Objective: To investigate the ability of different concentrations of piceatannol (PIC) solution to biomodify decalcified dentin matrices in primary teeth, thereby providing a theoretical basis for improving the durability of resin-dentin bonding. Methods: This study was approved by the Medical Ethics Committee of the institution. Molecular docking was performed to predict the interaction effects of PIC with type I collagen and matrix metalloproteinases (MMPs) in dentin. A total of 124 clinically extracted intact primary molars were selected due to retention; of these, 76 were prepared into 60 completely decalcified dentin beams and 24 dentin slices. The 60 beams were equally allocated for dry mass loss and swelling ratio testing (30 beams each). For both experiments, the beams were randomly divided into five groups (n = 6): a control group, 5% glutaraldehyde group, and 2.5, 5, and 10 mg/mL PIC solution groups. This was to evaluate the anti-enzymatic hydrolytic properties and mechanical performance of type I collagen. Of the 24 slices, 15 were assigned to the aforementioned five groups (n = 3) for Fourier-transform infrared spectroscopy (FTIR) to explore the cross-linking mechanism. The remaining nine slices were randomly divided into three groups (n = 3): distilled water group A (SEM examination prior to enzymatic hydrolysis), distilled water group B (SEM examination after enzymatic hydrolysis), and a 10 mg/mL PIC solution group (SEM examination after treatment with 10 mg/mL PIC and subsequent enzymatic hydrolysis). This was to evaluate the cross-linking effect on demineralized dentin collagen. The remaining 48 molars were fabricated into bonding specimens and randomly divided into four groups (n = 12): a control group (distilled water group) and 2.5, 5, and 10 mg/mL PIC groups. Immediate and aged shear bond strength (SBS) were measured, and failure modes were observed under a stereomicroscope to investigate the impact of different PIC concentrations on the bonding durability of primary tooth dentin. Results: Molecular docking revealed strong binding activity between PIC and type I collagen/MMPs via hydrogen bonds, electrostatic potential, and hydrophobic forces; the FTIR results confirmed hydrogen bond formation. In the dry mass loss test, mass loss rates in the 2.5, 5, and 10 mg/mL PIC groups were significantly lower than that in the control group (P < 0.05), with the 10 mg/mL PIC group showing the most optimized cross-linking effect. Swelling tests indicated that all three PIC concentrations reduced the swelling ratio of the demineralized matrix, effectively improving its mechanical properties. SEM showed that collagen from the 10 mg/mL PIC group retained its natural three-dimensional network post-enzymolysis, contrasting sharply with the disintegrated collagen in the enzymolyzed distilled water group B but resembling the morphology of the non-enzymolyzed distilled water group A. SBS results demonstrated that the 10 mg/mL PIC group exhibited significantly higher bond strengths than the control group in both the immediate and aged tests (P < 0.05); immediate SBS in the 10 mg/mL PIC group was also significantly greater than that in the 2.5 mg/mL PIC group (P < 0.05), while no other intergroup differences were found (P > 0.05). Failure mode analysis indicated predominantly mixed fractures, with the proportion of interfacial fractures decreasing as PIC concentration increased compared with the control group. Conclusion A 10 mg/mL PIC solution can effectively cross-link decalcified dentin matrices in primary teeth, enhancing the anti-enzymatic hydrolytic capacity and mechanical properties during clinical operation, thereby promoting bond strength and interface stability, which promises to improve the long-term durability of resin-dentin bonding.

Metabolic associated fatty liver disease (MAFLD) is fundamentally driven by an imbalance in hepatic fatty-acid flux: the influx of fatty acids exceeds the liver’s capacity for disposal, resulting in excessive hepatic lipid accumulation, predominantly in the form of triglycerides (TGs). The occurrence and progression of MAFLD depend on disordered regulation across multiple metabolic steps, including fatty-acid uptake, de novo lipogenesis (DNL), fatty-acid oxidation (FAO), and very low-density lipoprotein (VLDL) export. Forkhead box protein O1 (FOXO1) is a key transcriptional regulator within the hepatic network coordinating glucose and lipid metabolism. Under metabolic stress and insulin resistance (IR), FOXO1 expression is frequently increased, whereas its inhibitory phosphorylation is reduced. These changes enhance FOXO1 nuclear localization and transcriptional activity, thereby reprogramming the expression of genes related to metabolism in the liver. Because hepatic lipid deposition is the central pathological feature of MAFLD, the functional status of FOXO1 directly influences hepatic lipid homeostasis. Growing evidence suggests that FOXO1 can exert bidirectional, environment-dependent effects on hepatic lipid accumulation; however, the molecular basis for this functional switch remains incompletely understood. This review systematically summarizes the biological functions and regulatory mechanisms of FOXO1 and its roles in hepatic lipid metabolism, with a particular focus on its crosstalk with insulin signaling. FOXO1 expression is shaped by RNA modifications and epigenetic regulation mediated by non-coding RNAs. Its transcriptional output is precisely governed by post-translational modifications—such as phosphorylation and acetylation—as well as by coordinated nucleocytoplasmic shuttling. Notably, these regulatory patterns vary markedly across nutritional states, degrees of insulin resistance, and stages of disease. In the fed state, insulin/IGF-1 signaling activates the PI3K-AKT pathway, promoting the inhibitory phosphorylation of FOXO1 and facilitating additional modifications, including acetylation, methylation, and ubiquitination. Together, these events drive FOXO1 export from the nucleus and dampen its transcriptional activity, suppressing gluconeogenesis and constraining lipogenic programs. Conversely, during fasting or when insulin signaling is weakened, FOXO1 inhibition is relieved. FOXO1 accumulates in the nucleus, binds to DNA, and regulates the transcription of downstream target genes. Mechanistically, FOXO1 can aggravate hepatic lipid accumulation by activating genes involved in TG synthesis while repressing FAO-related pathways, thereby favoring storage over oxidation. However, under specific conditions, FOXO1 may also alleviate the hepatic lipid burden by promoting TG hydrolysis and enhancing VLDL secretion, thereby reducing the net hepatic lipid load. In addition, lipotoxic signals mediated by ceramides and diacylglycerols (Cer/DAG) activate atypical protein kinase C (aPKC), further exacerbating the disruption of the AKT-FOXO1 axis. This vicious cycle ultimately produces a metabolic paradox in which increased hepatic glucose output coexists with persistent, insulin-independent lipogenesis, accelerating MAFLD progression. Importantly, FOXO1 regulation is not uniform: during early metabolic overload, insulin-mediated suppression may remain effective, whereas in advanced insulin resistance, the loss of AKT control permits sustained FOXO1 activity. Such stage-dependent dynamics may help explain why FOXO1 can either promote steatosis or, in certain contexts, support programs that facilitate lipid turnover. Accordingly, interventions should be liver-specific and tuned to the disease stage, aiming to curb maladaptive FOXO1 signaling while preserving its capacity to promote triglyceride hydrolysis and VLDL secretion when advantageous. Overall, this review offers an important perspective on MAFLD pathogenesis, emphasizing FOXO1 as a potential therapeutic target and providing a theoretical basis for developing liver-specific, disease-course-dependent precision interventions.

ObjectiveTo analyze the potential risk of infection sources during the consolidation phase of schistosomiasis elimination in Lushan County (a mountainous region) of Sichuan Province, and to provide prevention and control strategies for the consolidation of schistosomiasis elimination achievements in mountainous areas. MethodsIn 2024, one to two villages with historically severe epidemics were selected in the heavily endemic townships of Lushan County as monitoring sites to carry out monitoring for wild animal feces, domestic animals, wild rats, free-roaming dogs, local residents, and mobile populations. Follow-up monitoring for previously infected individuals was carried out in Caoping Village of Siyan Town. Statistical analyses were performed to assess the risks associated with infection sources. ResultsA total of 115 fecal samples from 13 species of wildlife were incubated, with all negative. Blood tests were conducted on 492 cattle, 34 sheep, and 261 dogs, with all negative. A total of 2 520 rodent traps were set, capturing 67 wild rats with a capture rate of 2.66%, and no positive wild rats were found upon dissection. The activity track of 25 loose dogs was 2 212 meters at the farthest, 236 meters at the nearest, and 744 meters on average. a total of 68 wild droppings (all dog feces) were picked up along the way, with all negative. Blood tests were performed on 3 540 local population, yielding 39 blood-positive cases with a blood positive rate of 1.1%. Fecal examinations were conducted on 193 individuals, with all negative. A total of 315 blood tests were performed on the mobile population, identifying 1 positive case with a blood-positive rate of 0.32%. One person received a fecal examination, with zero positive. A follow-up survey of 505 previously infected individuals revealed 5 blood-positive cases, with a positive rate of 0.99%. Fecal examinations were conducted on 15 individuals, with all negative. ConclusionIn this investigation, no local or imported sources of schistosomiasis transmission were found. However, there was a wide variety and a large number of potential sources of infection in the local area. It is necessary to actively explore regional monitoring models for schistosomiasis elimination flexibly adjust prevention and control strategies according to local conditions, achieve precise prevention and control, and consolidate the achievements of elimination.

Background: and Purpose Live cell-based assays (LCBA) are increasingly used for serological antibody detection due to their ability to preserve antigen conformation, offering moderately higher sensitivity than fixed cell-based assays. However, the clinical necessity of prioritizing LCBA for the detection of aquaporin-4 immunoglobulin G (AQP4-IgG) in neuromyelitis optica spectrum disorder (NMOSD) remains unclear, especially when compared to its established role in diagnosing myelin oligodendrocyte glycoprotein antibody-associated disease. Methods: We compared the performance of live cell-based assays using immunofluorescence (LCBA-IF) and fixed cell-based assays using immunofluorescence (FCBA-IF) in detecting AQP4-IgG in 90 cases of NMOSD meeting 2015 International Panel for Neuromyelitis Optica Diagnosis criteria, alongside 40 controls. Additionally, we further investigated the relationship between AQP4-IgG titers as measured by LCBA-IF and FCBA-IF and clinical parameters in NMOSD patients. Results: Results showed 96.9% agreement between LCBA-IF and FCBA-IF (Cohen’s κ=0.935), with a strong Spearman correlation (0.977, p<0.001). Both methods demonstrated 100% specificity, with LCBA-IF showing slightly higher sensitivity compared to FCBA-IF. Within LCBAIF-tested groups, statistically significant differences in annualized relapse rates were observed across all pairwise comparisons (low-titer vs. moderate-titer, low-titer vs. high-titer, and moderate-titer vs. high-titer; all p<0.050). However, this association reached statistical significance in some FCBA-IF-tested groups. Conclusions Overall, there is a strong concordance between LCBA-IF and FCBA-IF in detecting AQP4-IgG, where LCBA-IF shows slightly higher sensitivity. Furthermore, there is a potential link between elevated AQP4-IgG titers and an increased risk of relapse, and this correlation may appear more pronounced when using LCBA-IF.

Background and aims Hepatocellular carcinoma (HCC) cells are metabolically reprogrammed for excessive uptake and metabolism of many nutrients. The tumor suppressive microRNA-148a-3p (miR-148a-3p) is downregulated in HCC, whereas its function in regulating HCC cell metabolism remains obscure. Herein we aimed to delineate the role of miR-148a-3p in HCC cell metabolism by using novel bioengineered miR-148a-3p (BioRNALeu/miR-148a-3p) agent produced in vivo. Methods BioRNALeu/miR-148a-3p was designed by using human leucyl transfer RNA fused hsa-pre-miR-34a carrier, overexpressed in Escherichia coli (E. coli), and purified to high homogeneity. After transfection into HCC cells, the released miR-148a-3p levels were assessed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Cell proliferation was determined by CellTiter-Glo assays. Targets were validated by dual-luciferase reporter assays, immunoblotting, and immunofluorescence confocal imaging. Glycolysis capacity was evaluated by Seahorse XF assays, and glucose, lactate, and amino acid levels were quantified by liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods. Results BioRNALeu/miR-148a-3p was efficiently processed into target miR-148a-3p in HCC cells to effectively inhibit cell proliferation in a dose- and time-dependent manner. Mechanistically, miR-148a-3p suppressed the protein levels of glucose transporter GLUT1/SLC2A1 and L-type amino acid transporter LAT1/SLC7A5 via acting on their 3′-untranslated regions, as well as amino acid transporter ASCT2/SLC1A5. These, in turn, led to a reduction of glucose uptake, lactate production, and glycolytic flux in HCC cells, and alteration of intracellular amino acid metabolome including glutamine, leucine, phenylalanine, tyrosine, and methionine. Conclusions Reintroduction of miR-148a-3p into HCC cells modulates glucose and amino acid metabolism via regulating multiple SLC transporters, thereby suppressing HCC cell viability. These findings highlight the role of miR-148a-3p in HCC cell metabolism and potential of bioengineered miRNA molecules for functional studies and therapeutic development.

Immobilized enzyme-based enzyme electrode biosensors, characterized by high sensitivity and efficiency, strong specificity, and compact size, demonstrate broad application prospects in life science research, disease diagnosis and monitoring, etc. Immobilization of enzyme is a critical step in determining the performance (stability, sensitivity, and reproducibility) of the biosensors. Random immobilization (physical adsorption, covalent cross-linking, etc.) can easily bring about problems, such as decreased enzyme activity and relatively unstable immobilization. Whereas, directional immobilization utilizing amino acid residue mutation, affinity peptide fusion, or nucleotide-specific binding to restrict the orientation of the enzymes provides new possibilities to solve the problems caused by random immobilization. In this paper, the principles, advantages and disadvantages and the application progress of enzyme electrode biosensors of different directional immobilization strategies for enzyme molecular sensing elements by specific amino acids (lysine, histidine, cysteine, unnatural amino acid) with functional groups introduced based on site-specific mutation, affinity peptides (gold binding peptides, carbon binding peptides, carbohydrate binding domains) fused through genetic engineering, and specific binding between nucleotides and target enzymes (proteins) were reviewed, and the application fields, advantages and limitations of various immobilized enzyme interface characterization techniques were discussed, hoping to provide theoretical and technical guidance for the creation of high-performance enzyme sensing elements and the manufacture of enzyme electrode sensors.

Radiation-induced heart disease(RIHD)is a severe complication in patients with thoracic cancer undergoing radiotherapy,with important impacts on long-term survival among cancer survivors.There is an urgent need to investigate the pathogenesis of RIHD and to develop effective therapeutic agents,and the establishment of high-quality RIHD animal models is pivotal to addressing these issues.This review summarizes the critical factors to consider in establishing RIHD animal models,including species selection,radiation type,dosage,fractionation,and target fields,and modeling timeline,along with the evaluation method and success criteria.We also consider the potential pathogenic mechanisms underlying RIHD,including DNA damage,oxidative stress,inflammatory responses,mitochondrial dysfunction,renin-angiotensin-aldosterone system activation,and myocardial fibrosis,as well as their interrelationships.These insights provide a comprehensive reference framework for constructing RIHD animal models and advancing mechanistic investigations into this condition.

Objective To explore the effects of different concentrations of simvastatin on nerve regeneration after sciatic nerve injury.Methods Rats were randomly divided into the normal group,the control group,the low-dose group and the high-dose group,with 3 rats in each group.Except for the normal group,adult rat sciatic nerve crush injury models were established in the other groups.Rats in the normal group and the control group were orally administered with water,while those in the low-dose group and high-dose group were orally administered with 98%simvastatin at dosages of 4 mg/mL and 40 mg/mL,respectively.The sciatic nerve regeneration in rats was evaluated by sciatic function index(SFI),HE staining,luxol fast blue(LFB)staining and immunofluorescence staining,etc.Results The SFI of rats in the high-dose group 7 days and 14 days after surgery were higher than those in the control group(P<0.05);there was no significant difference in SFI of rats between the low-dose group and the control group 7 days and 14 days after surgery(P>0.05).HE staining and LFB staining results showed that compared with the control group,the number of neurons of rats in the high-dose group increased,the nerve fibers and myelin were clearer and denser,and the nerve function was significantly restored;while no significant improvement was observed in the sciatic nerve of rats in the low-dose group.The immunofluorescence staining results showed that compared with the control group,the immunofluorescence intensity in the high-dose group increased,while that in the low-dose group decreased,the differences were statistically significant(P<0.05).Conclusion High-dose simvastatin can promote peripheral nerve regeneration by regulating the expression of M2 macrophages.

Objective To examine the level of sperm flagellar tubulin glycosylation(Gly-Tubulin)in asthenospermia patients(AP)and discuss its significance.Methods According to the principle of inclusion and exclusion criteria,108 patients treated in the Department of Andrology in Xinjiang Uygur Autonomous Region Maternal and Child Health Hospital from June 2021 to May 2022 were rolled in this study.According to the results of semen examine,they were divided into group AP(n=74),and normal control(NC)group(n=34).Colleced the clinical date of both group,such as the age,the sterility period.The levels of sex hormones were detected by chemiluminescence method.The glycosylated Tubulin levels of the sperm were detected by Western blot and immunofluorescence was used for localization analysis,and the relationship between the Gly-Tubulin of sperm flagellar and asthenospermia was analyzed by Multivariate Logistic regression analysis.Results Compared to NC group,the sterility period of group AP was prolong(3.98±0.30 vs 0.78±0.08),the percent of forward sperm motility was decreased(18.55±0.97 vs 46.24±1.89)and the expression level of Gly-Tubulin in the sperm flagellar was decreased(0.64±0.11 vs 1.00±0.00),the differences with statistical significance(t=62.038,χ2=14.394,3.148,all P＜0.05).There were no significant differences in follicle-stimulating hormone(FSH),luteinizing hormone(LH),prolactin(PRL),estradiol(E2),testosterone,semen volume,sperm concentration and total sperm between the two groups(t/χ2=0.043～1.503,all P>0.05).Multivariate Logistic regression analysis showed that the percent of forward sperm motility and the sperm flagellar Gly-Tubulin expression level were independent risk factors for male asthenospermia(Wald χ2=4.406,7.492,P<0.05).Conclusion Abnormal level of Gly Tubulin in sperm flagella may be closely related to the occurrence and development of asthenospermia.

Objective To examine the changing prevalence and antimicrobial resistance profiles of Burkholderia cepacia in 52 hospitals across China from 2015 to 2021.Methods A total of 9 261 strains of B.cepacia were collected from 52 hospitals between January 1,2015 and December 31,2021.Antimicrobial susceptibility of the strains was tested using Kirby-Bauer method or automated antimicrobial susceptibility testing systems according to a unified protocol.The results were interpreted according to the breakpoints released in the Clinical & Laboratory Standards Institute(CLSI)guidelines(2023 edition).Results A total of 9 261 strains of B.cepacia were isolated from all age groups,especially elderly patients.The proportion was 11.1％(1 032 strains)in children,significantly lower than the proportion in adults.About half(46.5％,4 310/9 261)of the strains were isolated from patients at least 60 years old and 42.3％(3 919/9 261)of the strains were isolated from young adults.Most isolates(71.1％)were isolated from sputum and respiratory secretions,followed by urine(10.7％)and blood samples(8.1％).B.cepacia isolates were highly susceptible to the five antimicrobial agents recommended in the CLSI M100 document(33rd edition,2023).B.cepacia isolates showed relatively higher resistance rates to meropenem and levofloxacin.However,the resistance rates to ceftazidime,trimethoprim-sulfamethoxazole,and minocycline remained below 8.1％.The percentage of B.cepacia strains resistant to levofloxacin was the highest compared to other antibiotics in any of the three age groups(from 12.4％in the patients＜18 years old to 20.6％in the patients aged 60 years or older).Conclusions B.cepacia is one of the clinically important non-fermenting gram-negative bacteria.Accurate and timely reporting of antimicrobial susceptibility test results and ongoing antimicrobial resistance surveillance are helpful for rational prescription of antimicrobial agents and proper prevention and control of nosocomial infections.