A skin-interfaced microfluidic platform supports dynamic sweat biochemical analysis during human exercise.

Blood lactate concentration is an established circulating biomarker for measuring muscle acidity and can be evaluated for monitoring endurance, training routines, or athletic performance. Sweat is an alternative biofluid that may serve similar purposes and offers the advantage of noninvasive collection and continuous monitoring. The relationship between blood lactate and dynamic sweat biochemistry for wearable engineering applications in physiological fitness remains poorly defined. Here, we developed a microfluidic wearable band with an integrated colorimetric timer and biochemical assays that temporally captures sweat and measures pH and lactate concentration. A colorimetric silver nanoplasmonic assay was used to measure the concentration of lactate, and dye-conjugated SiO2 nanoparticle-agarose composite materials supported dynamic pH analysis. We evaluated these sweat biomarkers in relation to blood lactate in human participant studies during cycling exercise of varying intensity. Iontophoresis-generated sweat pH from regions of actively working muscles decreased with increasing heart rate during exercise and was negatively correlated with blood lactate concentration. In contrast, sweat pH from nonworking muscles did not correlate with blood lactate concentration. Changes in sweat pH and blood lactate were observed in participants who did not regularly exercise but not in individuals who regularly exercised, suggesting a relationship to physical fitness and supporting further development for noninvasive, biochemical fitness evaluations.

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. CONCLUSION: These findings contribute to greater understanding concerning gallstone and renal stone prevalence and associated risk factors in patients with intestinal BD.

Inhibition of IRP2-dependent reprogramming of iron metabolism suppresses tumor growth in colorectal cancer.

BACKGROUND: Dysregulation of iron metabolism is implicated in malignant transformation, cancer progression, and therapeutic resistance. Here, we demonstrate that iron regulatory protein 2 (IRP2) preferentially regulates iron metabolism and promotes tumor growth in colorectal cancer (CRC). METHODS: IRP2 knockdown and knockout cells were generated using RNA interference and clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 methodologies, respectively. Cell viability was evaluated using both CCK-8 assay and cell counting techniques. Furthermore, IRP2 inhibition was determined by surface plasmon resonance (SPR) and RNA immunoprecipitation (IP). The suppressive effects of IRP2 were also corroborated in both organoid and mouse xenograft models, providing a comprehensive validation of IRP2's role. RESULTS: We have elucidated the role of IRP2 as a preferential regulator of iron metabolism, actively promoting tumorigenesis within CRC. Elevated levels of IRP2 expression in patient samples are correlated with diminished overall survival, thereby reinforcing its potential role as a prognostic biomarker. The functional suppression of IRP2 resulted in a pronounced delay in tumor growth. Building on this proof of concept, we have developed IRP2 inhibitors that significantly reduce IRP2 expression and hinder its interaction with iron-responsive elements in key iron-regulating proteins, such as ferritin heavy chain 1 (FTH1) and transferrin receptor (TFRC), culminating in iron depletion and a marked reduction in CRC cell proliferation. Furthermore, these inhibitors are shown to activate the AMPK-ULK1-Beclin1 signaling cascade, leading to cell death in CRC models. CONCLUSIONS: Collectively, these findings highlight the therapeutic potential of targeting IRP2 to exploit the disruption of iron metabolism in CRC, presenting a strategic advancement in addressing a critical area of unmet clinical need.

From lab to wearables: Innovations in multifunctional hydrogel chemistry for next-generation bioelectronic devices.

Functional hydrogels have emerged as foundational materials in diagnostics, therapy, and wearable devices, owing to their high stretchability, flexibility, sensing, and outstanding biocompatibility. Their significance stems from their resemblance to biological tissue and their exceptional versatility in electrical, mechanical, and biofunctional engineering, positioning themselves as a bridge between living organisms and electronic systems, paving the way for the development of highly compatible, efficient, and stable interfaces. These multifaceted capability revolutionizes the essence of hydrogel-based wearable devices, distinguishing them from conventional biomedical devices in real-world practical applications. In this comprehensive review, we first discuss the fundamental chemistry of hydrogels, elucidating their distinct properties and functionalities. Subsequently, we examine the applications of these bioelectronics within the human body, unveiling their transformative potential in diagnostics, therapy, and human-machine interfaces (HMI) in real wearable bioelectronics. This exploration serves as a scientific compass for researchers navigating the interdisciplinary landscape of chemistry, materials science, and bioelectronics.

Degassing 4-tert-Butylpyridine in the Spiro-MeOTAD Film Improves the Thermal Stability of Perovskite Solar Cells.

The organic molecular 2,2',7,7'-tetrakis(4,4'-dimethoxy-3-methyldiphenylamino)-9,9'-spirobifluorene (Spiro-MeOTAD) is known as a typical hole transport material in the development of an all-solid-state perovskite solar cell (PSC). Spiro-MeOTAD requires additives of lithium bifurflimide (LiTFSI) and 4-tert-butylpyridine (tBP) to increase the conductivity and solubility for enhancing the photovoltaic performance of PSCs. However, those additives have an adverse effect on the thermal stability. We report on the origin of instability of additive-containing Spiro-MeOTAD at 85 °C and the methodology to solve the thermal instability. We have found that the interaction of LiTFSI with the underneath perovskite surface facilitated by diffusive tBP is responsible for thermal degradation. Degasification of tBP from the Spiro-MeOTAD film is found to be the key to achieving thermally stable PSCs, where the optimal degassing process achieves 90% of the initial power conversion efficiency (PCE) at 85 °C after 1000 h.

Primary surgery versus pharmacotherapy for newly diagnosed ileocecal Crohn's disease: a hospital-based cohort study.

BACKGROUND/AIMS: Limited knowledge exists regarding the optimal timing and relative advantages of primary surgery compared to medical treatment in ileocecal Crohn's disease (CD). This study aimed to compare long-term outcomes between medication-based treatment versus surgery in newly diagnosed ileocecal CD patients in an Asian population. METHODS: Among the 885 patients diagnosed with CD and enrolled in the study site hospital cohort between 1980 and 2013, 93 (10.5%) had ileocecal CD. Patients were categorized into either the surgical or medical remission group based on their initial management strategy that led to remission. The rates of relapse, hospitalization, and surgery after achieving remission were compared using Kaplan-Meier curves. RESULTS: The numbers of patients assigned to surgical and medical remission groups were 15 (17.0%) and 73 (83.0%), respectively. The surgical remission group exhibited a lower relapse rate and longer maintenance of remission (10.7 vs. 3.7 yr; p = 0.017) during a median follow-up of 6.6 years. Hospitalization after the first remission tended to be lower in the surgical remission group (p = 0.054). No cases required repeated intestinal resection after the initial surgical remission, whereas a 23% surgery rate was reported at 5 years after initial medical treatment (p = 0.037). In the multivariable analysis, the initial medication-based treatment was significantly associated with relapse (hazard ratio = 3.23, p = 0.039). CONCLUSION: In selected cases of localized ileocecal CD, ileocolic resection might be a favorable alternative to medication- based treatment, as it demonstrates a lower relapse rate and longer maintenance of remission.

Materials and Structural Designs toward Motion Artifact-Free Bioelectronics.

Bioelectronics encompassing electronic components and circuits for accessing human information play a vital role in real-time and continuous monitoring of biophysiological signals of electrophysiology, mechanical physiology, and electrochemical physiology. However, mechanical noise, particularly motion artifacts, poses a significant challenge in accurately detecting and analyzing target signals. While software-based "postprocessing" methods and signal filtering techniques have been widely employed, challenges such as signal distortion, major requirement of accurate models for classification, power consumption, and data delay inevitably persist. This review presents an overview of noise reduction strategies in bioelectronics, focusing on reducing motion artifacts and improving the signal-to-noise ratio through hardware-based approaches such as "preprocessing". One of the main stress-avoiding strategies is reducing elastic mechanical energies applied to bioelectronics to prevent stress-induced motion artifacts. Various approaches including strain-compliance, strain-resistance, and stress-damping techniques using unique materials and structures have been explored. Future research should optimize materials and structure designs, establish stable processes and measurement methods, and develop techniques for selectively separating and processing overlapping noises. Ultimately, these advancements will contribute to the development of more reliable and effective bioelectronics for healthcare monitoring and diagnostics.

Strain-invariant stretchable radio-frequency electronics.

Wireless modules that provide telecommunications and power-harvesting capabilities enabled by radio-frequency (RF) electronics are vital components of skin-interfaced stretchable electronics1-7. However, recent studies on stretchable RF components have demonstrated that substantial changes in electrical properties, such as a shift in the antenna resonance frequency, occur even under relatively low elastic strains8-15. Such changes lead directly to greatly reduced wireless signal strength or power-transfer efficiency in stretchable systems, particularly in physically dynamic environments such as the surface of the skin. Here we present strain-invariant stretchable RF electronics capable of completely maintaining the original RF properties under various elastic strains using a 'dielectro-elastic' material as the substrate. Dielectro-elastic materials have physically tunable dielectric properties that effectively avert frequency shifts arising in interfacing RF electronics. Compared with conventional stretchable substrate materials, our material has superior electrical, mechanical and thermal properties that are suitable for high-performance stretchable RF electronics. In this paper, we describe the materials, fabrication and design strategies that serve as the foundation for enabling the strain-invariant behaviour of key RF components based on experimental and computational studies. Finally, we present a set of skin-interfaced wireless healthcare monitors based on strain-invariant stretchable RF electronics with a wireless operational distance of up to 30 m under strain.

Effects of COVID-19 vaccines on patient-reported outcomes in patients with inflammatory bowel disease: a multicenter survey study in Korea.

BACKGROUND/AIMS: The impact of vaccination on inflammatory bowel disease (IBD) patients is still unknown, and no studies have assessed the changes in patient-reported outcomes (PROs) after vaccination in patients with IBD. Therefore, in this study, we investigated the impact of vaccines on the PROs of patients with IBD. METHODS: We conducted a questionnaire survey of patients with IBD who visited outpatient clinics at 4 specialized IBD clinics of referral university hospitals from April 2022 to June 2022. A total of 309 IBD patients were included in the study. Patient information was collected from a questionnaire and their medical records, including laboratory findings, were reviewed retrospectively. Risk factors associated with an increase in PROs after COVID-19 vaccination were analyzed using logistic regression analyses. In addition, we assessed whether there were differences in variables by vaccine order using the linear mixed model. RESULTS: In multivariate analysis, young age ( < 40 years) and ulcerative colitis (UC) were found to be independent risk factors for aggravation of PROs in patients with IBD. In all patients, platelet count significantly increased with continued vaccination in multiple pairwise comparisons. In UC patients, PROs such as the short health scale, UC-abdominal signs and symptoms, and UC-bowel signs and symptoms were aggravated significantly with continued vaccination. There was no significant increase in the variables of patients with Crohn's disease. CONCLUSIONS: Therefore, there may be a need to counsel patients with IBD younger than 40 years of age, and patients with UC before they receive COVID-19 vaccinations.

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.