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Open Access Publications from the University of California

Comparative Evaluation of R134a and HFO‐1234ze Cryogen Spray Cooling Using a Mouse Model With Controllable Epidermal Pigmentation

(2026)

OBJECTIVES: Cryogen spray cooling (CSC) is critical for protecting the epidermis during laser dermatologic procedures. The widely used cryogen, R134a, has a high global warming potential (GWP), motivating interest in environmentally favorable alternatives such as HFO-1234ze. This study evaluated whether HFO-1234ze provides epidermal protection comparable to R134a during laser exposure and investigated the mechanistic basis underlying any differences in cooling performance. METHODS: Laser-induced epidermal injury in conjunction with two cryogens was assessed in K14-SCF Mc1re/e mice with pharmacologically controllable interfollicular epidermal pigmentation. Laser treatment sites were assigned fluences relative to baseline skin lightness (L*) to span subthreshold to suprathreshold injury conditions, with cryogen assignment randomized. Hypopigmentation at Day 7 served as the primary injury endpoint and was scored independently by three blinded raters. Surface cooling induced by each cryogen was measured separately using thin-film thermocouples on a skin phantom, and subsurface temperature distributions were estimated using one-dimensional transient heat-transfer modeling. RESULTS: Mean hypopigmentation scores did not differ significantly between R134a- and HFO-1234ze-cooled sites across the full range of pigmentation and fluence studied (p = 0.46). Heat-map analysis and regression modeling confirmed that hypopigmentation increased with fluence and darker pigmentation but was independent of cryogen type. Surface temperature measurements using skin phantom revealed that R134a produced more aggressive transient cooling than HFO-1234ze, reaching approximately 10°C lower minimum temperatures. However, numerical modeling of skin cooling using heat flux inferred from phantom measurement showed that this surface advantage decayed rapidly with depth, resulting in ≤ 2°C-3°C differences within the viable epidermis. CONCLUSIONS: Despite differences in surface cooling magnitude, R134a and HFO-1234ze provided equivalent epidermal protection under clinically relevant conditions. These findings support HFO-1234ze as an effective, lower-GWP alternative to R134a for CSC in laser dermatologic applications.

Synergizing Chemical and AI Communities for Advancing Laboratories of the Future

(2026)

The development of automated experimental facilities and the digitization of experimental data have introduced numerous opportunities to radically advance chemical laboratories. As many laboratory tasks involve predicting and understanding previously unknown chemical relationships, machine learning (ML) approaches trained on experimental data can substantially accelerate the conventional design-build-test-learn process. This outlook article aims to help chemists understand and begin to adopt ML predictive models for a variety of laboratory tasks, including experimental design, synthesis optimization, and materials characterization. Furthermore, this article introduces how artificial intelligence (AI) agents based on large language models can help researchers acquire background knowledge in chemical or data science and accelerate various aspects of the discovery process. We present three case studies in distinct areas to illustrate how ML models and AI agents can be leveraged to reduce time-consuming experiments and manual data analysis. Finally, we highlight existing challenges that require continued synergistic effort from both experimental and computational communities to address.

Unlocking Two‐Photon Chiral Signatures in DNA‐Stabilized Silver Nanoclusters: Two‐Photon Circular Dichroism and Circularly Polarized Luminescence

(2026)

Near-infrared (NIR) emitters with chiroptical properties are a novel class of materials with significant promise for chiral sensing and optoelectronic applications. Chiral nanoparticles, in particular, offer distinct advantages over molecular chiral agents. However, their practical applications remain significantly hindered due to challenges to precisely control nanoparticle chirality and reduce heterogeneity. Here, we investigate one-photon (1P) and two-photon (2P) chiroptical properties of DNA-stabilized silver nanoclusters (DNA-AgN) as atomically defined, water-soluble chiral nanoprobes. We perform a detailed analysis of 1P and 2P circular dichroism (1P-CD and 2P-CD, respectively) and circularly polarized luminescence (CPL) of (DNA)2[Ag16Cl2]8+ , a NIR emissive DNA-AgN with solved crystal structure, over a broad wavelength range. We observe that (DNA)2[Ag16Cl2]8+ exhibits 2P-CD two orders of magnitude higher than 1P anisotropy factor, with additional CD bands in the NIR range. Interestingly, (DNA)2[Ag16Cl2]8+ also presents CPL with high anisotropy factors, upon both 1P and 2P excitation, with significant 2P CPL brightness. These findings demonstrate that DNA-AgN exhibits significant 1P- and 2P- excited chiroptical properties, highlighting their potential for chiral sensing and bioimaging at NIR wavelengths in the tissue transparency window.

Cerebral microhemorrhages in a mouse model of sickle cell disease

(2026)

Objectives: Stroke in sickle cell disease (SCD) is often attributed to large vessel involvement in the disorder, whereas the contribution of cerebral microvascular disease has been less explored. In this study, we investigated the formation of cerebral microvascular lesions and the involvement of mast cells in a humanized SCD mouse model. Methods: We studied hemorrhagic microvascular disease in a well-characterized mouse model of humanized transgenic sickle (HbSS-BERK) expressing >99% human sickle hemoglobin (HbS) and a control (HbAA-BERK) mouse model expressing normal human hemoglobin A (HbA). Mouse brains were analyzed by Prussian blue staining to detect cerebral microhemorrhage (CMH) formation. Mast cell identification was performed by toluidine blue staining. Results: SCD brain sections exhibited approximately 86% more CMH than controls (mean ± SE of 1.17 ± 0.22 vs. 0.63 ± 0.13 number/cm2, P = .02). Mast cells were positively correlated with CMH number in SCD mice (Spearman r = 0.42, P < .05), but not in control mice. Conclusion: SCD mice demonstrated significantly increased CMH load compared with control mice, and SCD microhemorrhages were associated with the number of mast cells. These findings highlight the significance of cerebral microvascular disease in SCD and imply that cerebral mast cells may be a novel therapeutic target in SCD.

Cover page of Effects of Tobacco Use on Oral Cancer Screening Algorithm Performance

Effects of Tobacco Use on Oral Cancer Screening Algorithm Performance

(2026)

Background/Objectives: Effective screening for oral cancer (OC) remains challenging. Inaccuracies contribute to delayed diagnosis and poor outcomes. Tobacco-related changes in oral mucosa may compromise the accuracy of oral screening approaches, and, in emerging "smart" screening modalities, they may overshadow the influence of other predictive variables. The objective of this study was to evaluate the screening accuracy of an imaging- and risk factor-based OC screening platform in individuals practicing different types of tobacco usage. Methods: 318 subjects who had previously screened positive for increased OC risk were recruited and sorted into "tobacco smoker", "tobacco vaper", "tobacco chewer", "hookah user", "multiple tobacco usage", or "tobacco non-user" groups. Next, demographic information, risk factors, outcome of clinical examination, as well as AFI and pWLI were recorded using a prototype OC screening platform. The OC risk assessment outcome from the OC screening platform was compared to that from an oral medicine specialist. Results: The screening platform demonstrated high sensitivity in tobacco chewers and hookah users, and it also exceeded 90% in smokers, vapers, and multi-product users. In tobacco non-users, 80% screening sensitivity was recorded. Screening specificity was considerably better in tobacco non-users than in the tobacco-user groups, and low in tobacco chewers (33.3%), vapers (55.6%), and smokers (62.5%). Across all groups, agreement between the screening platform outcome and specialist evaluation exceeded 80%. Significant differences in probe accuracy were noted between tobacco non-users and users (p < 0.05), except for tobacco vapers. Conclusions: These findings highlight the need to consider the effects of type of tobacco use on the OC screening approach, and to integrate these variables into imaging-and risk-factor-based algorithms for OC screening.

Cover page of A standardized data specification for reproducible, verifiable structured light and multispectral image sets

A standardized data specification for reproducible, verifiable structured light and multispectral image sets

(2026)

Spatial Frequency Domain Imaging (SFDI) is a quantitative wide-field imaging technique that uses light and diffuse optical spectroscopic principles to rapidly generate tissue optical property images. However, SFDI datasets present significant workflow challenges: they can be large (on the order of gigabytes), contain multiple image formats, and require computationally intensive processing. Additionally, SFDI images typically require calibration measurements, further complicating data organization. The proliferation of calibration data, imaging data, and processing options creates technical overhead and leads to reproducibility issues. While multiple "Open SFDI"initiatives exist, no standardized storage format has emerged, making the replication of published SFDI research difficult. Commercial solutions like Modulim's directory-based format contain trade secrets and lack open-source processing options. We are developing an open standard for SFDI images, extensible to multispectral images, dubbed SpectralMaps. This specification leverages modern Xarray data structures saved in Zarr format, offering fast loading of complete datasets or selected data chunks. Zarr permits lossless compression with partial loading of data, making data loading faster and partial data processing possible without loading the entire dataset. Metadata for measurements and processing history are included in the file. Datasets are identified by hashes included for verification. This specification provides a unified, transparent framework for storing, sharing, and processing SFDI data, reducing technical overhead and improving reproducibility across research groups. By adopting an open, extensible standard, the community can accelerate method development, enable cross-platform interoperability, and foster collaborative validation of SFDI techniques.

Cover page of Short-wave infrared (SWIR) spectroscopy and imaging of biological tissues: a decade of advancements (2016-2025)

Short-wave infrared (SWIR) spectroscopy and imaging of biological tissues: a decade of advancements (2016-2025)

(2026)

Significance: Short-wave infrared (SWIR) light has recently gained popularity in tissue spectroscopy and imaging applications for a wide range of biomedical applications, primarily due to advancements in hardware (e.g., cameras). Aim: We aim to provide a detailed review of SWIR-based biomedical optics studies from the past decade, during which there has been a proliferation of SWIR-based tissue-optics studies. Approach: We report literature occurring after the publication of our previous (2015) review of this space, describing next-generation SWIR-based techniques that hold significant promise for enhanced in vivo tissue characterization and clinical translation. Results: Interest from the biophotonics field in SWIR technology is typically attributable to (1) the capability of SWIR light to provide greater sensitivity to chromophores such as water and lipids, with absorption peaks not as prominent in the visible-to-near-infrared (VIS-NIR) spectral region, and (2) the potential for SWIR photons to penetrate through superficial tissue layers due to lower scattering in the SWIR than in the VIS-NIR, as well as substantially reduced attenuation from hemoglobin and melanin. Conclusion: This review of emerging SWIR biophotonic technologies illustrates the rapid growth in the use of SWIR light for in vivo tissue spectroscopy and imaging.

Cover page of Conspiracy thinking in American politics.

Conspiracy thinking in American politics.

(2026)

Conspiratorial thinking is an indelible part of American politics; indeed, conspiracy theories proliferated in North America even before the founding of the United States. A current headwind of trends appears to facilitate a surge in conspiratorial thinking, including the increased spread and accessibility of misinformation, steady declines in public trust in authority figures, and an increasingly polarized electorate marked by mutual partisan animosity. The annual symposium of the UC Irvine Center for Neuropolitics brought together experts in law, political science, neuroscience, philosophy, and psychology to discuss why and how conspiracy thought develops and persists. This paper synthesizes the insights from that symposium, addressing the foundations of conspiracy thinking in both individuals and society as a whole, and its place in the current American political landscape. Through integrating various disciplinary perspectives, the symposium aimed to identify possible pathways to alleviating the prevalence and influence of conspiratorial thinking.