Ipamorelin CJC-1295 Blend

Research Overview

Ipamorelin + CJC-1295 Blend serves as a valuable research tool for investigating synergistic growth hormone secretion mechanisms through dual pathway activation in laboratory settings. This formulation combines two distinct peptide compounds that act through complementary receptor systems to produce amplified GH release significantly exceeding effects of either compound administered alone. Research applications have expanded to encompass investigations of synergistic signaling mechanisms, optimal ratio determination, temporal dynamics of combined stimulation, and downstream metabolic and anabolic effects of enhanced GH pulsatility.

The scientific rationale for combining GHRH analogs with GHRPs derives from extensive research demonstrating synergistic rather than merely additive GH release when both pathways are activated simultaneously. Laboratory studies investigating this phenomenon reveal that combined GHRH and GHRP administration can produce 2-3 fold greater GH secretion compared to summed effects of individual compounds. This synergy occurs through convergent intracellular signaling pathways within pituitary somatotrophs, where GHRH receptor activation (adenylyl cyclase/cAMP pathway) and ghrelin receptor activation (phospholipase C/calcium pathway) combine to produce amplified transcriptional activation and GH secretory vesicle release.

Ipamorelin + CJC-1295 Blend research specifically investigates this synergistic interaction using two optimized peptide components. Ipamorelin, a fifth-generation GHRP, provides selective ghrelin receptor activation without the cortisol elevation or appetite stimulation associated with earlier GHRPs or native ghrelin. CJC-1295 without DAC offers enhanced stability compared to native GHRH while maintaining the shorter half-life necessary for pulsatile rather than sustained GH elevation. This combination enables investigation of physiological pulsatile GH patterns amplified through dual pathway activation.

Component Analysis: Ipamorelin

Molecular Characteristics:

• CAS Number: 170851-70-4
• Molecular Weight: 711.85 Da
• Molecular Formula: C₃₈H₄₉N₉O₅
• Sequence: Aib-His-D-2-Nal-D-Phe-Lys-NH₂
• Classification: Selective growth hormone secretagogue (fifth-generation GHRP)

Ipamorelin represents a significant advancement in GHRP development, incorporating structural modifications that maximize GH-releasing potency while minimizing non-selective pathway activation. The pentapeptide structure includes aminoisobutyric acid (Aib) at position 1 for N-terminal stability, D-2-naphthylalanine (D-2-Nal) and D-phenylalanine (D-Phe) at positions 3 and 4 for protease resistance and receptor binding, and a C-terminal amidated lysine preventing carboxypeptidase degradation.

Mechanism of Action:
Ipamorelin functions as a selective GHSR-1a (growth hormone secretagogue receptor type 1a) agonist, binding to ghrelin receptors on pituitary somatotroph cells. Receptor activation initiates Gq/11 protein-coupled signaling, activating phospholipase C (PLC) and generating inositol trisphosphate (IP3) and diacylglycerol (DAG). IP3 mobilizes intracellular calcium stores, while DAG activates protein kinase C (PKC). This calcium-dependent signaling cascade triggers GH secretory vesicle fusion with the plasma membrane, resulting in rapid GH release.

Selectivity Profile:
Unlike earlier generation GHRPs (GHRP-6, GHRP-2, Hexarelin), Ipamorelin demonstrates exceptional selectivity for GH release without significant activation of ACTH/cortisol or prolactin pathways. This selectivity profile enables investigation of GH-specific effects without confounding hormonal changes. Ipamorelin also lacks the appetite-stimulating effects associated with ghrelin or less selective GHRPs, providing cleaner experimental conditions for metabolic research.

Pharmacokinetic Properties:
Ipamorelin exhibits a plasma half-life of approximately 2 hours following IV or SC administration in research models. This moderate half-life enables investigation of pulsatile GH stimulation patterns with 2-3 daily administrations. GH elevation peaks 30-45 minutes post-administration with duration of 2-3 hours before return to baseline. The pharmacokinetic profile supports both acute stimulation studies and chronic pulsatile GH elevation research protocols.

Component Analysis: CJC-1295 (No DAC)

Molecular Characteristics:

• CAS Number: 863288-34-0
• Molecular Weight: 3,647.28 Da
• Molecular Formula: C₁₆₅H₂₆₉N₄₇O₄₆
• Amino Acid Count: 29 amino acids (modified GHRH 1-29)
• Classification: Synthetic GHRH analog, modified growth hormone-releasing hormone

CJC-1295 without DAC represents a strategically modified analog of growth hormone-releasing hormone, incorporating four amino acid substitutions designed to overcome the rapid enzymatic degradation limiting native GHRH’s research utility. Native GHRH exhibits a plasma half-life of only 7-10 minutes due to dipeptidyl peptidase-IV (DPP-IV) cleavage and other proteolytic degradation. CJC-1295’s modifications at positions 2 (D-Ala), 8 (Gln), 15 (Ala), and 27 (Leu) confer DPP-IV resistance and enhanced metabolic stability while preserving high-affinity GHRH receptor binding.

Mechanism of Action:
CJC-1295 binds to GHRH receptors (class B G-protein coupled receptors) on anterior pituitary somatotrophs, initiating Gs protein-coupled signaling. Receptor activation stimulates adenylyl cyclase, increasing intracellular cyclic AMP (cAMP) levels. Elevated cAMP activates protein kinase A (PKA), which phosphorylates cAMP response element-binding protein (CREB). Phosphorylated CREB binds to promoter regions of the growth hormone gene, increasing GH transcription. Simultaneously, increased cAMP and PKA activity enhance GH secretory vesicle priming and calcium channel activity, promoting GH release from existing stores.

No DAC Version Rationale:
The No DAC designation indicates absence of the Drug Affinity Complex modification present in the extended half-life version of CJC-1295. The DAC moiety binds to serum albumin, dramatically extending plasma half-life to approximately one week and producing sustained rather than pulsatile GH elevation. The No DAC version maintains a half-life of 30 minutes to 1 hour (significantly longer than native GHRH’s 7-10 minutes but much shorter than the DAC version), enabling investigation of amplified pulsatile GH secretion patterns rather than sustained elevation. This shorter duration allows multiple daily administrations mimicking physiological GH pulsatility while benefiting from enhanced stability compared to native GHRH.

Pharmacokinetic Properties:
CJC-1295 No DAC exhibits rapid GH elevation following administration with peak levels at 30-60 minutes and return to baseline within 2-3 hours in research models. The intermediate half-life between native GHRH and CJC-1295 with DAC provides experimental flexibility for investigating various dosing schedules. Subcutaneous bioavailability is well-documented in animal models, enabling diverse research protocol designs.

Synergistic Mechanisms and Pathway Convergence

The scientific foundation for combining Ipamorelin and CJC-1295 derives from well-characterized synergistic interactions between GHRH and GHRP pathways at multiple biological levels:

Cellular Signaling Convergence:
GHRH receptor activation (CJC-1295) and ghrelin receptor activation (Ipamorelin) engage distinct but convergent intracellular signaling cascades within somatotroph cells. The GHRH pathway elevates cAMP through adenylyl cyclase activation, while the ghrelin receptor pathway mobilizes intracellular calcium through phospholipase C activation. These second messenger systems converge on transcriptional regulation and secretory vesicle release mechanisms. Elevated cAMP activates PKA-dependent transcription factors, while calcium influx and PKC activation enhance GH gene expression through calcium-responsive elements. This dual signaling pathway activation produces synergistic transcriptional amplification exceeding effects of either pathway alone.

Transcriptional Synergy:
Research demonstrates that combined GHRH and GHRP pathway activation produces synergistic effects on growth hormone gene transcription. PKA-dependent CREB phosphorylation (GHRH pathway) and calcium/PKC-dependent transcription factor activation (ghrelin receptor pathway) act cooperatively on the GH gene promoter. Studies using GH promoter-reporter constructs demonstrate that combined pathway activation produces 2-4 fold greater transcriptional activity compared to additive effects of individual stimuli. This transcriptional synergy contributes to enhanced GH synthesis capacity supporting sustained pulsatile GH secretion during chronic combined treatment.

Secretory Vesicle Release Amplification:
Beyond transcriptional effects, GHRH and GHRP pathways synergistically enhance GH secretory vesicle fusion and release. GHRH-stimulated cAMP/PKA signaling primes secretory vesicles and enhances calcium channel function. Ghrelin receptor-mediated calcium mobilization directly triggers vesicle fusion through calcium-dependent SNARE protein interactions. Combined pathway activation produces rapid, high-amplitude GH release pulses exceeding the sum of individual pathway effects. This secretory synergy enables investigation of maximal GH secretory capacity and somatotroph responsiveness.

Somatostatin Regulation:
Both GHRH and GHRP pathways interact with somatostatin’s inhibitory regulation of GH secretion, though through partially distinct mechanisms. GHRH and somatostatin exert opposing effects on cAMP levels, with somatostatin inhibiting adenylyl cyclase. GHRP pathway activation can partially override somatostatin’s inhibitory effects through calcium-dependent mechanisms that are less sensitive to somatostatin’s cAMP suppression. Combined GHRH and GHRP pathway activation may provide enhanced capacity to overcome somatostatin’s inhibitory tone, contributing to synergistic GH release. This interaction becomes particularly relevant in research examining age-related or pathological states where elevated somatostatin tone suppresses GH secretion.

Receptor Regulation and Desensitization:
Long-term research applications must consider receptor regulation and potential desensitization. GHRH receptors can undergo desensitization with continuous agonist exposure, involving receptor phosphorylation, internalization, and downregulation. The pulsatile stimulation pattern enabled by CJC-1295 No DAC’s intermediate half-life helps minimize receptor desensitization compared to sustained agonist exposure. Similarly, ghrelin receptors undergo activity-dependent regulation. Alternating pathway activation through combined but pulsatile GHRH and GHRP administration may help maintain receptor responsiveness during chronic research protocols. Studies examining long-term combined treatment investigate whether dual pathway stimulation preserves GH responsiveness better than single-pathway continuous activation.

Pharmacokinetic Compatibility

The combination of Ipamorelin and CJC-1295 No DAC provides pharmacokinetic compatibility important for research protocol design:

Matched Half-Lives:
Both components exhibit plasma half-lives in the 30 minutes to 2 hour range (CJC-1295 No DAC approximately 30-60 minutes, Ipamorelin approximately 2 hours), providing temporal alignment for synergistic receptor activation. This pharmacokinetic matching enables simultaneous dual pathway stimulation when administered together, producing maximal synergistic GH release during overlapping plasma exposure periods.

Pulsatile Stimulation Pattern:
The moderate half-lives of both components enable investigation of amplified pulsatile GH secretion patterns rather than sustained elevation. Multiple daily administrations (typically 2-3 times daily in research protocols) produce repeated high-amplitude GH pulses with return to baseline between administrations. This pattern more closely mimics physiological GH secretion compared to sustained elevation produced by longer-acting compounds, while achieving pulse amplitudes exceeding physiological levels for investigating downstream GH/IGF-1 pathway effects.

Temporal Flexibility:
The similar pharmacokinetic profiles provide flexibility in research protocol design. Simultaneous administration maximizes acute synergistic GH release for studies examining immediate signaling events or peak GH levels. Staggered administration enables investigation of temporal sequence effects or prolonged stimulation windows. The intermediate half-lives support both acute studies (single administration) and chronic protocols (days to weeks of repeated dosing) for investigating time-dependent adaptations.

Research Applications

Synergistic GH Secretion Studies

Ipamorelin + CJC-1295 Blend serves as a primary research tool for investigating synergistic growth hormone release mechanisms:

• Synergy Quantification Research: Studies measuring GH release following individual component administration versus combined treatment to quantify synergistic amplification magnitude
• Dose-Response Relationship Investigation: Research characterizing optimal ratios of GHRH analog to GHRP for maximal synergistic GH release
• Temporal Dynamics Studies: Investigation of time course of synergistic GH elevation, including onset kinetics, peak amplitude, and duration
• Mechanism Characterization: Research examining intracellular signaling pathway convergence underlying synergistic GH release
• Somatotroph Responsiveness Studies: Investigation of pituitary cell capacity for GH synthesis and secretion under maximal dual pathway stimulation

Research protocols employ in vitro pituitary cell cultures for mechanistic studies, ex vivo pituitary explants for tissue-level investigation, and in vivo animal models for integrated physiological assessment of synergistic GH secretion.

GH/IGF-1 Axis Investigation

Substantial research focuses on downstream pathway activation resulting from enhanced GH secretion:

• IGF-1 Production Studies: Research examining hepatic IGF-1 synthesis in response to amplified GH pulsatility versus sustained GH elevation
• IGF-1 Receptor Signaling: Investigation of downstream IGF-1 receptor activation, PI3K/Akt pathway stimulation, and anabolic signaling cascades
• IGFBP Modulation Research: Studies on insulin-like growth factor binding protein expression and regulation affecting IGF-1 bioavailability
• Feedback Regulation Investigation: Research examining negative feedback effects of elevated IGF-1 on hypothalamic GHRH neurons and pituitary responsiveness
• Tissue-Specific IGF-1 Effects: Studies investigating autocrine/paracrine IGF-1 production in peripheral tissues responding to systemic GH elevation

Laboratory protocols investigate GH/IGF-1 axis dynamics using time-course sampling, tissue-specific IGF-1 measurements, and molecular analysis of IGF-1 signaling pathway activation in target tissues.

Anabolic Research Applications

Laboratory studies investigate Ipamorelin + CJC-1295 Blend in anabolic process research:

• Muscle Protein Synthesis Studies: Investigation of GH/IGF-1-mediated activation of muscle protein synthesis, mTOR pathway stimulation, and myofibrillar protein accretion
• Nitrogen Retention Research: Studies examining whole-body nitrogen balance, protein turnover rates, and amino acid uptake in response to enhanced GH/IGF-1 signaling
• Muscle Fiber Characterization: Research on muscle fiber type distribution, fiber cross-sectional area, and contractile protein expression
• Bone Formation Studies: Investigation of osteoblast activity, bone mineral density changes, and skeletal modeling/remodeling under enhanced GH/IGF-1 stimulation
• Collagen Synthesis Research: Studies on connective tissue collagen production, extracellular matrix remodeling, and tendon/ligament strength properties

Experimental models include muscle cell cultures (C2C12, primary myoblasts), bone cell systems (osteoblasts, osteocytes), and in vivo assessment of lean body mass, muscle morphology, and bone density using animal models with multiple weeks of treatment.

Body Composition Research

Research applications extend to body composition investigation:

• Fat Mass Reduction Studies: Examination of GH-mediated lipolysis, adipose tissue reduction, and mechanisms underlying fat mass decrease
• Lean Mass Preservation/Gain: Research on muscle mass maintenance or increase during energy restriction or aging models
• Body Composition Remodeling: Studies investigating simultaneous fat mass reduction and lean mass preservation/gain under enhanced GH/IGF-1 signaling
• Regional Fat Distribution: Investigation of preferential visceral versus subcutaneous adipose tissue responses to GH axis stimulation
• Adipokine Modulation Research: Studies on leptin, adiponectin, and other adipose-derived hormone regulation by GH/IGF-1 axis

Laboratory protocols employ body composition assessment techniques (DEXA, MRI, CT scanning in research animals) to quantify fat mass, lean mass, and regional distribution changes during chronic treatment protocols.

Metabolic Pathway Investigation

Research applications include metabolic process investigation:

• Glucose Metabolism Studies: Examination of GH effects on glucose uptake, insulin sensitivity, gluconeogenesis, and glucose homeostasis
• Lipid Metabolism Research: Investigation of lipolysis activation, fatty acid oxidation, lipid profile changes, and hepatic lipid metabolism
• Protein Metabolism Studies: Research on whole-body protein synthesis rates, amino acid kinetics, and nitrogen metabolism
• Energy Expenditure Investigation: Studies examining basal metabolic rate changes, substrate utilization shifts, and thermogenic responses
• Metabolic Flexibility Research: Investigation of metabolic adaptation and substrate switching capacity under altered GH/IGF-1 axis activity

Laboratory protocols investigate metabolic effects using indirect calorimetry, glucose and insulin tolerance testing, hyperinsulinemic-euglycemic clamps, metabolic tracer techniques (stable isotopes), and tissue-specific metabolic gene expression analysis.

Recovery and Tissue Repair Research

Emerging research areas include recovery and repair investigation:

• Post-Exercise Recovery Studies: Research examining GH/IGF-1 effects on muscle recovery, glycogen repletion, and adaptation to training stimuli
• Tissue Repair Mechanism Investigation: Studies on wound healing, tissue regeneration capacity, and repair processes in various tissue types
• Angiogenesis Research: Investigation of vascular growth factor expression (VEGF) and blood vessel formation supporting tissue growth and repair
• Anti-Catabolic Effect Studies: Research on GH/IGF-1 pathway protection against muscle protein breakdown during injury, immobilization, or catabolic stress
• Sleep and Recovery Research: Investigation of relationships between GH secretion patterns, sleep architecture, and recovery processes

Research protocols employ various tissue injury models, exercise/recovery paradigms, and immobilization/re-ambulation studies to investigate GH/IGF-1 effects on recovery processes.

Aging Research Applications

Substantial research focuses on age-related process investigation:

• Age-Related GH Decline Studies: Research on somatopause (age-related GH decline), mechanisms underlying decreased GH secretion, and somatotroph responsiveness changes
• Restoration of GH Pulsatility: Studies examining whether enhanced GH stimulation through dual pathway activation can restore more youthful GH secretion patterns
• IGF-1 Level Investigation: Research on age-related IGF-1 decline and factors regulating IGF-1 production capacity in aging
• Body Composition Changes: Studies investigating age-related sarcopenia (muscle loss) and adiposity changes, and potential modulation through GH axis stimulation
• Functional Capacity Research: Investigation of strength, physical function, and quality of life parameters in relation to GH/IGF-1 status in aging models

Research employs aged animal models (rats, mice) comparing responses in young versus aged subjects, and examining whether chronic treatment affects age-related phenotypic changes.

Optimal Dosing and Ratio Research

Important research considerations include determination of optimal component ratios and dosing strategies:

Ratio Investigation:
Published research examining GHRH and GHRP combinations has investigated various molar ratios to determine optimal synergistic effects. Studies typically examine ratios ranging from 1:1 to 1:3 (GHRH:GHRP) based on molar concentrations. Given the molecular weight difference (CJC-1295: 3,647.28 Da; Ipamorelin: 711.85 Da), equivalent molar dosing requires approximately 5-fold higher CJC-1295 mass. Research protocols should establish dose-response relationships for specific experimental models and research objectives.

Temporal Considerations:
Simultaneous administration typically produces maximal acute synergistic GH release. Alternative protocols investigating staggered administration examine whether sequential pathway activation affects synergy magnitude or duration. The overlapping pharmacokinetic profiles (both compounds active for 2-3 hours) provide flexibility in administration timing while maintaining synergistic interaction windows.

Frequency Optimization:
The moderate half-lives of both components enable 2-3 daily administrations for investigating enhanced pulsatile GH patterns. Research comparing once-daily, twice-daily, and three-times-daily administration examines effects of pulse frequency on downstream outcomes including IGF-1 production, body composition changes, and metabolic effects. Consideration of circadian GH rhythms informs optimal timing in research protocols.

Laboratory Handling and Storage Protocols

Lyophilized Powder Storage:

• Store at -20°C to -80°C in original sealed vials (separate vials for each component)
• Protect from light exposure and moisture
• Desiccated storage environment essential for long-term stability
• Stability data available for 24+ months at -20°C for both components

Reconstitution Guidelines:

• Reconstitute each component separately with sterile water, bacteriostatic water (0.9% benzyl alcohol), or appropriate buffer
• Add solvent slowly down vial side to minimize foaming
• Gentle swirling motion recommended (avoid vigorous shaking which may denature peptides)
• Allow complete dissolution before combining or use (typically 1-3 minutes)
• Final pH should be 6.0-7.5 for optimal stability of both components
• Combine reconstituted components in appropriate ratio based on research protocol requirements

Reconstituted Solution Storage:

• Short-term storage: 4°C for up to 7 days for both components
• Long-term storage: -20°C in single-use aliquots to avoid repeated freeze-thaw cycles
• Single-use aliquots strongly recommended to maintain peptide integrity
• Avoid repeated freeze-thaw cycles (maximum 2-3 cycles before significant degradation)
• If combining components, prepare fresh combinations for each experiment when possible

Stability Considerations:
Both Ipamorelin and CJC-1295 No DAC demonstrate good stability as lyophilized powders under proper storage conditions. Ipamorelin’s synthetic amino acid modifications (D-amino acids, Aib) confer protease resistance. CJC-1295’s modifications provide enhanced stability compared to native GHRH. Combined formulations should be stored under conditions appropriate for the less stable component.

Quality Assurance and Analytical Testing

Each Ipamorelin + CJC-1295 Blend batch undergoes comprehensive analytical characterization for both components:

Purity Analysis:

• High-Performance Liquid Chromatography (HPLC): ≥98% purity verified for each component
• Analytical method: Reversed-phase HPLC with UV detection
• Separate peak integration for each peptide component
• Verification of component ratio accuracy in pre-combined formulations

Structural Verification:

• Electrospray Ionization Mass Spectrometry (ESI-MS): Confirms molecular weights (711.85 Da for Ipamorelin, 3,647.28 Da for CJC-1295)
• Amino acid analysis: Verifies sequence composition for both peptides
• Peptide content determination: Quantifies actual peptide content by weight for each component

Contaminant Testing:

• Bacterial endotoxin: <5 EU/mg for each component (LAL method)
• Heavy metals: Below detection limits per USP standards
• Residual solvents: TFA and acetonitrile within acceptable limits
• Water content: Karl Fischer titration (<8% for each component)

Documentation:

• Certificate of Analysis (COA) provided with each batch including data for both components
• Third-party analytical verification available upon request
• Stability data documented for recommended storage conditions
• Batch-specific QC results traceable by lot number for each component

Research Considerations

Experimental Design Factors:

Researchers should consider several critical factors when designing experiments with Ipamorelin + CJC-1295 Blend:

1. Synergy Verification: Include experimental groups receiving each component individually at equivalent doses to verify synergistic versus additive effects in specific research models.

2. Ratio Optimization: Determine optimal component ratios for specific research objectives through preliminary dose-response studies if using pre-combined formulations or mixing separately.

3. Timing Considerations: Plan measurement timepoints based on pharmacokinetic profiles (30-60 minutes for peak GH, hours to days for IGF-1, weeks for body composition changes).

4. Model Selection: Choose appropriate experimental systems based on research questions (cell culture for mechanistic studies, animal models for integrated physiological responses).

5. Control Groups: Include appropriate vehicle controls, individual component groups, and potentially reference compounds (native GHRH, ghrelin) depending on research objectives.

6. Duration Considerations: Acute studies examine immediate GH release and signaling, while chronic studies (multiple weeks) investigate sustained effects on body composition, metabolism, and downstream adaptations.

Mechanism Investigation:

The synergistic mechanisms of Ipamorelin + CJC-1295 Blend have been characterized through multiple research approaches:

• Convergent intracellular signaling through cAMP (GHRH pathway) and calcium (ghrelin receptor pathway)
• Synergistic transcriptional activation of GH gene expression
• Amplified secretory vesicle release through combined pathway activation
• Potential enhancement of somatostatin override capacity
• Preserved receptor responsiveness through pulsatile stimulation patterns

Research protocols investigating these mechanisms employ molecular biology techniques (reporter gene assays, transcription factor analysis), cellular imaging (calcium imaging, vesicle trafficking), and electrophysiology approaches in addition to hormone measurements.

Compliance and Safety Information

Regulatory Status:
Ipamorelin + CJC-1295 Blend is provided as a research chemical blend for in-vitro laboratory studies and preclinical research only. These compounds have not been approved by the FDA as a combination therapy for human therapeutic use, dietary supplementation, or medical applications.

Intended Use:

• In-vitro cell culture studies examining synergistic signaling mechanisms
• In-vivo preclinical research in approved animal models with appropriate IACUC protocols
• Laboratory investigation of GH axis biology and synergistic pathway activation
• Academic and institutional research applications investigating dual-pathway GH secretagogue effects

NOT Intended For:

• Human consumption or administration
• Therapeutic treatment or diagnosis
• Dietary supplementation
• Veterinary therapeutic applications without appropriate regulatory oversight
• Performance enhancement purposes

Safety Protocols:
Researchers should follow standard laboratory safety practices when handling Ipamorelin + CJC-1295 Blend:

• Use appropriate personal protective equipment (lab coat, nitrile gloves, safety glasses)
• Handle in well-ventilated areas or chemical fume hood when preparing solutions
• Follow institutional biosafety guidelines and chemical hygiene protocols
• Dispose of waste according to local regulations for biological/chemical waste
• Consult material safety data sheets (MSDS) for both components for additional safety information
• Maintain proper documentation of handling and usage per institutional requirements

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