Trapped in Cells: A Selective Accumulation Approach for Type-I Photodynamic Ablation of Cancer Stem-like Cells.

Aldehyde dehydrogenase (ALDH) is an enzyme responsible for converting aldehyde functional groups into carboxylate metabolites. Elevated ALDH activity is a characteristic feature of cancer stem-like cells (CSCs). As a novel approach to target the CSC trait of overexpressing ALDH, we aimed to utilize ALDH activity for the selective accumulation of a photosensitizer in ALDHHigh CSCs. A novel ALDH substrate photosensitizer, SCHO, with thionylated coumarin and N-ethyl-4-(aminomethyl)benzaldehyde was developed to achieve this goal. Our study demonstrated the efficient metabolism of the aldehyde unit of SCHO into carboxylate, leading to its accumulation in ALDHHigh MDA-MB-231 cells. Importantly, we established the selectivity of SCHO as an ALDHHigh cell photosensitizer as it is not a substrate for ABC transporters. SCHO-based photodynamic therapy triggers apoptosis and pyroptosis in MDA-MB-231 cells and further reduces the characteristics of CSCs. Our study presents a novel strategy to target CSCs by exploiting their cellular metabolism to enhance photosensitizer accumulation, highlighting the potential of photodynamic therapy as a powerful tool for eliminating ALDHHigh CSCs.

Accelerometer-Based Physical Activity and Health-Related Quality of Life in Korean Adults: Observational Study Using the Korea National Health and Nutrition Examination Survey.

BACKGROUND: Health-related quality of life (HRQoL) reflects an individual's perception of their physical and mental health over time. Despite numerous studies linking physical activity to improved HRQoL, most rely on self-reported data, limiting the accuracy and generalizability of findings. This study leverages objective accelerometer data to explore the association between physical activity and HRQoL in Korean adults. OBJECTIVE: The objective of this study is to analyze the relationship between objectively measured physical activity using accelerometers and HRQoL among Korean adults, aiming to inform targeted interventions for enhancing HRQoL through physical activity. METHODS: This observational study included 1298 participants aged 19-64 years from the Korea National Health and Nutrition Examination Survey (KNHANES) VI, who wore an accelerometer for 7 consecutive days. HRQoL was assessed using the EQ-5D questionnaire, and physical activity was quantified as moderate-to-vigorous physical activity accelerometer-total (MVPA-AT) and accelerometer-bout (MVPA-AB). Data were analyzed using logistic regression to determine the odds ratio (ORs) for low HRQoL, adjusting for socioeconomic variables and mental health factors. RESULTS: Participants with higher HRQoL were younger, more likely to be male, single, highly educated, employed in white-collar jobs, and had higher household incomes. They also reported less stress and better subjective health status. The high HRQoL group had significantly more participants meeting MVPA-AB ≥600 metabolic equivalents (P<.01). Logistic regression showed that participants meeting MVPA-AB ≥600 metabolic equivalents had higher odds of high HRQoL (OR 1.55, 95% CI 1.11-2.17). Adjusted models showed consistent results, although the association weakened when adjusting for mental health factors (OR 1.45, 95% CI 1.01-2.09). CONCLUSIONS: The study demonstrates a significant association between HRQoL and moderate to vigorous physical activity sustained for at least 10 minutes, as measured by accelerometer. These findings support promoting physical activity, particularly sustained moderate to vigorous activity, to enhance HRQoL. Further interventional studies focusing on specific physical activity domains such as occupational, leisure-time, and commuting activities are warranted.

Ursodeoxycholic acid is associated with better clinical outcomes in COVID-19 patients: A population-based cohort study.

BACKGROUND: Several studies have investigated the relationship between ursodeoxycholic acid (UDCA) and coronavirus disease 2019 (COVID-19). However, complex and conflicting results have generated confusion in the application of these results. OBJECTIVE: We aimed to investigate whether the association between UDCA and COVID can also be demonstrated through the analysis of a large-scale cohort. METHODS: This retrospective study used local and nationwide cohorts, namely the Jeonbuk common data model cohort (JBUH CDM) and the Korean National Health Insurance claim-based database (NHIS). We investigated UDCA intake and its relationship with COVID-19 susceptibility and severity using validated propensity score (PS) matching. RESULTS: Regarding the COVID-19 susceptibility, the adjusted hazard ratio (aHR) value of the UDCA intake was significantly lowered to 0.71 in the case of JBUH CDM (95% confidence interval (CI): 0.52-0.98), and was significantly lowered to 0.93 (95% CI: 0.90-0.96) in the NHIS. Regarding the COVID-19 severity, the UDCA intake was found to be significantly lowered to 0.21 (95% CI: 0.09-0.46) in the case of JBUH CDM. It was also found that the aHR value was significantly lowered to 0.77 in the case of the NHIS (95% CI: 0.62-0.95). CONCLUSIONS: Using a large-scale local and nationwide cohort, we confirmed that UDCA intake was significantly associated with the reduction of COVID-19 susceptibility and severity. These trends remained consistent regardless of the UDCA dosage. This suggests the potential of UDCA as a preventive and therapeutic agent for COVID-19.

Diaminonaphthalene Boronic Acid (DANBA): New Approach for Peroxynitrite Sensing Site.

Selective detection of reactive oxygen species (ROS) is vital for studying their role in brain diseases. Fluorescence probes can distinguish ONOO- species from other ROS; however, their selectivity toward ONOO- species depends on the ONOO- recognition group. Aryl-boronic acids and esters, which are common ONOO- recognition groups, are not selective for ONOO- over H2O2. In this study, we developed a diaminonaphthalene (DAN)-protected boronic acid as a new ONOO- recognition group that selectively reacts with ONOO- over H2O2 and other ROS. Three DAN-protected boronic acid (DANBA)-based fluorophores that emit fluorescence over visible to near-infrared (NIR) regions, Cou-BN, BVP-BN, and HDM-BN, and their aryl-boronic acid-based counterparts (Cou-BO, BVP-BO, and HDM-BO), were developed. The DANBA-based probes exhibited enhanced selectivity toward ONOO- over that of their control group, as well as universality in MTT assays and in vitro experiments with PC12 cells. The NIR-emissive HDM-BN was optimized to delineate in vivo ONOO- levels in mouse brains with Parkinson's disease. This DAN-protected boronic acid belongs to a new generation of recognition groups for developing ONOO- probes, and this strategy could be extended to other common hydroxyl-containing dyes to detect ONOO- levels in complex biological systems and processes.

RNA-Activatable Near-Infrared Photosensitizer for Cancer Therapy.

Photodynamic therapy (PDT) has recently come to the forefront as an exceptionally powerful and promising method for the treatment of cancer. Existing photosensitizers are predominantly engineered to target diverse biomolecules, including proteins, DNA, lipids, and carbohydrates, and have proven to greatly enhance the efficacy or specificity of PDT. However, it is noteworthy that there exists a conspicuous scarcity of photosensitizers specifically designed to target RNAs. Recognizing the crucial and multifaceted roles played by RNAs in various cellular processes and disease states, we have ventured into the development of a novel RNA-targeting photosensitizer, named Se-718, designed specifically for PDT-based cancer therapy. Se-718 has been engineered to exhibit a high molar absorption coefficient in the NIR region, which is crucial for effective PDT. More importantly, Se-718 has demonstrated a distinct RNA-targeting capability, as evidenced through rigorous testing in both circular dichroism and fluorescence experiments. Furthermore, Se-718 has been shown to display both type I and type II photodynamic properties. This unique characteristic enables the efficient killing of cancer cells under a wide range of oxygen conditions, both normoxic (21% O2) and hypoxic (2% O2). The IC50 of Se-718 can be as low as 100 nM, and its light-to-dark toxicity ratio is an impressive 215 times higher, outperforming most photosensitizers currently available. Moreover, in vivo studies conducted with tumor-bearing mice have demonstrated the excellent antitumor effects and high safety profile of Se-718. Considering the outstanding PDT efficacy of Se-718, we are optimistic that the development of RNA-targeting photosensitizers may provide an innovative and highly effective option for cancer therapeutics in the near future.

Status and Trends of the Digital Healthcare Industry.

OBJECTIVES: This review presents a comprehensive overview of the rapidly evolving digital healthcare industry, aiming to provide a broad understanding of the recent landscape and directions for the future of digital healthcare. METHODS: This review examines the key trends in sectors of the digital healthcare industry, which can be divided into four main categories: digital hardware, software solutions, platforms, and enablers. We discuss electroceuticals, wearables, standalone medical software, non-medical health management services, telehealth, decentralized clinical trials, and infrastructural systems such as health data systems. The review covers both global and domestic perspectives, addressing definitions, significance, revenue trends, major companies, regulations, and socioenvironmental factors. RESULTS: Diverse growth patterns are evident across digital healthcare sectors. The applications of electroceuticals are expanding. Wearables are becoming more ubiquitous, facilitating continuous health monitoring and data collection. Artificial intelligence in standalone medical software is demonstrating clinical efficacy, with regulatory frameworks adapting to support commercialization. Non-medical health management services are expanding their scope to address chronic conditions under professional guidance. Telemedicine and decentralized clinical trials are gaining traction, driven by the need for flexible healthcare solutions post-pandemic. Efforts to build robust digital infrastructure with health data are underway, supported by data banks and data aggregation platforms. CONCLUSIONS: Advancements in digital healthcare create a dynamic, transformative landscape, integrating, complementing, and offering alternatives to traditional paradigms. This evolution is driven by continuous innovation, increased stakeholder participation, regulatory adaptations promoting commercialization, and supportive initiatives. Ongoing discussions about optimal digital technology integration and effective healthcare strategy implementation are essential for progress.

Dual oxidative stress biomarkers co-recognition in periodontal microenvironment: A flexible and low-power consumption nanozyme sensing platform.

Sensing platforms with high interference immunity and low power consumption are crucial for the co-detection of dual oxidative stress biomarkers and clinical diagnosis of periodontitis. Herein, we constructed a bifunctional nanozyme to identify hydrogen peroxide (H2O2) and ascorbic acid (AA) with low crosstalk at zero or low bias voltage. To target H2O2 and AA, Fe(III) meso-tetra(4-carboxyphenyl) porphine (TCPP(Fe)) and Pt nanoclusters were selected as active sites respectively, and titanium carbide nanosheets were additionally introduced as a sensitizer. Due to their highly efficient catalytic properties, self-powered detection of H2O2 without bias voltage and distinguishable AA detection at 0.45 V were successfully achieved. Density functional theory calculations further confirmed the binding sites for target molecules and elucidated the sensing mechanism. On this basis, a dual-channel screen-printed electrode was fabricated to further ensure the discriminative detection of dual biomarkers at the device level. The constructed flexible, low-power consumption sensing platform was successfully applied to raw clinical samples, effectively distinguishing between healthy individuals and patients with varying degrees of periodontitis. This work is expected to provide new insights into the design of highly specific nanozymes and low-power consumption electrochemical sensing systems, which will contribute to the accurate and convenient diagnosis of periodontitis.

Activatable Heavy-Atom-Free Photosensitizer with Large Stokes Shift and a NIR-II Emission Harnessing Rhodamine Ring-Opening Strategy.

Activatable photosensitizers (PSs) generating 1O2 only under specific conditions can minimize concomitant injury to normal tissues. Heavy-atom-free PSs hold the merits of low dark toxicity, long triplet-state lifetimes, good photostability, and relatively low cost. PSs with emission in the second near-infrared (NIR-II) window are highly valuable for deep-tissue, high-contrast imaging. Herein, we have designed and synthesized a series of heavy-atom-free PSs by a one-step reaction between an easily accessible rhodamine derivative and commercially available thiophene aldehydes. One of the as-prepared PSs, 2b-3T, exhibits emission maxima at 810 nm and tails to the NIR-II region at 1140 nm, together with large Stokes shift (178 nm). Importantly, the newly developed PSs, featuring functional carboxylic acid groups, present promising opportunities as versatile platforms for creating activatable PSs. To validate our concept, we developed Cu2+/pH-activatable PSs using the spirocyclization mechanism of rhodamine. Ultimately, we showcased the effectiveness of these innovative PSs in photodynamic therapy through in vitro experiments.

PCSK9 Inhibitors and the Risk of Vitiligo: A Mendelian Randomization Study.

Lipid-lowering agents have been suggested as a therapeutic option for vitiligo on the basis of the potential pathogenic role of lipid metabolism abnormalities. We aimed to explore the impact of genetically proxied lipid-lowering agents on the risk of vitiligo and potentially associated mediators. GWAS summary statistics for European ancestry were extracted from the largest available meta-analysis for vitiligo: the Global Lipids Genetics Consortium for 7 lipid profiles and 2 large biobanks, UK Biobank and deCODE, for 4719 proteins. After identifying lipid-lowering agents with genetically proxied protective effects against vitiligo using lipid-lowering and protein-inhibition Mendelian randomization (MR) analyses, multivariable and 2-step MR analyses were conducted to identify potential mediators between lipid-lowering agents and vitiligo. Lipid-lowering MR indicated a potential role of PCSK9 in reducing the vitiligo risk (OR [95% confidence interval] = 0.71 [0.52-0.95]), which was replicated in PCSK9-inhibition MR analyses across 2 separate biobanks (UK Biobank: OR [95% confidence interval] = 0.82 [0.71-0.96]; deCODE: OR [95% confidence interval] = 0.78 [0.67-0.91]). Multivariable MR suggested that well-known lipid profiles do not mediate the relationship between PCSK9 and vitiligo, whereas 2-step MR analyses identified 5 potential protein mediators (CCN5, CXCL12, FCRL1, legumain, and FGF2). Hence, PCSK9 inhibitor may attenuate the vitiligo risk; PCSK9 and the potential protein mediators can serve as promising novel therapeutic targets for its effective treatment.

Lutetium Texaphyrin-Celecoxib Conjugate as a Potential Immuno-Photodynamic Therapy Agent.

Immuno-photodynamic therapy (IPDT) has emerged as a new modality for cancer treatment. Novel photosensitizers can help achieve the promise inherent in IPDT, namely, the complete eradication of a tumor without recurrence. We report here a small molecule photosensitizer conjugate, LuCXB. This IPDT agent integrates a celecoxib (cyclooxygenase-2 inhibitor) moiety with a near-infrared absorbing lutetium texaphyrin photocatalytic core. In aqueous environments, the two components of LuCXB are self-associated through inferred donor-acceptor interactions. A consequence of this intramolecular association is that upon photoirradiation with 730 nm light, LuCXB produces superoxide radicals (O2-•) via a type I photodynamic pathway; this provides a first line of defense against the tumor while promoting IPDT. For in vivo therapeutic applications, we prepared a CD133-targeting, aptamer-functionalized exosome-based nanophotosensitizer (Ex-apt@LuCXB) designed to target cancer stem cells. Ex-apt@LuCXB was found to display good photosensitivity, acceptable biocompatibility, and robust tumor targetability. Under conditions of photoirradiation, Ex-apt@LuCXB acts to amplify IPDT while exerting a significant antitumor effect in both liver and breast cancer mouse models. The observed therapeutic effects are attributed to a synergistic mechanism that combines antiangiogenesis and photoinduced cancer immunotherapy.

An ATP-responsive metal-organic framework against periodontitis via synergistic ion-interference-mediated pyroptosis.

Periodontitis involves hyperactivated stromal cells that recruit immune cells, exacerbating inflammation. This study presents an ATP-responsive metal-organic framework (Mg/Zn-MOF) designed for periodontitis treatment, utilizing ion interference to modulate immune responses and prevent tissue destruction. Addressing the challenges of synergistic ion effects and targeted delivery faced by traditional immunomodulatory nanomaterials, the Mg/Zn-MOF system is activated by extracellular ATP-a pivotal molecule in periodontitis pathology-ensuring targeted ion release. Magnesium and zinc ions released from the framework synergistically inhibit membrane pore formation by attenuating Gasdermin D (GSDMD) expression and activation. This action curtails pyroptosis, lactate dehydrogenase and IL-1ß release, thwarting the onset of inflammatory cascades. Mechanistically, Mg/Zn-MOF intervenes in both the NLRP3/Caspase-1/GSDMD and Caspase-11/GSDMD pathways to mitigate pyroptosis. In vivo assessments confirm its effectiveness in diminishing inflammatory cell infiltration and preserving collagen integrity, thereby safeguarding against periodontal tissue damage and bone loss. This investigation highlights the promise of ion-interference strategies in periodontitis immunotherapy, representing a significant stride in developing targeted therapeutic approaches.

Does COVID-19 vaccination increase the risk of interstitial lung disease at a population level?

This study showed a significantly lower incidence of ILD among COVID-19 vaccinated individuals compared to unvaccinated, suggesting that the risk of COVID-19 vaccine-related ILD is not as high as previously reported https://bit.ly/3TWzzxP.

Bifunctional black phosphorus quantum dots platform: Delivery and remarkable immunotherapy enhancement of STING agonist.

Cancer immunotherapy has been developed to improve therapeutic effects for patients by activating the innate immune stimulator of interferon gene (STING) pathway. However, most patients cannot benefit from this therapy, mainly due to the problems of excessively low immune responses and lack of tumor specificity. Herein, we report a solution to these two problems by developing a bifunctional platform of black phosphorus quantum dots (BPQDs) for STING agonists. Specifically, BPQDs could connect targeted functional groups and regulate surface zeta potential by coordinating metal ions to increase loading (over 5 times) while maintaining high universality (7 STING agonists). The controlled release of STING agonists enabled specific interactions with their proteins, activating the STING pathway and stimulating the secretion release of immunosuppressive factors by phosphorylating TBK1 and IFN-IRF3 and secreting high levels of immunostimulatory cytokines, including IL-6, IFN-α, and IFN-ß. Moreover, the immunotherapy was enhanced was enhanced mild photothermal therapy (PTT) of BPQDs platform, producing enough T cells to eliminate tumors and prevent tumor recurrence. This work facilitates further research on targeted delivery of small-molecule immune drugs to enhance the development of clinical immunotherapy.

An NIR Type I Photosensitizer Based on a Cyclometalated Ir(III)-Rhodamine Complex for a Photodynamic Antibacterial Effect toward Both Gram-Positive and Gram-Negative Bacteria.

Type I photosensitizers offer an advantage in photodynamic therapy (PDT) due to their diminished reliance on oxygen levels, thus circumventing the challenge of hypoxia commonly encountered in PDT. In this study, we present the synthesis and comprehensive characterization of a novel type I photosensitizer derived from a cyclometalated Ir(III)-rhodamine complex. Remarkably, the complex exhibits a shift in absorption and fluorescence, transitioning from "off" to "on" states in aprotic and protic solvents, respectively, contrary to initial expectations. Upon exposure to light, the complex demonstrates the effective generation of O2- and ·OH radicals via the type I mechanism. Additionally, it exhibits notable photodynamic antibacterial activity against both Gram-positive and Gram-negative bacteria, demonstrated through in vitro and in vivo experiments. This research offers valuable insights for the development of novel type I photosensitizers.

Risk of vitiligo in patients with SARS-CoV-2 vaccination or infection: a nationwide cohort study.

As recent sporadic case reports of newly developed vitiligo after SARS-CoV-2 infection or vaccination have been -published, a convincing large-scale study addressing this association is warranted. To investigate the association between SARS-CoV-2 infection or vaccination and vitiligo using the Korean National Health Insurance Service database. SARS-CoV-2-positive patients and those vaccinated against SARS-CoV-2 were recruited. In studies 1 and 2, control groups were selected based on 1:1 propensity score matching with vaccinated and SARS-CoV-2-positive patients, respectively. The occurrence of vitiligo was the main outcome. Each individual was monitored for six months. The hazard ratio (HR) for vitiligo was calculated using the Cox proportional hazards model. In study 1, the incidence of vitiligo in the vaccination group was 2.22-fold higher than that in the non-vaccination group (adjusted HR [aHR]: 2.22; 95% confidence interval [CI]: 1.54-3.19). Rheumatoid arthritis was a risk factor for vitiligo (aHR: 1.99; 95% CI: 1.12-3.54). Conversely, two factors associated with decreased incidence of vitiligo were male sex (aHR: 0.58; 95% CI: 0.40-0.82) and rural residency (aHR: 0.68; 95% CI: 0.49-0.96). In study 2, the incidence of newly-diagnosed vitiligo was not significantly different between SARS-CoV-2-positive patients and uninfected controls (aHR: 0.95; 95% CI: 0.51-1.78). SARS-CoV-2 vaccination may increase the risk of developing vitiligo in South Korea, although additional studies in other countries or with extended periods are needed. Clinicians should be aware of the impact of SARS-CoV-2 infection and vaccination on autoimmune skin diseases, including vitiligo.

Association between obstructive sleep apnea and risk of Benign vocal fold lesions: A nationwide 9-year follow-up cohort study.

Since obstructive sleep apnea (OSA) affects various parts of the body, there has been little interest about the effect of OSA on voice. The objective of this study was to evaluate the risk of benign vocal fold lesions (BVFL) in OSA patients. This study used data from the National Health Insurance Service (NHIS) database. The study group was defined as the group diagnosed with OSA between 2008 and 2011. Non-OSA groups were selected based on propensity score (PS) matching. Incidence of BVFL among participants during the follow-up was analyzed. Cox proportional hazard regression analyses were performed to evaluate the association between OSA and incident BVFL. The HR value of the OSA group calculated by considering 8 variables indicates that the risk of developing BVFL is 79% higher than that of the control group. Further, among OSA patients, patients with a history of OP had a 35% lower risk of developing BVFL. The relationships between BVFL and 7 individual variables considered were as follows: For age, HR for the 40 to 59 years group was 1.20 (95%CI, 1.09-1.32). For sex, the HR in the female group was 1.22 (95%CI, 1.10-1.35). For residential areas, the HR values for "Seoul" 1.39 (95%CI, 1.23-1.59). In the high economic status group, the HR was 1.10 (95%CI, 1.01-1.21). This observational study indicated that OSA is associated with an increased incidence of BVFL. The incidence of BVFL increased with older age, female sex, and high SES.

Gold core@CeO2 halfshell Janus nanocomposites catalyze targeted sulfate radical for periodontitis therapy.

The sulfate radical (SO4•-), known for its high reactivity and long lifespan, has emerged as a potent antimicrobial agent. Its exceptional energy allows for the disruption of vital structures and metabolic pathways in bacteria that are usually inaccessible to common radicals. Despite its promising potential, the efficient generation of this radical, particularly through methods involving enzymes and photocatalysis, remains a substantial challenge. Here, we capitalized on the peroxidase (POD)-mimicking activity and photocatalytic properties of cerium oxide (CeO2) nanozymes, integrating these properties with the enhanced concept of plasma gold nanorod (GNR) to develop a half-encapsulated core@shell GNRs@CeO2 Janus heterostructure impregnated with persulfate. Under near-infrared irradiation, the GNRs generate hot electrons, thereby boosting the CeO2's enzyme-like activity and initiating a potent reactive oxygen species (ROS) storm. This distinct nanoarchitecture facilitates functional specialization, wherein the heterostructure and efficient light absorption ensured continuous hot electron flow, not only enhancing the POD-like activity of CeO2 for the production of SO4•- effectively, but also contributing a significant photothermal effect, disrupting periodontal plaque biofilm and effectively eradicating pathogens. Furthermore, the local temperature elevation synergistically enhances the POD-like activity of CeO2. Transcriptomics analysis, as well as animal experiments of the periodontitis model, have revealed that pathogens undergo genetic information destruction, metabolic disorders, and pathogenicity changes in the powerful ROS system, and profound therapeutic outcomes in vivo, including anti-inflammation and bone preservation. This study demonstrated that energy transfer to augment nanozyme activity, specifically targeting ROS generation, constitutes a significant advancement in antibacterial treatment.

Luciferase-Decorated Gold Nanorods as Dual-Modal Contrast Agents for Tumor-Targeted High-Performance Bioluminescence/Photoacoustic Imaging.

Gold nanorods (AuNRs) have been considered highly compelling materials for early cancer diagnosis and have aroused a burgeoning fascination among the biomedical sectors. By leveraging the versatile tunable optical properties of AuNRs, herein, we have developed a novel tumor-targeted dual-modal nanoprobe (FFA) that exhibits excellent bioluminescence and photoacoustic imaging performance for early tumor diagnosis. FFA has been synthesized by anchoring the recombinant bioluminescent firefly luciferase protein (Fluc) on the folate-conjugated AuNRs via the PEG linker. TEM images and UV-vis studies confirm the nanorod morphology and successful conjugation of the biomolecules to AuNRs. The nanoprobe FFA relies on the ability of the folate module to target the folate receptor-positive tumor cells actively, and simultaneously, the Fluc module facilitates excellent bioluminescent properties in physiological conditions. The success of chemical engineering in the present study enables stronger bioluminescent signals in the folate receptor-positive cells (Skov3, Hela, and MCF-7) than in folate receptor-negative cells (A549, 293T, MCF-10A, and HepG2). Additionally, the AuNRs induced strong photoacoustic conversion performance, enhancing the resolution of tumor imaging. No apparent toxicity was detected at the cellular and mouse tissue levels, manifesting the biocompatibility nature of the nanoprobe. Prompted by the positive merits of FFA, the in vivo animal studies were performed, and a notable enhancement was observed in the bioluminescent/photoacoustic intensity of the nanoprobe in the tumor region compared to that in the folate-blocking region. Therefore, this synergistic dual-modal bioluminescent and photoacoustic imaging platform holds great potential as a tumor-targeted contrast agent for early tumor diagnosis with high-performance imaging information.

Herpesviral Keratitis Following COVID-19 Vaccination: Analysis of NHIS Database in Korea.

PURPOSE: The purpose of this study was to determine the risk of herpesviral keratitis associated with 4 coronavirus disease 2019 (COVID-19) vaccines approved in South Korea, using large-scale data from the National Health Insurance Service. METHODS: The study included 8,528,254 individuals, with cohorts categorized based on COVID-19 vaccination status. Two investigations were conducted: The first aimed to assess the risk of new-onset herpesviral keratitis while the second study focused on the risk of relapse in individuals with a preexisting diagnosis. Propensity score matching was used for cohort balancing, and various covariates, including vaccine types and comorbidities, were considered. Statistical analyses, including Cox proportional hazard regression, were used to calculate adjusted hazard ratio (aHR) and assess the risk of herpesviral keratitis. RESULTS: Individuals receiving COVID-19 vaccination exhibited a higher risk of new-onset herpesviral keratitis compared with the unvaccinated control group (aHR 1.43, 95% confidence interval, 1.19-1.73). Both mRNA and non-mRNA vaccines demonstrated an increased risk. Individuals with preexisting herpetic keratitis who received COVID-19 vaccination showed a higher risk of relapse herpesviral keratitis compared with the unvaccinated control group (aHR 1.98, 95% CI, 1.29-3.03). Sensitivity analyses supported the robustness of the results. CONCLUSIONS: This analysis of a large national health insurance database suggests an increased risk of both new-onset and relapse of herpesviral keratitis associated with COVID-19 vaccination in South Korea. While COVID-19 vaccination is crucial for pandemic control, health care providers should be aware of potential herpesvirus reactivation and consider appropriate prophylaxis and treatment for at-risk individuals.