Advancing Electrically Conductive Metal-Organic Frameworks for Photocatalytic Energy Conversion.

ConspectusPhotocatalytic energy conversion is a pivotal process for harnessing solar energy to produce chemicals and presents a sustainable alternative to fossil fuels. Key strategies to enhance photocatalytic efficiency include facilitating mass transport and reactant adsorption, improving light absorption, and promoting electron and hole separation to suppress electron-hole recombination. This Account delves into the potential advantages of electrically conductive metal-organic frameworks (EC-MOFs) in photocatalytic energy conversion and examines how manipulating electronic structures and controlling morphology and defects affect their unique properties, potentially impacting photocatalytic efficiency and selectivity. Moreover, with a proof-of-concept study of photocatalytic hydrogen peroxide production by manipulating the EC-MOF's electronic structure, we highlight the potential of the strategies outlined in this Account.EC-MOFs not only possess porosity and surface areas like conventional MOFs, but exhibit electronic conductivity through d-p conjugation between ligands and metal nodes, enabling effective charge transport. Their narrow band gaps also allow for visible light absorption, making them promising candidates for efficient photocatalysts. In EC-MOFs, the modular design of metal nodes and ligands allows fine-tuning of both the electronic structure and physical properties, including controlling the particle morphology, which is essential for optimizing band positions and improving charge transport to achieve efficient and selective photocatalytic energy conversion.Despite their potential as photocatalysts, modulating the electronic structure or controlling the morphology of EC-MOFs is nontrivial, as their fast growth kinetics make them prone to defect formation, impacting mass and charge transport. To fully leverage the photocatalytic potential of EC-MOFs, we discuss our group's efforts to manipulate their electronic structures and develop effective synthetic strategies for morphology control and defect healing. For tuning electronic structures, diversifying the combinations of metals and linkers available for EC-MOF synthesis has been explored. Next, we suggest that synthesizing ligand-based solid solutions will enable continuous tuning of the band positions, demonstrating the potential to distinguish between photocatalytic reactions with similar redox potentials. Lastly, we present incorporating a donor-acceptor system in an EC-MOF to spatially separate photogenerated carriers, which could suppress electron-hole recombination. As a synthetic strategy for morphology control, we demonstrated that electrosynthesis can modify particle morphology, enhancing electrochemical surface area, which will be beneficial for reactant adsorption. Finally, we suggest a defect healing strategy that will enhance charge transport by reducing charge traps on defects, potentially improving the photocatalytic efficiency.Our vision in this Account is to introduce EC-MOFs as an efficient platform for photocatalytic energy conversion. Although EC-MOFs are a new class of semiconductor materials and have not been extensively studied for photocatalytic energy conversion, their inherent light absorption and electron transport properties indicate significant photocatalytic potential. We envision that employing modular molecular design to control electronic structures and applying effective synthetic strategies to customize morphology and defect repair can promote charge separation, electron transfer to potential reactants, and mass transport to realize high selectivity and efficiency in EC-MOF-based photocatalysts. This effort not only lays the foundation for the rational design and synthesis of EC-MOFs, but has the potential to advance their use in photocatalytic energy conversion.

Maximizing the Potential of Electrically Conductive MOFs.

ConspectusElectrically conductive metal-organic frameworks (EC-MOFs) have emerged as a compelling class of materials, drawing increasing attention due to their unique properties facilitating charge transport within porous structures. The synergy between electrical conductivity and porosity has opened a wide range of applications, including electrocatalysis, energy storage, chemiresistive sensing, and electronic devices that have been underexplored for their insulating counterparts. Despite these promising prospects, a prevalent challenge arises from the predominant adoption of two-dimensional (2D) structures by most EC-MOFs. These 2D frameworks often show modest surface areas and short interlayer distances, hindering molecular accessibility, which deviates from the inherent characteristics of conventional MOFs. Furthermore, the quest for efficient charge transport imposes design constraints, leading to a restricted selection of functional building blocks. Additionally, there is a lack of established functionalization methods within EC-MOFs, limiting their functional diversity. Thus, these challenges have impeded EC-MOFs from reaching their full potential.In this Account, we summarize and discuss our group's efforts aimed at enhancing molecular accessibility and deploying the functional diversity of EC-MOFs. Our focus on enhancing molecular accessibility involves several strategies. First, we employed macrocyclic ligands with intrinsic pockets as the building blocks for EC-MOFs. The integrated intrinsic pockets in the frameworks supplement surface areas and additional pores to enhance molecular accessibility. The resulting macrocyclic ligand-based EC-MOFs exhibit exceptionally high surface areas and confer advantages in electrochemical performances. Second, our efforts extend to addressing the structural limitations, frequently associated with EC-MOFs' 2D structures. Through the pillar insertion strategy, we transformed a 2D EC-MOF platform into a three-dimensional (3D) structure, thereby achieving higher porosity and enhanced molecular accessibility. In pursuing functional diversity, we have delved into molecular-level tuning of EC-MOF building blocks. We demonstrated that electron-rich alkyne-based pockets in the macrocyclic ligands can host transition metals and alkali ions, enabling ion selectivity and showcasing diverse use of EC-MOFs. We utilized a postsynthetic approach to further functionalize metal nodes on the molecular level within an EC-MOF framework, introducing a proton-conducting pathway while preserving its electrical conductivity.We aspire for this Account to provide practical insights and strategies to surmount structural and functional diversity limitations in the realm of EC-MOFs. By integrating enhanced molecular accessibility and diverse functionality, our endeavor to propel the utility of these materials will inspire further rational development for future EC-MOFs and unlock their full potential.

Photocatalytic Hydrogen Peroxide Production through Functionalized Semiconductive Metal-Organic Frameworks.

Hydrogen peroxide (H2O2) holds significance as a vital chemical with the potential to serve as an energy carrier. Compared with the conventional anthraquinone process, photocatalytic H2O2 production has emerged as an appealing alternative because of its energy efficiency and environmental sustainability. However, the existing photocatalysts suffer from low catalytic efficiency, limited tunability of optical properties, and reliance on sacrificial agents due to high energy loss caused by inefficient charge separation. Therefore, developing catalysts with tunable optical properties and efficient charge separation is desirable. In this work, we introduce postsynthetic functionalization into an electrically conductive metal-organic framework, namely, DPT-MOF. Leveraging DPT (3,6-di(4-pyridyl)-1,2,4,5-tetrazine) as a pillar ligand, we exploited click-type chemistry to manipulate band position and charge separation efficiency, allowing for photocatalytic nonsacrificial H2O2 production. Notably, the fluorine-functionalized MOF exhibited the highest H2O2 production rate of 1676 µmol g-1 h-1 under visible light in O2-saturated water among our other samples. This high production rate is attributed to the tuned electronic structure and prolonged charge lifetime facilitated by the fluorine groups. This work highlights the effectiveness of postsynthetic methodology in tuning optical properties, opening a promising avenue for advancing the field of semiconductive MOF-based photocatalysis.

Quantitative Analysis and Molecular Docking Simulation of Flavonols from Eruca sativa Mill. and Their Effect on Skin Barrier Function.

Eruca sativa is a commonly used edible plant in Italian cuisine. E. sativa 70% ethanol extract (ES) was fractionated with five organic solvents, including n-hexane (EHex), chloroform (ECHCl3), ethyl acetate (EEA), n-butyl alcohol (EBuOH), and water (EDW). Ethyl acetate fraction (EEA) had the highest antioxidant activity, which was correlated with the total polyphenol and flavonoid content. ES and EEA acted as PPAR-α ligands by PPAR-α competitive binding assay. EEA significantly increased cornified envelope formation as a keratinocyte terminal differentiation marker in HaCaT cells. Further, it significantly reduced nitric oxide and pro-inflammatory cytokines (IL-6 and TNF-α) in lipopolysaccharide-stimulated RAW 264.7 cells. The main flavonol forms detected in high amounts from EEA are mono-and di-glycoside of each aglycone. The main flavonol form of EEA is the mono-glycoside of each aglycone detected, and the most abundant flavonol mono-glycoside is kaempferol 3-glucoside 7.4%, followed by quercetin-3-glucoside 2.3% and isorhamnetin 3-glucoside 1.4%. Flavonol mono-glycosides were shown to be a potent PPAR-α ligand using molecular docking simulation and showed the inhibition of nitric oxide. These results suggest that the flavonol composition of E. sativa is suitable for use in improving skin barrier function and inflammation in skin disorders, such as atopic dermatitis.

Intravascular Casting Radiopaque Hydrogel Systems for Transarterial Chemo/Cascade Catalytic/Embolization Therapy of Hepatocellular Carcinoma.

This paper introduces catheter-directed intravascular casting hydrogels for transarterial chemo/starvation/chemodynamic embolization (TACSCE) therapy of hepatocellular carcinoma (HCC). Comprising Mn ion-crosslinked hyaluronic acid-dopamine (HD) with glucose oxidase (for glucose decomposition to H2O2 in starvation therapy), doxorubicin (for chemotherapy), and iopamidol (for X-ray imaging), these hydrogels are fabricated for transarterial embolization therapy guided by X-ray fluoroscopy. Mn4+ (from MnO2) demonstrates strong coordination with the catechol group of HD, providing hypoxia relief through O2 generation and cellular glutathione (GSH) consumption, compared to the OH radical generation potential of Mn2+. The gelation time-controlled, catheter-injectable, and rheologically tuned multitherapeutic/embolic gel system effectively reaches distal arterioles, ensuring complete intravascular casting with fewer complications related to organic solvents. Glucose deprivation, cascade reactive oxygen species (ROS) generation, GSH depletion, and sustained release profiles of multiple drug cargos from the hydrogel system are also achieved. The combined chemo/starvation/chemodynamic efficacies of these designed hydrogel systems are confirmed in HCC cell cultures and HCC-bearing animal models. The developed radiopaque/injectable/embolic/sol-to-gel transformable systems for TACSCE therapy may offer enhanced therapeutic efficacies compared to typical transarterial embolization and transarterial chemoembolization procedures for HCC.

Red Fluorescence from Organic Microdots: Leveraging Foldamer-Linked Azobenzene for Enhanced Stability and Intensity in Bioimaging Applications.

Azobenzene, while relevant, has faced constraints in biological system applications due to its suboptimal quantum yield and short-wavelength emission. This study presents a pioneering strategy for fabricating organic microdots by coupling foldamer-linked azobenzene, resulting in robust fluorescence intensity and stability, especially in aggregated states, thereby showing promise for bioimaging applications. Comprehensive experimental and computational examinations elucidate the mechanisms underpinning enhanced photostability and fluorescence efficacy. In vitro and in vivo evaluations disclose that the external layer of cis-azo-foldamer microdots performs a self-sacrificial function during photo-bleaching. Consequently, these red-fluorescent microdots demonstrate extraordinary structural and photochemical stabilities over extended periods. The conjugation of a ß-peptide foldamer to the azobenzene chromophore through a glycine linker instigates a blue-shifted and amplified π*-n transition. Molecular dynamics simulations reveal that the aggregated state of cis-azo-foldamers fortifies the stability of cis isomers, thereby augmenting fluorescence efficiency. This investigation furnishes crucial insights into conceptualizing novel, biologically inspired materials, promising stable and enduring imaging applications, and carries implications for diverse arenas such as medical diagnostics, drug delivery, and sensing technologies.

Revealing the pathogenesis of keloids based on the status: Active vs inactive.

Recently, the pathomechanisms of keloids have been extensively researched using transcriptomic analysis, but most studies did not consider the activity of keloids. We aimed to profile the transcriptomics of keloids according to their clinical activity and location within the keloid lesion, compared with normal and mature scars. Tissue samples were collected (keloid based on its activity (active and inactive), mature scar from keloid patients and normal scar (NS) from non-keloid patients). To reduce possible bias, all keloids assessed in this study had no treatment history and their location was limited to the upper chest or back. Multiomics assessment was performed by using single-cell RNA sequencing and multiplex immunofluorescence. Increased mesenchymal fibroblasts (FBs) was the main feature in keloid patients. Noticeably, the proportion of pro-inflammatory FBs was significantly increased in active keloids compared to inactive ones. To explore the nature of proinflammatory FBs, trajectory analysis was conducted and CCN family associated with mechanical stretch exhibited higher expression in active keloids. For vascular endothelial cells (VECs), the proportion of tip and immature cells increased in keloids compared to NS, especially at the periphery of active keloids. Also, keloid VECs highly expressed genes with characteristics of mesenchymal activation compared to NS, especially those from the active keloid center. Multiomics analysis demonstrated the distinct expression profile of active keloids. Clinically, these findings may provide the future appropriate directions for development of treatment modalities of keloids. Prevention of keloids could be possible by the suppression of mesenchymal activation between FBs and VECs and modulation of proinflammatory FBs may be the key to the control of active keloids.

Impact of age at diagnosis on long-term prognosis in patients with intestinal Behçet's disease.

BACKGROUND AND AIM: Although age at disease onset is considered to be a significant factor in the prognosis of Crohn's disease, little is known about its influence on the long-term prognosis of those with intestinal Behçet's disease (BD). This study aimed to evaluate the long-term clinical outcomes of patients with intestinal BD according to age of disease onset. METHODS: Patients diagnosed with intestinal BD at < 18, 18-60, and > 60 years of age were classified into early-onset, adult-onset, and late-onset groups, respectively. The influence of disease onset time on clinical prognosis, including specific medical requirements, BD-related intestinal surgery, hospitalization, and emergency room visits, was compared using the log-rank test in a large cohort of patients with intestinal BD. RESULTS: Among 780 patients, 21 (2.7%), 672 (86.2%), and 87 (11.1%) comprised the early-onset, adult-onset, and late-onset groups, respectively. Patients in the early-onset group were more likely to require immunosuppressants than those in the adult-onset group (P = 0.048). Nine (42.9%), 158 (23.5%), and 18 (20.7%) patients in the early-onset, adult-onset, and late-onset groups, respectively, underwent intestinal resection. The early-onset group exhibited a higher risk for intestinal resection than the late-onset (P = 0.043) and adult-onset (P = 0.030) groups. The late-onset group exhibited a higher risk for BD-related hospitalization than the adult-onset group (P = 0.023). CONCLUSIONS: Age at diagnosis affected the clinical course of intestinal BD, including intestinal surgery, hospitalization, and specific medical requirements. Different treatment strategies should be established according to age at diagnosis.

Population pharmacokinetic, pharmacodynamic and efficacy modeling of SB12 (proposed eculizumab biosimilar) and reference eculizumab.

PURPOSE: To describe, compare similarity of pharmacokinetic (PK), pharmacodynamic (PD) and efficacy of SB12 and reference eculizumab (ECU) and find clinically significant covariate relationships. METHODS: The PK, PD (terminal complement activity) and efficacy (LDH) data of SB12 and ECU were obtained from 289 subjects from phase I and phase III studies. One- and two-compartment PK models with first-order elimination were evaluated for SB12 and ECU. For PD and efficacy, both direct and indirect models were tested. The impact of covariates on PK, PD and efficacy parameters was assessed. Relationship between PK/PD and PD/efficacy was characterized. This modeling was performed using NONMEM version 7.4 (Icon Development Solutions, Ellicott City, MD, USA). RESULTS: The two-compartment model adequately described the PK of SB12 and ECU, and the subject's weight was chosen as a clinically significant covariate affecting drugs' clearance and central volume of distribution. Treatment group was not a significant covariate affecting clearance. The direct response model using inhibitory sigmoid Emax and sigmoid Emax relationship well described the PK/PD relationship and PD/efficacy relationship of SB12 and ECU, respectively. Through this modeling, the relationships between PK, PD and efficacy were characterized. There were no differences in PK, PD and efficacy parameters between SB12 and ECU in pooled populations of healthy subjects and paroxysmal nocturnal haemoglobinuria (PNH) patients. CONCLUSION: The population modeling showed PK, PD and efficacy similarities between SB12 and ECU in pooled population of healthy subjects and PNH patients, supporting the totality of evidence on biosimilarity for SB12.

The concept of onychodermis containing onychofibroblasts has histological (microanatomical), immunohistochemical as well as molecular basis.

The terms "onychofibroblast" (nail-specific fibroblast) and onychodermis (nail-specific dermis) were first introduced in 2006 and 2012, respectively, based on distinctive histologic and immunohistochemical features from the dermis of the surrounding skin and have been demonstrated in multiple studies. Recently, based on molecular research, the definition of onychodermis containing onychofibroblasts has been expanded to encompass the area located between the nail matrix and bed epithelium and periosteum. Single-cell RNA sequencing and in situ hybridization demonstrated that onychofibroblasts within the onychodermis express the genes including RSPO4, MSX1, WIF-1, and BMP5, which are implicated in nail formation and/or in disorders with nail phenotype. A mutation in RSPO4, a component of the Wnt signaling pathway, causes anonychia congenita. Nail matrix onychodermis and nail bed onychodermis share many similar characteristics which differ from the surrounding normal dermis of the skin. Comparative spatial transcriptomic and single-cell analyses of human nail units and hair follicles suggest that onychodermis is the counterpart of follicular dermal papilla, which plays a key role in hair follicle growth and morphogenesis. Onychomatricoma, as a nail-specific tumor, has been demonstrated to be a mesenchymal tumor that originates from onychofibroblasts and is associated with the upregulation of Wnt signaling. Collectively, the onychodermis and onychofibroblasts play crucial roles in nail development and these specialized nail mesenchymal elements are key components in the pathogenesis of onychomatricoma. The concept of onychodermis containing onychofibroblasts is very important for nail biology and pathology.

Effectiveness and Tolerability of Methotrexate Combined with Biologics in Patients with Crohn's Disease: A Multicenter Observational Study.

BACKGROUND: Methotrexate (MTX) combination therapy with biological agents has gained increasing interest. Here, we assessed the efficacy and tolerability of the MTX combination therapy in patients with Crohn's disease (CD). METHODS: We performed a multicenter observational study with 185 patients with CD with MTX and biologics combination therapy; the patients were recruited from three IBD Clinics in Korea. We evaluated the outcomes of the MTX combination therapy and examined the predictive factors of clinical and endoscopic remission. RESULTS: MTX was administered orally to 62.7% of patients; the mean dose was 15.5 mg per week, and the mean treatment duration was 36 months. Of the 169 patients treated with MTX combination therapy for over 6 months, the steroid-free clinical remission rates were 34.3%, 26.0%, 29.8%, and 32.7% at 4, 12, 18, and 24 months, respectively. Previous thiopurine use was a significant negatively associated independent factor (p < 0.001), and a higher dose of MTX (≥ 15 mg/week) was a positively associated independent factor of steroid-free clinical remission (p = 0.035). Ninety-six patients underwent follow-up endoscopy after 28 months, and 36 (37.5%) achieved endoscopic remission. Longer disease duration (p = 0.006), ileocolonic type of Montreal location (p = 0.036), and baseline C-reactive protein (CRP) level of more than 5 mg/L (p = 0.035) were significant negatively associated independent factors and a higher dose of MTX (≥ 15 mg/week) was a positively associated independent factor of endoscopic remission (p = 0.037). CONCLUSIONS: MTX combination therapy with biologics was effective and tolerable in patients with CD.

Start-up strategy of single-stage partial nitrification-anammox process for anaerobic digestion effluent.

The objective of this study was to improve the nitrogen removal efficiency and reduce the start-up period of a single-stage partial nitritation-anammox (SPNA) system using iron particle-integrated anammox granules (IP-IAGs). Anammox granules were enriched in sequencing batch and expanded granular sludge bed (EGSB) reactors. The EGSB reactor produced larger and more uniform granules with higher specific anammox activity. IP-IAGs were then inoculated into a two-stage partial nitritation-anammox reactor treating anaerobic digestion (AD) effluent, followed by an internal recirculation strategy to acclimate the granules to oxygen exposure for SPNA. Finally, the SPNA process operated to treat real AD effluent under optimal conditions of 0.05 L/min aeration intensity (0.01 vvm) and 24 h of hydraulic retention time, achieving TNRE of 86.01 ± 2.64 % and nitrogen removal rate of 0.74 ± 0.04 kg-N/m3·d for 101 d.

Comparison of intraocular pressure fluctuation and glaucoma progression rate between phakic and pseudophakic eyes in pseudoexfoliation glaucoma.

The management of patients with concurrent pseudoexfoliation glaucoma (PXG) and cataract is challenging given its worse prognosis compared to other glaucoma types and the increased risk associated with cataract surgery. In this retrospective study, we investigated the long-term outcomes of cataract surgery in patients with PXG. We enrolled patients with PXG who had undergone cataract surgery at least 2 years previously and compared them with mean deviation (MD) matched patients with phakic eyes. The results showed that both groups experienced a decrease in MD, with the group of pseudophakic eyes exhibiting a significantly higher rate of decline (-2.15 ± 2.66 dB/year vs. -0.86 ± 0.95 dB/year; P = 0.040). Similarly, there was a trend towards more rapid thinning of the retinal nerve fiber layer in the pseudophakic group (-2.92 ± 2.34 µm/year vs. -1.79 ± 1.71 µm/year; P = 0.074). No significant differences in the intraocular pressure parameters were observed between the two groups. Multivariate analysis revealed that pseudophakic lens status was significantly associated with a faster rate of MD decline in patients with PXG (regression coefficient, -1.391; P = 0.022). These findings underscore the importance of close monitoring of patients with pseudophakic PXG to effectively manage glaucoma progression.

Threading Subunits for Polymers to Predict the Equilibrium Ensemble of Solid Polymer Electrolytes.

We present a computational method for polymer growth called "threading subunits for polymers (TSP)" that can efficiently sample solid polymer electrolyte structures with extended conformations. The TSP method involves equilibrating subunit (e.g., monomer) conformations that form favorable solvation ion shells, followed by consecutively connecting the subunits and minimizing the structures. The TSP method can sample polymers with good solvent-like conformations and from near-equilibrium structures in which ions are well-dispersed, avoiding unusual ion clustering under ambient conditions. Using the TSP method, the equilibration time can be reduced significantly by effectively sampling the polymer conformations near equilibrium. We anticipate that the TSP method can be applied to simulate various polymer electrolytes.

Identification of DNA methylation biomarkers for evaluating cardiovascular disease risk from epigenome profiles altered by low-dose ionizing radiation.

BACKGROUND: Environmental exposure, medical diagnostic and therapeutic applications, and industrial utilization of radionuclides have prompted a growing focus on the risks associated with low-dose radiation (< 100 mGy). Current evidence suggests that such radiation can induce epigenetic changes. Nevertheless, whether exposure to low-dose radiation can disrupt endothelial cell function at the molecular level is unclear. Because endothelial cells play crucial roles in cardiovascular health and disease, we aimed to investigate whether low-dose radiation could lead to differential DNA methylation patterns at the genomic level in endothelial cell (EC) lines. METHODS: We screened for changes in DNA methylation patterns in primary human aortic (HAECs) and coronary artery endothelial cells following exposure to low-dose ionizing radiation. Using a subset of genes altered via DNA methylation by low-dose irradiation, we performed gene ontology (GO) analysis to predict the possible biological network mediating the effect of low-dose radiation. In addition, we performed comprehensive validation using methylation and gene expression analyses, and ChIP assay to identify useful biomarkers among candidate genes for use in detecting low-dose radiation exposure in human primary normal ECs. RESULTS: Low-dose radiation is sufficient to induce global DNA methylation alterations in normal EC lines. GO analysis demonstrated that these hyper- or hypo-methylated genes were linked to diverse biological pathways. Our findings indicated a robust correlation between promoter hypermethylation and transcriptional downregulation of four genes (PGRMC1, UNC119B, RERE, and FNDC3B) in response to low-dose ionizing radiation in HAECs. CONCLUSIONS: Based on these findings, the identified genes can serve as potential DNA methylation biomarkers for the assessment of cardiovascular risk upon exposure to low-dose radiation.

Iron particle-integrated anammox granules in baffled reactor: Enhanced settling property and nitrogen removal performance.

This study evaluates iron particle-integrated anammox granules (IP-IAGs) to enhance wastewater treatment efficiency. The IP-IAGs resulted in notable improvements in settleability and nitrogen removal. The settling velocity of IP-IAGs increased by 17.91 % to 2.92 ± 0.20 cm/s, and the total nitrogen removal efficiency in batch mode improved by 6.82 %. These changes indicate enhanced biological activity for effective treatment. In continuous operation, the IP-IAGs reactor showed no accumulation of nitrite until 40 d, reaching a peak nitrogen removal rate (NRR) of 1.54 kg-N/m3·d and a nitrogen removal efficiency of 82.61 %. Furthermore, a partial nitritation-anammox reactor that treated anaerobic digestion effluent achieved a NRR of 1.41 ± 0.09 kg-N/m3·d, proving the applicability of IP-IAGs in real wastewater conditions. These results underscore the potential of IP-IAGs to enhance the efficiency and stability of anammox-based processes, marking a significant advancement in environmental engineering for wastewater treatment.

Prevalence and risk factors for gallstone and renal stone formation in patients with intestinal Behçet's disease.

Background/Aims: The association between inflammatory bowel disease (IBD) and gallstone and renal stone formation has been established. However, few studies have investigated this association in patients with intestinal Behçet's disease (BD). We aimed to examine the prevalence of gallstones and renal stones in patients with intestinal BD and identify potential risk factors. Methods: We analyzed gallstone and renal stone occurrences in 553 patients diagnosed with intestinal BD who had undergone cross-sectional imaging examinations between March 2005 and April 2021 at the IBD Center, Severance Hospital, Seoul, South Korea. Logistic regression models were used to identify risk factors for gallstone and renal stone formation. Results: Of 553 patients over a mean 12.1-year duration, 141 (25.4%) patients had gallstones and 35 (6.3%) had renal stones. In multivariate logistic regression analysis, disease duration > 19 years (OR 2.91, 95% CI 1.56-5.44, 0.002). No significant correlation 0.001), prior intestinal BD-related surgery (OR 2.29, 95% CI 1.42-3.68, p < 0.001), and disease activity index for intestinal BD scores ≥ 75 (OR 2.23, 95% CI 1.12-4.45, p = 0.022) were associated with increased gallstone occurrence. A positive correlation was observed between renal stones, disease duration > 19 years (OR 5.61, 95% CI 1.98-15.90, p = 0.001) and frequent hospitalization (> 3 times) (OR 3.29, 95% CI 1.52-7.13, p = 0.002). No significant correlation was observed between gallstone and renal stone occurrence. Conclusions: These findings contribute to greater understanding concerning gallstone and renal stone prevalence and associated risk factors in patients with intestinal BD.

CXCL10 upregulation in radiation-exposed human peripheral blood mononuclear cells as a candidate biomarker for rapid triage after radiation exposure.

PURPOSE: In case of a nuclear accident, individuals with high-dose radiation exposure (>1-2 Gy) should be rapidly identified. While ferredoxin reductase (FDXR) was recently suggested as a radiation-responsive gene, the use of a single gene biomarker limits radiation dose assessment. To overcome this limitation, we sought to identify reliable radiation-responsive gene biomarkers. MATERIALS AND METHODS: Peripheral blood mononuclear cells (PBMCs) were isolated from mice after total body irradiation, and gene expression was analyzed using a microarray approach to identify radiation-responsive genes. RESULTS: In light of the essential role of the immune response following radiation exposure, we selected several immune-related candidate genes upregulated by radiation exposure in both mouse and human PBMCs. In particular, the expression of ACOD1 and CXCL10 increased in a radiation dose-dependent manner, while remaining unchanged following lipopolysaccharide (LPS) stimulation in human PBMCs. The expression of both genes was further evaluated in the blood of cancer patients before and after radiotherapy. CXCL10 expression exhibited a distinct increase after radiotherapy and was positively correlated with FDXR expression. CONCLUSIONS: CXCL10 expression in irradiated PBMCs represents a potential biomarker for radiation exposure.

A Comprehensive Understanding of Post-Translational Modification of Sox2 via Acetylation and O-GlcNAcylation in Colorectal Cancer.

Aberrant expression of the pluripotency-associated transcription factor Sox2 is associated with poor prognosis in colorectal cancer (CRC). We investigated the regulatory roles of major post-translational modifications in Sox2 using two CRC cell lines, SW480 and SW620, derived from the same patient but with low and high Sox2 expression, respectively. Acetylation of K75 in the Sox2 nuclear export signal was relatively increased in SW480 cells and promotes Sox2 nucleocytoplasmic shuttling and proteasomal degradation of Sox2. LC-MS-based proteomics analysis identified HDAC4 and p300 as binding partners involved in the acetylation-mediated control of Sox2 expression in the nucleus. Sox2 K75 acetylation is mediated by the acetyltransferase activity of CBP/p300 and ACSS3. In SW620 cells, HDAC4 deacetylates K75 and is regulated by miR29a. O-GlcNAcylation on S246, in addition to K75 acetylation, also regulates Sox2 stability. These findings provide insights into the regulation of Sox2 through multiple post-translational modifications and pathways in CRC.