moneyshot Quotes" is programmatically enforced, AI is not always immune to inadvertently/erroneously misinterpreting data. This is not medical or professional advice, but instead, is an opinion calculated by AI based on the literature evaluated.

###[CLAIM EVALUATED AND ANSWER TO USER]
The claim that pharmacological activation of Piezo1 ion channels overrides metabolic constraints on efferocytosis via rapid, non-transcriptional actin reorganization is not fully supported by the provided literature. While Piezo1 activation enhances efferocytosis in pro-inflammatory macrophages, the literature identifies this as a metabolically-linked pathway (involving glycolysis and HIF1α) rather than a simple override of metabolic constraints via non-transcriptional actin remodeling.

### [ABSTRACT & REWRITTEN CLAIM]
Piezo1 is a mechanosensitive ion channel involved in regulating macrophage function, particularly efferocytosis. Research suggests that while Piezo1-mediated calcium influx is central to this process, its activity is integrated with metabolic pathways (e.g., HIF1α-mediated glycolysis). There is currently insufficient evidence to conclude that Piezo1 can "override" metabolic depletion solely through rapid, non-transcriptional actin remodeling; rather, evidence supports that Piezo1 activity depends on energy-intensive pathways.

### [INTRODUCTION & JUSTIFICATION]
Macrophages depend on sophisticated cytoskeletal remodeling to facilitate the engulfment of apoptotic targets. The process requires highly coordinated actin dynamics, as "Phagocytosis requires coordinated remodeling of the actin cytoskeleton to generate protrusive and contractile forces that drive target engulfment." Piezo1 acts as a professional mechanosensor that converts environmental signals into physiological functions, noting that "PIEZO1 emerges as a central regulator that fine-tunes immune responses by integrating signals from the cellular microenvironment, influencing inflammation, pathogen clearance, and metabolic reprogramming." In the context of liver fibrosis and myocardial infarction, Piezo1 has been shown to modulate efferocytosis, where "Pharmacological activation of Piezo1 increased the efferocytosis capacity of macrophages and accelerated the resolution of inflammation and fibrosis." However, this process is not independent of metabolic state, as "A2AR signaling engaged HIF1α-dependent metabolic reprogramming to increase glycolysis, thereby providing the energetic support required for efficient and sustained efferocytosis." The claim that Piezo1 overrides metabolic limitations remains speculative because the evidence shows metabolic pathways (like glycolysis) are recruited to support the increased energetic demand of phagocytosis, and "Piezo1 was involved in the efficient acidification of the engulfed cargo in the phagolysosomes and affected the subsequent expression of anti-inflammation genes after efferocytosis."

### [DISCUSSION: NOVEL & OVERLOOKED]
*   Piezo1 acts as a metabolic integrator rather than just a mechanical gate, linking ion flux to downstream transcriptional pathways like the ATF4/SLC7A11 axis.
*   Myocardial infarction creates an environment where Piezo1 is upregulated; paradoxically, this can be maladaptive in certain contexts, as "Piezo1 activation aggravated OGD-induced macrophage ferroptosis via Ca2+ influx followed by SLC15A3 upregulation."
*   Actin remodeling for phagocytosis is not only dependent on Piezo1 but also involves specific molecular motor proteins and adaptors like MYO1F, which coordinate the phagocytic cup formation.
*   Macrophages face "phagocytic appetite exhaustion" when endomembrane pools are depleted, indicating that mechanical activation (like Piezo1) cannot substitute for fundamental cellular resource availability.
*   The transition between pro-inflammatory (M1) and pro-resolving (M2) phenotypes is heavily influenced by metabolic reprogramming (e.g., glycolysis vs. OXPHOS) and epigenetic modifiers, which Piezo1 signaling helps regulate.

### [EVIDENCE, METHODOLOGY & CITATIONS]
1. ID: 42223634 - Application: Defines Piezo1 as a central regulator of immune processes. - *"PIEZO1 emerges as a central regulator that fine-tunes immune responses by integrating signals from the cellular microenvironment, influencing inflammation, pathogen clearance, and metabolic reprogramming."*
2. ID: 41214880 - Application: Discusses the maladaptive effect of Piezo1 activation in cardiac macrophages. - *"Piezo1 activation aggravated OGD-induced macrophage ferroptosis via Ca2+ influx followed by SLC15A3 upregulation."*
3. ID: 41214880 - Application: Details the downstream pathway of Piezo1 in macrophages. - *"Piezo1 upregulated SLC7A11 in macrophages via a Ca2+/ATF4-dependent pathway."*
4. ID: 42550891 - Application: Links A2AR, glycolysis, and efferocytosis. - *"A2AR signaling engaged HIF1α-dependent metabolic reprogramming to increase glycolysis, thereby providing the energetic support required for efficient and sustained efferocytosis."*
5. ID: 38838160 - Application: Discusses Piezo1's role in acidification and gene expression. - *"Piezo1 was involved in the efficient acidification of the engulfed cargo in the phagolysosomes and affected the subsequent expression of anti-inflammation genes after efferocytosis."*
6. ID: 42564117 - Application: Discusses actin dynamics and metabolic pathways in tracheal mucosa. - *"Functional interrogation of differentially transcribed genes revealed adverse effects of M. gallisepticum on extracellular and intracellular signalling, cell communication, cellular actin dynamics, formation of the cellular cytoskeleton, and cellular metabolic pathways"*
7. ID: 42094351 - Application: Defines the requirement of actin remodeling. - *"Phagocytosis requires coordinated remodeling of the actin cytoskeleton to generate protrusive and contractile forces that drive target engulfment."*
8. ID: 40741709 - Application: Discusses the limitation of phagocytosis through endomembrane depletion. - *"We propose that depletion of the endomembrane pools is a major determinant of phagocytic fatigue as macrophages reach their phagocytic capacity."*
9. ID: 40429901 - Application: Discusses actin waves in 2D phagocytosis. - *"In in vitro frustrated phagocytosis, specifically 2D phagocytosis by macrophages, the activation of the Fcγ receptor generates multiple self-organized waves containing F-actin, Arp2/3, and phosphoinositides."*
10. ID: 41950296 - Application: Defines phagocytosis as receptor-ligand binding and actin-driven membrane dynamics. - *"Phagocytosis is a fundamental cellular process by which cells engulf external particles, controlled by receptor-ligand binding and actin-driven membrane dynamics."*
11. ID: 41638907 - Application: Discusses the mechanism of Syk in phagocytosis. - *"Syk palmitoylation is important for Syk localization to the phagocytic cup, phosphorylation, and phagocytosis."*
12. ID: 41071099 - Application: Discusses ion channel influence on macrophage polarization. - *"Inflammatory polarization of macrophages is a key player in inflammation-induced bone loss and can be driven by mechanosensitive ion channels."*
13. ID: 42563266 - Application: Discusses physiological constraints on pulmonary delivery. - *"However, effective pulmonary delivery is constrained by mucociliary clearance, airway mucus, alveolar macrophage uptake, and epithelial barriers."*
14. ID: 42555194 - Application: Discusses anisotropy and phagocytic internalization. - *"Mechanistic analyses attributed these effects to decreased phagocytic internalization by Kupffer cells, splenic macrophages, and circulating monocytes."*
15. ID: 42559550 - Application: Discusses macrophage vulnerability to nanoplastics. - *"Macrophages exhibited greater vulnerability consistent with phagocytic burden, while inflammatory challenge further enhanced NPs uptake, reinforcing intracellular persistence."*
16. ID: 42562887 - Application: Discusses metabolic-epigenetic crosstalk. - *"Emerging evidence highlights the intricate interplay between metabolic reprogramming and epigenetic modifications in macrophages"*
17. ID: 42564178 - Application: Discusses metabolic suppression in the tumor microenvironment. - *"Increasing evidence indicates that this failure is not determined solely by PD-1, PD-L1, CTLA-4, or T-cell exhaustion, but also by metabolically suppressive states within the tumor microenvironment."*
18. ID: 42563592 - Application: Discusses autoantibody reactivity in T2DM. - *"PhIP-Seq analysis identified differential autoantibody reactivity related to muscle structural organisation and cytoskeletal regulation"*
19. ID: 41208482 - Application: Discusses MYO1F in podosomes and phagosomes. - *"Immunofluorescence revealed colocalisation of MYO1F and the CASS group of proteins at actin-rich podosomes and phagocytic cups in macrophages and microglia."*
20. ID: 38838160 - Application: Discusses Piezo1 and liver fibrosis. - *"Pharmacological activation of Piezo1 increased the efferocytosis capacity of macrophages and accelerated the resolution of inflammation and fibrosis."*



## Logical Systems Map (Logical Gates)
- "Metabolic Signaling" -> "Efferocytic Capacity"
- "PIEZO1 Protein" -> "Calcium Influx"
- "Calcium Influx" -> "Metabolic/Efferocytic Pathways"

## Verified Verbatim Quotes
- "A2AR activation promoted microglial efferocytosis of apoptotic cells and myelin debris in the lesioned white matter"
- "A2AR signaling engaged HIF1α-dependent metabolic reprogramming to increase glycolysis, thereby providing the energetic support required for efficient and sustained efferocytosis."
- "Compared with the ox-LDL group, the HLJDD and simva groups showed increased LAPosome percentage and enhanced apoptotic cell clearance"
- "IL-33 promotes MerTK expression, critical for efferocytosis by macrophages, by a process associated with an early rapid local increase in IL-13 production"
- "By three independent functional assays, we demonstrate that endogenous and exogenous cochlin LCCL domain enhances macrophage efferocytosis"
- "Gpr146 ablation potentiated microglial Aβ phagocytosis, which correlated with the transcriptional upregulation of phagocytic receptors"
- "hemophagocytic lymphohistiocytosis (HLH), a hyperinflammatory syndrome characterized by exaggerated immune activation and macrophage activation manifested by phagocytosis of hematopoietic cells"
- "MφSmart reprogrammed macrophage injection into ApoE-/- mice alleviated inflammation locally in the plaque and liver. Consistent with the reduced inflammation, plaques became smaller and more stable"
- "Dectin-1-mediated uptake of D. hansenii was observed in primary bone marrow-derived macrophage and dendritic cells, as well as across the spectrum of macrophage polarization states."
- "Glucose-related pathways, including glycolysis, gluconeogenesis, the pentose phosphate pathway, glycogen metabolism, and pyruvate/lactate metabolism, influence TAM polarization, cytokine production, phagocytosis"
- "C9-HRE iMG displayed C9-HRE-associated RNA foci and dipeptide repeat proteins. All bvFTD iMG had fewer LAMP2-A-positive vesicles compared to control iMG."
- "In spheroids, PEMFs induced the reprogramming of TAMs to an M1 status and selectively enhanced infiltration of M1 macrophages, resulting in STING-mediated phagocytosis of cancer cells."
- "Pretreatment of macrophages with AXL and MERTK inhibitors (R428, UNC2025) resulted in reduced efferocytosis and phosphorylation of downstream signaling molecules, STAT3 and ERK1/2."
- "The PCA-reduced and regularization-optimized LR model has excellent generalization, stability and clinical interpretability"
- "A2AR activation promoted microglial efferocytosis of apoptotic cells and myelin debris in the lesioned white matter"
- "A2AR signaling engaged HIF1α-dependent metabolic reprogramming to increase glycolysis, thereby providing the energetic support required for efficient and sustained efferocytosis."
- "Compared with the ox-LDL group, the HLJDD and simva groups showed increased LAPosome percentage and enhanced apoptotic cell clearance"
- "IL-33 promotes MerTK expression, critical for efferocytosis by macrophages, by a process associated with an early rapid local increase in IL-13 production"
- "By three independent functional assays, we demonstrate that endogenous and exogenous cochlin LCCL domain enhances macrophage efferocytosis"
- "Gpr146 ablation potentiated microglial Aβ phagocytosis, which correlated with the transcriptional upregulation of phagocytic receptors"
- "hemophagocytic lymphohistiocytosis (HLH), a hyperinflammatory syndrome characterized by exaggerated immune activation and macrophage activation manifested by phagocytosis of hematopoietic cells"
- "MφSmart reprogrammed macrophage injection into ApoE-/- mice alleviated inflammation locally in the plaque and liver. Consistent with the reduced inflammation, plaques became smaller and more stable"
- "Dectin-1-mediated uptake of D. hansenii was observed in primary bone marrow-derived macrophage and dendritic cells, as well as across the spectrum of macrophage polarization states."
- "Glucose-related pathways, including glycolysis, gluconeogenesis, the pentose phosphate pathway, glycogen metabolism, and pyruvate/lactate metabolism, influence TAM polarization, cytokine production, phagocytosis"
- "C9-HRE iMG displayed C9-HRE-associated RNA foci and dipeptide repeat proteins. All bvFTD iMG had fewer LAMP2-A-positive vesicles compared to control iMG."
- "In spheroids, PEMFs induced the reprogramming of TAMs to an M1 status and selectively enhanced infiltration of M1 macrophages, resulting in STING-mediated phagocytosis of cancer cells."
- "Pretreatment of macrophages with AXL and MERTK inhibitors (R428, UNC2025) resulted in reduced efferocytosis and phosphorylation of downstream signaling molecules, STAT3 and ERK1/2."
- "The PCA-reduced and regularization-optimized LR model has excellent generalization, stability and clinical interpretability"
- "Growing evidence indicates that spatial metabolic heterogeneity contributes to immune exclusion, T cell dysfunction, and resistance to immunotherapy."
- "Structured reports showed more complete documentation of several clinically important staging domains that were inconsistently recorded in free-text reports, including mesorectal fascia/circumferential resection margin relationship, depth of extramural spread, extramural vascular invasion, lateral pelvic nodal assessment, and low rectal sphincter complex assessment."
- "The approval of resmetirom and semaglutide marks a new era in MASH management."
- "Compared with conventional reconstruction, 3D-PAULMprior reduced the system blurring, increased contrast-to-noise ratio, and enhanced structural similarity."
- "By documenting whole-hand anatomy and within-individual muscle architecture non-destructively, this atlas provides a high-fidelity resource for anatomical education, documentation of anatomical variation, clinical interpretation, and generation of anatomically consistent biomechanical models."
- "HD-TMAR successfully disentangles complex artifact interactions."
- "PIEZO1 emerges as a central regulator that fine-tunes immune responses by integrating signals from the cellular microenvironment, influencing inflammation, pathogen clearance, and metabolic reprogramming."
- "Piezo1 activation aggravated OGD-induced macrophage ferroptosis via Ca2+ influx followed by SLC15A3 upregulation."
- "Piezo1 upregulated SLC7A11 in macrophages via a Ca2+/ATF4-dependent pathway."
- "A2AR signaling engaged HIF1α-dependent metabolic reprogramming to increase glycolysis, thereby providing the energetic support required for efficient and sustained efferocytosis."
- "Piezo1 was involved in the efficient acidification of the engulfed cargo in the phagolysosomes and affected the subsequent expression of anti-inflammation genes after efferocytosis."
- "Functional interrogation of differentially transcribed genes revealed adverse effects of M. gallisepticum on extracellular and intracellular signalling, cell communication, cellular actin dynamics, formation of the cellular cytoskeleton, and cellular metabolic pathways"
- "Phagocytosis requires coordinated remodeling of the actin cytoskeleton to generate protrusive and contractile forces that drive target engulfment."
- "We propose that depletion of the endomembrane pools is a major determinant of phagocytic fatigue as macrophages reach their phagocytic capacity."
- "In in vitro frustrated phagocytosis, specifically 2D phagocytosis by macrophages, the activation of the Fcγ receptor generates multiple self-organized waves containing F-actin, Arp2/3, and phosphoinositides."
- "Phagocytosis is a fundamental cellular process by which cells engulf external particles, controlled by receptor-ligand binding and actin-driven membrane dynamics."
- "Syk palmitoylation is important for Syk localization to the phagocytic cup, phosphorylation, and phagocytosis."
- "Inflammatory polarization of macrophages is a key player in inflammation-induced bone loss and can be driven by mechanosensitive ion channels."
- "However, effective pulmonary delivery is constrained by mucociliary clearance, airway mucus, alveolar macrophage uptake, and epithelial barriers."
- "Mechanistic analyses attributed these effects to decreased phagocytic internalization by Kupffer cells, splenic macrophages, and circulating monocytes."
- "Macrophages exhibited greater vulnerability consistent with phagocytic burden, while inflammatory challenge further enhanced NPs uptake, reinforcing intracellular persistence."
- "Emerging evidence highlights the intricate interplay between metabolic reprogramming and epigenetic modifications in macrophages"
- "Increasing evidence indicates that this failure is not determined solely by PD-1, PD-L1, CTLA-4, or T-cell exhaustion, but also by metabolically suppressive states within the tumor microenvironment."
- "PIEZO1 emerges as a central regulator that fine-tunes immune responses by integrating signals from the cellular microenvironment, influencing inflammation, pathogen clearance, and metabolic reprogramming."
- "Piezo1 activation aggravated OGD-induced macrophage ferroptosis via Ca2+ influx followed by SLC15A3 upregulation."
- "Piezo1 upregulated SLC7A11 in macrophages via a Ca2+/ATF4-dependent pathway."
- "A2AR signaling engaged HIF1α-dependent metabolic reprogramming to increase glycolysis, thereby providing the energetic support required for efficient and sustained efferocytosis."
- "Piezo1 was involved in the efficient acidification of the engulfed cargo in the phagolysosomes and affected the subsequent expression of anti-inflammation genes after efferocytosis."
- "Functional interrogation of differentially transcribed genes revealed adverse effects of M. gallisepticum on extracellular and intracellular signalling, cell communication, cellular actin dynamics, formation of the cellular cytoskeleton, and cellular metabolic pathways"
- "Phagocytosis requires coordinated remodeling of the actin cytoskeleton to generate protrusive and contractile forces that drive target engulfment."
- "We propose that depletion of the endomembrane pools is a major determinant of phagocytic fatigue as macrophages reach their phagocytic capacity."
- "In in vitro frustrated phagocytosis, specifically 2D phagocytosis by macrophages, the activation of the Fcγ receptor generates multiple self-organized waves containing F-actin, Arp2/3, and phosphoinositides."
- "Phagocytosis is a fundamental cellular process by which cells engulf external particles, controlled by receptor-ligand binding and actin-driven membrane dynamics."
- "Syk palmitoylation is important for Syk localization to the phagocytic cup, phosphorylation, and phagocytosis."
- "Inflammatory polarization of macrophages is a key player in inflammation-induced bone loss and can be driven by mechanosensitive ion channels."
- "However, effective pulmonary delivery is constrained by mucociliary clearance, airway mucus, alveolar macrophage uptake, and epithelial barriers."
- "Mechanistic analyses attributed these effects to decreased phagocytic internalization by Kupffer cells, splenic macrophages, and circulating monocytes."
- "Macrophages exhibited greater vulnerability consistent with phagocytic burden, while inflammatory challenge further enhanced NPs uptake, reinforcing intracellular persistence."
- "Emerging evidence highlights the intricate interplay between metabolic reprogramming and epigenetic modifications in macrophages"
- "Increasing evidence indicates that this failure is not determined solely by PD-1, PD-L1, CTLA-4, or T-cell exhaustion, but also by metabolically suppressive states within the tumor microenvironment."
- "PhIP-Seq analysis identified differential autoantibody reactivity related to muscle structural organisation and cytoskeletal regulation"
- "Immunofluorescence revealed colocalisation of MYO1F and the CASS group of proteins at actin-rich podosomes and phagocytic cups in macrophages and microglia."
- "Pharmacological activation of Piezo1 increased the efferocytosis capacity of macrophages and accelerated the resolution of inflammation and fibrosis."