In the hospital settings, performing clinical trials is an intricate process that is generally hampered by several institutional, technical, and record-keeping challenges. Hence, we evaluated the effectiveness and efficiency of our established integrated clinical trial management system (CTMS) in terms of analyzing core functionalities, assessing integration with existing systems, measuring time, and cost efficiency. Our CTMS (version 10.1, August 2024) is integrated into one of the largest teaching hospitals with the human research audit system, biobank management system, biological sample management system, enterprise resource system service, institutional review, and single sign-on system. The total number of trials, subjects enrolled, products developed, investigators, new drug and indication, devices, and new medical technology are found to be 913, 53969, 851, 159, 784, and 98, respectively, with a total budget of 3539846777 New Taiwan Dollar (approx. 106881045 US$). Our CTMS is efficient in updating data, with improved user interface experience, and controlled access according to the defined policy. Integrating CTMS with other components provides effective tracking and monitoring of the clinical study. Conclusively, our integrated CTMS is designed for comprehensive evaluation and supervision of clinical trials, supporting full-process data management and seamless integration with clinical systems of hospitals through a unified interface. The increasing number of trials, subjects enrolled, products developed, investigators, new drugs and indications, devices, and new medical technology indicates its robustness and efficacy.

In rodents, the whiskers and paws are essential for somatosensory perception, yet their preference for specific textures remains unclear. Here, we examined the preference for rough versus smooth surfaces in rats using a custom open-field paradigm with a water-based motivator to ensure consistent and unbiased movement. We found that rats strongly preferred rough textures with longer interactions and increased dwell time. Notably, this preference persisted in darkness, confirming the tactile, but not visual, influence. These findings highlight the primacy of tactile input in behavioral choices and provide key insights into optimizing rodent environments.

Mechanical hyperalgesia is commonly evaluated using von Frey filaments (vFFs) in the rodent hind paw plantar. However, it is difficult to select the plantar location to stimulate with the vFFs. In the present study, we investigated the effective location of the plantar surface for the evaluation of mechanical hyperalgesia using vFFs in mice treated with paclitaxel (PTX). PTX or vehicle was injected intraperitoneally once daily, 4 times every other day. On Day 14, mechanical hyperalgesia was evaluated using vFFs. The evaluation was performed by stimulation with vFFs on the skin directly under the 3rd and 4th paw pads (base of the index and middle fingers) from closest to the heel on the thumb side, in the central skin surrounded by the pads, and in the plantar skin one-third of the way down from the heel toward the toe. In comparison to vehicle-treated mice, mechanical hyperalgesia was significantly observed in the skin directly under the 3rd and 4th paw pads counted from closest to the heel, and in the plantar skin one-third of the way down from the heel toward the toe. However, this was not significant in the central skin surrounded by the pads. Interestingly, in vehicle-treated mice, the paw withdrawal threshold varied for each location evaluated. In contrast, in PTX-treated mice, the thresholds were similar across all evaluated locations. These results suggest that the selection of the location on the plantar surface to be stimulated is important for pain evaluation using vFFs.

Circadian rhythms regulate essential physiological functions, including body temperature and hormone secretion, in a 24-h cycle. These rhythms are synchronized with environmental cues, primarily light, through the suprachiasmatic nucleus. Disruptions, such as jet lag, misalign internal rhythms with external time, leading to fatigue and insomnia. This study explores the potential of dietary sweetening agents as non-pharmacological interventions to facilitate circadian re-entrainment in a mouse jet lag model. Male C57BL/6 mice, maintained on a 12-h light/dark cycle, underwent a 6-h phase advance to simulate jet lag. Mice received drinking water with or without sweeteners (sucrose, sucralose, xylitol, maltitol), and locomotor activity was assessed using wheel-running behavior and intraperitoneally implanted nanotags measuring 3dimensional acceleration and body temperature. Sucrose and sucralose significantly accelerated re-entrainment, with phase-shifting rates of 0.93 and 1.28 h/d, respectively, compared to 0.76 h/d in controls. Both sweeteners also enhanced post-shift activity, whereas xylitol had a minor effect and maltitol showed no significant impact. Sweeteners did not affect rest duration during the jet lag period. These findings indicate that sweet taste can facilitate circadian adaptation, offering a potential dietary approach to mitigate jet lag symptoms. This study provides insights into how taste perception influences circadian regulation, with implications for managing circadian misalignment in frequent travelers and shift workers.

Small interfering RNAs (siRNAs) hold great therapeutic promise due to their ability to selectively silence disease-associated genes. Although chemically modified siRNAs have demonstrated clinical efficacy, their development remains hindered by challenges such as stability and delivery under physiological conditions. Furthermore, in vitro screening of chemically modified siRNAs using cultured cells is cost-effective but often fails to recapitulate in vivo complexity, limiting predictive accuracy. To address this, we have developed a transfection-free siRNA evaluation platform using Gryllus bimaculatus (Gb), an insect model with natural RNA uptake capacity. We first demonstrated that 21-nucleotide siRNAs induced RNA interference upon abdominal injection under conditions of free uptake. We then generated transgenic lines harboring an EGFP reporter fused to the therapeutic siRNA target sequence and integrated into the β-actin locus via clustered regularly interspaced short palindromic repeats (CRISPR)–CRISPR-associated protein 9-mediated knock-in. Two transgenic strains (s1 and d1) were established and validated. We compared unmodified and chemically modified siRNAs designed using enhanced stabilization chemistry (ESC), a clinically validated modification pattern incorporating 2′-O-methyl, 2′-fluoro, and phosphorothioate modifications. While ESC-modified siRNAs showed reduced activity compared to unmodified natural siRNAs in conventional cell-based assays requiring transfection reagents, they exhibited consistent gene silencing in Gb, reflecting their enhanced biochemical stability under free uptake conditions at picomole-scale doses. These results establish Gb as a scalable, cost-effective, and biologically relevant platform for evaluating therapeutic siRNAs, particularly those incorporating chemical modifications.

This study aimed to clarify the optimal value for the unbound cefmetazole concentration to remain above the minimum inhibitory concentration (MIC) (fT ≥ MIC) for efficacy of de-escalation to cefmetazole in patients with bacteremic urinary tract infection by extended-spectrum β-lactamase-producing Escherichia coli. This double-center retrospective observational study was conducted at Tokyo Bay Urayasu Ichikawa Medical Center and Keio University Hospital from January 2012 to October 2022. Efficacy was determined via clinical evaluation (mortality rate, recurrence rate, vital changes) and bacteriological evaluation, and the optimal fT ≥ MIC was calculated via receiver operating characteristic curve analysis. As a result, the number of patients evaluated were 40 (35 and 5 in the treatment success and treatment failure groups, respectively). Univariate analysis showed that fT ≥ MIC, recurrence rate, and MIC for cefmetazole against bacteria were significantly different for the two groups (p < 0.05). Receiver operating characteristic curve analysis showed that the optimal fT ≥ MIC indicating efficacy was 57% (area under the curve: 0.94, 95% confidence interval: 0.86–1.00, p = 0.002). All patients with fT ≥ MIC ≥ 57% had successful treatment, whereas the frequency of treatment failure was high among those with fT ≥ MIC <57%. The optimal fT ≥ MIC for the clinical efficacy of de-escalation to cefmetazole in patients with bacteremic urinary tract infection by extended-spectrum β-lactamase-producing E. coli was fT ≥ MIC ≥ 57%. This finding would be useful for optimal dosing of cefmetazole.

The central histamine system is involved in several physiological behaviors and neurological disorders, including the sleep–wake cycle, anxiety-related behaviors (both high and low anxiety), and attention deficit hyperactivity disorder (ADHD). Histamine is synthesized from l-histidine by histidine decarboxylase (HDC) and primarily metabolized by histamine-N-methyltransferase (HNMT) in the central nervous system. We previously reported that mice with intermittent sleep deprivation may exhibit impulsive-like symptoms resembling ADHD and low-anxiety behavior. However, the specific role of histaminergic systems in these behaviors remains unclear. In this study, we evaluated HDC expression levels in the hypothalamus as well as the expression of histamine H1 to H4 receptors and HNMT in the hypothalamus and frontal cortex of sleep-deprived mice. Moreover, the effects of administering histidine, a histamine precursor, and inhibitors of each histamine receptor on sleep deprivation-induced low-anxiety and impulsive-like behaviors were examined using an elevated plus maze test. The expressions of HDC and histamine H1 and H3 receptors in the hypothalamus increased, while that of histamine H1 receptors in the frontal cortex of sleep-deprived mice decreased. The low-anxiety and impulsive-like behaviors in intermittent sleep-deprived mice significantly decreased and increased, respectively, following the administration of histamine H1 and H3 receptor blockers and histidine. Collectively, these findings suggest that the low-anxiety behavior and impulsive-like ADHD symptoms induced by intermittent sleep deprivation may result from the overstimulation of histamine H1 and H3 receptors by elevated histamine, together with increased hypothalamic HDC expression. Furthermore, they suggest that sufficient sleep may contribute to ameliorating ADHD symptoms.

Detecting low-frequency genetic mutations is crucial for genetic testing, especially in cancer diagnostics. Wild-type blocking PCR identifies these genetic mutations using a blocking oligonucleotide that is fully complementary to wild-type DNA. The blocking oligonucleotide selectively binds to wild-type DNA, inhibiting its amplification by DNA polymerase and allowing preferential amplification of mutant DNA. Bridged nucleic acids (BNAs), with high binding affinities for cDNA, are often incorporated into the blocking oligonucleotide to enhance inhibition. However, the effects of BNA positioning within the blocking oligonucleotide on wild-type DNA amplification inhibition are poorly understood. To address this issue, we evaluated the effects of different BNA positions on amplification inhibition efficacy by comparing blocking oligonucleotides with varying numbers of BNAs at the 5′ end, 3′ end, and central region. Results indicated that BNAs at the 5′ end enhanced the inhibition efficacy, whereas BNAs at the 3′ end notably diminished the inhibition efficacy. Likewise, increasing the number of BNAs in the central region generally decreased the inhibition efficacy. This is one of the first studies to report the importance of BNA positioning in the amplification inhibition efficacy of blocking oligonucleotides.

Ergothioneine (ERGO) has antioxidant and anti-inflammatory activities in UV-irradiated skin cells in vitro; however, there is no evidence about the effects of dietary ERGO on UV-induced skin damage or ERGO skin distribution in vivo. This study examined the protective effects of ERGO-rich edible mushrooms Pleurotus species against UVB-induced skin damage and the exposure to ERGO in the plasma and skin. Hos : HR-1 hairless mice were fed with or without freeze-dried cross-bred Pleurotus species (PS) or Pleurotus eringii (PE) and were exposed to UVB. Dietary intake of PS or PE significantly alleviated UVB-induced reductions in skin moisture content, increases in transepidermal water loss and oxidative stress markers, and epidermal thickening at plasma ERGO concentrations of 30–40 μM. Additionally, ingestion of PS significantly suppressed UVB-induced expression of pro-inflammatory cytokines. These results suggest that ingesting PS and PE may protect against UVB-induced skin disorders through antioxidant and anti-inflammatory activities at clinically relevant ERGO concentrations. Ingestion of PS and PE led to an increase in epidermal ERGO concentration to levels that were approx. 100 times higher than the ERGO concentration required for significant suppression of UVB-induced intracellular reactive oxygen species in immortalized human keratinocyte HaCaT cells. This suggests that the beneficial effects of PS and PE may be at least partly due to the antioxidant effects of ERGO in murine skin. Overall, ingestion of ERGO-rich Pleurotus species resulted in efficient distribution of ERGO to the skin and protective effects against UVB-induced skin damage, suggesting that these mushrooms may have beneficial effects in humans.

mRNA vaccines have emerged as promising platforms for the prevention of infectious diseases and cancer treatment. The antigenic protein has a signal peptide added to the N-terminus for extracellular secretion. However, it remains unclear whether the optimization of signal peptides has been sufficiently compared and examined for antigen protein secretion and immunogenicity. This study investigated the effects of various signal peptides on the extracellular secretion of a model protein, NanoLuc luciferase (Nluc), in different cell lines. We compared the secretion efficiency of Nluc fused to artificial (#38 and #34) and natural signal peptides (cystatin S, lactotransferrin, and tissue plasminogen activator) in human embryonic kidney 293, C2C12, and HepG2 cells. Luciferase assays and Western blot analysis revealed that the cystatin S signal peptide consistently induced the highest secretion of Nluc among all cell types tested. Notably, the cystatin S signal peptide outperformed previously reported tissue plasminogen activator signal peptides in terms of secretion efficiency. Furthermore, we observed no correlation between Nluc secretion and mRNA expression levels for each signal peptide, suggesting that enhanced secretion was not attributable to increased transcription. Our findings highlight the potential of the cystatin S signal peptide in enhancing the extracellular secretion of antigenic proteins in mRNA vaccines by improving the efficiency of protein translation.

The optimal pharmacokinetics (PK) of orally administered nanoparticles (NPs) varies depending on their application (e.g., drug delivery, adsorbent, and adjuvant). Therefore, engineering NPs to achieve optimal PK is essential for the development of drug designs. Some studies have demonstrated that individual NP factors change the intestinal absorption of NPs; however, no technology has been established to control the biodistribution of orally administered NPs. In this study, a database about the influence of NP characteristics on biodistribution after oral administration was provided. A library of N-isopropylacrylamide polymer NPs with various characteristics that could influence the biodistribution after oral administration, such as size, flexibility, hydrophobicity, surface charges, and surface chemistries, were prepared. NPs with various sizes were synthesized by tuning the surfactant concentration only during synthesis, whereas NPs with different flexibility, hydrophobicity, surface charge, and surface chemistry were synthesized by feeding the corresponding functional monomer. The total amount of NPs accumulated in the organs decreased with increasing NP size, rigidity, hydrophobicity, electric potential (whether positive or negative), and polyethylene glycol modification. The results indicated that the absorption of orally administered NPs can be controlled by optimizing the characteristics of NP such as size, flexibility, hydrophobicity, surface charge, and surface chemistry. The results of this study will provide useful information to design NP formulations.

Selenium (Se) is an essential micronutrient for animals. Various chemical forms of Se exist in nature, each with distinct physiological, nutritional, and toxicological properties. In this study, we aimed to determine whether dimethyldiselenide (DMDSe, a monomethylated Se (MMSe) compound) and dimethylselenide (DMSe, a dimethylated Se compound), known gut bacterial metabolites, could serve as Se sources in rats. DMDSe could be utilized for selenoprotein biosynthesis and was metabolized into urinary selenometabolites. By contrast, DMSe was not utilized for selenoprotein biosynthesis but was further methylated to trimethylselenonium ion (TMSe), one of the urinary Se metabolites. Our findings indicate that dimethylated Se is not readily available as an Se source in rats, unlike MMSe. Selenoprotein biosynthesis requires selenide, an unmethylated form of Se, in the metabolic pathway. Our observations support the hypothesis that demethylation occurs on MMSe as a reversible methylation step but not on dimethylated Se. This suggests that the second methylation step is crucial for inactivating Se and plays a significant role in metabolism to maintain Se homeostasis in animals. Gut microbiota, which can synthesize both DMDSe and DMSe, may contribute to host Se metabolism through methylation processes.

Mineralocorticoid receptor (MR) blockers reduce cardiovascular complications as MRs play a crucial role in cardiovascular regulation. Diabetic cardiovascular complications are caused by vascular endothelial dysfunction. This study used a type 2 diabetic mouse model (DM) to investigate whether esaxerenone (ESAX), an MR blocker, ameliorates vascular endothelial dysfunction. ESAX (3 mg/kg/d) was administered via diet to KK-Ay mice or C57BL/6J mice, a nondiabetic control (Control), for 8 weeks, and metabolic parameters and blood pressure were measured. Vascular responses of the aortic segments were analyzed with acetylcholine, sodium nitroprusside, UK14304, or phenylephrine (PE). The other aortas were used for Western blot analysis. DM mice exhibited higher plasma glucose, insulin, metabolic parameters, and blood pressure levels than those of the Control mice. Parameters that did not include blood pressure were unaltered by DM or ESAX-administered DM (DM + ESAX). However, DM impaired UK14304-induced endothelial-dependent relaxation and nitric oxide production and elevated PE-induced contraction. ESAX administration ameliorated endothelial dysfunction and improved the protein kinase B (Akt) phosphorylation under α₂-agonist UK14304 stimulation in the aorta from DM mice compared with that of the Control mice. However, ESAX did not recover the increased G protein-coupled receptor kinase 2 (GRK2) expression and activity in the DM aorta. Furthermore, the DM-induced phosphorylation of serum and glucocorticoid-regulated kinase 1 (SGK1) was inhibited by ESAX. Overall, ESAX attenuates the development of DM-induced endothelial dysfunction by reducing SGK1 activity and enhancing Akt activity without affecting the GRK2 pathway. These results suggest that the vascular protective effects of ESAX could be employed for diabetic vascular complications.

Elastic fibers, which contribute to the flexibility of tissues such as the skin, alveoli, and arteries, have a long half-life and are not regenerated once formed during the fetal stage. Consequently, the degradation of elastic fibers due to aging or inflammation can significantly impact tissue function. In the dermis, degeneration of elastic fibers is characterized by degradation in photoaging, driven by UV radiation, and structural abnormalities of elastic fibers in intrinsic aging. However, the mechanisms driving the abnormalities associated with intrinsic aging remain incomplete. This study aimed to identify the factors involved in the elastic fiber abnormalities associated with intrinsic aging of the dermis. Through a comprehensive analysis of gene expression, this study focused on microfibril-associated protein 5 (MFAP5) as a candidate gene responsible for the elastic fiber abnormalities associated with intrinsic aging. Immunofluorescence staining revealed that aged fibroblasts highly expressed MFAP5 and strongly localized it to aggregated elastic fibers. Furthermore, the elimination of MFAP5 expression suppressed elastic fiber aggregation. The exogenous addition of MFAP5 induced thickening and disorganization of elastic fibers, effects that were not observed with the overexpression of MFAP5 in young fibroblasts, which merely express MFAP5. Moreover, MFAP5 inhibited the interaction between latent transforming growth factor β binding protein 4 and fibulin-5, which are crucial for elastic fiber formation. These results suggest that excess MFAP5 expression associated with aging causes abnormalities in elastic fibers. Understanding the role of MFAP5 in elastic fiber abnormalities highlights its potential as a therapeutic target for mitigating intrinsic dermal aging and improving skin elasticity.

One of the side effects of calcineurin inhibitors, such as tacrolimus (FK506) and cyclosporin A (CsA), is intestinal mucosal damage leading to ulceration and bleeding. However, it remains to be elucidated whether these side effects are direct effects of calcineurin inhibitors on intestinal epithelial cells (IECs). To determine whether IECs are directly damaged by calcineurin inhibitors, we analyzed the effects of calcineurin inhibitors on the intestinal barrier in Caco-2 cells, a human intestinal cell line. Treatment of Caco-2 with calcineurin inhibitors such as FK506, CsA, and deltamethrin inhibited expression of zonula occludens-1, a tight junction protein, and increased permeability of Lucifer Yellow. These effects were observed in confluent cells, but not clear in subconfluent cells. Our findings suggest that calcineurin inhibitors can directly damage IECs.

Recently, the epidemic types of methicillin-resistant Staphylococcus aureus (MRSA) in hospital and community settings in Japan have changed significantly. Before 2010, approximately 80% of the MRSA strains isolated from hospitals were typical healthcare-associated MRSA (HA-MRSA) with staphylococcal cassette chromosome (SCC) mec type II. However, USA400-like community-associated MRSA (CA-MRSA) with SCCmec type IV (defined as USA400/J) has become dominant in hospitals since 2014. By contrast, skin infections caused by the highly virulent CA-MRSA USA300 clone have increased. The USA300 clone is associated with intractable skin infections and necrotizing pneumonia because it carries a cytolytic pore-forming toxin, Panton–Valentine leukocidin (PVL), and an arginine catabolic mobile element that promotes skin colonization. In the past decade, the USA300 clone has shown limited prevalence and has not been considered a serious problem in Japan. However, the USA300 clone has recently spread in community and hospital settings. This review discusses the evolution and current status of the molecular epidemiological features of HA-MRSA and CA-MRSA strains in Japan.

Antimicrobial resistance (AMR) is a serious global concern. AMR pathogens are found in hospitals and communities. Haemophilus influenzae is a common pathogen associated with community-acquired infections. H. influenzae infections are usually treated with β-lactams, macrolides, and quinolones. However, the drug-resistant strains have emerged. The resistance mechanisms of H. influenzae are complex but are roughly characterized by the acquisition of a mutation in antimicrobial-targeting genes and exogenous resistant genes. Generally, the former cannot be transferred horizontally to a susceptible strain. However, several studies have demonstrated that, in the case of H. influenzae, both the former and the latter can be transferred horizontally. In this review, we provide an overview of the bacterial features and antimicrobial resistance of H. influenzae. We also summarize the unique and ingenious antimicrobial resistance mechanisms used by this pathogen based on the findings of recent studies. These are expected to facilitate the understanding of AMR pathogens in the community and develop strategies to combat infections.

In this study, we investigated (1) the functional role of large-conductance Ca²⁺-activated K⁺ (BK_Ca) channels in the regulation of guinea pig vas deferens smooth muscle (VDSM) contractions and (2) the potential contractile effects of 33 physiologically active substances and related chemicals that have not been previously reported to contract VDSM. Iberiotoxin (an inhibitor of BK_Ca channels, 10^–7 M) was the most potent enhancer of both noradrenaline (10^–5 M)- and ATP (10^–6 M)-induced contractions among the 6 types of K⁺ channel inhibitors. In addition, BK_Ca channel mRNA expression was the highest among the 32 types of K⁺ channel mRNAs. Iberiotoxin also enhanced the contractions induced by acetylcholine (10^–6 M), histamine (5 × 10^–5 M), bradykinin (10^–6 M), neurokinin A (10^–6 M), neurokinin B (10^–6 M), and substance P (10^–6 M). In the 33 tested physiologically active substances and related chemicals (15 peptides, 5 amino acids and their derivatives, 11 prostanoid- and isoprostane-related drugs, 1 endocannabinoid, and 1 phospholipid), we found that 3 bombesin-like peptides, neuromedin B (NMB) (10^–6 M), gastrin-releasing peptide (GRP, 10^–8 M), and NMC (10^–6 M), contracted VDSM in the absence of iberiotoxin, and these contractions were strongly enhanced in the presence of iberiotoxin. Among the 3 bombesin receptor subtypes, the mRNA expression level of Grpr (BB₂ receptor) was the highest. These findings suggest that (1) BK_Ca channels are the most powerful negative regulator of VDSM contractility and (2) NMB, GRP, and NMC are physiologically active substances that contract VDSM.

Vitiligo vulgaris is an acquired disorder that is thought to arise from the suppression of melanin synthesis by melanocytes in the basal epidermal layer. To develop therapeutic agents for vitiligo vulgaris, it is critical to identify compounds that promote melanization. In this study, we established a digital image-based method to quantify melanization that does not require biochemical procedures. B16F10 cells were seeded in a white-bottom 96-well microplate. After treatment with or without α-melanocyte-stimulating hormone, followed by fixation of the cells, digital images of the microplates were captured, and the total signal intensity of each well on the image was measured. The extent of melanization in the cells in each well was defined after the subtraction of the signal from the corresponding blank well. This method was found to quantify melanization more sensitively than the conventional technique that measures the absorbance of cell lysates at UV-A wavelengths. We obtained statistical parameters showing that this method was applicable to a high-throughput screening assay; thus, this method appears to be useful for screening and identifying molecules that suppress or promote melanization, the latter of which may be developed as therapeutic agents for vitiligo vulgaris.

Gestational diabetes mellitus (GDM) is a glucose metabolism abnormality that first emerges during pregnancy and may negatively affect the behavioral and neurodevelopmental outcomes of offspring. Quetiapine (QUE) has been shown to promote differentiation of oligodendrocyte precursor cells (OPCs) and protect oligodendrocytes and myelination. To explore the effects of QUE on improving the expression of conditioned place preference (CPP) and myelination in the infralimbic cortex (IL) of the medial prefrontal cortex in alcohol-exposed GDM offspring mice, we evaluated CPP expression in 5-week-old alcohol-exposed GDM offspring and treated them with QUE and the extracellular-regulated protein kinase (ERK) inhibitor U0126. Immunohistochemical staining compared the numbers of mature oligodendrocytes, OPCs, and myelin expression levels. Immunofluorescence staining was employed to examine OPC differentiation and the activation of the ERK1/2 signaling pathway. In GDM offspring, CPP expression increased considerably following alcohol exposure, whereas early treatment with QUE or U0126 significantly decreased CPP expression. Meanwhile, alcohol exposure resulted in substantial activation of the ERK1/2 signaling pathway within OPCs in the IL region, as well as a substantial reduction in OPC differentiation, mature oligodendrocyte count, and myelin expression. QUE or U0126 inhibited the activation of the ERK1/2 signaling pathway within OPCs in the IL region of alcohol-exposed GDM offspring and markedly restored OPC differentiation, mature oligodendrocyte numbers, and myelin expression. Collectively, QUE enhanced the differentiation of OPCs in the IL region of GDM offspring after alcohol exposure by regulating the overactivation of the ERK1/2 signaling pathway, thus partially reversing myelination loss and ultimately improving CPP expression.