The journal retracts the article titled “Repurposing Diltiazem for Its Neuroprotective Anti-Dementia Role against Intra-Cerebroventricular Streptozotocin-Induced Sporadic Alzheimer’s Disease-Type Rat Model” [...]
The Journal retracts the article “Secukinumab and Black Garlic Downregulate OPG/RANK/RANKL Axis and Devitalize Myocardial Interstitial Fibrosis Induced by Sunitinib in Experimental Rats” [...]
The present study aimed to design, synthesize, and evaluate a new series of thieno[3,2-d]pyrimidin-4(3H)-one-based Schiff bases as potential antileishmanial agents against Leishmania major (L. major). A series of twenty thieno[3,2-d]pyrimidine Schiff base derivatives were synthesized and characterized using FTIR, NMR, and HRMS techniques. Their antipromastigote activities were evaluated in vitro against L. major, while cytotoxic effects were assessed on HUVECs to determine selectivity indices. The most active compound was further investigated using molecular docking against several L. major proteins. Among the tested compounds, compound 12, bearing a 2-hydroxy-5-bromophenyl moiety, exhibited the most potent activity against L. major promastigotes with an IC50 value of 13.7 µM, along with a favorable selectivity index (SI = 17.5), outperforming the reference drug miltefosine (IC50 = 31 µM and SI = 0.2). Docking studies demonstrated that compound 12 showed the strongest binding affinity toward phosphodiesterase B1, supported by a docking score of −9.042 kcal/mol and an MM-GBSA value of −67.21 kcal/mol. This study highlights thieno[3,2-d]pyrimidin-4(3H)-one as a promising scaffold in the context of in vitro antileishmanial screening and suggests the role of ortho-phenolic substitution in enhancing activity and selectivity. Compound 12 emerges as a promising lead, warranting further optimization and biological evaluation in future studies.
Capillary malformation–arteriovenous malformation syndrome is a rare spectrum of vascular anomalies characterized by capillary malformations and high-flow vascular malformations, caused by loss-of-function mutations in the RASA1 and/or EPHB4 genes. These mutations disrupt vascular differentiation and lead to complex malformations involving the brain, skin, and systemic vasculature. Since the first description in 2003, more than 200 cases have been reported, but intracranial arteriovenous shunts during the neonatal period remain extremely rare, as well as reports of the dual mutation RASA1 + EPHB4 or the immunological impact of the EPHB4 mutation. We report three cases of neonates presenting with early-onset high-flow shunts, each exhibiting a distinct genetic signature: CM-AVM1 (RASA1 mutation), CM-AVM2 (EPHB4 mutation), and dual variant (combined EPHB4 and RASA1 mutations). We analyzed and compared the clinical evolution, Doppler ultrasound trends, EEG, MRI and genetic data to highlight the distinct genotype–phenotype spectrum. Early multimodal hemodynamic evaluation of neonates with CM-AVM allows the identification and optimum management of life-threatening shunts at the earliest possible stage.
Background: This study aimed to compare the effects of unstable strength training (UST) and traditional strength training (TST) on lower-body stability in adolescent volleyball players in China. Methods: This stratified randomized controlled trial recruited 62 eligible athletes from Shandong Province. Participants were assigned to either the UST group or the TST group, and both groups completed a 10-week training program. Results: Multivariate analysis of variance (MANOVA) for within-group effects revealed statistically significant improvements in all dependent variables for both the UST and TST groups (p < 0.05), FMS [F = 35.112, p < 0.001, η2 = 0.377]; and balance ability differences, left-side score (LS) [F = 8.268, p < 0.001, η2 = 0.125], right-side score (RS) [F = 8.094, p < 0.001, η2 = 0.122]. Furthermore, after controlling for covariates, MANCOVA analysis for between-group effects still showed statistically significant differences between the UST and TST groups on all post-test dependent variables. These differences included: functional differences, FMS [F = 34.412, p < 0.001, η2 = 0.389]; LS [F = 8.079, p < 0.01, η2 = 0.130]; and RS [F = 8.532, p < 0.001, η2 = 0.136]. Conclusion: UST is more effective than TST in improving athletes’ lower-body stability performance. Future studies should explore the application of UST in other sports and examine its effects on parameters beyond functional movement and balance.
Background: A previous short-term retrospective analysis from our center suggested early improvement in pain, function, and sleep outcomes after fixed-dose tramadol/paracetamol therapy in patients with early-stage symptomatic knee osteoarthritis (KOA). However, the durability of these outcomes beyond the initial treatment phase remains insufficiently described in routine clinical practice. Objective: To describe short- and mid-term patient-reported outcomes and safety during extended follow-up in adults with symptomatic KOA treated with fixed-dose tramadol/paracetamol in routine outpatient care. Methods: This single-center retrospective observational extension study analyzed a fixed cohort of 30 adults with symptomatic knee osteoarthritis and Kellgren–Lawrence grade I–II treated with fixed-dose tramadol/paracetamol in routine outpatient care. Patients were evaluated at baseline (T0), 15 days (D15), 3 months (M3), and 6 months (M6), where evaluable follow-up data were available. The primary outcome was change in pain intensity measured by the Numeric Rating Scale (NRS). Secondary outcomes included WOMAC total and subscale scores, Pittsburgh Sleep Quality Index (PSQI) score, adverse events, and treatment discontinuation. Results: Patients had a mean age of 64.8 ± 9.6 years and a mean BMI of 27.3 ± 5.0 kg/m2. NRS pain improved from a median of 6.0 (5.0–7.0) at baseline to 4.0 (2.0–5.3) at D15 and 3.0 (2.0–5.0) at both M3 and M6. WOMAC total score improved from 47.8 ± 12.8 at baseline to 35.6 ± 13.8 at D15, 33.8 ± 13.6 at M3, and 33.9 ± 13.5 at M6. Sleep score improved from 9.5 (7.0–15.0) at baseline to 7.0 (5.0–9.0) at D15 and remained improved at M3 and M6. Mild adverse events were reported in 10.0% of patients, and discontinuation occurred in 6.7%. Conclusions: In this small, uncontrolled, single-center retrospective cohort of adults with early-stage symptomatic KOA, fixed-dose tramadol/paracetamol was associated with early improvement in pain, WOMAC outcomes, and sleep, with group-level benefits remaining evident through 6 months. These findings should be considered exploratory and hypothesis-generating rather than comparative evidence of effectiveness. Larger controlled studies are needed to confirm durability, comparative benefit, and long-term safety.
Morus alba L. fruit extract (MFE), which is rich in cyanidin 3-glucoside (C3G), demonstrates antioxidant properties and pharmacological effects, but its reproductive safety remains poorly understood. Polyphenols modulate steroidogenesis, spermatogenesis, and sperm acrosome integrity; therefore, toxicity assessment is needed for use. This study aimed to evaluate the antioxidant profiles and subchronic reproductive effects of MFE. MFE was standardized using high-performance liquid chromatography (HPLC), 2,2-diphenyl-1-picrylhydrazyl (DPPH), and ferric reducing antioxidant power (FRAP) assays. Male rats were administered MFE (250 or 500 mg/kg BW) for 56 days. Assessments included computer-assisted sperm analysis (CASA), testosterone, seminal fructosamine, and testicular CYP11A1 and androgen receptor (AR) expression. Acrosomal status was determined using PNA lectin staining. The results showed that MFE contained C3G (119.42 mg/g), antioxidant capacity (DPPH IC50: 0.101 mg/mL; FRAP: 465.01 µmol Fe (II)/g), and total contents (phenolics: 41.15 mg GAE/g; flavonoids: 3.15 mg CE/g; anthocyanidins: 11.04 mg C3G/g). MFE did not alter testicular histology and seminiferous stages VII-IX. High doses significantly increased sperm concentration, while both doses reduced sperm beat cross frequency. Testosterone, fructosamine, and CYP11A1/AR expressions showed increasing trends. Significantly, high doses induced a precocious acrosome reaction. In conclusion, MFE has no reproductive toxicity and pro-fertility effects on sperm quantity or androgenic markers, supporting safe subchronic use.
The effect of periodic temperature variation on short and partially matching interacting RNA strands is demonstrated using three pairs of competing RNA duplexes as simplified model systems. They represent random base-pairing interactions between short RNA chains at very early stages of RNA evolution. The molecular interaction kinetics are simulated based on the experimental thermodynamic data obtained by M. E. Christiansen et al. and on the Eyring theory. The simulated time developments demonstrate the impact of shifting reaction kinetics and a state of continuous non-equilibrium. The product mix that develops slowly at low temperatures releases chemical (free) energy quickly at high temperatures, and the product mix that develops quickly at high temperatures releases chemical (free) energy slowly at low temperatures. Regarding heat flow and energy storage, the chosen model system represents a generalized Carnot engine, similar to most comparable reactions during RNA evolution. Its action provides a perpetual driving force for selection processes, creating ideal conditions for an ongoing molecular evolution.
Temperature is a state variable that affects all life. While it is known that archaea can grow at 120 °C and many bacteria can grow at over 100 °C, no eukaryote is known to complete a life cycle at above 65 °C. This paper explores why the difference in the maximum temperature of eukaryotes and other kingdoms of life might occur. It finds that chemical and genome structural differences between the domains of life are unlikely to explain the difference in maximum growth temperature, with the exception of the Saccharomycotina, which are different from other fungi, possibly because of their unique ecology. The distribution of inherently disordered proteins (IDPs), however, is significantly correlated with maximum and minimum growth temperature in fungi, and with the range of temperatures over which fungi can grow. I also demonstrate that the range of temperatures over which a species can grow is correlated with its maximum temperature. I postulate that the range is correlated with maximum temperature because all real-world ecologies fluctuate between elevated and average surface temperatures, and the thermodynamics of IDP-based structures in eukaryotes inherently limits the range over which they can operate. Thus, the 65 °C maximum temperature limit for eukaryotes is a result of a combination of thermodynamic properties of their organization and the temperature regime on the modern Earth; I suggest an experimental approach to testing this.
Handball requires athletes to sustain intermittent high-intensity effort while maintaining rapid cognitive processing and technical skills. Caffeine is widely used as an ergogenic aid, yet its dose-dependent effects across physical, cognitive, and technical performance outcomes remain unclear in female handball players. This randomized, double-blind, placebo-controlled crossover study examined the acute effects of low-dose caffeine (LCAF; 3 mg/kg), moderate-dose caffeine (MCAF; 6 mg/kg), and placebo (PLA) in trained female handball players. Participants (n = 20) completed three experimental sessions separated by 72 h. Cognitive performance was assessed using the Simplified Eriksen Flanker Test, throwing performance was evaluated through maximal ball velocity, and intermittent running capacity was measured with the Yo-Yo Intermittent Recovery Test Level 1. Both LCAF and MCAF significantly improved Yo-Yo performance compared with PLA (η2p = 0.415, representing improvements of approximately ~23.5% and 29.0%), with no difference between caffeine doses. MCAF significantly reduced overall Flanker response time (η2p = 0.486, ~18.5%) and congruent and incongruent trial response time compared with PLA and LCAF. No significant effects were observed for throwing velocity, Flanker accuracy and interference scores. These findings suggest that acute caffeine intake has performance-specific effects in female handball players: intermittent running performance responded to both doses, whereas cognitive enhancement was limited to response time, with no improvements in inhibitory control or accuracy.
Aphasia is a complex neurological syndrome that includes a multitude of signs and symptoms that describe a patient's inability to use language (understanding and producing spoken and/or written language) after it has already been acquired, which is caused by cerebral lesions situated in the dominant (left) cerebral hemisphere in right-handed people. Aphasia has a prevalence of 25-30% in acute ischemic stroke (especially in arterial infarcts). In patients who suffered cerebral venous and dural sinuses thrombosis (CVST), aphasia has been noticed in almost 20% of cases, its presence being considered a negative predictive factor. We report the case of a 22-year-old right-handed woman with obesity and active smoking (10 cigarettes/day), undergoing treatment with oral contraceptives who presented to the Emergency Department with an intense headache, resistant to usual analgesic treatment, accompanied by language disorders onset within 24 h. The neurological examination was normal, except for language assessment, which revealed the severe impairment of the repetition domain (she was unable to repeat simple words), and difficulty in naming objects with some hesitations and mild comprehension difficulties (especially in complex orders). She underwent neuroimaging examinations at admission. Native Head Computed Tomography revealed spontaneous hyperdensity (parenchymatous hematoma) in the left temporal lobe. Cranial magnetic resonance imaging (MRI) confirmed venous infarction in the left temporal area and a hypointense signal on MRI T2*SW (susceptibility-weighted) in the region of the left lateral sinus and left jugular vein bulb, which confirmed the thrombosis at this level. Associated cortical vein thrombosis was diagnosed on indirect radiological grounds, since hemorrhagic transformation obscured the direct visualization of the adjacent cortical veins. MR venography was not performed at that time, but instead at the 1-month follow-up, MR venography confirmed the chronic, partial thrombosis of the left lateral sinus and left jugular vein bulb. Laboratory data demonstrated an elevated D-dimer and the presence of homozygosity for MTHFR C677T and PAI-1 4G/4G. Anticoagulation in the form of low-molecular-weight heparin was immediately started, followed by chronic treatment with oral anticoagulant (apixaban) and folic acid. The headaches resolved within three days, and her neurological examination was almost normal: the repetition continued being altered for complex phrases. We did not observe any left lateral sinus thrombosis recurrence, or other extra-cerebral embolic events (deep vein thrombosis or pulmonary embolism) during the follow-up year. The immediate anticoagulation since the admission resulted in a favorable outcome. Taking into consideration our interest in monitoring patients with aphasia secondary to CVST, we also analyzed data from the literature regarding the incidence of conduction aphasia and other aphasic syndromes in this CVST. Due to the limited number of articles identified in the last 21 years (2005-2026) in the literature, we concluded that conduction aphasia is an extremely rare clinical presentation in this kind of pathology and further studies should be conducted in order to identify significant statistical data.
Several studies on diet and microbiome have predominantly focused on the gut microbiome. However, much of the salivary microbiome remains unexplored. This study examined the influence of Thai desserts with varying glycemic indices on the salivary microbiome. A total of 30 healthy adults aged 18–45 years were enrolled in a randomized trial and allocated to one of three intervention groups, with each receiving a culturally specific Thai dessert standardardized to provide 50 g of available carbohydrates: Phetchaburi’s Custard Cake (PCC; low-GI, 192 g), Saraburi’s Curry Puff (SCP; medium-GI, 98 g), or Lampang’s Crispy Rice Cracker (LCRC; high-GI, 68 g). Salivary and dessert microbiome compositions were characterized at baseline and 24 h post-intervention using 16S rRNA sequencing to evaluate bacterial diversity and relative abundance across multiple taxonomic levels. Firmicutes were highly abundant (over 76%) in all Thai desserts tested. Proteobacteria were found in both SCP (15.1 ± 6.6%) and LCRC (6.5 ± 3.4%). Actinobacteriota was slightly higher in the high-GI group (6.3 ± 3.1%) compared to the medium-GI group (3.0 ± 2.2%). Bacillus was dominant in PCC, while Streptococcus, Carnobacterium, and Clostridium sensu stricto 1 were prevalent in SCP. Anoxybacillus, Clostridium sensu stricto 12, Terrilactibacillus, Geobacillus, and Weissella were found in LCRC. Desserts with different types of glycemic index showed modest short-term changes in the relative abundance of some salivary bacteria. Notably, Porphyromonas showed a relative increase in the high-GI group compared to the low-GI group (1.8 [0.3, 4.0] vs. −1.9 [−3.2, 0.8], p < 0.05), while Streptococcus, saccharolytic bacteria, slightly increased in both the high-GI and medium-GI groups. Prevotella showed a slight relative decrease in the low-GI group. Although these microorganisms have been previously associated with dysbiosis and periodontitis in longer-term studies, the clinical relevance of these short-term compositional changes remains unclear and should be interpreted with caution. These preliminary findings suggest that local Thai desserts with varying GIs may be associated with transient shifts in salivary microbiota composition; however, whether such changes contribute to dysbiosis or adverse oral health outcomes requires further investigation through longitudinal studies with larger sample sizes.
In addition to its role in energy storage, adipose tissue contributes substantially to energy metabolism, endocrine regulation, and inflammatory processes. Sujiang pigs, a hybrid breed approved by the National Livestock and Poultry Genetic Resources Committee of China as a new national breed in 2013, possess a genetic predisposition for substantial fat deposition, making them an ideal model for investigating the mechanisms underlying adipose tissue accumulation. In this study, back fat (BF; subcutaneous adipose tissue), greater omentum (GOM; visceral adipose tissue), and mesenteric adipose tissue (MAD; visceral adipose tissue) were collected from three 6-month-old male Sujiang pigs for RNA-seq analysis. Comparative analyses identified 3005 differentially expressed genes (DEGs) between BF and GOM, 975 DEGs between BF and MAD, and 892 DEGs between GOM and MAD. To validate the reliability of the sequencing data, five DEGs were randomly selected for RT-qPCR verification. The DEGs were further subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. By integrating protein-protein interaction (PPI) networks with bioinformatics analyses, we identified candidate genes potentially associated with lipid metabolism (e.g., WNT9A, WNT5A, and PDGFRA) and inflammatory responses in adipose tissue (e.g., CSF1R, C1QB, and CD4). These findings indicate potential molecular differences between porcine visceral and subcutaneous adipose tissues and may serve as a reference for further studies on the molecular regulation of adipose tissue metabolism.
Evidence on the interplay between perceived stress, dietary behaviour, and weight-related psychosocial burden in Romanian young adults remains scarce. This cross-sectional study assessed associations between BMI, perceived stress, multi-system somatic symptom severity, and psychosocial burden in 117 participants aged 16 to 20 years (89.7% female; mean age 19.23 ± 0.74 years; mean BMI 22.66 ± 3.85 kg/m2), recruited by convenience sampling in Târgu Mureș, Romania, during June 2025. Non-parametric methods were used throughout. Female participants scored significantly higher than males across digestive (p < 0.001), neurological (p = 0.001), cutaneous (p = 0.014), and total symptom domains (p < 0.001), with a median total symptom score of 21.0 versus 3.0 in males. Perceived stress correlated positively with neurological (rS = 0.445), cardiovascular (rS = 0.350), digestive (rS = 0.316), and total symptom scores (rS = 0.401; all p < 0.001). BMI was not associated with somatic symptoms but correlated with weight-related stigma (rS = 0.391, p < 0.001). Emotional distress was prevalent regardless of weight status: 60.7% reported food-related guilt and 59.8% reduced self-confidence, yet only 6.0% had consulted a mental health professional. Stress management, nutritional counselling, and body image support should target young adults across all BMI categories.
Primary sclerosing cholangitis (PSC) and ulcerative colitis (UC) exhibit a striking clinical comorbidity, with 60-80% of PSC patients concurrently harboring UC, yet the shared immunogenetic mechanisms remain poorly understood. Here, we constructed a multi-omics integrative framework to systematically dissect the cellular and molecular basis of this comorbidity. GWAS meta-analyses were performed for each disease, followed by tissue-level enrichment assessment using QTLEnrich, MAGMA, and gsMap spatial mapping. Single-cell transcriptomic atlases were constructed, and cell-type prioritization was conducted using four complementary methods. Core genes were identified through cross-validation of five algorithms, with subsequent genomic fine-mapping via FUMA and GCTA-COJO. Tissue-level analyses consistently identified the intestine and immune-related tissues as commonly affected. Multi-dimensional evidence integration prioritized natural killer (NK) cells as the core effector cell type for both diseases, supported principally by CELLECT (Cell-type Expression-specific Integration for Complex Traits) heritability enrichment and single-cell differential analysis. Convergence of five gene-level algorithms pinpointed STAT3 as the sole high-confidence comorbidity gene, broadly expressed across immune cell populations and exhibiting tissue-differential alternative splicing. Colocalization identified a high-risk variant (rs3736161) within the STAT3 locus, with conditional analysis revealing 35 additional independent signals. These findings identify the NK cell-STAT3 axis as a central immunogenetic hub connecting PSC and UC, offering potential therapeutic targets for comorbidity management.
Background: A significant proportion of individuals with Takayasu arteritis (TA) experience relapses notwithstanding standard treatment with glucocorticoids, and conventional synthetic or biologic disease-modifying antirheumatic drugs (DMARDs). As the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway contributes to the pathogenesis of TA, JAK inhibitors (JAKi) could represent a viable therapeutic alternative. This study assessed the effectiveness of JAKi in patients with relapsing TA within a real-world setting in a country with a low incidence of TA such as Spain and included a comprehensive review of the literature. Methods: we conducted a retrospective analysis of TA patients managed with JAKi for recurrent disease across three Spanish centers. Evaluated outcomes comprised clinical remission, clinical and analytical remission, glucocorticoid-sparing effect, improvement in imaging techniques, and adverse events. A systematic literature search was performed to identify further cases of TA treated with JAKi. Results: six patients (83.3% females) with a mean age 48.5 years and relapsing TA received JAKi therapy: baricitinib (n = 2); tofacitinib (n = 2), and upadacitinib (n = 2). Before JAKi therapy, all (100%) patients had received conventional synthetic immunosuppressants, and four (66.7%) biologics. Clinical remission was achieved in 2/6 (33.3%), 3/5 (60%), 3/5 (60%), 2/3 (66.7%), and 2/2 (100%) patients at 1, 3, 6, 12 and 18 months, respectively. Clinical + analytical remission was observed in 1/6 (16.7%), 2/5 (40%), 2/5 (40%), 2/3 (66.7%), and 2/2 (100%) patients, respectively. Two patients who underwent a follow-up PET/CT imaging showed partial improvement in both. After a median (IQR) follow-up of 9.5 (6.0-16.7) months, one (16.7%) patient discontinued the initial JAKi due to no improvement and one patient discontinued it because was diagnosed with tonsillar neoplasia. The literature search identified another 166 JAKi-treated TA cases with clinical improvement reported for the majority of them. Conclusions: this real-world analysis and literature review suggest that JAKi could be effective in the management of TA, including for those patients who have failed established glucocorticoid-sparing strategies.
This study aims to investigate the effects of cysteamine zinc supplementation on milk production, composition, amino acid profile, and metabolites in mares. Building on prior experimental findings, a dose of 7 mg/kg body weight of CS-Zn was selected for the experimental group, which was compared with a control group. Milk samples were collected at various time points, and milk yield was recorded each time. Routine analysis of milk components, as well as the determination of milk metabolites and amino acids, were performed. The results indicated that, compared to the control group, the experimental group exhibited increases in milk yield and the content of milk fat, lactose, and non-fat solids (p < 0.05), with an extremely significant increase in milk protein (p < 0.01). Conversely, the levels of L-glutamine and L-proline in milk were significantly reduced (p < 0.05). Metabolomic analysis revealed that differentially expressed metabolites were enriched in pathways such as ABC transporters, D-aminoadipate metabolism, aminoacyl-tRNA biosynthesis, and protein digestion and absorption. Notably, milk metabolites including cAMp, biotin, and taurine showed a tendency to be upregulated, while oxoglutaric acid, methionine, and diacetyloxyxanthone were downregulated. Based on evidence from the literature other species, it is speculated that CS-Zn supplementation may be associated with alterations in endocrine and amino acid metabolism pathways, potentially influencing lactation performance in mares. However, because no hormones were directly measured in this study, such a mechanism remains speculative and requires direct experimental validation.
The orthogonal design further optimized the culture medium to a combination of ammonium nitrate, sucrose, and magnesium sulfate, achieving a mycelial growth rate of 1.379 mm/d. The mycelia of Gerhardtia borealis contained 26.01% crude protein, 6.03% crude fat, and 1.24% crude polysaccharides. A total of 17 amino acids were detected, with a total content of 26.09 g/kg. The iron and zinc contents in the mycelia were 28.09 mg/kg and 22.17 mg/kg, respectively. The concentrations of arsenic, cadmium, mercury, and lead were all below the national food safety limits. This study provides fundamental data supporting the domestication and functional utilization of Gerhardtia borealis as an edible and medicinal resource.
Mori Cortex Radicis (MCR), which is abundant in resources and low in cost, is a Chinese herbal medicine with antitussive, anti-inflammatory, analgesic, and hypoglycemic effects; however, its application in the prevention and control of aquatic pathogens remains understudied. In this study, a MCR water extract (MCR-WE) was prepared, and its contents of polysaccharides, polyphenols, and proteins were found to be 0.63%, 1.17%, and 2.79%, respectively. LC-MS metabolomics revealed that L(+)-Arginine, 9,12,13-Todea, Citric acid, 1-Deoxynojirimycin, and 4-Guanidinobutanoic acid were the most abundant compounds. Subsequently, by feeding the MCR-WE to crucian carp (Carassius auratus) and challenging them with Aeromonas veronii, it was found that the MCR-WE enhanced the activities of immune factors (AKP, ACP, LZM) and the phagocytic activity of leukocytes (p < 0.05). Furthermore, the MCR-WE improved the survival rate of crucian carp (p < 0.05), reduced the bacterial load in the kidneys (p < 0.05), decreased the mRNA expression of inflammatory factors (IL-6, IL-1β, TNF-α), and lowered the expression levels of antioxidant-related factors (CAT, GSH-Px, SOD, MDA) and the mRNAs of oxidative stress pathway factors (Nrf2, HO-1, Keap1) (p < 0.05). Histopathological sections and immunofluorescence assays showed that the MCR-WE maintained the structural integrity of internal organs and reduced renal cell apoptosis and DNA damage. Therefore, MCR-WE is rich in immunologically active substances, can activate the immune response of crucian carp, reduce fish mortality, exert anti-inflammatory and antioxidant activities, and maintain the structural and functional integrity of internal organs. Thus, the MCR-WE holds promise as a therapeutic agent against A. veronii infection in fish.
Transepithelial photorefractive keratectomy (Trans-PRK) offers superior re-epithelialization and visual recovery. This study evaluates the impact of preoperative refractive status on clinical outcomes and identifies prognostic factors across varying myopic severities. This retrospective observational study included 125 eyes [64 patients; age > 20 years; best-corrected visual acuity (BCVA) ≥ 20/25] that underwent Trans-PRK between March and December 2022. Patients were stratified into low myopia (LM: > −5.0 D), moderate-to-high myopia (MHM: −5.0 D to −8.0 D), and extremely high myopia (EHM: ≤ −8.0 D) groups. Analysis focused on preoperative refraction, intraoperative parameters, postoperative uncorrected visual acuity (UCVA), and corneal conditions of superficial punctate keratitis (SPKs) and haze. The mean age was 30.20 ± 6.34 years, with a mean initial manifest sphere (MS) of −6.42 ± 2.27 diopter (D) overall and −3.73 ± 0.15 D, −6.28 ± 0.13 D, and −9.17 ± 0.15 D in the LM, MHM, and EHM groups, respectively. At a mean follow-up of 6.69 ± 3.73 months, the overall mean final manifest spherical equivalent (MSE) was −0.12 ± 0.73 D, and the mean final UCVA was 0.01 [Snellen equivalent (SE), 205/200] ± 0.08 logMAR. Predictability was 94.4%, 88.88%, and 94.3% for the final MS ≤ −1.0 D, final MSE ≤ −1.0 D, and UCVA 0.8, respectively. In the LM and MHM groups, cycloplegic and subjective refractions showed the highest concordance with emmetropia, whereas initial manifest refractions were most accurate for the EHM group. Corneal SPK incidence declined from 32.2% (1 month) to 1.6% (6 months), primarily localized to EHM eyes. Corneal haze peaked at 28.2% at three months before receding to 9.4% by 6 months. Refractive and visual stability were achieved by the third month for the LM and MHM groups, whereas the EHM group (mean MSE: −9.59 ± 0.15 D) required six months to reach both refractive and visual plateaus. Despite transiently higher rates of corneal SPKs and haze in EHM eyes, final visual outcomes remained excellent, achieving a mean UCVA of 18/20.
