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Engineering physiologically relevant anisotropic tissues remains a major challenge due to limitations in replicating native structural cues across complex geometries. Here, we developed a cryogenic extrusion bioprinting platform by precisely guiding ice crystal growth to achieve centimeter-scale anisotropic constructs, even with ultrasoft, low-viscosity inks (2% weight/volume GelMA). This approach enables the fabrication of anatomically matched, patient-specific constructs with tunable anisotropy, including bone graft substitutes and osteoporotic disease models. To overcome the height constraints of cryo-printing, we further developed cryo-assembly and LEGO-assembly strategies that allow integration of anisotropic units while maintaining continuous internal alignment. In vivo studies across wound healing, cranial defect, and femoral defect models validated that these anisotropic cues drive spatially guided cell migration, extracellular matrix (ECM) remodeling, and tissue site-specific regeneration, as evidenced by the ECM deposition. Our platform offers a scalable, clinically adaptable solution for engineering structurally and functionally relevant tissues, redefining the boundaries of anisotropic soft tissue fabrication.
Antibiotic resistance and oxidative stress-associated infections demand next-generation antimicrobial platforms that move beyond conventional drug mechanisms. Here, we present a nanozybiotic system comprising antibiotic-derived multienzyme-mimic carbon quantum dots co-doped with Cu/Ru (Cu/Ru-Moxi CDs). Engineered through a one-step hydrothermal approach, this platform incorporates a "One-Arrow-Three Hawks" strategy: (i) the retention of intrinsic antibacterial activity from Moxifloxacin, (ii) the emergence of dual peroxidase- (POD)- and catalase (CAT)-like nanozyme activities, and (iii) a pH-dependent catalytic response for potential reactive oxygen species (ROS) modulation. Cu/Ru-Moxi CDs exhibit strong POD- and CAT-like catalytic activity toward H2O2 (Km-TMB = 45.3 µM, Km-H2O2 = 555.3 µM). The nanozyme behavior further confers free-radical scavenging capability and pH-dependent POD- and CAT-like activity toward potential ROS modulation. The biological studies show retained antimicrobial activity against Gram-positive and Gram-negative bacteria, including multidrug-resistant MRSA, and even Mycobacterium tuberculosis (M. tuberculosis) (H37Rv/H37Ra). The Cu/Ru-Moxi CDs show enhanced biofilm inhibition against MRSA as compared to tested antibiotics. Moreover, the Cu/Ru-Moxi CDs show good cytocompatibility with CC50 > 100 µg/mL. The integration of precursor-derived antibiotic functionality with bimetallic catalytic centers, provides bactericidal action, dual nanozyme activity, and pH-dependent catalytic response, making Cu/Ru-Moxi CDs a promising multifunctional nanozybiotic platform.
Broadly neutralizing antibodies (bnAbs) targeting conserved regions of the betacoronavirus spike are important for pan-betacoronavirus protection and pandemic preparedness. Here, we report the isolation of a human monoclonal antibody, CC65.1, from a SARS-CoV-2 convalescent donor that targets the conserved S2 stem helix region. CC65.1 neutralizes various sarbecoviruses, including SARS-CoV-2, and binds to the MERS-CoV spike but lacks MERS-CoV-neutralizing activity due to insufficient binding affinity. We utilized directed evolution to enhance the binding affinity of CC65.1 for the MERS-CoV S2 stem helix, yielding engineered antibody variants with newly acquired MERS-CoV-neutralizing activity. High-resolution structural analysis reveals key paratope mutations that enhance binding and stabilize epitope engagement. Our findings demonstrate the potential of in vitro affinity maturation to expand the neutralization breadth of stem-helix-targeting antibodies across divergent betacoronaviruses. This work supports the development of engineered bnAbs for broadly protective betacoronavirus countermeasures and provides a strategy for achieving cross-lineage neutralization.
NK2 homeobox 1 (NKX2-1), a master regulator robustly expressed in lung, thyroid, and forebrain, is indispensable for specifying lung epithelial fate and serves as a definitive marker of lung progenitors. Here, we generated a human induced Pluripotent Stem Cell (iPSC) line harboring a doxycycline (dox)-inducible Cas9 and an NKX2-1-EGFP-puro reporter via CRISPR/Cas9-mediated homology-directed repair. This dual-function line combines inducible genome editing with real-time tracing of early lung progenitors, enabling their prospective isolation and screening for stage-specific maturation regulators. Therefore, this engineered iCas9-NKX2-1 EGFP line is a key resource for dissecting human lung development, modeling pulmonary disease, and advancing regenerative therapies.
Flat electronic bands enable fascinating emergent phenomena such as superconductivity and charge orders. A prevailing approach to realizing flat bands is to engineer lattice geometric constraints in twisted or kagome-like materials. An alternative approach is to utilize purely electronic-interaction-driven flat bands, yet a fundamental challenge is that extreme flatness requires ultrastrong interaction strength, which often leads to incoherent states. Here we demonstrate the concurrent formation of an interaction-driven flat band at the Fermi level and a [Formula: see text] charge order in a van der Waals magnet Fe5GeTe2 using high-resolution angle-resolved photoemission spectroscopy. This charge order is manifested by band folding within 30 meV below the Fermi level, with its nesting driven by flat bands. The presence of this flat band throughout the Brillouin zone and the logarithmic temperature dependence of its spectral weight suggest a phenomenological Kondo-like, coherent Fermi liquid emerging from strong correlations. Our work establishes a paradigm where an interaction-driven flat band promotes large-scale electronic ordering.
Laser and light-based energy devices have become integral to modern dermatologic practice, offering versatile, minimally invasive solutions for both clinical and aesthetic indications. This narrative review synthesizes current evidence on laser and light technologies, focusing on skin resurfacing, vascular and pigmented lesions, scar modulation, and adjunctive therapeutic roles. Foundational principles such as selective photothermolysis have evolved into advanced modalities, including fractional, nonablative, picosecond, and hybrid systems, enabling improved efficacy with reduced downtime and enhanced safety across diverse skin phototypes. While ablative lasers, particularly CO2 and Er:YAG, remain the gold standard for advanced photoaging and scar remodeling, nonablative and fractional devices offer comparable outcomes with improved tolerability. Vascular-specific lasers, such as the pulsed dye laser and Nd:YAG, demonstrate high efficacy in treating superficial and deep vascular lesions. Pigment-targeting technologies, including Q-switched and picosecond lasers, provide effective treatment for dyschromia and tattoo removal, with emerging evidence favoring picosecond platforms for improved safety and patient comfort. Multimodal approaches, including combination laser therapies, integration with radiofrequency, microneedling, platelet-rich plasma, and laser-assisted drug delivery, enhance clinical outcomes by targeting multiple tissue layers and pathophysiologic processes. Careful patient selection, parameter optimization, and attention to phototype-specific risks remain critical for minimizing complications such as postinflammatory hyperpigmentation. Advances in laser engineering and combination strategies continue to expand therapeutic capabilities. An individualized, evidence-based approach incorporating these technologies is essential for optimizing outcomes in dermatologic practice.
There is substantial interest in developing novel engineering strategies to promote the sustained metabolic fitness of therapeutic T cells. We previously showed that overexpression of RAS homologue enriched in brain (RHEB), a positive regulator of mammalian target of rapamycin complex 1 (mTORC1), promotes aerobic glycolysis and increases the anti-tumor functions of effector CD8+ T cells. To address whether these effects are conserved in CD4+ T cells, we have now examined how enforced activation of mTORC1 activity affects CD4+ T cell differentiation and function. Rheb overexpression induced a more balanced metabolic shift in CD4+ T cells than in CD8+ T cells, with increases in both oxidative phosphorylation and aerobic glycolysis. Although Rheb overexpression initially increased CD4+ T cell activation and proliferation in vitro, the underlying population architecture was complex, involving a shift to both more proliferative, cytotoxic-like cell states as well as more quiescent cell clusters characterised by counter-regulation of mTORC1 activity. Following adoptive transfer, tumor antigen-specific Rheb-transduced CD4+ T cells showed greater persistence but were less efficient than controls in eliminating tumor. This functional deficiency could be explained by a greater propensity of persisting Rheb-transduced CD4+ T cells to develop features of immune exhaustion, as evidenced by expression of multiple co-inhibitory receptors and impaired proliferation upon tumor rechallenge. Together, these data demonstrate the dynamic population response to tuning of T cell mTORC1 and the need to separately appraise cellular outputs of therapeutic CD4+ versus CD8+ T cells when metabolic pathways are manipulated by the same method.
Internal solitary waves (ISWs) are powerful underwater disturbances that can vertically displace water by more than 200 meters, driving ocean mixing and affecting offshore engineering. Yet, their global distributions and vertical imprints remain poorly characterized. Traditional satellite sensors are constrained by cloud cover or limited sampling. The Surface Water and Ocean Topography (SWOT) mission provides near-continuous, cloud-independent ocean observations at unprecedented resolution. Here, we develop an artificial intelligence framework to automatically detect ISWs worldwide. Using 29 SWOT orbital cycles (July 2023 to March 2025), this study reveals a global map of ISW distribution and amplitude variations, identifying energetic hot spots and distinct seasonal and tidal variations. These findings provide insights into ISW dynamics and offer a foundation for assessing their role in global energy redistribution and ocean-climate interactions.
Oral and periodontal diseases are among the most prevalent chronic disorders worldwide and arise from complex interactions between microbial biofilms and dysregulated host immune responses. Despite significant advances in conventional therapies, clinical management remains challenging because of limited drug penetration, rapid clearance within the oral cavity, and poor patient compliance. In this context, microneedle (MN)-based drug delivery systems have emerged as promising minimally invasive platforms for localized and controlled therapeutic delivery. However, the adaptation of MN technologies from transdermal to oral applications requires application-specific redesign owing to the unique anatomical, physiological, and mechanical characteristics of oral tissues. Current literature also remains fragmented, particularly regarding the integration of oral tissue biology, advanced manufacturing strategies, and multifunctional MN design. This review provides a comprehensive and critical analysis of MN systems for oral and periodontal applications, with particular focus on the enabling role of additive manufacturing (AM). First, the biological characteristics of oral tissues and their implications for drug delivery are discussed, followed by an overview of MN technologies, biomaterials, and fabrication approaches. Particular emphasis is placed on oral application-specific design considerations, including mechanical constraints, penetration depth, bioadhesion, retention, and controlled drug release. Emerging therapeutic applications, ranging from antibacterial and anti-inflammatory therapies to immunomodulatory and regenerative strategies, are also critically evaluated. Recent advances in 3D-printed MNs are highlighted, emphasizing their potential for customizable architectures, integrated drug delivery systems, and patient-specific therapeutic platforms. In parallel, major translational challenges, including mechanical reliability, retention under salivary conditions, regulatory complexity, and manufacturing scalability, are critically discussed. Future perspectives involving the integration of artificial intelligence (AI), smart biomaterials, biosensor technologies, and precision medicine approaches are also explored. Beyond summarizing recent advances, this review identifies the key scientific challenges, current knowledge gaps, and emerging engineering strategies required for the successful clinical translation of 3D-printed oral and periodontal MN systems. Overall, it provides a critical roadmap for the rational design and development of next-generation personalized MN platforms, highlighting the convergence of advanced biomaterials, biofabrication technologies, and precision medicine as a foundation for future oral healthcare.
Low-efficiency p-type impurity doping has long impeded the practical adoption of wide-bandgap semiconductors in integrated circuits (ICs). In wide-bandgap III-nitride semiconductors, the inherent polarization effects provide an alternative approach to engineering electrical properties. Here, we report the monolithic integration of polarization-doped InGaN p-channel FETs with polarization-doped GaN n-channel FETs for complementary logic (CL) circuitry. The enhancement-mode (E-mode) InGaN p-FET achieves a high current density exceeding 20 mA/mm. We construct a series of III-nitride CL building blocks, including inverter, ring oscillator (RO), NAND, NOR, RS latch, and 6T-SRAM. The inverter exhibits a high maximum voltage gain of 154.1 V/V, and the RO achieves a record short propagation delay per stage of 10.4 ns. Additionally, we demonstrate the monolithic integration of CL buffers with high-voltage GaN power transistors. These results establish the polarization-doped III-nitride CL platform as a promising solution for high-frequency power management ICs and harsh-environment electronics.
Recent advancements in dislocation engineering are reshaping the traditional view towards ceramics being brittle. Here, we use KTaO3 (KTO), a perovskite oxide that is newly discovered with room-temperature bulk plasticity, and demonstrate that the seeded dislocations can effectively tune both mechanical and functional properties. We uncover a brittle-ductile-brittle (BDB) transition: low dislocation densities lead to brittle failure, intermediate densities (∼1014 m-2) enable superior compression plastic deformation capacity with strains over 20%, and high dislocation densities (∼1015 m-2) induce brittle fracture again. This dislocation density-dependent non-monotonic mechanical response challenges the traditional behavior of ceramics and offers design opportunities. Furthermore, dislocation densities can monotonically decrease thermal conductivity, revealing a tradeoff between mechanical strength and functionality. The findings reveal a critical threshold of dislocation density in optimizing the performance of functional oxides, and provide a framework for using dislocations to design advanced materials where mechanical durability and enhanced functionality are intertwined.
Human metapneumovirus (hMPV) is a major respiratory pathogen that causes a substantial global disease burden, particularly in infants, older adults, and immunocompromised individuals. Despite more than two decades of research, no licensed vaccines or antiviral therapies are available, underscoring a persistent unmet clinical need. The viral fusion (F) glycoprotein is the leading target for vaccine and immunotherapeutic development due to its essential role in viral entry and its ability to elicit neutralizing antibodies. However, hMPV-F is highly metastable and undergoes conformational transitions from a prefusion (pre-F) state on infectious virions to a more stable postfusion (post-F) conformation. Although neutralizing antibodies can target epitopes in both conformations, the pre-F state is particularly important for eliciting the most potent neutralizing responses and is therefore the preferred immunogen for vaccine and antibody-based therapeutic design. This review summarizes recent structure-guided strategies to stabilize hMPV-F in its pre-F conformation, including proline substitutions, disulfide bond engineering, cavity-filling mutations, and scaffold-based approaches. We also synthesize preclinical immunogenicity data from multiple animal models and discuss implications for rational vaccine design. Collectively, these advances, combined with emerging immunological tools and the clinical success of respiratory syncytial virus (RSV) pre-F vaccines, provide a strong foundation to accelerate the development of effective hMPV vaccines and immunotherapeutics.
Oral squamous cell carcinoma (OSCC) remains a highly prevalent malignancy with limited improvement in 5-year survival rates, underscoring the need for novel therapeutic strategies. Plant-derived nanovesicles (PDNVs) have emerged as a new class of bioactive nanoparticles with intrinsic anticancer properties. In this study, we successfully isolated Rehmannia-derived nanovesicles (RDNVs) from fresh Rehmannia glutinosa roots and evaluated their antitumor efficacy and biosafety in OSCC. Characterization revealed that RDNVs exhibit typical exosome-like morphology and size distribution. In vitro, RDNVs were efficiently internalized by OSCC cells in a time- and concentration-dependent manner, leading to significant inhibition of cell proliferation via G1-phase arrest, as well as suppression of migration and invasion. In vivo, systemically administered RDNVs accumulated in tumor tissues and markedly suppressed tumor growth in a tongue orthotopic OSCC mouse model, with no observable systemic toxicity. Mechanistically, RDNVs exert their antitumor effects by downregulating the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway, thereby disrupting cell cycle progression. These findings identify RDNVs as a promising natural nanotherapeutic candidate for OSCC and provide a novel research paradigm bridging traditional herbal resources and modern nanomedicine.
Density dependence is a key characteristic of quorum sensing (QS) in fungi; however, no relevant reports have been found in Monascus. Therefore, this study aimed to investigate the effects of initial spore density on the morphological development and polyketide secondary metabolism of Monascus purpureus to elucidate the regulatory role of QS. At the high initial spore density, more active conidial development and secondary metabolism were observed in the early fermentation stage, accompanied by rougher hyphal surfaces, increased secretion and larger vacuoles. Gene set enrichment analysis (GSEA) based on transcriptomic data revealed that high initial spore density activated ribosome biosynthesis to support rapid cell growth and secondary metabolism, whereas low initial spore density upregulated genes associated with peroxisome biosynthesis, the enzymatic antioxidant system, fatty acid degradation, fatty acid biosynthesis, and asexual sporulation. Furthermore, the reduction in linoleic acid content at high initial spore density suggested that linoleic acid and its derivatives may function as putative quorum sensing molecules (QSMs). Finally, a potential regulatory network integrating initial spore density with secondary metabolism and development was proposed. These findings enhance the understanding of the QS network in Monascus and offer a theoretical basis for the optimization of fermentation processes.
Advanced packaging technologies have enabled electronic devices toward miniaturization, higher integration densities, and scalable optoelectronic applications. Among the key materials for low-dielectric redistribution layers, photosensitive polyimides (PSPIs) have emerged as a suitable candidate, owing to their combined capabilities in photo-patterning ability, mechanical strength, and low dielectric loss. However, recent research challenges the conventional view of performance trade-offs, demonstrating that molecular design and thermal management can be synergistically codesigned to enhance device performance. This review summarizes the latest advances in the molecular design of multifunctional PSPI design and highlights their integration into wafer-level packaging architectures. We focus on their role in promoting efficient heat dissipation from chip to external package and on reducing dielectric losses to improve signal integrity. Finally, future directions for PSPI-based materials are proposed, offering a forward-looking perspective for next-generation high-performance and flexible electronics.
Adoptive T cell therapy requires T cells to infiltrate vascular tissues and preserve immune function. In solid tumor treatment, however, the surrounding microenvironment produces abnormal vasculature that impedes T cell infiltration. An approach that enables vascular normalization and enhances adoptive T cell function in parallel is essential for effective therapy but has not been reported. Here, we report the use of lenvatinib (LEN) to induce transient vascular normalization, thereby facilitating T cell infiltration. Moreover, LEN enhances T cell persistence by promoting the differentiation of T cells toward a memory phenotype. Our results indicate that the differentiation is by suppressing the PI3K-AKT-mTOR pathway, which drives effector differentiation, and by activating FOXO1, a transcription factor that promotes memory formation. To coordinate the transient vascular normalization and T cell enhancement, we link LEN-loaded, PD-L1-blocking micelles to T cells through acid-labile click chemistry, forming pH-responsive T cell-nanodrug conjugates. The conjugates synchronize the intratumoral release of LEN and the PD-L1 antagonist peptide OPBP-1, thereby coordinating vascular normalization, T cell differentiation, and checkpoint blockade. In vivo, the conjugates increased intratumoral CD8+ T cells and splenic memory T cells by over sixfold in B16-OVA tumors and achieved complete regression in a subset of MC38-OVA tumors without systemic toxicity, providing a promising strategy for solid tumor immunotherapy.
This study aimed to determine public interest in intra-articular injection treatments for knee osteoarthritis (KOA) using Google Trends data. Relative search volumes (RSVs) for platelet-rich plasma (PRP), hyaluronic acid (HA), and stem cell treatments used in KOA treatment were analyzed using Google Trends data collected over the past decade (2015-2025). The annual search volume changes for each treatment were assessed using polynomial regression analysis. A subgroup analysis was performed based on the changes caused by COVID-19. The seasonal search trends were evaluated using the autoregressive integrated moving average model. Over the last 10 years, interest in the use of intra-articular injections for the treatment of KOA has increased. This increase was most pronounced in PRP. Although HA had a lower RSV than the other treatments, its trend toward a moderate increase was observed. Finally, although stem cells were the most common treatment between 2015 and 2020, their use has decreased in recent years. An increasing RSV trend was observed for PRP and HA over the past decade (R2 = 0.869, β = 7.364, P < .001; R2 = 0.880, β = 2.670, P < .001, respectively). Stem cells were the most common treatment between 2015 and 2020. They exhibited a decreasing trend in 2020 and beyond (R2 = 0.103, β = -1.002, P = .355). Seasonal analyses revealed no statistically significant differences in the number of searches across seasons. A dramatic decrease in the number of searches occurred during the COVID-19 pandemic. This decline is expected to revert to an increasing trend by 2022.
To date, the identity and maintenance of postnatal thymic epithelial progenitor cells (TEPCs) remain unclear, as does the persistence of bipotent TEPCs after birth or whether lineage-restricted progenitors independently maintain separate TEC compartments. Using an inducible lineage-tracing system based on expression of the thymoproteasomal protein β5t, which is expressed in embryonic and a subset of postnatal TEPCs, we explored the early dynamics of the relationships between thymic epithelial cell (TEC) progenitors and their progeny. Our results identified two potential lineage-biased progenitor subpopulations, distinguished by Ly6d expression. Additionally, we observed that aging disproportionately affects Ly6d- compared to Ly6d+ TEPCs, with implications for rejuvenation of aging thymic epithelia. This study provides insights into the developmental pathways of TEC lineages and their maintenance, contributing to strategies for enhancing thymic function in aging and disease.
Cognard type V dural arteriovenous fistulas (dAVFs), defined by spinal perimedullary venous drainage, represent a rare and aggressive neurovascular pathology. Comprehensive multicenter data remain scarce. The authors present the largest multicenter analysis to date, characterizing presentation, radiology, treatment, complications, and functional outcomes of Cognard type V dAVFs. The authors retrospectively analyzed patients with angiographically confirmed Cognard type V dAVFs from the Consortium for Dural Arteriovenous Fistula Outcomes Research (CONDOR), spanning 16 academic centers. Patient demographics, imaging features, treatment strategies, procedural complications, and modified Rankin Scale (mRS) scores were recorded. Among 1077 patients with dAVFs, 37 (3%) had Cognard type V lesions. The mean patient age was 57 years, and 59.5% of patients were male. Most presented with nonhemorrhagic neurological deficits (68%), while 14% had hemorrhage. The most common location was the foramen magnum (32%). Embolization was the primary treatment in 67% of cases, complete obliteration was achieved in 71% of cases. Upfront microsurgery was performed in 22% of patients (obliteration rate 88%), and radiosurgery in 14% (success rate 40%). Salvage treatment further improved obliteration outcomes. Temporary complications occurred in 8% of patients (3/37): 2 with transient neurological deficits postembolization and 1 with transient hydrocephalus after surgery. Permanent complications were observed in 3% (1/37) due to treatment-related hemorrhage. At the last follow-up (mean 2.4 years), 69% (24/35) of patients maintained or improved to an mRS score ≤ 2. No deaths occurred. Functional improvement was seen in 29% (10/35), while mRS decline was in 40% of patients (14/35), all unrelated to the dAVF itself. Cognard type V dAVFs carry a high risk of neurological morbidity. However, favorable functional outcomes are achievable with timely, multimodal intervention. Complication rates remain low, with most being transient. These data support aggressive but tailored management to prevent permanent disability in this high-risk population.
Digital phenotyping-the use of continuous data streams from digital devices such as smartphones to assess behavioral, psychological, and physiological states-holds transformative potential for health monitoring and personalized care. However, real-time analysis of large multimodal data often exceeds mobile devices' computational resources, leading most platforms to rely on sequential processing and cloud-based computation. We propose the Stanford Screenomics platform as a software reference architecture that uses a modular design to integrate parallel processing and edge computing, enabling scalable, real-time digital phenotyping on smartphones. Two prototype apps were developed: one following the parallel, on-device architecture (Stanford Screenomics platform) and another based on a traditional sequential, cloud-based design (traditional). Both processed identical multimodal data streams at the same intensity; only the location and sequence of computation differed. In two 48-hour experiments, performances were compared across four load profiles: low (≈10 MB/min), medium (≈30 MB/min), heavy (≈40 MB/min), and very heavy (≈60 MB/min). In the first experiment, offline resource performance was assessed under continuous simulated smartphone use. Virtual users completed six tasks in a fixed five-minute sequence: watching YouTube (Google LLC), reading eBooks, browsing TikTok (ByteDance Ltd), web surfing, listening to Spotify, and scrolling Instagram Reels (Meta). Minute-by-minute measurements of CPU usage (%), RAM usage (MB), battery drain (%/h), and data loss (%) were collected. Descriptive statistics (mean±SD) summarized performance, and independent t tests compared architectures. Data loss trajectories were analyzed to determine whether growth was linear or exponential under increasing load. In the second experiment, end-to-end phenotyping latency was evaluated over stable Wi-Fi. Five key-stage timestamps per trial tracked local writes, preprocessing, memory parsing, phenotype analysis, and intervention delivery. Total phenotype update time per trial was the primary outcome, and latency differences between architectures were analyzed using linear mixed-effects models, with IQRs reported to capture variability across load conditions. The Stanford Screenomics platform consistently demonstrated lower CPU usage (3.9%-14.6% vs 10.5%-26.9%) and RAM usage (97-132  MB vs 101-155  MB) than the traditional, with reduced battery drain (0.9%-2.1%/h vs 1.4%-3.2%/h). Data fidelity was higher in the Stanford Screenomics, with shallow linear data loss (0.4%-1.5%/h) compared to exponential growth in the traditional (2%-7.1%/h), achieving up to 9.4× greater data retention under very heavy load. The Stanford Screenomics completed phenotype updates in 0.90 seconds under low load and 9.32 seconds under very heavy load, compared to 30.1-398.1  seconds for traditional, representing 34-43×faster processing with substantially narrower variability (IQR 0.3-6 s vs 11  s-5  min). These results demonstrate that the Stanford Screenomics platform architecture enables real-time, on-device digital phenotyping with high fidelity and low latency. This validated prototype architecture establishes a resilient foundation for the next generation of scalable, reliable, and context-aware deployment of real-world mobile health interventions on mobile devices.