2026-10-07T08:31:42Z https://api.figshare.com/v2/oai

oai:figshare.com:article/34150259 2026-10-07T08:15:44Z category_1 category_4 category_7 category_12 category_64 category_146 category_873 category_915 portal_63 item_type_6 month_year_10_2026

Microsolvation Controls Ultrafast Relaxation Pathways in Hydrated Pyridine Deepthy Maria Mootheril (25405598) Anna D. Skitnevskaya (12511981) Xueguang Ren (8629311) Alexander I. Kuleff (2203747) Alexander B. Trofimov (2074384) Lorenz S. Cederbaum (1280112) Thomas Pfeifer (2122777) Alexander Dorn (8629314) Biophysics Biochemistry Medicine Cell Biology Cancer Space Science Chemical Sciences not elsewhere classified Physical Sciences not elsewhere classified prototypical nucleobase analogue induced damage pathways find evidence consistent 2s vacancy states electron impact ionization pyridine vacancies compete 0 < sub initiated icd shapes radiation results reveal related systems pyridine dimers neighboring molecule identify water hydrated pyridine following medium dual role biorelevant molecules auger decay additional pyridine 103 ev Hydration critically reshapes ultrafast electronic relaxation in biorelevant molecules, yet its mechanistic role remains poorly understood. Here, we investigate intermolecular Coulombic decay (ICD) following medium-energy (E0 = 103 eV) electron impact ionization of hydrated pyridine, a prototypical nucleobase analogue. Combining multiparticle momentum coincidence spectroscopy with high-level electronic structure calculations, we identify water-initiated ICD and find evidence consistent with an additional pyridine-initiated ICD pathway, in which inner-valence ionization leads to ionization of the neighboring molecule. Water vacancies decay exclusively via the ICD, establishing a highly efficient direct channel. In contrast, pyridine vacancies compete with Auger decay, reducing the efficiency of the pyridine-to-water ICD pathway. As in pyridine dimers, heterocycle-initiated ICD is dominated by N 2s vacancy states. Our results reveal a dual role of water: it opens a highly efficient direct ICD pathway via O 2s vacancy states and acts as an energy-accepting partner following biomolecular inner-valence ionization. These results reveal how microsolvation governs ultrafast relaxation and shapes radiation-induced damage pathways in DNA-related systems. 2026-10-07T00:00:00Z Text Journal contribution 10.1021/acs.jpca.6c05980.s001 https://figshare.com/articles/journal_contribution/Microsolvation_Controls_Ultrafast_Relaxation_Pathways_in_Hydrated_Pyridine/34150259 CC BY-NC 4.0

oai:figshare.com:article/34150257 2026-10-07T08:15:43Z category_1 category_4 category_12 category_14 category_19 category_21 category_46 category_272 category_873 category_915 portal_63 item_type_6 month_year_10_2026

Decagram Scale Synthesis and Deployment of a Picolinamide Ligand for a Copper-Catalyzed C–N Cross-Coupling Andrew McGrath (12610501) Dan Lehnherr (2062849) Biophysics Biochemistry Cell Biology Molecular Biology Pharmacology Biotechnology Immunology Environmental Sciences not elsewhere classified Chemical Sciences not elsewhere classified Physical Sciences not elsewhere classified one step via induced crystallization affords decagram scale renders 70 g scale 20 g scale process chemistry applications decagram scale synthesis commercially available 6 scalable access hydroxypicolinic acid friendly solvent excellent performance column chromatography The synthesis of a picolinamide ligand is demonstrated on a 70 g scale in a process-friendly solvent, and its application in a copper-catalyzed C–N cross-coupling on a 20 g scale is reported. The ligand can be accessed in one step via an amide coupling using inexpensive, commercially available 6-hydroxypicolinic acid and 6-methylquinolin-5-amine. A simple aqueous workup followed by a pH-swing-induced crystallization affords the ligand without the need for column chromatography. The combination of the scalable access to the ligand and its excellent performance in copper-catalyzed C–N cross-coupling on decagram scale renders this ligand attractive for deployment in process chemistry applications. 2026-10-07T00:00:00Z Text Journal contribution 10.1021/acs.oprd.6c00198.s001 https://figshare.com/articles/journal_contribution/Decagram_Scale_Synthesis_and_Deployment_of_a_Picolinamide_Ligand_for_a_Copper-Catalyzed_C_N_Cross-Coupling/34150257 CC BY-NC 4.0

oai:figshare.com:article/34150221 2026-10-07T08:15:05Z category_7 category_15 category_39 category_45 category_64 category_122 category_132 category_135 category_873 category_931 portal_63 item_type_6 month_year_10_2026

Attributing PM2.5 and NO2 Changes One Year after New York City’s Congestion Pricing Policy Polina M. Goldberg (25405572) Abhishek Anand (3245445) Daniel L. Goldberg (7543259) Daniel M. Westervelt (11331878) Medicine Neuroscience Ecology Sociology Cancer Mental Health Infectious Diseases Computational Biology Chemical Sciences not elsewhere classified Information Systems not elsewhere classified program may nonetheless differences regression attributes air quality policies across metropolitan nyc 2022 – 2024 congestion relief zone changes one year congestion pricing policy crz sites showed 5 </ sub 3 </ sup 2 </ sub congestion pricing crz sites p </ crz ). satellite observations outer boroughs nearby non meaningfully attributed lower manhattan january 2025 first year decline alongside columns declined broader landscape 50 μg 44 μg 34 ). 33 μg 2025 relative 096 ). 001 ). 001 ), In January 2025, New York City implemented the Central Business District Tolling Program (CBDTP), a congestion pricing policy targeting lower Manhattan. We evaluate its first-year air quality effects using ground-based and satellite observations. Comparing New York City Community Air Survey (NYCCAS) real-time PM2.5 measurements from the first year of CBDTP with 2022–2024, we find statistically significant decreases within the congestion relief zone (CRZ). Difference-in-differences regression attributes a 1.44 μg/m3 PM2.5 reduction at CRZ sites to the CBDTP (p < 0.001). Accounting for spillovers, the CRZ decrease remained similar (1.33 μg/m3, p < 0.001), while nearby non-CRZ sites showed a nonsignificant 0.50 μg/m3 increase (p = 0.34). TROPOMI tropospheric NO2 columns declined over 20% across metropolitan NYC in 2025 relative to a 2018–2024 baseline. Decreases were larger in lower Manhattan than the outer boroughs, but not enough to be meaningfully attributed to the CBDTP, which was associated with a nonsignificant 1.23% decrease in tropospheric NO2 (p = 0.096). The program may nonetheless have contributed to the regional NO2 decline alongside other air quality policies. These findings offer critical early evidence that congestion pricing can deliver measurable air quality benefits, while contextualizing local improvements within the broader landscape. 2026-10-07T00:00:00Z Text Journal contribution 10.1021/acs.estlett.6c00610.s001 https://figshare.com/articles/journal_contribution/Attributing_PM_sub_2_5_sub_and_NO_sub_2_sub_Changes_One_Year_after_New_York_City_s_Congestion_Pricing_Policy/34150221 CC BY-NC 4.0

oai:figshare.com:article/34150209 2026-10-07T08:14:51Z category_7 category_21 category_69 category_134 category_272 category_734 portal_63 item_type_6 month_year_10_2026

Elucidating pH-Dependent Silica Removal Mechanisms in Aluminum-Based Coagulation Tyler A. Malkoske (25405569) Sergi Garcia-Segura (6391304) Tiezheng Tong (622195) Medicine Biotechnology Inorganic Chemistry Virology Environmental Sciences not elsewhere classified Biological Sciences not elsewhere classified silicic acid polymerization major limiting factor improve process efficiency employed experimental investigations coagulant types considered alternative water sources silica removal mechanisms silica removal capacity enhance silica removal ph ≤ 8 2 +</ sup silica removal bound silica work provides synergistic interactions silanol groups saline brines rising ph rational operation precipitates showed ph 10 mechanistic basis level understanding ion exchange incomplete knowledge elucidating ph dependent increase chemical coagulation binding resulted based coagulation al − activated sites Silica scaling is a major limiting factor to the treatment and valorization of saline brines as alternative water sources. While coagulation provides competitive silica removal capacity compared to ion exchange and adsorption, the incomplete knowledge of silica removal mechanisms hinders efforts to improve process efficiency. In this study, we employed experimental investigations and materials characterization to advance the molecular-level understanding of silica removal during electrocoagulation (EC) and chemical coagulation (CC). EC provided greater silica removal compared to CC for all coagulant types considered. For both EC and CC, silica removal capacity increased 2- to 5-fold with rising pH. Characterization of precipitates showed that the pH-dependent increase in silica removal capacity was driven by Al−O−Si bond formation and silicic acid polymerization. A novel titration method revealed that at pH ≤ 8.0, silica binding occurred via η−OH2+ activated sites on aluminum precipitate, whereas at pH 10.0, binding resulted from reactions among partially deprotonated η−OH sites, bound silica, and silanol groups. Silica removal mechanisms were validated using synthetic brackish groundwater, where synergistic interactions between aluminum and Ca2+/Mg2+ substantially increased silica removal. This work provides a mechanistic basis for the rational operation of aluminum-based coagulation to enhance silica removal from saline brines. 2026-10-07T00:00:00Z Text Journal contribution 10.1021/acs.est.6c12764.s001 https://figshare.com/articles/journal_contribution/Elucidating_pH-Dependent_Silica_Removal_Mechanisms_in_Aluminum-Based_Coagulation/34150209 CC BY-NC 4.0

oai:figshare.com:article/34150194 2026-10-07T08:14:33Z category_4 category_12 category_13 category_14 category_16 category_19 category_21 category_46 category_64 category_128 category_135 category_873 portal_63 item_type_6 month_year_10_2026

Magnoflorine Ameliorates Metabolic Dysfunction-Associated Steatotic Liver Disease by Targeting the NDUFV1 Subunit of Complex I to Regulate the ROS/AMPK Signaling Pathway Jiali Rao (25405560) Xuefei Li (164781) Yushuang Zhang (7167923) Juan Guo (384038) Baomin Feng (682320) Yujie Lu (2257369) Xiaoyao Ma (3470258) Biochemistry Cell Biology Genetics Molecular Biology Physiology Pharmacology Biotechnology Immunology Cancer Hematology Computational Biology Chemical Sciences not elsewhere classified prevalent metabolic disorder fat cell models activated protein kinase natural bioactive compound disease target databases maintain lipid homeostasis inhibiting lipid biosynthesis natural alkaloid key target alleviates lipid study reveals significantly attenuated lowering effects limited therapeutics knockdown cells edible plants core subunit Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent metabolic disorder with limited therapeutics. Magnoflorine (MAG), a natural alkaloid from edible plants, ameliorates MASLD; however, its direct targets remain unclear. Here, by integrating thermal proteome profiling and disease target databases, we identified NADH ubiquinone oxidoreductase core subunit V1 (NDUFV1), a core subunit of mitochondrial Complex I, as a key target of MAG. MAG directly binds NDUFV1, suppresses mitochondrial electron transport chain activity, and alleviates lipid-induced reactive oxygen species (ROS) accumulation. In high-fat cell models and MASLD mice, MAG contributes to the restoration of AMP-activated protein kinase (AMPK) signaling, promoting fatty acid β-oxidation and inhibiting lipid biosynthesis to maintain lipid homeostasis. Notably, the lipid-lowering effects of MAG were significantly attenuated in NDUFV1-knockdown cells. This study reveals that MAG regulates lipid metabolism by targeting NDUFV1, highlighting its potential as a natural bioactive compound for MASLD. 2026-10-07T00:00:00Z Text Journal contribution 10.1021/acs.jafc.6c05636.s001 https://figshare.com/articles/journal_contribution/Magnoflorine_Ameliorates_Metabolic_Dysfunction-Associated_Steatotic_Liver_Disease_by_Targeting_the_NDUFV1_Subunit_of_Complex_I_to_Regulate_the_ROS_AMPK_Signaling_Pathway/34150194 CC BY-NC 4.0

oai:figshare.com:article/34150173 2026-10-07T08:14:04Z category_4 category_8 category_15 category_21 category_39 category_69 category_873 portal_63 item_type_6 month_year_10_2026

Cobalt-Doped CeO2 Nanozyme with Peroxidase-Like Activity for Broad-Spectrum and Recyclable Degradation of Aflatoxins Hongshuai Zhu (10758074) Ziyue Chen (4255657) Xinhua Xie (384078) Lei Bai (631944) Zhiguang Suo (9378498) Bobo Zhang (3702049) Jieqiong Qin (3843097) Huifu Ji (25405542) Biochemistry Microbiology Neuroscience Biotechnology Ecology Inorganic Chemistry Chemical Sciences not elsewhere classified step hydrothermal method six consecutive cycles serious health threat experimental characterization revealed ecosar predictions suggested demonstrating excellent reusability abundant oxygen vacancies optimized electronic structure food chain poses current degradation strategies sustainable nanozyme strategy exhibited remarkable peroxidase enabling efficient broad 2 </ sub 1 </ sub optimized nanozyme food matrices recyclable degradation degradation products degradation efficiency work provides nanozyme maintained mycotoxin detoxification mild conditions mass ratio like activity insufficient efficiency aqueous solution aflatoxins aflatoxins aflatoxin b Aflatoxins (AFs) contamination in the food chain poses a serious health threat, and current degradation strategies are limited by insufficient efficiency and stability. We developed a series of cobalt-doped CeO2 (Co@CeO2) nanozymes via a one-step hydrothermal method. The optimized nanozyme (Co-to-CeO2 mass ratio of 2:1) exhibited remarkable peroxidase-like activity, enabling efficient broad-spectrum degradation of aflatoxin B1, G1, and M1 under mild conditions, with removal efficiencies exceeding 90% in aqueous solution and approximately 80% in spiked edible oil samples. Density functional theory calculations and experimental characterization revealed that the enhanced catalytic performance originates from optimized electronic structure, abundant oxygen vacancies, and sustained reactive oxygen species generation. Notably, the nanozyme maintained over 80% degradation efficiency over six consecutive cycles, demonstrating excellent reusability. ECOSAR predictions suggested that the degradation products had reduced aquatic toxicity compared to the parent AFs. This work provides a sustainable nanozyme strategy for mycotoxin detoxification in food matrices. 2026-10-07T00:00:00Z Text Journal contribution 10.1021/acs.jafc.6c09097.s001 https://figshare.com/articles/journal_contribution/Cobalt-Doped_CeO_sub_2_sub_Nanozyme_with_Peroxidase-Like_Activity_for_Broad-Spectrum_and_Recyclable_Degradation_of_Aflatoxins/34150173 CC BY-NC 4.0

oai:figshare.com:article/34150155 2026-10-07T08:13:44Z category_1 category_14 category_21 category_39 category_64 category_272 category_734 category_873 portal_63 item_type_6 month_year_10_2026

Engineering a Single-Plasmid Dual-Pigment Escherichia coli Biosensor for Simultaneous Colorimetric Detection of Pb(II) and Hg(II) Zhaobo Hu (6198434) Yan Guo (83742) Peishuo Cao (25405530) Keyan Wei (3959672) Zongjie Ma (22274635) Boxin Li (10793172) Dong Li (212687) Liang Zhou (85586) Chang-ye Hui (8378499) Biophysics Molecular Biology Biotechnology Ecology Cancer Environmental Sciences not elsewhere classified Biological Sciences not elsewhere classified Chemical Sciences not elsewhere classified throughput screening platform site environmental monitoring response assays afforded escherichia coli top10 emergency pollution response crosstalk remaining within concentration matrix experiment cocontaminated environmental samples alongside nanomolar sensitivity standard microplate assay simultaneous colorimetric detection detection limits approach class iii surface 2 </ sup spiked surface water two pigment pathways water standard surface water pigment whole free pigment work presents signal interference seawater matrices seawater ). seawater ), robust performance orthogonal decoupling linear range eye discrimination dimensional cross dependent responses coexposure conditions cell biosensor acceptable range 977 μm 977 nm 620 nm 570 nm 488 μm 488 nm 244 μm 244 nm This work presents an engineered single-plasmid, dual-pigment whole-cell biosensor for simultaneous colorimetric detection of Pb(II) and Hg(II). To address the challenge of signal interference in cocontaminated environmental samples, a Pb(II)-responsive PbrR regulatory module driving indigo biosynthesis (blue, 620 nm) and an Hg(II)-responsive MerR module driving deoxyviolacein biosynthesis (purple, 570 nm) were integrated into Escherichia coli TOP10. The orthogonal decoupling of the two pigment pathways, combined with a unified 10 h induction protocol, enables independent chromogenic readout of both metals from a single cultivation. Dose-response assays afforded a broad linear dynamic range for Pb(II) of 0.977–2000 μM (R2 = 0.9503) with a limit of detection (LOD) of 0.977 μM, alongside nanomolar sensitivity for Hg(II) with a linear range of 0.244–250 nM (R2 = 0.9800) and an LOD of 0.244 nM. A two-dimensional cross-concentration matrix experiment further demonstrated that the two detection channels maintain distinguishable dose-dependent responses under coexposure conditions, with crosstalk remaining within an acceptable range. Robust performance was retained in spiked surface water and seawater matrices, yielding Pb(II) LODs of 0.244 μM (surface water) and 0.488 μM (seawater), and Hg(II) LODs of 0.488 nM (surface water) and 0.977 nM (seawater). These detection limits approach or fall below relevant environmental regulatory thresholds, including the Class III surface-water standard for Hg(II). This self-contained, instrument-free pigment-based approach enables naked-eye discrimination of both metals in a standard microplate assay, offering a low-cost, high-throughput screening platform that complements standard instrumental methods for on-site environmental monitoring and emergency pollution response. 2026-10-07T00:00:00Z Text Journal contribution 10.1021/acsomega.6c07888.s001 https://figshare.com/articles/journal_contribution/Engineering_a_Single-Plasmid_Dual-Pigment_Escherichia_coli_Biosensor_for_Simultaneous_Colorimetric_Detection_of_Pb_II_and_Hg_II_/34150155 CC BY-NC 4.0

oai:figshare.com:article/34150125 2026-10-07T08:13:12Z category_1 category_4 category_13 category_19 category_21 category_46 category_64 category_132 category_146 category_734 category_873 category_915 portal_63 item_type_6 month_year_10_2026

Cascade Thiol-Responsive Hydrogels Based on Poly(2-Isopropenyl-2-oxazoline) Cross-Linked with Ellman’s Reagent as Disulfide-Containing Cross-Linkers Peitao Yu (19233815) Tomáš Sedlačík (1488997) Richard Hoogenboom (1372614) Biophysics Biochemistry Genetics Pharmacology Biotechnology Immunology Cancer Infectious Diseases Space Science Biological Sciences not elsewhere classified Chemical Sciences not elsewhere classified Physical Sciences not elsewhere classified releasing thiophenolate moieties eye colorimetric detection essential physiological processes enables rapid naked released thiophenolate groups carboxylic acid groups generating red coloration oxazoline side groups responsive hydrogels based bearing reactive 2 oxazoline groups responsive hydrogels responsive materials widely explored upon exposure strong demand straightforward strategy programmable sensing nonbiomedical applications multilevel cascade mechanical properties hydrogel network hydrogel modulus events depends ellman ’ biological systems Thiol compounds play vital roles in environmental and biological systems, contributing to essential physiological processes, and there is a strong demand for methods to detect thiols and to design thiol-responsive materials. While stimuli-responsive hydrogels have been widely explored for biomedical and nonbiomedical applications, thiol-responsive hydrogels for thiol monitoring and detection remain scarcely reported. Herein, we present a straightforward strategy for synthesizing thiol-responsive hydrogels based on poly(2-isopropenyl-2-oxazoline) (PiPOx) bearing reactive 2-oxazoline side groups, cross-linked with Ellman’s reagent containing a disulfide linker. Disulfide bonds are incorporated into the hydrogel network through ester–amide junctions formed between the 2-oxazoline rings of PiPOx and the carboxylic acid groups of Ellman’s reagent. Upon exposure to thiols, the hydrogels undergo disulfide–thiol exchange reactions, releasing thiophenolate moieties and generating red coloration that enables rapid naked-eye colorimetric detection. Unexpectedly, the released thiophenolate groups further react with remaining 2-oxazoline groups of PiPOx, leading to decoloration accompanied by further evolution of the mechanical properties and enhancement of the hydrogel modulus. Consequently, a single thiol exposure induces a time-dependent cascade response involving swelling, softening, and coloration, followed by shrinking, stiffening, and decoloration. The timing of these events depends on thiol concentration, highlighting the potential of these hydrogels for time-programmable sensing and multilevel cascade-responsive materials. 2026-10-07T00:00:00Z Text Journal contribution 10.1021/acs.chemmater.6c01016.s001 https://figshare.com/articles/journal_contribution/Cascade_Thiol-Responsive_Hydrogels_Based_on_Poly_2-Isopropenyl-2-oxazoline_Cross-Linked_with_Ellman_s_Reagent_as_Disulfide-Containing_Cross-Linkers/34150125 CC BY-NC 4.0

oai:figshare.com:article/34145881 2026-10-07T07:15:14Z category_4 category_7 category_12 category_13 category_61 category_734 portal_63 item_type_3 month_year_10_2026

An Optimized Stem Cell Secretome Proteomics Platform: Application to Progranulin-Deficient iPSCs Jiawei Ni (13007757) Hope Tracey (25402591) Ling Hao (193154) Biochemistry Medicine Cell Biology Genetics Developmental Biology Biological Sciences not elsewhere classified powerful model systems growth factor deprivation secretome proteomics workflow human disease models abundance secreted proteins cell plating density media collection time deficient ipscs showed data analysis strategies progranulin deficiency reshapes ms acquisition methods standardized workflow preparation methods independent acquisition disease mechanisms derived proteins cell types cell confluency work establishes unlike many systematically optimized studying development step centrifugation regulate pluripotency regenerative medicine possible impairment optimized platform often masked ms provided media harvest lysosomal exocytosis intracellular proteomes intracellular contamination coordinated reduction Stem cells secrete diverse extracellular proteins that regulate pluripotency, differentiation, and cell–cell communication, making them powerful model systems for studying development, disease mechanisms, and regenerative medicine. However, robust stem cell secretome analysis remains technically challenging. Unlike many other cell types, pluripotent stem cells cannot tolerate serum starvation or growth factor deprivation, while low-abundance secreted proteins are often masked by media-derived proteins and intracellular contamination. Here, we systematically optimized the secretome proteomics workflow in induced pluripotent stem cells (iPSCs) by evaluating culture medium composition, conditioned-media collection time, cell plating density, media harvest and preparation methods, LC-MS acquisition methods, and data analysis strategies. Full-strength Essential 8 medium, 48 h media collection, 80% cell confluency, two-step centrifugation, and data-independent acquisition (DIA)LC-MS/MS provided the optimal secretome proteomics data quality. We then applied the optimized platform to an isogenic iPSC disease model to investigate how progranulin deficiency reshapes the extracellular and intracellular proteomes. Progranulin-deficient iPSCs showed a coordinated reduction of extracellular lysosomal hydrolases despite relatively modest intracellular proteome changes, suggesting altered lysosome trafficking and possible impairment of lysosomal exocytosis. Together, this work establishes a robust and standardized workflow for stem cell secretome proteomics and demonstrates its utility for investigating extracellular proteome remodeling in human disease models. 2026-10-07T00:00:00Z Dataset Dataset 10.1021/acs.jproteome.6c00588.s004 https://figshare.com/articles/dataset/An_Optimized_Stem_Cell_Secretome_Proteomics_Platform_Application_to_Progranulin-Deficient_iPSCs/34145881 CC BY-NC 4.0

oai:figshare.com:article/34145878 2026-10-07T07:15:13Z category_4 category_7 category_12 category_13 category_61 category_734 portal_63 item_type_3 month_year_10_2026

An Optimized Stem Cell Secretome Proteomics Platform: Application to Progranulin-Deficient iPSCs Jiawei Ni (13007757) Hope Tracey (25402591) Ling Hao (193154) Biochemistry Medicine Cell Biology Genetics Developmental Biology Biological Sciences not elsewhere classified powerful model systems growth factor deprivation secretome proteomics workflow human disease models abundance secreted proteins cell plating density media collection time deficient ipscs showed data analysis strategies progranulin deficiency reshapes ms acquisition methods standardized workflow preparation methods independent acquisition disease mechanisms derived proteins cell types cell confluency work establishes unlike many systematically optimized studying development step centrifugation regulate pluripotency regenerative medicine possible impairment optimized platform often masked ms provided media harvest lysosomal exocytosis intracellular proteomes intracellular contamination coordinated reduction Stem cells secrete diverse extracellular proteins that regulate pluripotency, differentiation, and cell–cell communication, making them powerful model systems for studying development, disease mechanisms, and regenerative medicine. However, robust stem cell secretome analysis remains technically challenging. Unlike many other cell types, pluripotent stem cells cannot tolerate serum starvation or growth factor deprivation, while low-abundance secreted proteins are often masked by media-derived proteins and intracellular contamination. Here, we systematically optimized the secretome proteomics workflow in induced pluripotent stem cells (iPSCs) by evaluating culture medium composition, conditioned-media collection time, cell plating density, media harvest and preparation methods, LC-MS acquisition methods, and data analysis strategies. Full-strength Essential 8 medium, 48 h media collection, 80% cell confluency, two-step centrifugation, and data-independent acquisition (DIA)LC-MS/MS provided the optimal secretome proteomics data quality. We then applied the optimized platform to an isogenic iPSC disease model to investigate how progranulin deficiency reshapes the extracellular and intracellular proteomes. Progranulin-deficient iPSCs showed a coordinated reduction of extracellular lysosomal hydrolases despite relatively modest intracellular proteome changes, suggesting altered lysosome trafficking and possible impairment of lysosomal exocytosis. Together, this work establishes a robust and standardized workflow for stem cell secretome proteomics and demonstrates its utility for investigating extracellular proteome remodeling in human disease models. 2026-10-07T00:00:00Z Dataset Dataset 10.1021/acs.jproteome.6c00588.s003 https://figshare.com/articles/dataset/An_Optimized_Stem_Cell_Secretome_Proteomics_Platform_Application_to_Progranulin-Deficient_iPSCs/34145878 CC BY-NC 4.0 eyJtZXRhZGF0YVByZWZpeCI6ICJvYWlfZGMiLCAidmVyYiI6ICJMaXN0UmVjb3JkcyIsICJvYWlfaGFuZGxlciI6IHRydWUsICJuZWVkc19tZXRhZGF0YSI6IGZhbHNlLCAiaW5zdGl0dXRpb25faWQiOiA2MywgInBhZ2UiOiAyLCAieEN1cnNvciI6ICJJbHN4TnpreE16VTNNekV6TURBd0xDQXpOREUwTlRnM09GMGkuYnM5LWR0RXFjUDJISUhjZHhnQ3BVYU5aN1ZZIiwgImV4cGlyYXRpb24iOiAiMjAyNi0xMC0wNyAwOTozMTo0MiJ9