Dexamethasone acetate loaded poly(ε-caprolactone) nanofibers for rat corneal chemical burn treatment.

Topical eye drop approaches to treat ocular inflammation in dry eyes often face limitations such as low efficiency and short duration of drug delivery. Nanofibers serve to overcome the limitation of the short duration of action of topical eye drops used against ocular inflammation in dry eyes. Several attempts to develop suitable nanofibers have been made; however, there is no ideal solution. Here, we developed polycaprolactone (PCL) nanofibers loaded with dexamethasone acetate (DEX), prepared by electrospinning, as a potential ocular drug delivery platform for corneal injury treatment. Thirty-nine Sprague Dawley rats (7 weeks old males) were divided into four treatment groups after alkaline burns of the cornea; negative control (no treatment group); dexamethasone eyedrops (DEX group); PCL fiber (PCL group); dexamethasone loaded PCL (PCL + DEX group). We evaluated therapeutic efficacy of PCL + DEX by examining the epithelial wound healing effect, the extent of corneal opacity and neovascularization. Additionally, various inflammatory factors, including IL-1ß, were investigated through immunochemistry, western blot analysis, and quantitative real-time RT-PCR (qRT-PCR). PCL + DEX group showed histologically alleviated signs of corneal inflammation compared with DEX group, which showed a decrease in IL-1ß and MMP9 in the corneal stroma. The quantitative expression on day 1 after alkaline burn of pro-inflammatory markers, including IL-1ß and IL-6, in the PCL + DEX group was significantly lower than that in the DEX group. Notably, PCL + DEX treatment significantly suppressed neovascularization, and enhanced the anti-inflammatory function of DEX during the acute phase of ocular inflammation. Collectively, these findings suggest that PCL + DEX may be a promising approach to effective drug delivery in corneal burn injuries.

Target-Enhanced Whole-Genome Sequencing (TE-WGS) Shows Clinical Validity Equivalent to Commercially Available Targeted Oncology Panel.

Purpose: Cancer poses a significant global health challenge, demanding precise genomic testing for individualized treatment strategies. Targeted-panel sequencing (TPS) has improved personalized oncology but often lacks comprehensive coverage of crucial cancer alterations. Whole-genome sequencing (WGS) addresses this gap, offering extensive genomic testing. This study demonstrates the medical potential of WGS. Materials and Methods: This study evaluates target-enhanced WGS (TE-WGS), a clinical-grade WGS method sequencing both cancer and matched normal tissues. Forty-nine patients with various solid cancer types underwent both TE-WGS and TruSight Oncology 500 (TSO500), one of the mainstream TPS approaches. Results: TE-WGS detected all variants reported by TSO500 (100%, 498/498). A high correlation in variant allele fractions (VAF) was observed between TE-WGS and TSO500 (r=0.978). Notably, 223 variants (44.8%) within the common set were discerned exclusively by TE-WGS in peripheral blood, suggesting their germline origin. Conversely, the remaining subset of 275 variants (55.2%) were not detected in peripheral blood using the TE-WGS, signifying them as bona fide somatic variants. Further, TE-WGS provided accurate copy number profiles, fusion genes, microsatellite instability (MSI), and homologous-recombination deficiency (HRD) scores, which were essential for clinical decision-making. Conclusion: TE-WGS is a comprehensive approach in personalized oncology, matching TSO500's key biomarker detection capabilities. It uniquely identifies germline variants and genomic instability markers, offering additional clinical actions. Its adaptability and cost-effectiveness underscore its clinical utility, making TE-WGS a valuable tool in personalized cancer treatment.

Impact of COVID-19 pandemic on neurodevelopmental outcome in very low birth weight infants: a nationwide cohort study.

Introduction: Children who have experienced the coronavirus disease 2019 (COVID-19) pandemic are at an increased risk of adverse neurologic developmental outcomes. Limited data exist on the environmental influences of during the COVID-19 pandemic on preterm infant development. This study aimed to investigate whether COVID-19 exposure affects the neurodevelopmental outcomes in preterm children up to 3 years of age. Methods: This prospective cohort study included all very low birth weight (VLBW) infants from the Korean Neonatal Network who had undergone a neurodevelopmental assessment between January 2015, and May 2022. The neurodevelopmental outcomes along with the scores on the Bayley Scales of Infant and Toddler Development (BSID) and the Korean Developmental Screening Test for Infants and Children of pediatric patients aged 18-24 and 33-39 months who were exposed to COVID-19 were compared with those of VLBW children born and tested before the pandemic. Results: The cohort included 1,683 VLBW infants. The pandemic group had significantly lower language scores on the BSID-III at ages 18-24 months (p = 0.021) and 33-39 months (p = 0.023) than the pre-pandemic group after adjusting for gestational age, morbidity, and environmental factors. At 2nd follow-up period, the pandemic group showed significantly lower scores in the cognitive (p = 0.026) domains with a mean difference of 7 points and had a significantly higher percentage of ≤-1SD in the gross motor domain (p < 0.001) compared with the pre-pandemic group. Conclusion: Preterm children who experienced the COVID-19 pandemic are at higher risk of abnormal neurodevelopmental outcomes in the first 3 years of life than preterm infants born before the COVID-19 pandemic.

Impact of variant histology in the prognosis of non­muscle invasive bladder cancer with low­tumor burden: A propensity score­matched analysis with conventional urothelial carcinoma.

Bladder cancer (BCa) with variant histology (VH) is associated with an increased risk of recurrence and progression, as well as worse survival. However, the available literature does not provide the prognostic value of VH based on its tumor burden in non-muscle invasive BCa (NMIBC). The purpose of the present study was to investigate the prognosis of VH in NMIBC with low-tumor volume compared with conventional urothelial carcinoma (UC) with a similar tumor burden. The present single-center study analyzed patients diagnosed with NMIBC and retrospectively characterized them based on their VH status. Propensity scores for VH status were calculated to match patients with VH with those with conventional UC (1:3). The VH group was further divided into two subgroups based on pathological aggressiveness: Aggressive and highly aggressive variants. Oncological outcomes were compared among the three groups. Among the 494 patients with NMIBC, 60 (12.1%) had VH. Patients with VH had a higher tumor stage and grade and more multiple tumors (all P<0.05). In the matched cohort, >80% had tumors <3 cm, and >65% had solitary tumors. During a median follow-up of 42.5 months (range, 4.0-122.0 months), 35.1% (85/240) experienced recurrence and 5.4% (13/240) progressed to muscle-invasive disease. Prognosis did not differ between patients with aggressive or highly aggressive variants and those with conventional UC, including 5-year recurrence-free and pathologic progression-free survival (log-rank, P=0.510 and 0.257, respectively). Intravesical Bacillus Galmette-Guerin was the only factor associated with reduced recurrence (P<0.001). In conclusion, NMIBC with low-tumor burden and VH have similar oncologic outcomes to conventional UC with a similar tumor burden, indicating that bladder-sparing methods currently used for high-risk conventional NMIBC may be effective for managing low-tumor burden NMIBC with VH.

Calcification following tongue necrosis induced by vasopressor use in a nonintubated patient with septic shock: a case report.

BACKGROUND: Tongue necrosis is a rare and relatively uncommon condition, usually caused by vasculitis, thrombosis, severe hypotension due to septic or cardiogenic shock, vasopressor use, or intubation. Following damage such as necrosis, dystrophic calcification, a type of soft tissue calcification, can occur. CASE PRESENTATION: Herein, we present a unique case of bilateral tongue necrosis in a patient with nonintubated septic shock. A 70-year-old East Asian man with no significant medical history presented to the emergency department with postprandial epigastric pain. The patient was admitted to the intensive care unit with hypotension due to septic shock and disseminated intravascular coagulation. After a short course of vasopressors, the patient developed tongue discoloration and swelling without limb ischemia. Computed tomography was performed to observe the tongue necrosis, and calcification of the tongue was found. The patient was successfully treated by wiping the area with a hexamidine-soaked gauze. CONCLUSION: Tongue necrosis remains a rare finding, and its occurrence as a complication of vasopressor use is even rarer. Therefore, even with relatively short courses of vasopressors in the intensive care unit, daily visualization of the tongue to check for discoloration, along with daily inspection and pulse checks of the limbs, can help identify vasospasms. These measures allow for prompt intervention, minimizing permanent damage and shortening the recovery time.

The impact of pulmonary tuberculosis on SARS-CoV-2 infection: a nationwide cohort study.

Background: The interaction between COVID-19 and tuberculosis (TB) is not yet fully understood, and large-scale research on the mortality outcome of such dual infection has been limited. This study aimed to investigate the impact of PTB on mortality among patients with COVID-19 within a Korean population by conducting an extensive analysis of a nationwide large dataset. Method: We investigated the mortality and disease severity among COVID-19 patients who had PTB in South Korea. This study analyzed 462,444 out of 566,494 COVID-19 patients identified between January 2020 and December 2021. Result: A total of 203 COVID-19 with PTB patients and 812 matched COVID-19 without PTB were analyzed using 1:4 propensity score matching. COVID-19 patients with PTB exhibited higher in-hospital mortality (odds ratio (OR) 3.02, 95% confidence interval (CI) 1.45-6.27, p-value = 0.003) and were at increased risk of requiring conventional oxygen therapy (OR 1.57, 95% CI 1.10-2.25, p-value = 0.013) as well as high flow nasal cannula (HFNC) or noninvasive ventilation (NIV) oxygen therapy (OR 1.91, 95 CI 1.10-3.32, p-value = 0.022) compared to those without PTB. Compared to matched COVID-19 without PTB, co-infected patients showed increased mortality rates across various timeframes, including during hospitalization, and at 30 day and 90 day intervals. In-hospital mortality rates were particularly elevated among women, individuals with malignancy, and those with lower incomes. Furthermore, the increased in-hospital mortality among PTB patients persisted irrespective of the timing of TB diagnosis or vaccination status against COVID-19. Conclusion: We suggest that physicians be aware of the risk of mortality and severity among COVID-19 patients with PTB; coinfection with COVID-19 is a critical situation that remains to be further explored and needs more attention in countries with an intermediate to high PTB burden.

The biphasic impact of apolipoprotein E ε4 allele on age-related hearing loss.

Both the ε4 variant of the apolipoprotein E (APOE) gene and hearing loss are well-known risk factors for Alzheimer's disease. However, previous studies have produced inconsistent findings regarding the association between APOE genotypes and hearing levels, necessitating further investigation. The aim of this study was to investigate the relationship between APOE genotypes and hearing levels. This retrospective study analyzed clinical data from a clinical data warehouse of seven affiliated Catholic Medical Center hospitals. The study included 1,162 participants with records of APOE genotypes, audiometric tests, and cognitive function tests. In Generalized linear mixed model analysis, ε4 carriers exhibited lower pure tone audiometry thresholds with an estimate of -0.353 (SE = 0.126, p = 0.005). However, the interaction term for age and APOE ε4 had a coefficient of 0.577 (SE = 0.214 p = 0.006), suggesting that the APOE ε4 gene may accelerate hearing deterioration with age. Subgroup analysis based on an age cut-off of 75 revealed that ε4 carriers had better hearing at younger ages, but showed no significant difference at older ages. These results indicate that the ε4 allele may have a biphasic effect on hearing levels depending on age.

Risk of incident chronic obstructive pulmonary disease during longitudinal follow-up in patients with nontuberculous mycobacterial pulmonary disease.

BACKGROUND: The Global Initiative for Chronic Obstructive Lung Disease 2023 revision proposed that chronic obstructive pulmonary disease (COPD) has various etiologies including infections (COPD-I), such as tuberculosis and human immunodeficiency virus. While nontuberculous mycobacterial pulmonary disease (NTM-PD) and pulmonary tuberculosis share similar clinical manifestations, research on COPD development during longitudinal follow-up in patients with NTM-PD is limited. In this study, we aimed to evaluate the incidence and risk of COPD development in patients with NTM-PD. METHODS: We retrospectively enrolled patients with NTM-PD with normal lung function and 1:4 age-, sex-, body mass index-, and smoking status-matched controls between November 1994 and January 2022. We compared the risks of spirometry-defined COPD between the NTM-PD and control groups (study 1). A nationwide cohort study using the health insurance claims database was conducted to validate the findings (study 2). RESULTS: In study 1, during a mean follow-up of 3.3 years, COPD occurred in 14.0% (241/1,715) and 4.3% (293/6,860) of individuals in the NTM-PD and matched control cohorts, respectively. The NTM-PD cohort exhibited a higher risk of incident COPD (adjusted hazard ratio [aHR], 2.57; 95% CI, 2.15-3.09) compared to matched controls. In study 2, COPD occurred in 6.2% (24/386) and 2.5% (28/1,133) of individuals with and without NTM-PD, respectively. The NTM-PD cohort had a higher risk of incident COPD (aHR, 2.04; 95% CI, 1.21-3.42) compared to matched controls. CONCLUSION: These findings suggest that NTM-PD could be considered a new etiotype of COPD-I and emphasize the importance of monitoring lung function in individuals with NTM-PD.

A 13.56-MHz 93.5%-Efficiency Optimal On/Off Timing Tracking Active Rectifier with Digital Feedback-Based Adaptive Delay Control.

This paper presents an adaptive active rectifier with digital feedback delay controllers (DFDC) which quickly tracks optimal on/off timing against input voltage and load variations. To efficiently generate the on/off transition, the proposed active rectifier adopts dynamically controlled coarse/fine delay lines rather than using conventional power-hungry static comparators, while removing the risk of unwanted multiple driving pulses to pass transistors. DFDC conducts the dual-loop digital feedback to independently adjust on/off timing with high-speed 13.56-MHz loop bandwidth, improving the voltage conversion ratio (VCR) and power conversion efficiency (PCE). DFDC can enable real-time power-saving mode control that automatically masks clock-toggling to non-essential blocks to minimize dynamic power loss while driving power transistors. To validate the efficacy of the proposed adaptive rectifier during digital feedback and settling procedures, experiments were carried out with 0.25 µm CMOS prototype at the carrier frequency of 13.56-MHz, input voltages between 1.7 and 2.6 V, and load ranges from 0.33 to 2.2 kΩ. The proposed active rectifier employing DFDC achieves a peak PCE of 93.5% and the peak VCR of 96.3% at the output power of 12.52 mW and 2.02 mW, respectively.

Recurrent and De Novo Focal Segmental Glomerulosclerosis After Kidney Transplantation: Comparison of Clinical Features and Transplant Outcomes.

BACKGROUND: Focal segmental glomerulosclerosis (FSGS) is a notable subtype of glomerulonephritis in kidney transplantation, often resulting in graft failure. Yet, research comparing transplant outcomes between de novo and recurrent FSGS is scarce. This study aims to compare clinical features and transplant outcomes between these two categories. METHODS: This retrospective study enrolled 773 kidney transplant recipients from two centers between January 2008 and October 2021. Patients diagnosed with FSGS through graft kidney biopsy were included. They were categorized into two groups based on the time of FSGS occurrence and results of native kidney biopsy: the recurrent FSGS group and the de novo FSGS group. RESULTS: Of 773 kidney transplant patients, 24 had primary FSGS-causing end-stage renal disease. During a median 65-month follow-up, 5 of these patients developed recurrent FSGS (incidence: 26.3%). Among 749 patients with other kidney diseases causing end-stage renal disease, 9 had de novo FSGS (incidence: 1.2%). In the recurrent FSGS group, 2 out of 5 patients experienced graft failure, with no deaths or acute rejections. Similarly, in the de novo FSGS group, 3 out of 9 patients experienced graft failure, with no deaths or acute rejections. Kaplan-Meier analysis showed slower graft loss in de novo FSGS, resulting in a higher graft survival rate compared to recurrent FSGS (probability of graft survival, 60% vs 33.3%, P = .036). CONCLUSIONS: Graft loss progresses more slowly in de novo FSGS compared to recurrent FSGS, resulting in a higher long-term graft survival rate in de novo FSGS than in recurrent FSGS.

Felodipine attenuates neuroinflammatory responses and tau hyperphosphorylation through JNK/P38 signaling in tau-overexpressing AD mice.

We previously demonstrated that felodipine, an L-type calcium channel blocker, inhibits LPS-mediated neuroinflammatory responses in BV2 microglial cells and wild-type mice. However, the effects of felodipine on tau pathology, a hallmark of Alzheimer's disease (AD), have not been explored yet. Therefore, in the present study, we determined whether felodipine affects neuroinflammation and tau hyperphosphorylation in 3-month-old P301S transgenic mice (PS19), an early phase AD mice model for tauopathy. Felodipine administration decreased tauopathy-mediated microglial activation and NLRP3 expression in PS19 mice but had no effect on tauopathy-associated astrogliosis. In addition, felodipine treatment significantly reduced tau hyperphosphorylation at S202/Thr205 and Thr212/Ser214 residues via inhibiting JNK/P38 signaling in PS19 mice. Collectively, our results suggest that felodipine significantly ameliorates tau hyper-phosphorylation and tauopathy-associated neuroinflammatory responses in AD mice model for tauopathy and could be a novel therapeutic agent for AD.

Implications of GLI spirometry reference equations in Northeast Asian patients with COPD.

BACKGROUND: Accurate spirometry interpretation is critical in the diagnosis and management of chronic obstructive pulmonary disease (COPD). With increasing efforts for a unified approach by the Global Lung Function Initiative (GLI), this study evaluated the application of race-specific 2012-GLI and race-neutral 2022-GLI reference equations compared to Choi's reference equations, which is derived and widely used in South Korea, for spirometry interpretation in Northeast Asian patients with COPD. RESEARCH QUESTION: What are the effects of applying race-specific 2012-GLI, race-neutral 2022-GLI, and Choi's reference equations on the diagnosis, severity grade, and clinical outcome associations of COPD STUDY DESIGN AND METHODS: Serial spirometry data from the Korea COPD Subgroup Study (KOCOSS) consisting of 3,477 patients were utilized for re-analyses using 2012-GLI, 2022-GLI, and Choi's reference equations. The COPD diagnosis and severity categorization, associations with disease manifestations and health outcomes, and longitudinal trajectories of lung function were determined. RESULTS: Although there was strong concordance in COPD diagnosis comparing 2012-GLI, and 2022-GLI reference equations to Choi's reference equations, a notable portion of patients were reclassified to milder disease severity (17.0% and 23.4% for 2012-GLI and 2022-GLI reference equations, respectively). Relationships between FEV1 percent-predicted values calculated using 2012-GLI, 2022-GLI, and Choi's equations with clinical outcomes including dyspnea severity, exercise capacity, health-related quality of life, and frequency of exacerbations remain consistently significant. Similar annual decline rates of FEV1 and FVC percent-predicted were observed among the reference equations used, except for slower annual decline rate of FEV1 in Choi's equation compared to 2022-GLI race-neutral equation. INTERPRETATION: Application of GLI reference equations for spirometry interpretation in Northeast Asian patients with COPD has potential implications on disease severity grade for clinical management and trial participation, and maintains consistent significant relationships with key disease outcomes.

Effects of a customized diet education program using a mobile instant messenger for people undergoing peritoneal dialysis: A feasibility test.

PURPOSE: The study was conducted to develop a customized diet education program using mobile instant messenger for people undergoing peritoneal dialysis (PD). Our goal was to examine the program's effects on diet-related self-efficacy, dietary self-care compliance, and physiological indices (hemoglobin, albumin, potassium, and phosphorus). METHODS: This was a quasi-experimental study with a non-equivalent control group pre-post-test design. We applied the Cox interaction model of client health behaviors. Overall, 43 patients (21 in the experimental group and 22 in the control group) attending the renal clinic and undergoing PD at three hospitals were included. The experimental group underwent a customized diet education program using a mobile instant messenger for five weeks. Patients in the control group received routine care. This study was conducted in the following order: pre-test, treatment, post-test 1 (immediately after), and post-test 2 (four weeks after). RESULTS: This study showed significant differences in dietary self-care compliance (F = 15.29, p < .001) and hemoglobin level (F = 7.55, p = .001) in interactions between times and groups. CONCLUSIONS: The diet education program is an effective strategies to preventing complications and helping PD patients perform dietary self-care compliance through systematic and continuous interactions with educational nurse who is an expert in PD management of people undergoing PD.

Mitochondrial RNA cytosolic leakage drives the SASP.

Senescent cells secrete proinflammatory factors known as the senescence-associated secretory phenotype (SASP), contributing to tissue dysfunction and aging. Mitochondrial dysfunction is a key feature of senescence, influencing SASP via mitochondrial DNA (mtDNA) release and cGAS/STING pathway activation. Here, we demonstrate that mitochondrial RNA (mtRNA) also accumulates in the cytosol of senescent cells, activating RNA sensors RIG-I and MDA5, leading to MAVS aggregation and SASP induction. Inhibition of these RNA sensors significantly reduces SASP factors. Furthermore, BAX and BAK plays a key role in mtRNA leakage during senescence, and their deletion diminishes SASP expression in vitro and in a mouse model of Metabolic Dysfunction Associated Steatohepatitis (MASH). These findings highlight mtRNA's role in SASP regulation and its potential as a therapeutic target for mitigating age-related inflammation.

A New Paradigm on Waste-to-Energy Applying Hydrovoltaic Energy Harvesting Technology to Face Masks.

The widespread use of single-use face masks during the recent epidemic has led to significant environmental challenges due to waste pollution. This study explores an innovative approach to address this issue by repurposing discarded face masks for hydrovoltaic energy harvesting. By coating the face masks with carbon black (CB) to enhance their hydrophilic properties, we developed mask-based hydrovoltaic power generators (MHPGs). These MHPGs were evaluated for their hydrovoltaic performance, revealing that different mask configurations and sizes affect their efficiency. The study found that MHPGs with smaller, more structured areas exhibited better energy output, with maximum open-circuit voltages (VOC) reaching up to 0.39 V and short-circuit currents (ISC) up to 65.6 µA. The integration of CB improved water absorption and transport, enhancing the hydrovoltaic performance. More specifically, MHPG-1 to MHPG-4, which represented different sizes and features, presented mean VOC values of 0.32, 0.17, 0.19 and 0.05 V, as well as mean ISC values of 16.57, 15.59, 47.43 and 3.02 µA, respectively. The findings highlight the feasibility of utilizing discarded masks in energy harvesting systems, offering both environmental benefits and a novel method for renewable energy generation. Therefore, this work provides a new paradigm for waste-to-energy (WTE) technologies and inspires further research into the use of unconventional waste materials for energy production.

New anti-mesenteric delta-shaped stapled anastomosis: Technical report with short-term postoperative outcomes in patients with Crohn's disease.

BACKGROUND: Medical treatment for Crohn's disease (CD) has continuously improved, which has led to a decrease in surgical recurrence rates. Despite these advancements, 25% of patients will undergo repeat intestinal surgery. Recurrence of CD commonly occurs on the mesentery side of the anastomosis site. AIM: To compare the new anti-mesenteric side-to-side delta-shaped stapled anastomosis (DSA) with the conventional stapled functional end-to-end anastomosis (CSA). METHODS: This retrospective study included CD patients who underwent ileo-ileal or ileo-colic anastomosis between January 2020 and December 2023. The DSA technique employed a stapler to maintain the concept of anti-mesentery side-to-side anastomosis by performing a 90° vertical closure of the open window compared with the CSA technique. At the corner where the open window is closed, the DSA avoids forming a pouch and creates an anastomosis resembling a delta shape within the intestinal lumen. We compared demographics, preoperative condition, operative findings, and operative outcomes for the two techniques. RESULTS: The study included 175 patients, including 92 in the DSA group and 83 in the CSA group. The two groups were similar in baseline characteristics, preoperative medical treatment, and operative findings except for the Montreal classification location. The 30-days postoperative complication rate was significantly lower in the DSA group compared with the CSA group (16.3% vs 32.5%, P = 0.009). Ileus incidence was significantly lower in the DSA group than in the CSA group (4.3% vs 14.5%, P = 0.033), and the hospital stay was shorter in the DSA group than in the CSA group (5.67 ± 1.53 days vs 7.39 ± 3.68 days, P = 0.001). CONCLUSION: The DSA technique was feasible and showed comparable postoperative outcomes with lower short-term complications compared with the CSA technique. Further studies on CD recurrence and long-term complications are warranted.

Functional-hydrogel-based electronic-skin patch for accelerated healing and monitoring of skin wounds.

Conductive hydrogels feature reasonable electrical performance as well as tissue-like mechanical softness, thus positioning them as promising material candidates for soft bio-integrated electronics. Despite recent advances in materials and their processing technologies, however, facile patterning and monolithic integration of functional hydrogels (e.g., conductive, low-impedance, adhesive, and insulative hydrogels) for all-hydrogel-based soft bioelectronics still poses significant challenges. Here, we report material design, fabrication, and integration strategies for an electronic-skin (e-skin) patch based on functional hydrogels. The e-skin patch was fabricated by using photolithography-compatible functional hydrogels, such as poly(2-hydroxyethyl acrylate) (PHEA) hydrogel (substrate), Ag flake hydrogel (interconnection; conductivity: ∼571.43 S/cm), poly(3,4-ethylenedioxythiophene:polystyrene) (PEDOT:PSS) hydrogel (working electrode; impedance: ∼69.84 Ω @ 1 Hz), polydopamine (PDA) hydrogel (tissue adhesive; shear strength: ∼725.1 kPa), and poly(vinyl alcohol) (PVA) hydrogel (encapsulation). The properties of these functional hydrogels closely resemble those of human tissues in terms of water content and Young's modulus, enabling stable tissue-device interfacing in dynamically changing physiological environments. We demonstrated the efficacy of the e-skin patch through its application to accelerated healing and monitoring of skin wounds in mouse models - efficient fibroblast migration, proliferation, and differentiation promoted by electric field (EF) stimulation and iontophoretic drug delivery, and monitoring of the accelerated healing process through impedance mapping. The all-hydrogel-based e-skin patch is expected to create new opportunities for various clinically-relevant tissue interfacing applications.

Activation of Toll-like receptor 2 promotes mesenchymal stem/stromal cell-mediated immunoregulation and angiostasis through AKR1C1.

Background: Mesenchymal stem/stromal cells (MSCs) maintain tissue homeostasis in response to microenvironmental perturbations. Toll-like receptors (TLRs) are key sensors for exogenous and endogenous signals produced during injury. In this study, we aimed to investigate whether TLRs affect the homeostatic functions of MSCs after injury. Methods: We examined the expression of TLR2, TLR3 and TLR4 in MSCs, and analyzed the functional significance of TLR2 activation using single-cell RNA sequencing. Additionally, we investigated the effects and mechanisms of TLR2 and its downstream activation in MSCs on the MSCs themselves, on monocytes/macrophages, and in a mouse model of sterile injury-induced inflammatory corneal angiogenesis. Results: MSCs expressed TLR2, which was upregulated by monocytes/macrophages. Activation of TLR2 in MSCs promoted their immunoregulatory and angiostatic functions in monocytes/macrophages and in mice with inflammatory corneal angiogenesis, whereas TLR2 inhibition attenuated these functions. Single-cell RNA sequencing revealed AKR1C1, a gene encoding aldo-keto reductase family 1 member C1, as the most significantly inducible gene in MSCs upon TLR2 stimulation, though its stimulation did not affect cell compositions. AKR1C1 protected MSCs against ferroptosis, increased secretion of anti-inflammatory cytokines, and enhanced their ability to drive monocytes/macrophages towards immunoregulatory phenotypes, leading to the amelioration of inflammatory corneal neovascularization in mice. Conclusion: Our findings suggest that activation of TLR2-AKR1C1 signaling in MSCs serves as an important pathway for the survival and homeostatic activities of MSCs during injury.

Spheroid-Hydrogel Integrated Biomimetic System (SHIBS): A New Frontier in Advanced 3D Cell Culture Technology.

BACKGROUND: Despite significant advances in three-dimensional (3D) cell culture technologies, creating accurate in vitro models that faithfully recapitulate complex in vivo environments remains a major challenge in biomedical research. Traditional culture methods often fail to simultaneously facilitate critical cell-cell and cell-extracellular matrix (ECM) interactions while providing control over mechanical and biochemical properties. SUMMARY: This review introduces the spheroid-hydrogel integrated biomimetic system (SHIBS), a groundbreaking approach that synergistically combines spheroid culture with tailored hydrogel technologies. SHIBS uniquely bridges the gap between traditional culture methods and physiological conditions by offering unprecedented control over both cellular interactions and environmental properties. We explore how SHIBS is revolutionizing fields ranging from drug discovery and disease modeling to regenerative medicine and basic biological research. The review discusses current challenges in SHIBS technology, including reproducibility, scalability, and high-resolution imaging, and outlines ongoing research addressing these issues. Furthermore, we envision the future evolution of SHIBS into more sophisticated organoid-hydrogel integrated biomimetic systems (OHIBS) and its integration with cutting-edge technologies such as microfluidics, 3D bioprinting, and artificial intelligence. KEY MESSAGES: SHIBS represents a paradigm shift in 3D cell culture technology, offering a unique solution to recreate complex in vivo environments. Its potential to accelerate the development of personalized therapies across various biomedical fields is significant. While challenges persist, the ongoing advancements in SHIBS technology promise to overcome current limitations, paving the way for more accurate and reliable in vitro models. The future integration of SHIBS with emerging technologies may revolutionize biomimetic modeling, potentially reducing the need for animal testing and expediting drug discovery processes. This comprehensive review provides researchers and clinicians with a holistic understanding of SHIBS technology, its current capabilities, and its future prospects in advancing biomedical research and therapeutic innovations.