UREA

The research study is dedicated towards synthesis of novel spiro[indoline-3,2'-pyrrolidines] incorporating a urea functionality. Crucially, the study seeks to elucidate their anticipated multi-targeted mechanism of action, moving towards the final objective of producing multi-functional antineoplastic agents. 1,3-Dipolar cycloaddition was used to construct the final compounds, the spiro-analogs 15a-m. 2-Propen-1-ones 12a-j provided a crucial part of the structure (the urea group). Isatins 13a,b and sarcosine 14, reacted together during the process to form in situ the necessary dipole, azomethine ylide. This synthetic protocol produced the targeted agents 15a-m with high yields. Biological evaluation identified compound 15l as a highly potent agent against the HCT116 colon cancer line, outperforming sunitinib and 5-fluorouracil by 3.7-fold and 7.9-fold, respectively. It is also identified with efficacy against MCF7 (breast cancer) close to that of 5-fluorouracil. Additionally, compound 15h exhibited exceptional potency against A431 skin squamous carcinoma surpassing 5-fluorouracil by 9.1-fold. Mechanistic studies confirmed the dual-action of rational design. Compound 15h demonstrated VEGFR-2 inhibition comparable to sorafenib, while 15g emerged as a dual MDM2 inhibitor and p53 activator, significantly outperforming doxorubicin. The correlation between MDM2 inhibition and p53 activation suggests that the disruption of the MDM2-p53 protein-protein interaction, alongside VEGFR-2 inhibition, drives the antiproliferative effects. Furthermore, compounds 15g, 15h, 15j, and 15k induced apoptosis through the upregulation of caspase-3 and BAX and the downregulation of Bcl-2. Cell cycle (flow cytometry) studies of 15h and 15j confirmed G0/G1 phase arrest. Moreover, the Annexin V-FITC/PI dual staining assay evidenced the apoptotic potential of compounds 15h and 15j. CAM assays supported the anti-angiogenic potential of 15g, 15h, 15j, and 15k. Finally, molecular docking (PDB ID: 5LAW) and dynamic simulations validated the binding stability and mechanism within the MDM2 pocket.

Urine collection from neonates and infants remains challenging. Non-invasive urine collection methods (UCMs) are preferred, but they are often associated with drawbacks, such as feces contamination, discomfort, and/or inaccurate urinary analysis. This study aimed to demonstrate the measurement accuracy and clinical usability of the Specturi urine collector device. 25 different urines were incubated in the Specturi urine collector device and three non-invasive UCMs, namely gauzes, urine collection bag, and PeeSpot, for 3 h at 37 °C. Albumin, calcium, chloride, creatinine, glucose, magnesium, phosphate, potassium, protein, sodium, and urea concentrations as well as osmolality and pH were measured in the extracted urines and compared to a control. The measurements were also compared between the different UCMs. In addition, a clinical pilot study was performed with the Specturi urine collector device to assess the usability and safety as indicated by nurses and parents. The novel Specturi urine collector device offered accurate measurements of the various urinary analytes. Its measurement accuracy was comparable to the urine collection bag and PeeSpot and more accurate than gauzes. Nurses indicated that the Specturi urine collector device was easy to use, noting the ease of application and removal. Both nurses and parents indicated that the participants experienced no discomfort while wearing the Specturi urine collector device and no significant skin reactions were observed, unlike for other UCMs. The Specturi urine collector device is a novel non-invasive UCM, offering accurate urinary analysis, ensuring patient safety and comfort, and providing easy usage by nurses.

Owing to advancements in implantable bioelectronic devices, there has been an increase in demand for biocompatible energy sources with long-term electrochemical and mechanical stability. In this study, we present the fabrication of a flexible asymmetric supercapacitor (MXene//AC) based on two-dimensional Ti 3 C 2 T x MXene nanosheets. The supercapacitor demonstrates excellent electrochemical performance with an areal capacitance of 66.43 mF cm -2 , energy density of 13.2 Wh kg -1 , and a high power density of 2300 W kg -1 . The supercapacitor retained 95% capacitance after 5000 charge-discharge cycles and displayed negligible performance degradation under various bending angles, highlighting its mechanical suitability for wearable electronics. Density functional theory (DFT) analysis revealed that the metallic Ti-C backbone of Ti3C2T x MXene and its O/F terminations work synergistically to enable rapid electron transport and reversible proton-coupled surface redox, supporting predominantly surface-controlled charge storage with a significant pseudocapacitive contribution. To complement device-level studies, we assessed the in vivo safety profile and antioxidant potential of Ti 3 C 2 T x MXene nanosheets in Sprague-Dawley (SD) rats through acute dermal, subchronic oral, and subchronic intraperitoneal toxicity evaluations. Acute dermal exposure up to 100 mg kg -1 caused mild skin responses without necrosis, while subchronic administration for 28 days revealed no considerable abnormalities in biochemical parameters (alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen, creatinine), inflammatory markers (IL-1β, IL-6), or oxidative stress biomarkers (malondialdehyde, glutathione). Histopathological evaluations confirmed the absence of structural damage or inflammation in vital organs. Additionally, MXene nanosheets demonstrated antioxidant activity by scavenging 2,2-azino-bis(3-ethyl)benzothiazoline-6-sulfonic acid free radicals in a dose-dependent manner, highlighting their potential to reduce oxidative stress in biomedical applications. Overall, this dual-focused study demonstrates that MXene nanosheets are not only highly effective for developing flexible, stable asymmetric supercapacitors but also exhibit favorable in vivo biocompatibility and antioxidant properties at the tested doses. These findings emphasize the potential of MXene-based materials as next-generation, fully biocompatible energy storage devices for advanced implantable bioelectronic systems.

Traditional sensors, in long-term skin contact, prone to microbial growth, risking skin allergies and infections. To address this issue, a novel deep eutectic gel composite-polyacrylamide-gelatin-Dalbergia benthamii Prain total flavonoids (PAMG-DbTF)-was developed by integrating betaine-urea-based natural deep eutectic solvent (NADES) with polyacrylamide (PAM) and gelatin-a biopolymer derived from collagen-via physicochemical crosslinking. As the core biopolymer, gelatin played a pivotal role in constructing the stable interpenetrating network: its intrinsic amino acid residues formed hydrogen bonds with PAM chains and NADES, which was confirmed by FT-IR, SEM, XRD, XPS and TGA analyses. This gelatin-driven network endowed the gel with excellent mechanical and stability properties, including a tensile strain of 330%, a swelling ratio of 220%, 90% water retention at 48 h, and antifreezing performance at -20°C. The DbTF-loaded gel showed synergistic antibacterial activity (100% against E. coli) and antioxidant capacity (70% DPPH scavenging rate). As a flexible strain sensor, PAMG-2 demonstrated stable relative resistance changes (ΔR/R 0 ) under cyclic loading (500 cycles at 40% strain) and real-time monitoring of human motions (throat vocalization, joint bending), where gelatin's elasticity ensures signal repeatability. This gelatin-centered multifunctional deep eutectic gel highlights the critical role of biopolymers in advanced wearable biomedical devices and environmental monitoring.

Atopic dermatitis (AD) is a prevalent chronic and recurrent inflammatory skin disease. Guidelines for the treatment and care of AD suggest that appropriate bathing can facilitate the repair of skin lesions. MuShengshu is a weakly acidic bath solution that contains traditional Chinese medicine ingredients. Previous studies indicate its potential to alleviate pruritus and promote the healing of skin lesions in patients with dermatosis. However, high-quality evidence is still limited. This randomized, double-blind, placebo-controlled clinical trial aims to assess the efficacy and safety of MuShengshu (MSS) combined with foundational therapies in patients with mild-to-moderate AD. A total of 66 patients with mild-to-moderate AD will be enrolled at the Shanghai Skin Disease Hospital from August 2025 to June 2026. Patients will be randomly assigned in a 2:1 ratio to either the treatment group (MSS combined with foundational therapies, n  = 44) or the control group (MSS placebo combined with foundational therapies, n  = 22). Patients will receive MSS or MSS placebo once daily, for 4 months. Meanwhile, the foundational therapies include desonide cream for mild AD and triamcinolone acetonide cream for moderate AD, both of which will be applied twice daily for 2 weeks. Additionally, all patients will receive urea ointment twice daily for 4 weeks. The primary outcome indicator is EASI 50 , defined as the proportion of patients achieving ≥50% improvement in the Eczema Area and Severity Index (EASI) score at week 4 from baseline. The secondary outcome indicators include the EASI, Visual Analogue Scale (VAS), Investigator's Global Assessment (IGA), and Dermatology Life Quality Index (DLQI), which will be assessed at baseline (week 0), weeks 1, 2, 4, and 16. In this study, statistical analyses will be conducted using SAS 9.4 software, with statistical significance being defined as a two-tailed α level of 0.05. In this study, ethical approval was granted in March 2025, with registration completed in the International Traditional Medicine Clinical Trial Registry in June 2025. Recruitment of participants began in August 2025 and is anticipated to completed by June 2026. Data analysis is set to start in August 2026, with preliminary trial results expected to be submitted for peer-reviewed publication by December 2026. Findings in this study are expected to provide evidence for the incorporation of traditional Chinese herbal bath solutions into the comprehensive management of AD. https://www.chictr.org.cn/, Identifier ITMCTR2025001206.

Male genital lichen sclerosus (MGLSc) is a chronic inflammatory dermatosis with significant morbidity, yet its pathogenesis remains incompletely understood. Two main hypotheses have emerged: an autoimmune model, and the urine/occlusion hypothesis, specific to male genital anatomy. This narrative review critically analyses evidence supporting each paradigm. Epidemiological data reveal that autoimmune comorbidities occur significantly less frequently in men with MGLSc than in women with vulvar disease, with some studies reporting prevalence no higher than general population rates. Histopathologically, cytotoxic CD8+ and CD57+ T-lymphocyte infiltration suggests immune-mediated tissue injury, yet extracellular matrix protein 1 autoantibodies show no significant seroreactivity in males. Conversely, the urine/occlusion hypothesis is supported by the near-universal association of MGLSc with intact foreskin, high prevalence of post-micturition micro-incontinence, anatomical mapping demonstrating disease concentration in maximally occluded preputial regions, and case series showing disease resolution following urinary diversion and induction at urostomy sites. Microbiome studies demonstrate convergence between balanopreputial and urinary microbial communities in affected patients, while molecular evidence shows urea-induced fibroblast changes consistent with fibrogenesis. Recent transcriptomic analyses identifying distinct molecular subtypes suggest heterogeneity, with autoimmune mechanisms potentially operative in only a subset of patients. The evidence reviewed supports urine exposure and occlusion as the predominant pathogenic drivers in most MGLSc cases, with autoimmune phenomena likely representing secondary responses to tissue injury rather than primary etiological mechanisms.

Although estrogen is known to confer cardioprotective benefits in cisgender women, transgender women on gender-affirming hormone therapy may experience unique cardiovascular risks. Emerging evidence suggests that feminizing hormone therapy may confer both beneficial and adverse effects on the cardiovascular, renal, and hepatic systems. In this cross-sectional study, transgender women receiving gender-affirming hormone therapy with orchiectomy ( n = 15) or without orchiectomy ( n = 15) were compared with age-matched cisgender men ( n = 15) and cisgender women ( n = 15). Transgender women had received hormone therapy for 11 ± 3 yr. Serum estradiol concentrations were significantly lower in cisgender men (33 ± 10 pg·mL -1 ) than in transgender women with orchiectomy (141 ± 47 pg·mL -1 ), transgender women without orchiectomy (116 ± 41 pg·mL -1 ), and cisgender women (131 ± 38 pg·mL -1 ), whereas serum testosterone concentrations were significantly higher in cisgender men (22.0 ± 6.1 nM) compared with the other groups (1.2 ± 1.1, 0.6 ± 0.3, and 1.0 ± 0.3 nM) (all P < 0.001). No statistically significant group differences were observed in brachial-ankle pulse wave velocity, brachial artery flow-mediated dilation, postocclusive skin reactive hyperemia, or blood nitric oxide concentrations (all P > 0.05). Blood urea nitrogen, creatinine, and liver enzyme concentrations were significantly higher in cisgender men than in the other groups (all P < 0.05). Collectively, these results indicate that no statistically significant differences were observed in macro- and microvascular function, as well as liver and renal function, between transgender women (with or without orchiectomy) and cisgender women. NEW & NOTEWORTHY The primary finding of the present study is that transgender women demonstrate similar macrovascular and microvascular function as well as renal and hepatic function to cisgender women. Regardless of marked differences in circulating sex hormone profiles, no evidence of vascular dysfunction or organ impairment was observed in transgender women. These findings suggest that prolonged exposure to an estrogen-dominant hormonal milieu is sufficient to induce a female-typical physiological phenotype across multiple organ systems.

Aquaporins (AQPs) are membrane proteins that facilitate the transport of small molecules such as water, glycerol, and urea. In mammals, 13 AQP isoforms (AQP0 to AQP12) exhibit tissue-specific expression. Over the past two decades, aquaporins (AQPs) have received considerable attention for their role in tumor biology. Squamous cell carcinoma (SCC) originates from stratified squamous cells and commonly affects the skin and oral cavity. SCC is prevalent in dogs and cats; however, no studies have reported an association between SCC and AQPs in these species. This study investigated the immunohistochemical expression of AQP1, AQP3, AQP5, E-cadherin, and Ki-67 in cutaneous and oral SCCs of dogs and cats. AQP1 and AQP5 were not expressed in tumor cells. In contrast, AQP3 and E-cadherin localized to the plasma membrane, primarily within island-like structures in both cutaneous and oral SCCs. Ki-67-positive cells appeared in small group and cord structures within tumor regions exhibiting reduced AQP3 expression. Therefore, AQP3 expression may be down-regulated in malignant tumor cells in SCCs of dogs and cats. These findings indicate that AQP3 may serve as a novel biomarker for assessing malignancy in SCCs of dogs and cats.

Cancer and its treatments frequently compromise skin integrity, leading to xerosis, pruritus, dermatitis, radiation-induced skin damage, and secondary infections. These cutaneous adverse events (cAEs) are not merely superficial; they profoundly impact patient quality of life (QoL), contributing to physical discomfort, psychosocial distress, and poorer treatment adherence. Even mild skin toxicities elevate dermatology-specific QoL measures, affecting mood and social function. Additionally, new targeted therapies, such as daraxonrasib-a KRAS inhibitor under development for pancreatic cancer-can cause a dose-limiting acneiform facial rash. In this study, relevant literature on skin care in cancer patients was identified using PubMed. Evidence from clinical studies, reviews, and expert guidelines was summarized. Evidence supports proactive skincare with gentle pH-balanced cleansers, ceramide- or urea-based moisturizers, and broad-spectrum photoprotection to lessen symptom severity and improve QoL. Sun protection remains essential because chemotherapy and immunomodulatory therapies increase photosensitivity, accelerate photoaging, and raise the risk of secondary skin cancers. Supportive skincare interventions have also shown emotional and functional benefits, including improved mood and self-image during chemotherapy and radiation treatment. Despite strong data supporting moisturization, barrier repair, and photoprotection, oncologic treatment plans often overlook these interventions. By integrating dermatologic education and skincare maintenance into standard oncologic practice, we can minimize cAEs, foster treatment compliance, and enhance patients' physical comfort and psychosocial well-being. This narrative review synthesizes mechanistic insights, clinical evidence, and practical recommendations for oncologists to champion comprehensive skincare in all cancer patients, whether directly affected by skin issues or not.

Oclacitinib is a Janus kinase inhibitor approved for the treatment of pruritus associated with allergic dermatitis in dogs and may be effective in horses. To evaluate the efficacy of oclacitinib in reducing pruritus and skin lesions in horses with allergic dermatitis. Sixteen horses aged ≥ 18 months. Horses received oclacitinib at 0.25 mg/kg orally once daily for 21 days. Changes in haematological and biochemical parameters were measured on Day (D)0 and D21. The owners were instructed to evaluate the horses using the pruritus Visual Analog Scale (PVAS) on D0, D4, D7, D10, D14, D17 and D21. A veterinary surgeon evaluated skin lesions using a veterinarian lesion score (VLS) and veterinarian alopecia score (VAS) on D0, D7, D14 and D21. From baseline to D21, the median (range) PVAS changed from 5 (4-8) to 2.5 (2-4.5), VLS from 19 (2-42) to 10 (1-38) and VAS from 2 (2, 3) to 2 (1, 2). Of all 16 horses, improvements in PVAS, VLS and VAS were observed in 15, 12 and 8 horses, respectively. Blood profiles revealed significantly increased aspartate aminotransferase, gamma-glutamyl transferase and creatinine levels. White blood cell count, lymphocyte count and blood urea nitrogen significantly decreased. Creatine kinase levels showed individual variability. Oclacitinib effectively reduced pruritus and improved skin lesions in horses with allergic dermatitis. However, caution is advised when administering the drug to horses with renal, hepatic or muscular disorders.

Over the past several decades, dietary fructose intake has increased significantly, along with the prevalence of obesity. Fructose malabsorption is associated with gastrointestinal symptoms and may lead to fructose intolerance. Evidence suggests a probable association between intestinal fructose malabsorption and increased body adiposity. To analyze the prevalence of intestinal fructose malabsorption and intolerance in asymptomatic adolescents and to investigate their relationship with fructose intake, body adiposity, systemic metabolic indicators, and intestinal permeability. This cross-sectional observational study included 37 adolescents without gastrointestinal symptoms. Fructose malabsorption was investigated using the hydrogen breath test along with the lactulose breath test. Food intake was evaluated using a habitual food survey. Nutritional status was assessed by measuring weight, height, skin folds, abdominal circumference, and via Bioelectrical Impedance Analysis (BIA). Systemic metabolic indicators and serum zonulin levels were also evaluated to determine intestinal permeability. Of the 37 adolescents tested 16 (43.2%) exhibited fructose malabsorption. Gastrointestinal symptoms compatible with fructose intolerance were reported by 8 (50.0%) of the 16 adolescents with fructose malabsorption, and by 5 (23.8%) of the 21 adolescents without fructose malabsorption (P=0.095). Fructose intake among adolescents with and without fructose malabsorption was 7.5 and 7.9 g/day, respectively (P=0.807). Body adiposity was comparable across groups in both females (34.2% and 33.2%; P=0.738) and males (21.0% and 22.2%; P=0.731). Metabolic indicators and zonulin levels were similar, except for urea, which was significantly higher in the malabsorption group (31.7±6.3 mg/dL) compared to those without fructose malabsorption (24.5±÷7.8 md/dL; P=0.012). Intestinal fructose malabsorption is common in asymptomatic adolescents and is not associated with adiposity, biochemical changes, or increased intestinal permeability. However, it correlates with elevated fermentation in the lactulose breath test. Fructose intolerance is linked to presence gastrointestinal symptoms following lactulose ingestion. Nas últimas décadas, a ingestão de frutose na dieta aumentou significativamente, juntamente com a prevalência da obesidade. Má absorção de frutose está associada a sintomas gastrointestinais e pode levar à intolerância à frutose. Evidências sugerem uma provável associação entre a má absorção intestinal de frutose e o aumento da adiposidade corporal. Analisar a prevalência de má absorção intestinal e intolerância à frutose em adolescentes assintomáticos e investigar sua relação com a ingestão de frutose, adiposidade corporal, indicadores metabólicos sistêmicos e permeabilidade intestinal. Este estudo observacional transversal incluiu 37 adolescentes sem sintomas gastrointestinais. Má absorção de frutose foi investigada utilizando o teste respiratório de hidrogênio. Foi realizado, também, teste respiratório com lactulose. A ingestão alimentar foi avaliada por meio de um questionário sobre os hábitos alimentares. O estado nutricional foi avaliado por meio da mensuração de peso, altura, pregas cutâneas, circunferência abdominal e Análise de Impedância Bioelétrica (BIA). Foram avaliados, também, indicadores metabólicos sistêmicos e níveis séricos de zonulina como iondicador da permeabilidade intestinal. Dos 37 adolescentes estudados, 16 (43,2%) apresentaram má absorção de frutose. Sintomas gastrointestinais compatíveis com intolerância à frutose foram relatados por 8 (50,0%) dos 16 adolescentes com má absorção de frutose e por 5 (23,8%) do

Pesticide-related poisoning remains an important but preventable public health problem in children, particularly in settings with limited regulatory control. Paraquat is a highly toxic herbicide associated with severe systemic organ damage and high mortality following human exposure. Although ingestion is the most common route of poisoning, dermal absorption can result in fatal toxicity, especially with prolonged contact or compromised skin integrity. We report a rare case series of three female siblings aged 4, 6, and 8 years who developed severe paraquat toxicity following scalp application of the chemical as a home remedy for head lice. In this setting, scalp shaving is commonly practiced as part of lice treatment, often resulting in abrasions that may enhance dermal absorption. All three children presented approximately 36 h after exposure with features of systemic toxicity. The youngest child, who had more extensive scalp injury, rapidly developed respiratory distress and died shortly after presentation despite emergency resuscitation. The two older siblings initially remained conscious but subsequently developed progressive acute kidney injury and worsening respiratory failure requiring intensive care admission, haemodialysis, corticosteroid therapy, oxygen supplementation, and supportive management. Laboratory investigations demonstrated rising urea and creatinine levels with transient improvement following dialysis before subsequent deterioration. Despite aggressive supportive care, the 6-year-old child died on the ninth day of admission, while the 8-year-old died on the tenth day due to progressive respiratory failure and multi-organ dysfunction. The variation in clinical progression among the siblings likely reflects differences in the extent of scalp injury, degree of dermal absorption, exposure dose, and individual susceptibility. This case series highlights the extreme toxicity of paraquat, the absence of a specific antidote, and the devastating consequences of inappropriate domestic use of agricultural chemicals. It further emphasizes the urgent need for improved public awareness, stricter regulatory enforcement, and strengthened preventive strategies to reduce pediatric exposure and associated mortality.