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关键词： Rosacea   erythema   telangiectasia   ktp   laser   ivermectin  

摘要： Objective: Facial erythema and telangiectasia in rosacea are commonly treated with vascular lasers. Combination with ivermectin 1% cream, may enhance outcomes when combined with laser therapy. This study assesses whether topical ivermectin improves the efficacy of Potassium Titanyl Phosphate (KTP) 532 nm laser for facial erythema in rosacea. Methods: This is a randomized, evaluator-blinded, split-face study. 24 patients with rosacea received four KTP laser sessions;one facial side was additionally treated daily with ivermectin 1% cream. The primary outcome was the change in Normalized Erythema Index (NEI). Secondary measures included Skin Redness Index (SRI), Clinical Erythema Assessment, Physician Global Assessment, telangiectasia score, inflammatory lesion counts, patient satisfaction, and safety. Results: At week 16, the combination side showed a significantly greater NEI reduction than laser alone (Delta NEI%: 16.6 vs 5.3;p = 0.04). No significant differences were observed in SRI, and all other scores. However, papule reduction across visits was significantly greater with ivermectin (p = 0.02). Both treatments were well tolerated, with no serious adverse events. Conclusion: KTP laser effectively reduces erythema and inflammatory lesions;adjunctive ivermectin may further enhance papulopustular lesions. The combination is well tolerated, suggesting a potential adjunctive role for topical ivermectin in laser-based rosacea therapy.

关键词： Antimicrobial peptide   hepcidin   anguillid herpesvirus 1   antiviral activity   envelope protein ORF51  

摘要： Frequent outbreaks of eel "mucus sloughing and hemorrhagic septicemia disease" caused by Anguillid herpesvirus 1 (AngHV) are a major epidemic in both wild and farmed eels. This virus has garnered global attention due to heavy losses on eel farms and the lack of protective vaccines or effective drugs, highlighting the urgent need for potent antiviral agents. In this study, we revealed a hepcidin homolog LJ-hep2 from Japanese seabass (Lateolabrax japonicus) can bind to AngHV and impede viral entry into cells. LJ-hep2 could directly destroy the viral envelope and showed a higher anti-AngHV activity than AA-hep (a hepcidin homolog cloned from Anguilla anguilla). It was found that the destruction of viral structure by LJ-hep2 was related to the binding of the peptide to AngHV envelope protein ORF51, and the two amino acid residues at the N-terminus of the peptide (lysine and phenylalanine) might play a key role. Comparative antiviral experiments with mutated LJ-hep2 (LJ-hep2A4A5) and multi-species hepcidin further confirmed this finding and demonstrated that these two amino acids were indispensable in the inhibition of AngHV infection by LJ-hep2. In an established eel immersion infection model, LJ-hep2 treatment reduced viral accumulation in tissues, inhibited horizontal transmission, alleviated skin lesions, and improved eel survival. Taken together, this study suggests that LJ-hep2 could inhibit AngHV infection in vitro and in vivo, and identify ORF51 as a potential target for the development of anti-AngHV drugs.

关键词： GM soybean   non-targeted metabolomics   substantial equivalence   omega-3 fatty acid  

摘要： The overexpression of the Physaria fendleri omega-3 fatty acid desaturase (PfFAD3-1) in soybean (Glycine max (L.) Merr.) substantially increases seed alpha-linolenic acid (18:3) content. To evaluate the compositional safety of PfFAD3-1 transgenic soybeans, we conducted a three-year, two-location field trial (Jeonju and Gunwi, Republic of Korea) and applied non-targeted metabolite profiling of polar and lipophilic metabolites. Multivariate analyses (PCA, PLS-DA) revealed that environmental factors (site and year) had a strong effect on seed metabolite composition. Volcano plot and variable importance in projection (VIP) analyses indicated that most metabolite differences between PfFAD3-1 lines and Kwangan (KA) varied across years and locations, reflecting gene - environment interactions. Importantly, the majority of metabolites in PfFAD3-1 lines remained within the natural variation range of non-GM reference cultivars, supporting substantial equivalence. The consistent deviation was an increase in beta-amyrin, a triterpenoid precursor of soyasaponins. LC - MS analysis further confirmed line- and environment-dependent increases in specific saponins, particularly soyasaponin I. Given the established safety of triterpenoids in soybean and the biological coherence of fatty acid - triterpenoid pathway cross-talk, these findings suggest that beta-amyrin accumulation represents an intended metabolic adjustment rather than an unintended effect. Collectively, our results demonstrate that non-targeted metabolomics complements conventional OECD-recommended compositional analyses, providing a robust framework for the safety assessment of nutritionally enhanced GM soybeans.

关键词： Adherence   efficacy   hepatitis B   people who use drugs   randomized controlled trial   vaccination schedule  

摘要： BackgroundTo compare the adherence and efficacy between the 0 - 7 - 21-day and the 0 - 1 - 6-month hepatitis B virus (HBV) vaccination schedules among people who use drugs (PWUD) in China. Research design and methodsA randomized controlled trial was conducted in 1261 HBV-susceptible PWUD from compulsory isolated detoxification centers (CIDCs) and methadone maintenance treatment (MMT) clinics in Xi'an. A 20 mu g per-dose vaccine was used. HBV surface antibody (anti-HBs), surface antigen, and core antibody were tested at months 7, 15, and 22 after the first ***-dose coverage was significantly higher in the 0 - 7 - 21-day group (74.40%) than in the 0 - 1 - 6-month group (51.58%, p < 0.001), mainly driven by participants from CIDCs (77.75% vs. 45.69%). Anti-HBs positive rates at months 7, 15, and 22 among participants who completed all three doses were significantly higher for the 0 - 1 - 6-month schedule (90.71%, 76.82%, and 67.35%) than for the 0 - 7 - 21-day schedule (74.23%, 49.40%, and 40.95%;all p < 0.001). HBV infection incidence was similar between schedules, but significantly different between vaccinees and non-vaccinees (p = 0.018). ConclusionsThe 0 - 7 - 21-day schedule substantially enhances three-dose completion in PWUD, but induces a notably weaker anti-HBs response and persistence. Schedules should be selected based on the management models for PWUD and their individual characteristics. Clinical trial registrationChinese Clinical Trial Registry (ChiCTR1900022403).

关键词： Myotonic dystrophy type 1 (DM1)   organ system involvement   clinical burden   economic burden   HCRU   healthcare cost   healthcare resource utilization  

摘要： Objectives: Myotonic dystrophy type 1 (DM1) is a multi-systemic disease affecting skeletal and smooth muscle, the eye, brain, and heart. No disease-modifying therapies are available. Prior studies on clinical care and economic burden combined DM1 and DM type 2. This study describes the US DM1 population aged >= 12 years, assessed organ system involvement over time, estimated healthcare resource utilization (HCRU), associated costs, and identified predictors of high-cost status. Methods: Linked open claims and EHR data (Clarivate) from 1 January 2015 to 25 August 2023 were analyzed. Eligible individuals had a DM1 diagnosis (index), >= 6 months pre-index data, and were aged >= 12 years;congenital DM was excluded. Organ system involvement rates up to 7 years post-index were estimated using the Kaplan-Meier method. Annual HCRU rates and costs to payers (2023 USD) were summarized by setting, type of care and specialty and compared by organ involvement. Predictors of high-cost status were evaluated using multivariable logistic regression. Results: The cohort included 1,343 people with DM1. Over 7 years, most experienced neurological, gastrointestinal, cardiac, pulmonary, and/or musculoskeletal system involvement. Annually post-index, approximately 24% of patients had emergency room visits, and 15% had inpatient visits. Common specialty visits included rehabilitation (13%), cardiology (13%), and neurology (11%). Frequent device use included noninvasive positive-pressure ventilation (12%), assistive devices (7%), and oxygen therapy (4%). Mean annual total cost of care was $20,687 (SD = $122,082), primarily driven by inpatient and outpatient hospital visits. Cardiac and pulmonary complications were significant predictors of high-cost status. Conclusion: DM1 imposes significant clinical and economic burden, marked by extensive organ involvement and variable healthcare costs. As any patient may progress to costly cardiac or pulmonary complications, early proactive management i

关键词： Influenza A virus   SARS-CoV-2   TMPRSS2   inhibitors   entry inhibitors   host-directed-antivirals   broad-spectrum antiviral drugs  

摘要： Human TMPRSS2 is a type II transmembrane serine protease and an essential host factor for SARS-CoV-2 and influenza A virus (IAV H1N1) infections. It facilitates the cleavage of viral surface glycoproteins, which are required for membrane fusion. This importance makes it an attractive target for host-directed antiviral therapies. We previously identified N-0385 and N-0920 as nanomolar TMPRSS2 inhibitors and demonstrated their antiviral potency against several SARS-CoV-2 variants. Here, we screened another twelve N-0385/N-0920 analogs with improved pharmacokinetics. Compounds 9 and 10 showed strong inhibition of TMPRSS2 activity and viral entry: they blocked pseudoviruses and authentic SARS-CoV-2 JN.1 and IAV H1N1 in Calu-3 cells. Compound 9 displayed a synergistic effect with baloxavir during IAV H1N1 infection. Both compounds highly reduced H1N1 infection in air-liquid interface cultures and mouse models, thus highlighting their broad antiviral potential. The discovery of broad-spectrum, host-directed antivirals against current and emerging human viruses is critical in preparing for future pandemics.

关键词： italic>Arabidopsis thaliana   CASEIN KINASE 1   brassinosteroid   transcription   hypocotyl   root   growth  

摘要： The CASEIN KINASE 1 (CK1) family plays diverse roles in the development, physiology, and disease in eukaryotes. In Arabidopsis thaliana, the CASEIN KINASE 1-LIKE (CKL) family has 13 members, but to date, the roles of these kinases remain largely unclear. Here, we characterize several insertion mutants, finding that CKL12 may contribute to hypocotyl and primary root growth. Differential effects of insertions at various parts of the gene suggest that the 3 ' end of the transcript may be important for CKL12 function. We provide evidence that CKL12 may be a transcriptional target of brassinosteroid (BR) signaling. The CKL12 promoter contains in vitro binding sites for BR-related transcription factors. Knock-down of these transcription factors using RNA interference reduces CKL12 transcript. Together, these data suggest that CKL12 may act downstream of BR signaling to regulate seedling growth.