Community-academic partnerships are increasingly recognized as essential for advancing equitable public health outcomes. Yet many partnerships struggle to move beyond short-term, project-based collaboration toward sustained, trust-based engagement with communities. This commentary draws on the experience of the University of California San Diego Center for Community Health (CCH) and its long-standing partnerships with immigrant, refugee, and other underserved communities in San Diego County. Over more than two decades of practice, CCH and its community partners developed the Community-Led Transformation (CLT) approach to guide authentic community-academic collaboration. We describe three interdependent pillars of CLT: valuing community expertise, fostering trust-based partnerships, and ensuring fair access to resources and power-sharing. Examples from CCH programs, coalitions, and research collaborations illustrate how these principles are operationalized in practice. We also reflect on structural challenges within academic institutions, including funding instability, administrative barriers, and limitations in partnership infrastructure, and strategies used to navigate these constraints while sustaining community partnerships. We provide specific recommendations for academic partners, community partners, and funders to facilitate community-academic partnerships via increased capacity building, infrastructural supports, and greater relationship and trust building. The CLT framework has therefore been a success within CCH, and can provide practical insights for a variety of partners and institutions seeking to build authentic, durable partnerships that meaningfully advance public health and health equity.
Non-invasive tear film metrics from automated topographers are used increasingly, yet device-specific analytical performance remains incompletely characterised. This study quantified the analytical performance of the Oculus Keratograph 5M for non-invasive break-up time (NIKBUT) and tear meniscus height (KTMH), evaluated agreement with conventional methods and characterised the spatial dynamics of tear film break-up. Thirty-five participants (18 symptomatic, 17 asymptomatic) attended three visits on consecutive days. NIKBUT (first and average), KTMH, fluorescein break-up time (FBUT) and slit-lamp tear meniscus height (TMH) were each measured three times per eye per visit. Precision (coefficient of variation, CV), reliability (intraclass correlation, ICC 3,1), standard error of measurement (SEM) and minimum detectable change at 95% confidence (MDC₉₅) were calculated. Method agreement was assessed using random-effects Bland-Altman analysis. Spatial distribution of break-up events was analysed by the corneal zone. KTMH demonstrated excellent precision (CV = 8.8%) and moderate-to-good reliability (ICC = 0.73), with an MDC₉₅ of 0.173 mm. NIKBUT showed poor precision (CV = 53.6% for First, 42.8% for Average) and symptom-dependent reliability. FBUT required a change exceeding 9.28 s to surpass its MDC₉₅. Bland-Altman analysis confirmed systematic bias between NIKBUT and FBUT, with limits of agreement spanning more than 19 s in width and significant proportional bias. Spatial analysis revealed that NIKBUT break-up occurred predominantly paracentrally (53-63%), while FBUT events concentrated centrally (86-97%), indicating the methods captured fundamentally different tear film phenomena. Intra-subject repeatability of break-up location was poor (Krippendorff's α = 0.12-0.31). KTMH is the most analytically robust Keratograph metric, suitable for longitudinal monitoring when changes exceed its MDC₉₅ of 0.173 mm. NIKBUT shows poor precision; only large changes exceeded noise. Spatial analysis confirms that NIKBUT and FBUT interrogate distinct biophysical processes-these methods are not interchangeable. These benchmarks should inform clinical interpretation and study design.
Regulatory agencies may require industry sponsors of new drugs or biologics to conduct clinical trials that assess the benefits versus the risks of these new medicines in pediatric patients as a means of facilitating their development and availability for children when there is a medical need. Amgen Inc. (henceforth "the company") agreed to conduct a randomized, controlled trial (RCT) in pediatric subjects with Glucocorticoid-induced Osteoporosis (GiOP) under a Paediatric Investigation Plan (PIP) and Pediatric Study Plan (PSP) with the European Medicines Agency (EMA) and the United States (US) Food and Drug Administration (FDA), respectively, as one of the pediatric studies that were a condition of registration for Prolia (denosumab). Enrollment of pediatric subjects with GiOP into the agreed clinical study was exceedingly low despite the implementation of multiple mitigation measures. As a result, the company explored the use of real-world epidemiological analyses of the disease in children with GiOP for further insight into the clinical feasibility challenges with the RCT design. We initiated a phase 3 randomized, double-blind, placebo-controlled, parallel-group study to evaluate the safety and efficacy of denosumab in pediatric subjects with GiOP (Study 20140444). Following difficulties in recruiting we re-assessed the enrollment potential and overall clinical trial feasibility of Study 20140444 using real-world epidemiological analyses evaluating the size of the pediatric GiOP population using real-world data (RWD) from 3 different databases: (1) the US MarketScan, (2) the United Kingdom (UK) Clinical Practice Research Datalink (CPRD), and (3) the IQVIA Disease Analyzer (Germany). The results from the RWD show that very few pediatric patients met the clinical diagnosis of GiOP, irrespective of the database used. In sum, approximately 1 eligible subject per 1,000,000 people per year was estimated to be available for Study 20140444. The results suggest a lack of feasibility of conducting an adequate and well-controlled randomized trial in a population of pediatric patients with GiOP. The results also called into question the feasibility of other types of clinical trial designs, including potential single-arm or hybrid study designs, to fulfill the regulatory requirements. Recommendations include considering the use of RWD-based epidemiological analyses prior to agreeing with health authorities to conduct postmarketing required pediatric studies or studies in other rare diseases. This approach to clinical trial feasibility using RWD helps ensure research goals are balanced with the needs of the individual patient, further ensuring the ethical conduct of clinical trials. CLINICAL TRIAL REGISTRATION (STUDY 20140444): ClinicalTrials.gov / NCT03164928 / URL: https://clinicaltrials.gov/search? term=NCT03164928 . EudraCT / 2016-003083-39 / URL: https://www.clinicaltrialsregister.eu/ctr-search/search? query=2016-003083-39 .
Background: Depression, anxiety,, and PTSD are leading global causes of disability. Standard interventions utilize slow mechanisms of action, high attrition, and significant accessibility barriers. While intravenous (IV) and intranasal ketamine are rapid-acting alternatives, high cost and intensive logistical requirements limit adoption. Sublingual (SL) at-home ketamine addresses some gaps but is constrained by low bioavailability and variable absorption. Subcutaneous (SC) administration offers high bioavailability and precise dosing, potentially bridging the gap between in-clinic effectiveness and at-home accessibility. Objective: This retrospective observational study evaluated the safety, feasibility, and clinical outcomes of a telehealth, at-home SC ketamine protocol using a convenience sample of de-identified health records collected via Mindbloom's telehealth platform across 38 states. Methods: A sample of N=3,870 patients with moderate-to-severe symptoms of depression (PHQ-9 ≥ 10), anxiety (GAD-7 ≥ 10), or PTSD (PCL-5 ≥ 33) participated in a structured program involving clinical assessment, mandatory peer monitoring, and remote physiological screening. Injection kits and blood pressure monitors were mailed home. Dosing followed a subanesthetic protocol starting at 0.5 mg/kg with clinician-guided titration. Primary outcomes were measured at baseline and after weeks 2, 4, and 6 using the PHQ-9, GAD-7, and PCL-5 via online survey. Linear mixed-effects models with cubic splines analyzed symptom trajectories and accounted for time-varying assessments. Statistical significance was defined as alpha = .05; effect sizes were reported. Sensitivity analyses utilized multiple imputation and LOCF. Results: Patients (mean age 44.7 years; 52.4% female) demonstrated high adherence, with 0.5% switching from SC to SL administration. After 6 sessions (approximately 44 days), adjusted marginal means showed significant declines: PHQ-9 scores dropped from 14.64 (13.99-15.29) to 6.30 (5.90-6.70), GAD-7 from 13.06 (12.45-13.67) to 6.09 (5.72-6.47), and PCL-5 from 46.7 (43.30-50.10) to 27.5 (25.40-29.70) with large effect sizes ($d_z$) ranging from 1.35 to 1.58. Minimal Clinically Important Difference (MCID) was achieved by 81.8% of MDD, 80% of GAD, and 84.6% of PTSD patients ($p < .001$ for all). Adverse events were low (2.8%-3.2%), with no serious complications related to SC administration. Conclusions: This study is the first large-scale evaluation of at-home SC ketamine. Results suggest at-home SC ketamine is a safe, feasible intervention associated with high rates of symptom reduction in depression, anxiety, and PTSD. It differs from existing literature by utilizing a high-bioavailability (93%) SC route in a remote setting, whereas patients typically receive infusions of this potency in-clinic. Patients achieved clinical outcomes comparable to or exceeding traditional and intranasal therapies, potentially closing the access gap for treatment-resistant populations and supporting the expansion of supervised telehealth models in mental health care.
Collectin Subfamily Member 12 (COLEC12), a C-type lectin family member with collagen-like and carbohydrate recognition domains, remains poorly characterized in pancreatic cancer (PC). COLEC12 expression was analyzed by bioinformatics and immunohistochemistry. Functional assays (CCK-8, colony formation, EdU, flow cytometry, Transwell) and a xenograft model were used to assess its tumor-promoting effects. Mechanistically, transcriptome sequencing, Western blotting, co-immunoprecipitation (Co-IP), molecular docking, truncation mutant mapping, cycloheximide (CHX) chase assay, and ubiquitination assays were performed. The Cancer Genome Atlas (TCGA) data were used for immune infiltration analysis, and quantitative real-time PCR (qRT-PCR) was used to examine the role of COLEC12 in macrophage polarization. Chemosensitivity to gemcitabine and 5-fluorouracil (5-FU) was also evaluated. COLEC12 was upregulated in PC and promoted cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT), while suppressing apoptosis. Mechanistically, COLEC12 directly bound to TGF-β1 via its collagen-like domain, as demonstrated using truncation mutants. CHX chase assays revealed that COLEC12 overexpression delayed TGF-β1 degradation, and ubiquitination assays showed that COLEC12 knockdown increased TGF-β1 ubiquitination, indicating that COLEC12 stabilizes TGF-β1 by suppressing its ubiquitin-proteasome degradation, thereby sustaining activation of the TGF-β/Smad pathway. Furthermore, COLEC12 expression positively correlated with immune cell infiltration levels in TCGA data, and qRT-PCR revealed that COLEC12 expression in PC cells promotes M2 polarization of co-cultured macrophages. Knockdown of COLEC12 increased the sensitivity of PC cells to gemcitabine and 5‑FU. This study reveals, for the first time, the tumor-promoting function of COLEC12 in PC and highlights its potential as a therapeutic target in PC.
The Rating-of-Fatigue (ROF) scale is increasingly used to quantify subjective sensations of fatigue in exercise science. However, despite its growing international use, its psychometric properties have not yet been examined in Arabic-speaking populations. This study aimed to translate the ROF into Arabic and evaluate its content validity, face validity, and construct validity relative to perceived exertion and heart rate (HR) responses during graded exercise and subsequent passive recovery. The study was conducted in Tunisia and followed established international best-practice guidelines for cross-cultural adaptation. The ROF and its instructions were forward-translated, synthesized, and back-translated using blinded translators, with linguistic and conceptual equivalence evaluated using Sperber's framework and expert committee review. Face validity was assessed in 68 Arabic-speaking adults. Construct validity was examined in 43 adult participants during a modified Bruce treadmill test followed by 10 min of seated recovery, with the Arabic Rating-of-Fatigue scale (ROF-Ar), Borg CR10, and HR recorded at each exercise stage and during recovery. Within-participant correlations were pooled using Fisher's r-to-z transformation. Sperber-based ratings indicated high linguistic and conceptual equivalence between the ROF-Ar and the original scale, with no item exceeding the predefined revision threshold. Face validity findings showed that participants predominantly interpreted the ROF-Ar as a measure of fatigue rather than exertion and that standardized instructions improved descriptor-related comprehensibility and reduced perceived difficulty. During graded exercise, ROF-Ar demonstrated very strong pooled correlations with Borg CR10 (r = 0.94; 95% CI 0.92-0.95; p < 0.001) and HR (r = 0.95; 95% CI 0.93-0.96; p < 0.001). During recovery, the association between ROF-Ar and Borg CR10 attenuated substantially (r = 0.35; 95% CI 0.15-0.52; p < 0.001), whereas the association with HR remained moderate (r = 0.63; 95% CI 0.49-0.74; p < 0.001). The Arabic version of the ROF demonstrated high linguistic and conceptual equivalence, adequate face validity, and strong construct validity. The recovery-phase dissociation between perceived fatigue and perceived exertion supports the intended conceptual distinction of the ROF and justifies the use of ROF-Ar for assessing subjective fatigue during exercise and recovery in Arabic-speaking research and applied settings.
Caspofungin is an antifungal agent used for the treatment of severe fungal infections, which is semi-synthesized from pneumocandin B0, a secondary metabolite produced by filamentous fungus Glarea lozoyensis. To identify new pneumocandin analogues, a chemical reinvestigation was carried out on G. lozoyensis. This endeavor resulted in the isolation of pneumocandin B0 and two previously undescribed pneumocandin derivatives, designated as pneumocandins B7 and B8. Their structures were elucidated using HRESIMS and NMR spectroscopic analyses. Pneumocandins B7 and B8 represent the first reported pneumocandin analogues with a hydroxylated 10,12-dimethylmyristate (DMM) moiety. Antifungal activity assays revealed that pneumocandins B7 and B8 exhibited reduced antifungal efficacy across all eight tested Candida strains in comparison to pneumocandin B0. These findings suggest that the introduction of a hydroxyl group in the DMM moiety has a negative effect on the antifungal activity. These results enrich the structural diversity of the pneumocandin family and provide new insights into the structure-activity relationship of pneumocandins.
A non-rhizobial endophyte bacterial strain, designated A2-2T, was isolated from a root nodule of Kummerowia striata collected in Bin County, Heilongjiang Province of China. It was Gram-stain-negative, aerobic and non-motile and was able to grow at 15-37 ℃ in medium with 0-1% (wt/vol.) salinity and pH 5-11. It showed activities of oxidase and catalase and produced potential auxin-related compounds. Phylogenetic analysis based on the 16S rRNA gene sequences showed that strain A2-2T was related to the type strains of Pseudoduganella namucuonensis, Pseudoduganella buxea, Pseudoduganella aquatica and Pseudoduganella plicata, having the highest sequence similarity (97.8%) with P. namucuonensis 333-1-0411T; however, two phylogenomic trees, including GTDB-Tk and BV-BRC phylogenies, consistently placed the strain within the genus Duganella, where it formed an independent lineage. The ANI, dDDH and AAI values between strain A2-2T and 23 validly published species of the genus Duganella were 77.4-80.8%, 21.5-28.9% and 69.5-75.9%, respectively, all of which were below the accepted species delineation thresholds. The genomic DNA G+C content of strain A2-2T was 66.1 mol%. The strain lacked the nodC gene but harboured a relatively complete nif and fix genes. The main respiratory quinone of strain A2-2T was ubiquinone-8, and its major polar lipids were diphosphatidylglycerol, phosphatidylethanolamine and phosphatidylglycerol. The main cellular fatty acid components were summed feature 3, C16 : 0 and summed feature 8. Based on the evidence obtained in this study, a novel species, Duganella kummerowiae sp. nov., is proposed and the type strain is A2-2T (=JCM 38047T=CCTCC AB 2025004T).
Within the metabolic dysfunction-associated steatotic liver disease (MASLD)/MASLD with increased alcohol intake (MetALD)/alcohol-associated liver disease (ALD) framework, cardiovascular risk varies by alcohol exposure. As small dense low-density lipoprotein cholesterol (sdLDL-C) is highly atherogenic, this study assessed the relative effects of steatotic liver disease (SLD) and alcohol consumption on sdLDL-C elevation and the effects of conventional fasting lipids [low-density lipoprotein cholesterol (LDL-C)/high-density lipoprotein cholesterol (HDL-C)/triglycerides (TGs)] on these associations. This cross-sectional study enrolled 55,745 participants who underwent health screenings in Niigata, Japan between April 2024 and March 2025. Alcohol consumption was self-reported as low, moderate, or excessive. Participants were grouped by SLD status and alcohol consumption. sdLDL-C was directly measured, with high sdLDL-C defined as ≥35 mg/dL. Multivariable linear regression (sdLDL-C) and logistic regression (high sdLDL-C) analyses used two models: model 1 was adjusted for age, sex, body mass index, smoking, lipid-lowering medication, antihypertensive medication, and diabetes, and model 2 was further adjusted for LDL-C, HDL-C, and TGs. Marginal standardized prevalence and standardized prevalence differences (PDs) were estimated using g-computation with 2000 bootstrap iterations. The crude prevalence of high sdLDL-C was influenced by SLD and alcohol consumption, being highest in the SLD(+)/excessive alcohol consumption group (76.4%). In model 2, SLD-related associations were attenuated, whereas alcohol-related associations remained robust, as the PD was lower for SLD(+) than for SLD(-) within each alcohol category. Alcohol exposure contributes to an atherogenic sdLDL-C phenotype beyond conventional fasting lipids within contemporary SLD categories, indicating potential relevance for risk profiling in MetALD/ALD.
The double mutant MsE of the methyltransferase EgtD from Mycobacterium smegmatis can catalyze the N-terminal trimethylation of L-tryptophan to produce the medicinal indole alkaloid L-hypaphorine. Structural comparison, loop deletion, and alanine scanning revealed that Loop34-39 and Loop163-168 are critical for MsE activity and substrate binding. Saturation and iterative saturation mutagenesis targeting hotspot residues in these loops yielded mutant M5 (P35C/K36R/F38L/T163G/T168F). Compared with the original enzyme MsE, M5 exhibits a 7.11-fold increase in relative activity and achieves a conversion rate of 58.93%. Molecular dynamics simulations, CAVER tunnel analysis, and ligand dissociation pathway studies reveal that M5 modulates the hydrogen bond network of the active site and remodels the conformation of the substrate access tunnel, thereby transforming the substrate tunnel into a methylation reaction microcompartment with a "capture-release" function. This study provides a theoretical and practical basis for loop optimization engineering and enzyme functional modification.
Auditory dysfunction such as tinnitus is a common sequelae of traumatic brain injury (TBI), and has been associated with neurobehavioral outcomes, including cognitive decline, depression, and anxiety. Few studies have examined associations between concussion history and tinnitus independent of confounding by blast injury or occupational noise exposure. This study investigated concussion history and tinnitus among former professional American-style football (ASF) players, and evaluated whether tinnitus mediates associations between concussion history and neurobehavioral outcomes. This cross-sectional study included former ASF players who contracted with a professional league after 1960 and completed self-administered questionnaires between 2019-2025. Surveys assessed football exposure, auditory dysfunction, and mental health. Cumulative head injury exposure was measured using self-reported concussion signs and symptoms during play. Tinnitus was self-reported and assessed concurrently with validated measures of perceived cognition, depression, and anxiety. Logistic regression evaluated associations between concussion symptom history and tinnitus, and linear regression models assessed mediation and interaction effects. Among 1085 participants (mean age 57.9 ± 13.5 years; 32.4% Black; 6.1 ± 3.7 seasons), greater concussion symptom history was associated with increased odds of tinnitus (highest vs. lowest quintile: OR = 2.90; 95%CI 1.91-4.43; p < 0.0001). Tinnitus did not mediate associations between concussion symptom history and neurobehavioral outcomes. However, associations with perceived cognition (p-interaction = 0.1), depression (p-interaction < 0.01), and anxiety (p-interaction < 0.01) were larger among participants reporting tinnitus. Greater concussion symptom history was associated with increased reporting of tinnitus, and neurobehavioral associations were stronger among those with tinnitus. Clinicians should consider tinnitus when evaluating long-term cognitive and mental health outcomes following repeated head injury.
Two novel bacterial strains, designated as YS3T and YS5T, were isolated from soil collected at Nogo Mountain, Gyeonggi-do, Republic of Korea. Strain YS3T is Gram-positive, aerobic, non-motile and rod-shaped, forming opaque, cream-coloured colonies with smooth surfaces. Phylogenetic analysis based on the 16S rRNA gene sequence revealed the highest similarity to Pseudarthrobacter humi RMG13T (99.2%) and Pseudarthrobacter siccitolerans 4J27T (99.2%). Strain YS3T grew at 4-35 °C (optimum, 30 °C), at pH 4.0-12.0 (optimum, pH 8.0), and tolerated up to 6% (w/v) NaCl, with optimal growth occurring in the absence of NaCl. The genomic G+C content of strain YS3T was 65.0 mol%. Average nucleotide identity (ANI) values between strain YS3T and related Pseudarthrobacter species ranged from 81.2% to 84.9%, while digital DNA-DNA hybridization (dDDH) values ranged from 20.7% to 39.0%. Strain YS5T is Gram-negative, aerobic, motile and rod-shaped, forming translucent, yellow colonies with smooth surfaces. Phylogenetic analysis based on the 16S rRNA gene sequence showed the highest similarity to Ideonella dechloratans CCUG 30898T (98.9%) and Ideonella alba 3Y2T (98.7%). Strain YS5T grew at 10-35 °C (optimum, 30 °C), at pH 4.0-12.0 (optimum, pH 8.0), and tolerated up to 1% (w/v) NaCl, with optimal growth in the absence of NaCl. The genomic G+C content of strain YS5T was 69.0 mol%. ANI values between strain YS5T and Ideonella species ranged from 77.9% to 81.2%, while dDDH values ranged from 15.1% to 22.4%. On the basis of phenotypic, genotypic, phylogenetic and chemotaxonomic evidence, strain YS3T represents a novel species of the genus Pseudarthrobacter, for which the name Pseudarthrobacter cremeus sp. nov. is proposed (type strain YS3T=KACC 24143T=TBRC 21184T). Similarly, strain YS5T represents a novel species of the genus Ideonella, for which the name Ideonella flava sp. nov. is proposed (type strain YS5T=KACC 24144T=TBRC 21186T).
Although mycovirus-based biopesticides have shown promise in laboratory studies, they are not yet widely available. Our previous characterization of soybean leaf-associated gemygorvirus 1 (SlaGemV1) indicated its unique property for extracellular transmission and to evaluate its effectiveness against Sclerotinia sclerotiorum, we tested three formulations in greenhouse and field settings. First, in greenhouse trials, introducing hypovirulent S. sclerotiorum infected with SlaGemV1 into soil at the time of planting led to significant improvements in leaf area, plant height, and photosynthetic efficiency (all P < 0.01) while also reducing disease symptoms from subsequent S. sclerotiorum infections (P < 0.001). In field tests, plant height increased (P < 0.01). Second, SlaGemV1-infected S. sclerotiorum was homogenized to create a slurry, which was sprayed at flowering. This treatment provided protection against S. sclerotiorum infection, reducing sclerotia formation and average lesion lengths on greenhouse tomato plants (P < 0.05) and reducing lesions on pinto bean plants (P < 0.01) while increasing aboveground dry mass under S. sclerotiorum inoculation (P < 0.05). Third, filtering the homogenate and spraying crude particle filtrates (PFs) successfully reduced lesion lengths in basil, geranium, and sunflower (P < 0.05) in greenhouse trials. In 2023, PF spray also lowered disease incidence in sunflower plots in the field (P < 0.05). In 2024, PF-treated soybean and sunflower plots showed a significantly reduced disease severity index at the end of the growing season (P < 0.05). Based on these findings, we conclude that SlaGemV1 is an effective biopesticide using the formulations and delivery methods described.
Cephaeline (CPL), a bioactive compound derived from the medicinal plant Ipecacuanha, has demonstrated inhibitory effects on several tumor types. Nevertheless, its role in breast cancer and the underlying molecular mechanisms remain largely unexplored. This research aimed to investigate the anti-cancer potential of CPL in breast cancer cells. The IC50 of CPL was determined using the CCK-8 assay. Subsequently, the effects of CPL on cell migration and proliferation were assessed through wound healing (scratch) and colony formation assays, respectively. Additionally, MDA and GSH levels were quantified using ELISA, while ROS production was visualized via DHE staining. Intracellular iron content was measured using an iron assay kit. Furthermore, the expression levels of p53, SLC7A11, and GPX4 were evaluated using Western blot. All experiments were performed in triplicate and independently repeated at least three times, and data were analyzed using Student's t-test or one-way ANOVA, as appropriate. CPL significantly inhibited the proliferation and viability of 4T1 and MDA-MB-231 breast cancer cells in a dose-dependent manner, with IC50 values of 38.89 nM and 50.29 nM, respectively, and concomitantly suppressed cell migration and colony formation at higher concentrations. It also increased intracellular MDA and ROS and downregulated GSH, SLC7A11 and GPX4, inducing ferroptosis. siRNA knockdown of p53 attenuated CPL's effects, indicating p53's key role in CPL's anti-cancer activity. This study provides evidence that CPL exerts anti-breast cancer effects by promoting ferroptosis through the p53/SLC7A11/GPX4 axis, highlighting its therapeutic potential as a novel agent for cancer treatment.
Ebola virus disease (EVD) is a severe and often fatal illness characterized by aggressive viral replication, dysregulated immunity, and multi-organ dysfunction. Emerging evidence demonstrates that microRNAs (miRNAs), both host-derived and virus-encoded, play essential regulatory roles throughout the course of Ebola virus (EBOV) infection. Host miRNAs are widely dysregulated across different tissues and cell types during infection and contribute to antiviral defense, viral persistence, immune suppression, endothelial dysfunction, and hemorrhagic pathology. In parallel, EBOV generates its own miRNA-like molecules that target key host signaling pathways, including nuclear transport, interferon responses, apoptosis regulation, and inflammatory cascades. These dual layers of miRNA crosstalk shape infection outcomes by modulating viral replication, immune evasion, cellular adhesion, and vascular leakage. Additionally, several host and viral miRNAs show strong potential as diagnostic and prognostic biomarkers, and recent work suggests that therapeutic modulation through miRNA mimics or inhibitors may offer new antiviral strategies. This review synthesizes current evidence on miRNA interactions during EBOV infection and outlines their implications for disease pathogenesis, clinical outcomes, and translational applications.
The selection of biventricular repair or Fontan completion for single-ventricle patients remains difficult to determine in borderline patients. We report how the use of a 3-dimensional virtual reality model informed an accurate estimation of a 34-month-old child's ventricular chamber size to confirm Fontan completion. Developed from CT scan imaging, the model simulated a virtual biventricular repair and demonstrated inadequate outflow tracts after patching and baffle rerouting. This case demonstrates the implications of virtual reality for congenital heart disease surgical planning, providing a shared, intuitive platform for multidisciplinary discussion and consensus-building among surgeons, cardiologists, imagers, and anesthesiologists.
In response to the increasing abuse of etomidate-related substances in China, this study developed and validated an ultra-high performance liquid chromatography-tandem mass spectrometry method for the simultaneous quantification of etomidate (ET), metomidate (MET), propoxate (PRO), isopropoxate (I-PRO), CF3-etomidate (CF3-ET), and their metabolite etomidate acid (ETA) in human nails. This method enabled the first investigation into their accumulation patterns in authentic samples, offering scientific support for forensic monitoring. A 20 mg portion of nail was cryogenically ground and extracted with methanol containing the internal standard. After vortex mixing, ultrasonication, and filtration, the extract was concentrated under nitrogen flow and analyzed by ultra-high performance liquid chromatography-tandem mass spectrometry. The limits of quantification (LOQs) for the target substances in nail samples ranged from 1 to 10 pg/mg. The calibration curves exhibited good linearity over the concentration range from the LOQ to 1000 pg/mg. All other evaluated validation parameters proved satisfactory. The validated method was applied to authentic nail samples to investigate the accumulation profiles of ET and its analogs. Analysis of the samples revealed that 52 tested positive. These positive cases showed a distinct accumulation pattern dominated by the parent drugs, with ETA as the sole metabolite detected. This study developed and validated a reliable method for the simultaneous quantification of ET, its analogues, and its metabolite in human nails. Notably, it is the first to be applied to authentic samples to investigate their accumulation profiles, supporting the use of nail analysis in forensic toxicology and drug abuse monitoring.
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Efficient sample pretreatment is a critical step for the subsequent accurate analysis of target analytes. Herein, a novel dual-function deep eutectic solvent (DES) was synthesized for integrated extraction of flavonoids and digestion of Dendrobium officinale Kimura et Migo (D. officinale), to enable dual-mode detection. The one-step pretreatment (integrated extraction and digestion) was not only completed within a mere 50 s but also demonstrated superior performance: it achieved a flavonoid extraction efficiency 1.6-5.6 times that of alcoholic extraction, under milder conditions than traditional digestion methods, while yielding trace element results consistent with microwave digestion-inductively coupled plasma optical emission spectrometry (ICP-OES). Various characterization results show the successful preparation of novel DES, and its mechanism for flavonoid extraction was elucidated through density functional theory calculations. Furthermore, the method's greenness and extraction capacity were rigorously evaluated. Overall, this developed one-step DES pretreatment strategy provided a green, simple, and efficient method for the flavonoid extraction and digestion of D. officinale.