Clinical guidelines for early hepatocellular carcinoma treatment options: a systematic review and bibliometric analysis.

BACKGROUND: Hepatocellular carcinoma (HCC) remains a major cause of cancer-related mortality worldwide, with treatment options including radiofrequency ablation (RFA) and surgical resection. This study evaluates the evolving guidelines for these treatments to identify the current consensus and divergences. METHOD: We conducted a systematic review following PRISMA 2020 guidelines of documents from 2017-2024 by major liver societies. The AGREE-II framework assessed guideline quality. This study is registered with PROSPERO (CRDXXXX). RESULTS: We analyzed 23 guidelines and noted significant shifts in treatment recommendations over recent updates. This analysis reveals an increasing endorsement of RFA for certain patient groups and sustained strong support for surgical resection based on robust evidence levels. All demonstrated high quality, with the 2023 Japan Guidelines receiving the highest AGREE-II score. A significant finding was the low level of stakeholder involvement in the development of guidelines. CONCLUSION: The study highlights the dynamic nature of clinical guidelines for early-stage HCC, underscoring the need for ongoing updates and direct, high-quality comparative studies. The evolving recommendations for RFA, especially its role in managing small, localized tumors, reflect its emerging importance in the treatment paradigm.

Nuclear factor interleukin 3 and metabolic dysfunction-associated fatty liver disease development.

This study investigates sex-specific effects in a gain-of-function model to evaluate Nfil3 function in relation to high-fat diet (HFD)-induced metabolic dysfunction-associated steatotic liver disease (MASLD) and gut microbiota (GM)-induced alterations in the bile acid (BA) profile. MASLD is induced in both wild type and Nfil3-deficient (NKO) C57BL/6 J mice through an HFD. The hepatic immune response is evaluated using flow cytometry, revealing that NKO mice exhibit lower body weight, serum triglyceride (TG) levels, tissue injury, inflammation, and fat accumulation. The Nfil3 deletion reduces macrophage counts in fibrotic liver tissues, decreases proinflammatory gene and protein expression, and diminishes gut barrier function. Alpha and beta diversity analysis reveal increased GM alpha diversity across different sexes. The Nfil3 gene deletion modifies the BA profile, suggesting that negative feedback through the Nfil3-FXR-FGF15 axis facilitates BA recycling from the liver via enterohepatic circulation. Therefore, inhibiting Nfil3 in the liver offers a viable treatment approach for MASLD.

Short-chain fatty acids ameliorate imiquimod-induced skin thickening and IL-17 levels and alter gut microbiota in mice: a metagenomic association analysis.

Short-chain fatty acids (SCFAs) have been proposed to have anti-inflammatory effects and improve immune homeostasis. We aimed to examine the effects of SCFAs on skin phenotype, systemic inflammation, and gut microbiota in mice with psoriasis-like inflammation. Imiquimod (IMQ)-treated C57BL/6 mice served as the study model. We conducted a metagenomic association study of IMQ-mice treated with SCFAs or anti-IL-17 antibody using whole-genome shotgun sequencing. The associations among SCFA supplements, skin thickness, circulating inflammatory profiles, and fecal microbiota profiles were investigated. The microbiome study was performed using pipelines for phylogenetic analysis, functional gene analysis, and pathway analysis. In IMQ-treated mice, there were increases in skin thickness and splenic weight, as well as unique fecal microbial profiles. SCFAs ameliorated IMQ-induced skin thickening, splenic weight gain, and serum IL-17F levels, with results that were comparable with those receiving anti-IL-17 treatment. IMQ-treated mice receiving SCFAs had greater microbial diversity than mice treated with IMQ alone. SCFAs and anti-IL17 treatment were associated with alteration of gut microbiota, with increased prevalences of Oscillospiraceae and Lachnopiraceae and decreased prevalences of Muribaculaceae and Bacteroides, which have been predicted to be associated with increased glycan degradation, phenylalanine metabolism, and xylene degradation. SCFAs may mitigate IMQ-induced skin thickening and IL-17F levels and alter fecal microbiota profiles in IMQ-treated mice.

Association between Air Quality Index and the risk of rosacea: A Nationwide population-based Cohort Study.

BACKGROUND: Air pollution is associated with several inflammatory skin disorders. However, the association between air quality and rosacea remains unclear. OBJECTIVE: To investigate the association between air quality index and incidence of rosacea. METHODS: Overall, 21,709,479 participants without rosacea before 2008 were recruited from the Taiwan National Health Insurance Research Database. The long-term average air quality index (AQI) value for each participant was acquired from the Taiwan Air Quality Monitoring System Network and calculated from 2008/1/1 until the diagnosis of rosacea, withdrawal from the National Health Insurance, or December 31, 2018. RESULTS: We observed a significant association between AQI and the incidence of rosacea, with each unit elevation in AQI increasing the risk of rosacea by 5 %. Compared with the Q1 group, the Q2, Q3, and Q4 cohorts exhibited 1.82-fold, 4.48-fold and 7.22-fold increased risk of rosacea, respectively. Additionally, exposure to PM2.5, SO2 and CO increased the risk of rosacea, whereas exposure to PM10 was associated with a lower risk. CONCLUSION: This study supported a significant dose-response relationship between AQI and the incidence of rosacea.

Liver resection had better disease-free survival rates compared with radiofrequency ablation in hepatocellular carcinoma: A meta-analysis based on randomized clinical trials.

BACKGROUND: Liver resection (LR) and radiofrequency ablation (RFA) are the most commonly used treatment modalities for early-stage hepatocellular carcinoma (ES-HCC). The comparative efficacy of LR and RFA in ES-HCC remains debated. We conducted a meta-analysis based on randomized trials to compare the outcomes of LR and RFA. METHODS: We searched PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov for randomized controlled trials (RCTs) comparing RFA and LR interventions for the treatment of ES-HCC. The primary outcomes were overall survival (OS) and disease-free survival (DFS). We used meta-regression to determine the source of heterogeneity and conducted a trial sequential analysis to examine whether the outcome was statistically reliable. RESULTS: Our meta-analysis included nine RCTs with a total of 1,516 HCC patients. Compared with patients receiving RFA, those receiving LR did not have significantly different 2-year OS (HR=1.28, 95% CI: 0.73-2.23) and 5-year OS (HR=1.49, 95% CI: 0.99-2.24). However, patients receiving LR showed a favorable trend in 2-year DFS (HR=1.40, 95% CI: 1.16-1.69) and 5-year DFS (HR=1.37; 95% CI: 1.05-1.77), although these results are not conclusive due to underpowered significance. The heterogeneity was low, and the outcomes were statistically reliable. DISCUSSION: Meta-analysis suggests that while LR shows a favorable trend in DFS compared to RFA for ES-HCC, the present evidence does not thoroughly support recommending LR over RFA. The inconclusive nature of these findings highlights the need for further large-scale RCTs to establish definitive comparative efficacy.

Hypersensitivity of the vimentin cytoskeleton to net-charge states and Coulomb repulsion.

As with most intermediate filament systems, the hierarchical self-assembly of vimentin into nonpolar filaments requires no nucleators or energy input. Utilizing a set of live-cell, single-molecule, and super-resolution microscopy tools, here we show that in mammalian cells, the assembly and disassembly of the vimentin cytoskeleton is highly sensitive to the protein net charge state. Starting with the intriguing observation that the vimentin cytoskeleton fully disassembles under hypotonic stress yet reassembles within seconds upon osmotic pressure recovery, we pinpoint ionic strength as its underlying driving factor. Further modulating the pH and expressing differently charged constructs, we converge on a model in which the vimentin cytoskeleton is destabilized by Coulomb repulsion when its mass-accumulated negative charges (-18 per vimentin protein) along the filament are less screened or otherwise intensified, and stabilized when the charges are better screened or otherwise reduced. Generalizing this model to other intermediate filaments, we further show that whereas the negatively charged GFAP cytoskeleton is similarly subject to fast disassembly under hypotonic stress, the cytokeratin, as a copolymer of negatively and positively charged subunits, does not exhibit this behavior. Thus, in cells containing both vimentin and keratin cytoskeletons, hypotonic stress disassembles the former but not the latter. Together, our results both provide new handles for modulating cell behavior and call for new attention to the effects of net charges in intracellular protein interactions.

Reduced atopic march risk in pediatric atopic dermatitis patients prescribed dupilumab versus conventional immunomodulatory therapy: A population-based cohort study.

BACKGROUND: Dupilumab effectively treats atopic dermatitis (AD); however, its role in halting the atopic march remains uncertain. OBJECTIVE: To investigate dupilumab's effect on atopic march in pediatric AD patients versus conventional immunomodulators. METHODS: This retrospective cohort study utilized data from the TriNetX US Collaborative Network (2011-2024). Pediatric AD patients (≤18 years) were categorized into DUPI-cohort (newly prescribed dupilumab) or CONV-cohort (prescribed conventional immunomodulators without dupilumab). After 1:1 propensity-score matching, we analyzed atopic march progression, defined by the incident asthma or allergic rhinitis (AR). Cumulative incidence was plotted using Kaplan-Meier, with risk assessment via Cox regression. RESULTS: The study included 2192 patients in each cohort. The 3-year cumulative incidence of atopic march progression was lower in the DUPI-cohort than the CONV-cohort (20.09% vs 27.22%; P < .001). The DUPI-cohort demonstrated significant risk reduction in atopic march progression (hazard ratio [HR] 0.68, 95% CI 0.55-0.83), individual asthma (HR 0.60, 0.45-0.81), and individual AR (HR 0.69, 0.54-0.88). Younger patients on dupilumab exhibited a greater risk reduction for atopic march progression and individual asthma, contrasting with the opposite age-related pattern for individual AR. LIMITATIONS: Observational study. CONCLUSION: Among pediatric AD patients, dupilumab was associated with reduced risk of atopic march progression compared with conventional therapies.

LC-MS/MS and EMIT measure the whole blood concentration of cyclosporine A: The two methods yield concordant results within the dynamic range of the latter, but the former shows broader application scenarios.

Cyclosporine A (CsA) is a widely used immunosuppressive drug with a narrow therapeutic index and large individual differences. Its therapeutic and toxic effects are closely related to blood drug concentrations, requiring routine therapeutic drug monitoring (TDM). The current main methods for TDM of CsA are enzyme multiplied immunoassay technique (EMIT) and liquid chromatography-tandem mass spectrometry (LC-MS/MS). However, few study on the method comparison of the EMIT and LC-MS/MS for the measurement of whole blood CsA concentration in children has been reported. In this study, we developed a simple and sensitive LC-MS/MS assay for the determination of CsA, and 657 cases of CsA concentrations were determined from 197 pediatric patients by a routine EMIT assay and by the validated in-house LC-MS/MS method on the same batch of samples, aimed to address the aforementioned concern. Consistency between the two assays was evaluated using linear regression and Bland-Altman analysis. The linear range of LC-MS/MS was 0.500-2000 ng/mL and that of the EMIT was 40-500 ng/mL, respectively. Overall, the correlation between the two methods was significant (r-value ranging from 0.8842 to 0.9441). Unsatisfactory consistency was observed in the concentrations < 40 ng/mL (r = 0.7325) and 200-500 ng/mL (r = 0.6851). Bland-Altman plot showed a mean bias of -18.0 % (±1.96 SD, -73.8 to 37.8 %) between EMIT and LC-MS/MS. For Passing-Bablok regression between EMIT and LC-MS/MS did not differ significantly (p > 0.05). In conclusion, the two methods were closely correlated, but the CsA concentration by LC-MS/MS assay was slightly higher than that by EMIT method. Switching from the EMIT assay to the LC-MS/MS method was acceptable, and the LC-MS/MS method will receive broader application in clinical settings due to its better analytical capabilities, but the results need to be further verified in different laboratories.

Direct effects of alcohol on gut-epithelial barrier: Unraveling the disruption of physical and chemical barrier of the gut-epithelial barrier that compromises the host-microbiota interface upon alcohol exposure.

The development of alcohol-associated diseases is multifactorial, mechanism of which involves metabolic alteration, dysregulated immune response, and a perturbed intestinal host-environment interface. Emerging evidence has pinpointed the critical role of the intestinal host-microbiota interaction in alcohol-induced injuries, suggesting its contribution to disease initiation and development. To maintain homeostasis in the gut, the intestinal mucosa serves as the first-line defense against exogenous factors in the gastrointestinal tract, including dietary contents and the commensal microbiota. The gut-epithelial barrier comprises a physical barrier lined with a single layer of intestinal epithelial cells and a chemical barrier with mucus trapping host regulatory factors and gut commensal bacteria. In this article, we review recent studies pertaining to the disrupted gut-epithelial barrier upon alcohol exposure and examine how alcohol and its metabolism can affect the regulatory ability of intestinal epithelium.

Association of air quality index (AQI) with incidence of atopic dermatitis in Taiwan: A nationwide population-based cohort study.

BACKGROUND: Air pollutants may aggravate atopic dermatitis (AD). However, the association between Air Quality Index (AQI) and incidence of AD remains unknown. OBJECTIVE: To investigate association between AQI and incidence of AD, using the nationwide cohort in the Taiwan National Health Insurance Research Database (NHIRD). METHODS: We included 21,278,938 participants from the NHIRD not diagnosed with AD before 2008. Long-term average AQI value, obtained from the Taiwan Air Quality Monitoring System Network, before AD diagnosis was calculated and linked for each participant. RESULTS: 199,205 incident cases of AD were identified from 2008 to 2018. Participants were classified into 4 quantiles (Q) by AQI value. With the lowest quantile, Q1, as reference, the AD risk increased significantly in the Q2 group (adjusted hazard ratio [aHR]: 1.29, 95% confidence interval [CI]: 1.04-1.65), Q3 group (aHR: 4.71, 95% CI: 3.78-6.04), and was highest in the Q4 group (aHR: 13.20, 95% CI: 10.86-16.60). As AQI treated as a continuous variable, an increase of 1 unit of AQI value added 7% of AD risk (aHR, 1.07, 95% CI: 1.07-1.08). LIMITATIONS: The NHIRD lacks detailed information on individual subjects. CONCLUSIONS: The results demonstrated a significant positive association between AQI and incidence of AD with a clear dose-response relationship.

Association between vitiligo and risk of retinal detachment: a population-based cohort study in Taiwan.

BACKGROUND: Vitiligo is reportedly associated with several ocular abnormalities. However, the relationship between vitiligo and retinal detachment (RD) remains unclear. OBJECTIVES: To examine the risk of RD in patients with vitiligo. METHODS: A nationwide population-based cohort study was conducted using data from the Taiwan National Health Insurance Database from 2007 to 2018. A total of 21 132 patients with vitiligo were matched in a 1 : 4 ratio with people without vitiligo by age, sex and comorbidity propensity score. Cumulative incidence and Cox proportional hazard models were used to investigate the risk of RD in patients with vitiligo. Subgroup analysis was performed. RESULTS: The cohort with vitiligo had a significantly higher rate of RD than the cohort without vitiligo [adjusted hazard ratio (aHR) 1.44, 95% confidence interval (CI) 1.20-1.72; P < 0.001]. Patients with vitiligo who required treatments such as phototherapy, systemic corticosteroids or immunosuppressants exhibited an even greater risk of RD (aHR 1.57, 95% CI 1.16-2.14; P = 0.004). CONCLUSIONS: Our study revealed a 1.44-fold increased risk of RD in patients with vitiligo, with an even higher risk in patients receiving phototherapy, systemic corticosteroids or immunosuppressants. The risk remained consistently higher over a 10-year follow-up period.

Global Prevalence of Helicobacter pylori Infection and Incidence of Gastric Cancer Between 1980 and 2022.

BACKGROUND & AIMS: We aimed to assess the secular trend of the global prevalence of Helicobacter pylori (H pylori) infection in adults and children/adolescents and to show its relation to that of gastric cancer incidence. METHODS: We performed a systematic review and meta-analysis to calculate overall prevalence, adjusted by multivariate meta-regression analysis. The incidence rates of gastric cancer were derived from the Global Burden of Disease Study and Cancer Incidence in Five Continents. RESULTS: Of the 16,976 articles screened, 1748 articles from 111 countries were eligible for analysis. The crude global prevalence of H pylori has reduced from 52.6% (95% confidence interval [CI], 49.6%-55.6%) before 1990 to 43.9% (95% CI, 42.3%-45.5%) in adults during 2015 through 2022, but was as still as high as 35.1% (95% CI, 30.5%-40.1%) in children and adolescents during 2015 through 2022. Secular trend and multivariate regression analyses showed that the global prevalence of H pylori has declined by 15.9% (95% CI, -20.5% to -11.3%) over the last 3 decades in adults, but not in children and adolescents. Significant reduction of H pylori prevalence was observed in adults in the Western Pacific, Southeast Asian, and African regions. However, H pylori prevalence was not significantly reduced in children and adolescents in any World Health Organization regions. The incidence of gastric cancer has decreased globally and in various countries where the prevalence of H pylori infection has declined. CONCLUSIONS: The global prevalence of H pylori infection has declined during the last 3 decades in adults, but not in children and adolescents. The results raised the hypothesis that the public health drive to reduce the prevalence of H pylori as a strategy to reduce the incidence of gastric cancer in the population should be confirmed in large-scale clinical trials.

The epidemiology of pediatric psoriasis: A nationwide cohort study in Taiwan.

Psoriasis can affect individuals of all age groups. While the epidemiology of psoriasis in adults has been extensively studied, there is limited research specifically investigating pediatric cases. This study aimed to investigate the prevalence and incidence of skin psoriasis (PsO) and psoriatic arthritis (PsA) among pediatric patients in Taiwan. A nationwide cohort of 17 535 patients with psoriatic diseases under the age of 18 was enrolled from the National Health Insurance Research Database for the period 2000-2013, including 16 129 PsO patients and 2022 PsA patients. The age- and sex-standardized prevalence and incidence of pediatric PsO and PsA were calculated. The 2007 yearly reports of age- and sex-specific distribution of the general population was adopted as a standard. The results showed that between 2000 and 2013, the prevalence for pediatric PsO increased from 0.03% to 0.07%, and from 0.003% to 0.014% for pediatric PsA. During the same period, the incidence slightly decreased from 19.81 to 17.55 per 100 000 for pediatric PsO but increased from 1.02 to 5.06 per 100 000 for pediatric PsA. Adolescents (12 to <18 years) had higher prevalence and incidence rates of PsO and PsA than children (aged ≤ 12 years), with no sex difference observed in either age group. PsA preceding PsO was more common among children than adolescents (27.07% vs. 13.46%). This study provides important insights into the prevalence and incidence of psoriatic diseases in the pediatric population. Further research is needed to identify risk factors for pediatric psoriasis and to investigate its long-term health outcomes.

Prevalence and temporal trend of gastric preneoplastic lesions in Asia: A systematic review with meta-analysis.

BACKGROUND: Gastric cancer is the fifth most common cancer globally, with about 75% of cases occurring in Asia. While chronic atrophic gastritis (CAG) and intestinal metaplasia (IM) are well-recognized preneoplastic gastric lesions, we determined the prevalence and temporal trend of CAG and IM in Asia over the past 50 years. METHODS: In this systematic review and meta-analysis, we searched PubMed, Embase, MEDLINE, Scopus, and Web of Science for studies reporting the prevalence of CAG and IM in Asia (according to the United Nations geoscheme) published between 1970 and 2022. Heterogeneity was assessed by the I2 index and Cochran Q test. We adopted the random effects model to estimate the pooled prevalence and 95% confidence interval (CI). The slope of prevalence was estimated as a function of time in simple linear regression and weighted meta-regression models to demonstrate the temporal trend. Studies that reported the odds ratio (OR) of Helicobacter pylori infection and CAG/IM were analyzed separately to compile a pooled OR with a 95% CI. This study was registered in INPLASY2022120028. RESULTS: Of the 81 studies from 19 Asian countries identified, the pooled prevalence for CAG and IM in Asia was 26.1% (95%CI: 22.7-30.0) and 22.9% (95%CI: 19.7-26.6), respectively. Over the past 5 decades, there was a significant decline in the prevalence of IM (slope in adjusted meta-regression models: -0.79 [95%CI: -1.28 to -0.26], P = 0.003), but there was no significant change in the pooled prevalence of CAG. Within Asia, the prevalence varied significantly among different regions. Southern Asia reported the highest pooled prevalence of CAG (42.9%, 95%CI: 27.5%-67.1%), while Western Asia reported the lowest level (12.7%, 95%CI: 5.0%-32.3%). For IM, Eastern Asia reported the highest prevalence (27.1%, 95%CI: 21.1-34.9), with the lowest prevalence reported in Western Asia (3.1%; 95% CI 1.2%-8.0%). H. pylori infection was linked to CAG and IM with OR of 2.16 (95%CI: 2.09-2.22) and 1.64 (95%CI: 1.57-1.72), respectively. CONCLUSION: This updated meta-analysis showed that up to 26% of study individuals in Asia harbored preneoplastic gastric lesions. There was a declining temporal trend in the prevalence of IM, but not for CAG, in Asia.

Risk of Type 1 Diabetes Mellitus in Patients with Atopic Dermatitis: A Nationwide Population-Based Cohort Study.

INTRODUCTION: Atopic dermatitis (AD) is a disease frequently occurring in children. The immune response is characterized by T-helper (Th)-2-dependent inflammation. Type 1 diabetes mellitus (T1DM) is an autoimmune disease that destroys pancreatic islet beta cells. In contrast, it is mainly mediated by a Th-1-dependent response. An inverted association has been hypothesized between T1DM and AD since Th1 and Th2 responses are mutually inhibitory. METHODS: Data was retrieved from a nationwide healthcare database in Taiwan. A logistic regression model was used to evaluate the association of T1DM in patients with AD within a year. A Cox proportional hazards analysis was used to evaluate the subsequent risk of developing T1DM 1 year after AD diagnosis. RESULTS: We identified 396,461 patients with AD and 1,585,844 age- and sex-matched controls. During the first year of follow-up, after adjusting variates, the association between T1DM and AD showed no statistical differences (odds ratio: 1.40; 95% confidence interval [CI]: 0.83-2.38, p = 0.207). After excluding those T1DM cases within 1 year of AD diagnosis and those with a follow-up duration of less than 1 year, AD did not significantly increase the risk of T1DM (hazard ratio [HR]: 1.02; 95% CI, 0.83-1.25, p = 0.843). CONCLUSIONS: Our study revealed that there was no significant association between AD and T1DM in the first year after AD diagnosis, and there was no increased risk of T1DM in AD patients in the average 5-year follow-up in our study.

Methotrexate did not add skin cancer risk in patients with psoriasis receiving narrow-band ultraviolet B phototherapy: a nationwide retrospective cohort study.

BACKGROUND: In the era of biologic therapy, phototherapy and methotrexate (MTX) are still commonly employed for patients with moderate-to-severe psoriasis. However, the skin cancer risk following a combination of MTX and narrow-band ultraviolet B (NB-UVB) has rarely been explored. OBJECTIVES: To investigate whether MTX plus NB-UVB increases skin cancer risk in patients with psoriasis. METHODS: We conducted a retrospective cohort study of data in Taiwan National Health Insurance Research Database from 1997 to 2013. We performed cumulative incidences and multivariate analysis using competing risk regression model, comparing skin cancer risk between cohorts of combination therapy and using NB-UVB alone, matched by relative confounders. We further conducted sensitivity analysis for those receiving higher MTX dosage. Standardized incidence ratio (SIR) was calculated for skin cancer risk. RESULTS: We enrolled 3203 subjects in each cohort. No significant differences in skin cancers were noted between the two cohorts in the cumulative incidences (log-rank test, p = 0.282) and hazard ratio (HR) (adjusted HR = 0.50, 95% CI 0.15, 1.63, p= 0.247) on the competing risk regression model. There were also no significant differences between those receiving higher dose MTX and UVB alone in the cumulative incidences of skin cancers (p = 0.227) and HR (adjusted HR = 0.29, 95% CI 0.04, 2.21, p = 0.231) in the multivariate analysis. There was no significant difference of SIR between the two cohorts compared to the general population. CONCLUSIONS: MTX does not increase skin cancer risk in patients with moderate-to-severe psoriasis receiving NB-UVB in the Taiwanese population.

Multidimensional Super-Resolution Microscopy Unveils Nanoscale Surface Aggregates in the Aging of FUS Condensates.

The intracellular liquid-liquid phase separation (LLPS) of biomolecules gives rise to condensates that act as membrane-less organelles with vital functions. FUS, an RNA-binding protein, natively forms condensates through LLPS and further provides a model system for the often disease-linked liquid-to-solid transition of biomolecular condensates during aging. However, the mechanism of such maturation processes, as well as the structural and physical properties of the system, remains unclear, partly attributable to difficulties in resolving the internal structures of the micrometer-sized condensates with diffraction-limited optical microscopy. Harnessing a set of multidimensional super-resolution microscopy tools that uniquely map out local physicochemical parameters through single-molecule spectroscopy, here, we uncover nanoscale heterogeneities in FUS condensates and elucidate their evolution over aging. Through spectrally resolved single-molecule localization microscopy (SR-SMLM) with a solvatochromic dye, we unveil distinct hydrophobic nanodomains at the condensate surface. Through SMLM with a fluorogenic amyloid probe, we identify these nanodomains as amyloid aggregates. Through single-molecule displacement/diffusivity mapping (SMdM), we show that such nanoaggregates drastically impede local diffusion. Notably, upon aging or mechanical shears, these nanoaggregates progressively expand on the condensate surface, thus leading to a growing low-diffusivity shell while leaving the condensate interior diffusion-permitting. Together, beyond uncovering fascinating structural arrangements and aging mechanisms in the single-component FUS condensates, the demonstrated synergy of multidimensional super-resolution approaches in this study opens new paths for understanding LLPS systems at the nanoscale.

Association between chronic kidney disease and risk of bullous pemphigoid: a nationwide population-based cohort study.

BACKGROUND: Studies have shown that bullous pemphigoid (BP) occurs in patients with chronic kidney disease (CKD). However, the risk of developing BP in patients with CKD remains inconclusive. OBJECTIVE: To investigate whether CKD increases the risk of BP. METHODS: Participants were recruited from the National Health Insurance Database of Taiwan between 2007 and 2018. Overall, 637,664 newly diagnosed patients with CKD and 637,664 age-, sex-, and comorbidity-matched non-CKD participants were selected. A competing risk model was used to evaluate the risk of development of BP. RESULTS: After adjusting for age, sex, and comorbid diseases in the multivariate model, CKD was a significant risk factor for BP (adjusted hazard ratio [aHR]: 1.29; 95% confidence interval [CI]: 1.17-1.42; p < 0.001). CKD patients were classified into the dialytic or non-dialytic groups and compared to non-CKD participants, and this revealed that patients with dialysis-dependent CKD had the highest risk of BP (aHR 1.75; 95% CI 1.51-2.03), followed by patients with non-dialysis-dependent CKD (aHR 1.20; 95% CI 1.08-1.32). LIMITATIONS: We lacked detailed laboratory data on the severity of CKD. CONCLUSIONS: Compared with individuals without CKD, those with CKD had a 1.3-fold increased risk of BP. Patients with dialysis-dependent CKD had an even higher BP risk (1.8-fold).