Investigating the importance of exercise tolerance test (ETT) in the diagnosis of coronary artery disease (CAD) among people with left-sided dominant coronary circulation is very important. This retrospective study aimed to explore the relevance of ETT in CAD diagnosis by analyzing medical records of 2084 patients who underwent ETT and coronary angiography in Urmia's educational therapeutic hospitals between 2018 and 2019. SPSS Version 16 was used for data analysis. The study included 5.58% males and 5.41% females. The prevalence of co-dominancy was 10.2%, right coronary dominance (RD) was 65%, and left coronary dominance (LD) was 24.8%. There were no significant differences between gender, age, smoking, blood pressure, diabetes mellitus (DM), the prevalence of hyperlipidemia (HLP), family history (FH) and left ventricular ejection fraction (LVEF). The frequency of non-significant CAD was higher in women than in men. Additionally, the frequency of women with LD was significantly higher than that of men. The results of angiography in normal cases, it was observed that the highest frequency was related to female patients with a history of DM. The sensitivity of the ETT was 94%, and the accuracy and diagnostic power of the exercise test for the presence of CAD in individuals with LD were 53% (p = 0.03). The study highlights the potential for false-positive exercise tests in diabetic individuals with left coronary dominance, providing valuable insights into the nuanced interplay of gender, cardiovascular health, and coronary circulation patterns in CAD risk.
Advanced oxidation processes are widely utilized to eliminate persistent organic pollutants from water. However, their practical effectiveness is significantly constrained by irreversible catalyst deactivation and limited tunability of oxidant pathways. In peroxymonosulfate activation, a central challenge remains sustaining metal redox turnover while maintaining complementary reactive oxygen species under prolonged operation. Here we show that a FeS2/MoS2 heterointerface functions as an internal redox shuttle, driving a self-sustaining charge-circulation loop that autonomously regenerates dual active sites. A built-in electric field enforces directional electron transfer from Mo to Fe, thereby stabilizing continuous iron redox cycling for the production of radicals (•OH and SO4 •-). Simultaneously, this architecture enables Mo-mediated generation of nonradical singlet oxygen, which mitigates catalyst deactivation and sustains oxidant output. As a result, the system achieves rapid removal of acetaminophen and retains 91.5% of its catalytic activity after 3000 min of continuous operation in various water matrices. These findings establish self-sustaining interfacial charge circulation as a broadly applicable and highly effective strategy for designing robust catalysts for sustainable water treatment.
Mac-2 binding protein glycosylation isomer (M2BPGi) is a validated biomarker for liver fibrosis in chronic liver disease. We investigated the clinical significance of serum M2BPGi concentrations in patients with Fontan circulation. We prospectively measured serum M2BPGi concentrations in 426 consecutive Fontan patients (mean [±SD] age 23±10 years) and analyzed their associations with patients' pathophysiology, including Fontan-associated liver disease (FALD), as well as all-cause unplanned hospitalization (UPH) and mortality. M2BPGi concentrations were associated with a wide range of Fontan-related pathophysiological features, including characteristic Fontan hemodynamics, total bile acid concentrations, FALD indices such as hepatic fibrosis markers and ultrasonographic image abnormalities, and impaired renal function. Among these variables, older age at Fontan operation, hypoxemia, C-reactive protein, total bile acid levels, and indices of hepatic fibrosis were independently associated with higher M2BPGi concentrations (P<0.05-0.001). During follow-up after the M2BPGi evaluation, 68 patients experienced UPH and 14 patients died. Elevated M2BPGi concentrations were associated with a higher risk of UPH and all-cause mortality (P<0.0001 for both), independent of elevated B-type natriuretic peptide levels. Serum M2BPGi concentrations reflect both FALD pathophysiology and hemodynamic burden, serving as a strong prognostic biomarker. M2BPGi can be a valuable tool for risk stratification in patients with Fontan failure, including those with FALD.
Duct-dependent congenital heart diseases (CHDs) require prompt postnatal intervention to prevent life-threatening deterioration. While prenatal diagnosis may improve outcomes, the impact of route of admission on preoperative mortality remains unclear in Japan. This cross-sectional study examines the impact of the route of admission on preoperative mortality in 2704 admissions of patients with duct-dependent CHD between 2014 and 2019, at hospitals employing the Diagnostic Procedure Combination payment system. The route of admission was categorized as either born in hospital or admitted from outside the hospital. The risk of preoperative death was higher among patients admitted from out-of-hospital in CHDs with duct-dependent systemic circulation (adjusted odds ratio = 3.41, 95% confidence interval (CI): 1.16, 10.04) compared with the ones born in the hospital. The risk was especially pronounced in those with hypoplastic left heart syndrome (adjusted odds ratio = 15.78, 95% CI: 3.36, 74.17). The population attributable fraction associated with out-of-hospital birth was 53.8% (95% CI: 7.2%, 81.4%) for CHDs with duct-dependent systemic circulation and 83.5% (95% CI: 44.7%, 96.2%) for hypoplastic left heart syndrome CONCLUSION: For CHDs with duct-dependent systemic circulation, particularly hypoplastic left heart syndrome, early diagnosis and planned delivery may improve pre-operative mortality. This study demonstrates a significantly higher risk of preoperative death among pediatric congenital heart diseases patients with duct-dependent systemic circulation, especially hypoplastic left heart syndrome, when admitted from out-of-hospital compared to being born in hospital. Early diagnosis and planned delivery at specialized facilities can substantially improve survival. By focusing specifically on preoperative mortality and distinguishing congenital heart diseases that require timely interventions, this study provides novel insights into the critical importance of the admission pathway for preoperative mortality, complementing previous research. The findings support strengthening prenatal screening and promoting planned deliveries to improve survival outcomes in congenital heart diseases with duct-dependent systemic circulation.
Seaweed is a nutrient-dense, sustainable food source with the potential to support global protein needs. However, its complex structure may limit protein bioavailability. Although seaweed is traditionally consumed with minimal processing and may provide amino acids without extensive processing, the quantity needed for meaningful protein intake raises safety, tolerance, and acceptability concerns that remain unexamined in humans. This study aimed to evaluate the impact of a minimally processed seaweed meal (SWM) on postprandial plasma amino acids, micronutrient bioavailability, safety, gastrointestinal tolerance, and sensory acceptability. In a single-blinded, randomized crossover trial, 20 healthy adults consumed SWM or a control meal (CON). Blood samples and questionnaires were collected over 4 hours and urine samples over 24 hours. Pooled plasma essential amino acids showed no statistically significant difference between meals (P>0.6); however, the pilot sample size may have limited the ability to detect meaningful differences. Compared to CON, SWM reduced postprandial asparagine, glutamine, alanine, proline, and tyrosine. Glucose, insulin and triglyceride responses were similar between meals. Increases in serum iodine (P=0.02), urinary iodine (P<0.001), and urinary arsenic (P=0.007) were observed following the SWM. Gastrointestinal symptoms, including distension and belching, were greater after SWM (treatment-time interaction P=0.03 and <0.001, respectively). Sensory evaluations indicated lower preference scores for the SWM compared to the CON for appearance and odour (both P=0.03). SWM and CON had similar EAA bioavailability. SWM was associated with greater gastrointestinal symptoms and lower satiety scores. For minimally processed seaweed-based foods to substantially contribute to protein requirements, optimisation for protein bioavailability and gastrointestinal comfort is required. This trial was registered at https://www.anzctr.org.au/ as ACTRN12624000335594.
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The implantable cardioverter defibrillator (ICD) is an effective therapeutic option for hypertrophic cardiomyopathy (HCM). However, a comprehensive quantitative synthesis in this field remains limited. This study aims to analyze the research landscape of ICD application in HCM from 2000 to 2025. Publications related to ICD use in HCM were retrieved from the Web of Science Core Collection between January 1, 2000, and November 3, 2025. Data were visually analyzed using VOSviewer and CiteSpace. A total of 864 publications from 251 countries/regions met the inclusion criteria, with the United States contributing the most. *Circulation* was identified as the most frequently cited journal in this field. Keyword cluster analysis revealed that research hotspots primarily focused on "hypertrophic cardiomyopathy," "sudden cardiac death," and "implantable cardioverter defibrillator." Furthermore, keyword burst analysis indicated that current research frontiers center on terms such as "outcome" and "association." The field of ICD application in HCM has matured and is now on the verge of a paradigm shift. Future research should focus on refining risk prediction models, evaluating long-term patient outcomes, and addressing challenges posed by novel targeted therapies.
The global incidence and mortality of cancer continue to increase, and various chemotherapeutic agents, while highly effective, are associated with serious side effects like immunosuppression, metabolic dysfunction, and drug resistance. As a complementary or alternative approach, traditional Chinese medicine (TCM), which is known for its multi-target mechanisms and low toxicity, has garnered increasing attention in cancer research. Magnolia officinalis (M. officinalis) is a member of the Magnoliaceae family, and dried bark from its stems, roots, and branches is its primary medicinal part. According to TCM theory, M. officinalis may resolve dampness, eliminate phlegm, promote qi circulation, and relieve stagnation, and it has been widely applied in the treatment of gastrointestinal disorders. Modern pharmacological studies have identified bioactive compounds, including lignans, volatile oils, alkaloids, and polysaccharides, in M. officinalis, but the mechanisms underlying these pharmacological effects are still unclear and their clinical applications are limited by the lack of robust clinical evidence. We conducted a systematic review of both contemporary research databases (e.g., PubMed, CNKI, ScienceDirect, and other Chinese medical databases) and classic TCM literature to compile the bioactive components of M. officinalis, their pharmacological mechanisms in oncology, and recent preclinical progress. We also discuss the prospects and challenges of developing M. officinalis as an anticancer agent to provide a theoretical basis for its future development and clinical application.
After a crush injury in sciatic nerve fibers, dynamic changes in blood circulation and immune-cell mobilization occur during axonal regeneration. High-resolution visualization under near-physiological conditions is crucial for understanding these mechanisms. Conventional histological techniques introduce perfusion- and dehydration-induced artifacts that obscure circulation. We employed the in vivo cryotechnique (IVCT) to visualize blood flow within sciatic nerve fibers and assess temporal changes during regeneration. In uninjured mice, IVCT preserved native tissue architecture with minimal shrinkage compared to perfusion fixation, with superiority quantitatively shown by fractal analysis. In the crush model, hematoxylin-eosin, Luxol fast blue, and immunohistochemical staining of IVCT-prepared, freeze-substituted sections revealed axonal degeneration and regrowth. The close association between regenerating fibers and vascular structures, along with erythrocyte distribution, indicates a morphological link between nerves and blood vessels. Electrophysiological assessment using compound muscle action potentials and functional recovery measured by the sciatic functional index demonstrated restored nerve function at 28 days, consistent with histology. These findings suggest that IVCT is a useful method for analyzing peripheral nerve regeneration and vascular dynamics, thereby highlighting its potential as a novel approach in peripheral nerve research.
Panama is a dengue endemic country which experienced a large outbreak in 2024 with over 32,000 reported cases and an incidence rate exceeding 700 cases per 100,000 inhabitants. Despite decades of circulation, the epidemiology of dengue and its heterogeneity in transmission intensity across Panama have not yet been characterised. We used 25 years of dengue case notification and population data from across Panama's 16 health regions and 82 districts to characterise dengue epidemiology and transmission intensity in the country. The analytic dataset comprised 128,890 dengue cases, of whom 52% were female and 48% were male; the mean age was 32.4 years (range 0-108 years). Ethnicity data are not collected in Panama's national dengue surveillance system and were therefore unavailable for this analysis. We characterised spatial heterogeneities in delay distributions by fitting parametric probability distributions to epidemiological delays, and demographic differences in the incidence risk ratio of dengue, and of dengue attributable hospitalisations and deaths. We also implemented catalytic models to infer the time-constant dengue force-of-infection (FOI) (i.e. the long-term average annual per capita risk of infection for a susceptible individual) from the age-stratified case notification data reported across Panama during 2000-2024 and explored age- and sex-related differences in dengue case reporting in sensitivity analyses. We observed spatial variation in delay distributions across health regions. The mean of the regional average time from symptoms onset to (i) reporting was 4.78 days (95% CI: 4.72-4.84 days), (ii) hospitalisation was 4.49 days (95% CI: 4.22-4.76), and (iii) recovery was 7.82 days (95% CI: 6.47-8.85 days). The dengue transmission intensity also showed spatial heterogeneity, with a mean regional per-serotype FOI of 0.008 (95% CrI: 0.004-0.015). The mean regional probability of detecting a secondary case was 0.415 (95% CrI: 0.233-0.871) and the probability of detecting a primary case relative to a secondary case was 0.131 (95% CrI: 0.049-0.348). We found evidence of age- and sex-related differences in dengue reporting. Given the estimated seroprevalence at nine years (obtained from the analysis of case-notification data) is below 40% across the whole country, dengue vaccination with TAK-003 is currently not recommended in Panama according to the WHO guidelines. In the future, age-stratified seroprevalence surveys would be useful to validate these estimates. This analysis provides a characterisation of dengue epidemiology and estimates of dengue FOI and infection burden in Panama across the last 25 years. This work will inform policy decisions at the Ministry of Health of Panama, providing guidance on resource allocation to strengthen the local surveillance system and to decision making on the potential implementation of new interventions. SENACYT-IFARHU (Panamá), UK Medical Research Council and Wellcome Trust.
The skin is the body's largest organ and is considered as a protective barrier which acts as a highly impermeable region of the human body. But in recent times, it is recognized as a specialized organ that aids in the delivery of a wide range of drug molecules into the skin (intradermal drug delivery) and across the skin into systemic circulation (transdermal drug delivery, TDD). Transdermal administration remains an active research and development area as an alternative route for long- acting drug delivery. It avoids major drawbacks of conventional oral (gastrointestinal side effects, low drug bioavailability, and need for multiple dosing) or parenteral routes (invasiveness, pain, and psychological stress and bio-hazardous waste generated from needles), thereby increasing patient appeal and compliance. The bioavailability of a drug administered transdermally can be improved by several penetration enhancement techniques, which are broadly classified into chemical and physical techniques. Application of the mentioned techniques together with efforts of various scientific and innovative companies had made TDD a multibillion-dollar market and this has led to a growing market with a steady pipeline of new transdermal products receiving regulatory approval. Out of various techniques, thermal therapeutic methods including chemical heating, laser ablation, thermoporation, radiofrequency and photothermal therapy are the top listed emerging techniques. This review article mainly discussed about these thermal ablation techniques with their available commercial products along with advantages and disadvantages. This review also presented anatomy of the skin, penetration pathways across the skin, affecting factors and different generations and mechanisms of TDD. Briefly, this article discussed basics, mechanism, challenges, and future research and development directions of thermal-based TDDS.
Augmentation of collateral circulation is an alternative method to improve cerebral hypoperfusion when revascularization is not suitable. DL-3-n-butylphthalide (NBP) has been shown to enhance cerebral collateral circulation and improve cerebral blood flow (CBF) in previous studies. The objective of this study was to explore the effect of NBP on cerebral hemodynamic impairment due to atherosclerotic stenosis in internal carotid system. This was a double-blind, placebo-controlled, randomized clinical trial conducted in 38 Chinese hospitals between 14 January 2022, and 11 April 2024. Eligible participants were aged 35-85 years with ≥ 70% stenosis in unilateral internal carotid artery or middle cerebral artery, accompanied by cerebral hypoperfusion and no recent cerebral ischemic events. The patients were randomly assigned in a 1:1 ratio to a treatment group receiving 600 mg NBP daily or a placebo group receiving an ineffective dose of NBP daily for 4 weeks. The cerebral perfusion was assessed by computed tomography perfusion. The grades of cerebral perfusion change from baseline to 12 weeks were classified into amelioration, stabilization, and deterioration. The primary efficacy outcome was the percentage of patients achieving CBF amelioration. Of 485 enrolled patients (median age 63 years, 66.6% men), 244 were assigned to the NBP group and 241 to the placebo group. At the end of follow-up, 204 in the NBP group and 212 in the placebo group completed second cerebral perfusion. NBP group had 113 (55.4%) patients with CBF amelioration in stenotic territory and placebo group had 93 (43.9%) comparable patients at 12 weeks (risk ratio 1.32; 95% confidence interval 1.08-1.61; p = 0.006). For cerebral hypoperfusion from atherosclerotic stenosis in internal carotid system, NBP treatment resulted in a higher proportion of patients achieving CBF amelioration than placebo. chictr.org.cn: ChiCTR2100053112.
One of the major challenges for malaria elimination is combating the highly efficient spread of the disease. Despite progress in understanding the development of malaria transmission stages, there remain many unanswered questions about how gametocytes transition from being immature to infectious. In Plasmodium falciparum, immature gametocytes are rigid and sequester outside of circulation in the extravascular space of the bone marrow, while deformable, mature stages are found in circulation and transmitted to mosquitoes. It is currently unclear whether deformable gametocytes are immediately infectious to mosquitoes, or whether they undergo activation upon release into circulation. We used a combination of phenotypic assays and transcriptional analysis to define the transition from immature non-infectious to mature infectious gametocyte. Specifically, we associated gene expression with distinct phenotypic traits: gametocyte deformability assessed by microsphere filtration, and gametocyte infectivity assessed by exflagellation and mosquito feeding assays. Our data revealed major transcriptional differences between input and deformable (i.e., filtered) gametocytes, but high similarity between deformable and infectious gametocytes. In combination with exflagellation and transmission results upon mosquito feeding assays, this suggests that deformable gametocytes are immediately infectious upon release from the bone marrow. The transcriptional analysis revealed a comprehensive set of infectivity markers that can be utilized to track gametocytes during their development and serve as diagnostic tools to map the human infectious reservoir. Malaria spreads when mosquitoes ingest specialized malaria life stages, called gametocytes, from infected people. For the deadliest malaria parasites, Plasmodium falciparum, gametocytes undergo a long maturation process. Young gametocytes of this parasite are stiff and hidden in the bone marrow. Following maturation, the gametocytes become more flexible and are released into the bloodstream. It remained unclear whether these flexible gametocytes are immediately infectious to mosquitoes or need further maturation. The current study examined changes in the gametocyte, from stiff to deformable and from non-infectious to infectious, in relation to gene activity. The results show that once gametocytes become flexible and enter the bloodstream, they are already infectious. The study also identified genetic markers linked to infectivity, which could help track malaria transmission and improve tools to identify people who can spread the disease.
Huangkui capsule (HKC), a proprietary traditional Chinese medicine, has been used for decades to clinically treat chronic kidney diseases. Gut microbiota may mediate its metabolism, yet inadequate research on HKC's in vivo metabolism hinders understanding of its pharmacodynamic basis. In this study, normal and pseudo-germ-free rats were orally administered HKC, with serum, urine, and fecal samples collected at serial time points. All samples were analyzed by UPLC-Q-TOF-MS/MS. Chemometrics tools were used for data processing, HKC-related xenobiotics (HRX) screening/identification, and dynamic profile characterization. Flora-related metabolites were screened via intergroup HRX comparison and validated by microbiota correlation analysis and literature evidence. As a result, a total of 112 HRX (20 prototypes and 92 metabolites) were identified and categorized into four structural types: 57 quercetin-related, 37 gossypetin-related, 7 myricetin-related, and 11 other HRX. HKC metabolism involved phase I biotransformations (mainly in quercetin-HRX) and phase II conjugations (mainly in gossypetin-HRX). Most HRX peaked in serum at 1 h post-administration, with urinary excretion occurring within 0-4 h and fecal excretion delayed to 12-24 h. Unique HRX showed distinct dynamics (e.g., serum double peaks), indicating the involvement of gut microbiota and enterohepatic circulation. The 39 differential HRX (DHRX) exhibited significant correlations with specific bacterial taxa such as Clostridium. Furthermore, based on three criteria, 63 of the 112 HRX that satisfied at least one criterion were classified as flora-related. Among these, 38 met at least two criteria and were designated as verified flora-related HRX. Finally, a total of 13 candidates were selected and proposed as PK markers. This study delineates the dynamic in vivo metabolite profiles of HKC in rats and clarifies the critical regulatory role of gut microbiota, and provide a scientific basis for the material basis of its nephroprotective effects.
Accurate neuroprognostication of cardiac arrest survivors who are initially comatose after restoration of spontaneous circulation is crucial for guiding patient management. Because hypoxic-ischaemic injury is typically diffuse, damage to a network of brain regions is likely involved in the patient's disorder of consciousness. To quantify these complex brain network changes, graph theoretical methods were applied. We hypothesize that structural connectivity metrics may provide insights into which patients will likely recover consciousness. Eighteen comatose patients (50 ± 22 years, 44% male) and four healthy participants (40 ± 20 years, 50% male) underwent multi-shell high angular diffusion MRI as part of a prospective study. Structural connectivity matrices were constructed using probabilistic tractography to measure the likelihood of connections between anatomical regions. Network topology alterations were quantified using clustering coefficient, global efficiency and degree. Hub index analysis was performed to explore the impact of anoxic injury on high-degree hubs. Network parameters were compared between patients with arousal recovery (AR, eye-opening to auditory or noxious stimulation) and without arousal recovery (No AR). Analyses were repeated for AR patients who achieved emergence from the minimally conscious state (EMCS) within one-year post-cardiac arrest and AR patients who did not achieve EMCS (AR'). Significant differences were observed between the Controls, AR and No AR for all four metrics (Kruskal-Wallis Tests, P < 0.05). Worsening disorders of consciousness were associated with decreasing brain complexity (Kendall's tau, P<0.01). Post-hoc testing showed Control values were significantly greater than No AR for all metrics (Wilcoxon rank sum, P < 0.05). Control values were greater than AR for all metrics (P < 0.05), except the clustering coefficient (P = 0.36). AR was significantly greater than No AR for all metrics (P < 0.05), except for the hub index (P = 0.12). Notable differences between AR' and Controls were observed for all metrics (P < 0.05), except clustering coefficient (P = 0.11). No significant differences were found between AR' and No AR groups. In contrast, for all metrics, EMCS values were not significantly different compared with the Controls but were significantly different than the No AR cohort values (P < 0.05). The hub index analysis revealed disproportionate damage to high-degree nodes such as the thalamus, putamen and precuneus, further linking topological disruption to the severity of outcomes. This study highlights the potential of graph theoretical measures of structural connectivity to guide decisions in the care of comatose cardiac arrest patients. By bridging structural connectivity with clinical outcomes, this research provides valuable insights into the neural mechanisms underlying consciousness and recovery after cardiac arrest.
Salmonella Kentucky has become a global concern due to its invasiveness and rapid increase in antimicrobial resistance. It is an emerging human pathogen which has surfaced as a multidrug-resistant (MDR) clone, jeopardizing public’s health. Here, we have focused on the molecular characterisation of S. Kentucky isolated from clinical samples of children in India. S. Kentucky, isolated from the clinical samples of children from different hospitals in India during March 2017 to February 2024 were sent to the Gastro-Intestinal Tract Pathogen Repository of the ICMR-National Institute of Research in Bacterial Infections (NIRBI) for confirmation by serotyping. After confirmation, the isolates were investigated for antimicrobial susceptibility, antimicrobial resistance genes (ARGs), plasmid profiling, multilocus sequence typing (MLST) & pulsed-field gel electrophoresis (PFGE) subtypes. Whole genome sequencing (WGS) was performed for representative MDR S. Kentucky isolates. Among the 45 S. Kentucky isolates, higher resistance rates of 97.77%, 93.3%, 86.7%, 77.8% and 64.44% were observed for ciprofloxacin, ampicillin, tetracycline, norfloxacin and 3rd generation cephalosporins respectively. All isolates were susceptible to chloramphenicol and carbapenems. WGS revealed the presence of ESBL genes, blaCTX−M−55, blaCTX−M−15, blaOXA−9 and multiple ARGs. Fluoroquinolone resistance was linked to mutations in gyrA (Ser83→Phe, Asp87→Tyr, ) and parC (Ser80→Iso) genes. Conjugative plasmid IncC and IncX4 harboring blaCTX−M−15 and blaCTX−M−55 respectively, were found in the study isolates. ST198 (n = 44) was found to be the predominant genotype by MLST. PFGE showed heterogeneous S. Kentucky strains in circulation. MDR S. Kentucky poses a potential health risk to the general public and alerts for the necessity of improved monitoring and investigation of this serovar by public health and food safety authorities. The online version contains supplementary material available at 10.1007/s42770-026-01950-8.
Oral and craniofacial diseases represent a significant global public health concern, profoundly impacting patient quality of life and imposing a substantial socioeconomic burden. While cell-based, particularly stem cell-based, regenerative strategies have shown promise in addressing the limitations of conventional therapies, they are also constrained by inherent challenges associated with cell therapy. Instead of relying on whole cells, cell-derived nanovesicles (CDNs), which inherit diverse biological functions from their parent cells, have emerged as a promising frontier in regenerative medicine. CDNs play a pivotal role in restoring microenvironmental homeostasis and modulating inflammation, thereby promoting angiogenesis and osteogenesis to support effective tissue regeneration. Furthermore, the therapeutic efficacy of CDNs can be enhanced through cell pretreatment and bioengineering strategies, such as cargo loading and surface modification. Owing to their ability to penetrate biological barriers, exhibit prolonged circulation, and achieve tissue-specific targeting, CDNs represent an advantageous drug delivery platform. Indeed, the development of engineered CDNs and hybrid composite systems has yielded excellent therapeutic outcomes by enhancing the precision and efficiency of drug delivery. This review systematically categorizes four major classes of CDNs, including exosomes (Exos), exosome mimetics (EMs), cell membrane nanovesicles (mNVs), and apoptotic extracellular vesicles (ApoEVs), evaluating their roles in treating craniofacial bone defects, osteoporosis, periodontitis, and dentin-pulp complex regeneration. Finally, we highlight the clinical potential of CDN-based therapies and outline future research directions for their application in oral and craniofacial tissue regeneration.
Solute carrier family 23 member 1 (SLC23A1) encodes sodium-dependent vitamin C transporter 1, which mediates intestinal vitamin C absorption. Although SLC23A1 variants are associated with vitamin C bioavailability, their relationship with gut microbiome remains unexplored. We aimed to investigate the associations of SLC23A1 polymorphism with serum vitamin C status and gut microbial profiles in healthy Korean adults. We genotyped the SLC23A1 rs6596473 polymorphism in 257 healthy individuals (20-39 years) and measured their serum vitamin C concentrations, which were categorized as optimal (≥50 μM) or suboptimal (<50 μM). Logistic regression analysis was used to evaluate the association between genotypes and suboptimal serum vitamin C status after adjusting for covariates. A subset of 43 participants with suboptimal serum vitamin C status underwent gut microbiota analysis and serum short-chain fatty acid (SCFA) measurements. Microbial profiles and SCFA concentrations were compared across the genotypes. The genotype distributions were 92 CC, 131 CG, and 34 GG, with G as the minor allele. After covariate adjustment, GG carriers had higher odds of suboptimal serum vitamin C status than CC carriers (odds ratio = 2.65; p = 0.03). Among individuals with suboptimal serum vitamin C status, GG carriers (n = 7) exhibited distinct microbial community structures compared with CC (n = 13) and CG (n = 23) carriers, with elevated richness and evenness. GG carriers had higher abundances of Bifidobacterium (vs. CC, p < 0.01; vs. CG, p = 0.054) and Ruminococcaceae incertae sedis (all p < 0.05) compared with CC and CG carriers. In line with these microbial findings, GG carriers had higher propionate and butyrate concentrations than CC and CG carriers (all p < 0.05). The SLC23A1 rs6596473 variant was associated with reduced vitamin C absorption into systemic circulation in the overall population; however, among individuals with suboptimal serum vitamin C status, it was associated with beneficial gut microbial profiles. Our findings suggest that this genetic variant in the vitamin C transporter has complex health effects that extend beyond circulating vitamin C levels to gut microbial ecology, supporting the use of genotype-informed nutritional approaches. Clinical Research Information Services KCT0005074 (https://cris.nih.go.kr/cris/search/detailSearch.do?seq=16832&status=5&seq_group=16832&search_page=M) and KCT0004276 (https://cris.nih.go.kr/cris/search/detailSearch.do?seq=14590&status=5&seq_group=14590&search_page=M).
Neonatal cardiopulmonary resuscitation (CPR) remains associated with high mortality and significant risk of neurodevelopmental impairment. Current neonatal resuscitation guidelines recommend a 3:1 compression-to-ventilation (C:V) ratio, which inherently requires frequent interruptions in chest compressions, limits ventilation efficiency, and may delay return of spontaneous circulation (ROSC). To address these limitations, we have examined chest compressions with sustained inflation (CC + SI) as an alternative approach. Preliminary data from animal studies and pilot human trials suggest (1) improved tidal volume delivery, (2) facilitation of passive ventilation during compressions, (3) uninterrupted chest compressions, and (4) more stable cerebral blood flow during resuscitation. Experimental studies in asphyxiated animal models have demonstrated that CC + SI improves oxygenation, shortens time to ROSC, and reduces mortality without increasing pulmonary or cerebral injury when compared with standard 3:1 CPR. Two small pilot trials in human neonates support the feasibility of CC + SI. However, larger randomized controlled trials are required to validate these findings and determine whether CC + SI can safely and effectively replace the current 3:1 C:V approach as the standard of care in neonatal resuscitation.