BackgroundThe middle school stage represents a crucial period for the development of borderline personality features. Negative parenting styles and emotional regulation strategies are associated with the formation of borderline personality features. However， the moderating role of emotional regulation strategies between negative parenting styles and borderline personality features among middle school students remains unclear. ObjectiveTo explore the moderating influence of emotional regulation strategies in the relationship between negative parenting styles and borderline personality features among middle school students， and to provide references for the intervention of borderline personality features. MethodsIn October 2023， a total of 5 965 middle school students from three middle schools in Nanning， Guangxi Zhuang Autonomous Region were selected by cluster sampling， and assessed by the Borderline Personality Features Scale for Children （BPFS-C）， the Egna Minnen Barndoms Uppfostran （EMBU）， and the Emotion Regulation Questionnaire-Chinese Revised Version （ERQ-CRV）. Pearson correlation analysis was used to test the correlation between the scores of each scale， and the model 1 of the Process macro program was used to conduct the moderating effect test. ResultsA total of 5 572 middle school students （93.41%） completed this study， and 1 388 of them （24.91%） were identified as having high borderline personality features. The BPFS-C score of middle school students was positively correlated with the score of the negative parenting style dimension of EMBU （r=0.367， P<0.01）， negatively correlated with the score of the cognitive reappraisal dimension of ERQ-CRV （r=-0.168， P<0.01）， and positively correlated with the score of the expression inhibition dimension of ERQ-CRV （r=0.344， P<0.01）. Cognitive reappraisal played a negative moderating effect between negative parenting styles and borderline personality features （β=-0.072， 95% CI： -0.104–-0.041， P<0.01）， while expressive suppression played a positive moderating effect （β=0.076， 95% CI： 0.055–0.097， P<0.01）. ConclusionCognitive reappraisal strategy may help mitigate the negative influence of negative parenting styles on middle school students' borderline personality features， while expressive suppression may exacerbate the harm of negative parenting styles to the borderline personality features of middle school students.

Objective To investigate the protective effect and underlying mechanism of human umbilical cord mesenchymal stem cell-derived exosomes (hucMSC-Exo) on renal ischemia-reperfusion injury (IRI). Methods hucMSC-Exos were isolated and characterized. A mouse renal IRI model was established and the animals were divided into Sham, IRI, IRI+hucMSC-Exo, IRI+hucMSC-Exo+JY-2 and Sham+JY-2 groups. Serum creatinine (Scr) and blood urea nitrogen (BUN) were measured. Hematoxylin-eosin (HE) staining was used to evaluate renal histopathology. Enzyme-linked immune absorbent assay was performed to determine serum interleukin (IL)-1β and IL-18 levels. Western blotting was used to detect the expression of activating transcription factor 3 (ATF3), Toll-like receptor 4 (TLR4), nuclear factor (NF)-κB, NOD-like receptor protein 3 (NLRP3), cysteineyl aspartate specific proteinase (Caspase)-1 p20 and Gasdermin D(GSDMD). Real-time fluorescent quantitative polymerase chain reaction was employed to measure ATF3, TLR4 and NF-κB messenger RNA (mRNA). Immunohistochemistry was conducted to examine NLRP3, Caspase-1 p20 and GSDMD. An in vitro hypoxia/reoxygenation (H/R) model was established in HK-2 cells and divided into Control, H/R, H/R+hucMSC-Exo, H/R+hucMSC-Exo+JY-2 and Control+JY-2 groups. Western blotting was used to detect the expression of ATF3, TLR4 and NF-κB. Real-time fluorescent quantitative polymerase chain reaction was used to measure NLRP3, GSDMD and Caspase-1 mRNA. Results HucMSC-Exos were successfully isolated and identified. Compared with the Sham group, the IRI group exhibited elevated Scr and BUN, higher tubular injury scores, increased protein expression levels of ATF3, TLR4, NF-κB p65, NLRP3, Caspase-1 p20 and GSDMD, and raised mRNA expression levels of ATF3, TLR4, NF-κB. Compared with the IRI group, the IRI+hucMSC-Exo group showed decreased Scr and BUN, lower tubular injury scores, up-regulated ATF3 protein and mRNA, down-regulated TLR4, NF-κB p65, NLRP3, Caspase-1 p20 and GSDMD protein, and declined TLR4 and NF-κB mRNA. Compared with the IRI+hucMSC-Exo group, the IRI+hucMSC-Exo+JY-2 group exhibited increased Scr and BUN levels, elevated renal tubular injury scores, decreased ATF3 protein expression levels, elevated protein expression levels of TLR4, NF-κB p65, NLRP3, Caspase-1 p20, and GSDMD, decreased ATF3 mRNA expression levels, and elevated mRNA expression levels of TLR4 and NF-κB. (all P < 0.05). Compared with the Control group, the expression levels of ATF3, TLR4 and NF-κB p65 proteins were increased in the H/R group, and the expression levels of NLRP3, Caspase-1 and GSDMD mRNA were increased. Compared with the H/R group, the expression level of ATF3 protein was increased, the expression levels of TLR4 and NF-κB p65 proteins were decreased, and the expression levels of NLRP3, Caspase-1 and GSDMD mRNA were decreased in the H/R+hucMSC-Exo group. Compared with the H/R+hucMSC-Exo group, the expression level of ATF3 protein was decreased, the expression levels of TLR4 and NF-κB p65 proteins were increased, and the expression levels of NLRP3, Caspase-1 and GSDMD mRNA were increased in the H/R+hucMSC-Exo+JY-2 group (all P < 0.05). Conclusions HucMSC-Exos alleviate renal IRI by up-regulating ATF3, thereby negatively regulating the TLR4/NF-κB signaling pathway and subsequently inhibiting pyroptosis.

Objective: To evaluate the effects of green tea extract (GTE) and its main catechin monomers on erythrocyte lesion (such as hemolysis, decreased energy metabolism and oxidative stress) during in vitro storage, and to explore its potential as a novel additive for erythrocyte preservation solutions. Methods: The composition of GTE was analyzed by high-performance liquid chromatography (HPLC). Using an in vitro simulated storage model, erythrocytes were stored in CPDA-1 preservation solution supplemented with GTE and the three most abundant catechin monomers (EGCG, ECG, EGC) for 60 days. Hemolysis rate and ATP content were dynamically monitored during storage. Flow cytometry was used to analyze phosphatidylserine (PS) exposure. Meanwhile, the protective effects of each component were verified in an acute oxidative stress model, and erythrocyte membrane stability was assessed by osmotic fragility test. Results: After 60 days of storage at 4℃, the hemolysis rate at the end of storage in the GTE group was <0.8%, which was superior to that in the control group and the single catechin-supplemented groups. Erythrocyte osmotic fragility assay showed that GTE could enhance the stability of erythrocyte membranes. In the acute oxidative stress experiment, the protective rate of GTE against erythrocyte injury exceeded 99%, which was better than that of the single catechin groups. At the initial stage of storage, ATP content decreased in all catechin-treated groups, but PS exposure was not significantly increased. Conclusion: The addition of GTE can effectively alleviate storage lesions of erythrocytes, with efficacy superior to that of single catechins. GTE enhances the antioxidant capacity and membrane stability of stored erythrocytes. Our results provide new experimental evidence for the development of GTE-based erythrocyte preservation additives.

[This corrects the article DOI: 10.1016/j.apsb.2022.05.019.].

OBJECTIVES: To analyze the differentially expressed exosomal miRNAs in patients with chronic heart failure (CHF) complicated by hyperuricemia (HUA) and explore their potential as novel diagnostic molecular markers and their target genes. METHODS: This study was conducted among 30 CHF patients with HUA (observation group) and 30 healthy volunteers (control group) enrolled between September, 2020 and September, 2023. Peripheral blood samples were collected from 6 CHF patients with HUA for analyzing exosomal miRNAs by high-throughput sequencing, and the results were validated in the remaining 24 patients using qRT-PCR. GO and KEGG enrichment analyses were performed to predict the the target genes of the identified differential miRNAs. We also validated the differentially expressed miRNAs by animal experiment. RESULTS: A total of 42 differentially expressed exosomal miRNAs were detected in observation group by high-throughput sequencing; among them, miR-27a-5p was significantly upregulated (P=0.000179), and miR-139-3p was significantly downregulated (P=0.000058). In the 24 patients with both CHF and PUA, qRT-PCR validated significant upregulation of miR-27a-5p (P=0.004) and downregulation of miR-139-3p (P=0.005) in serum exosomes. When combined, miR-27a-5p and miR-139-3p had a maximum area under the curve (AUC) of 0.899 (95% CI: 0812-0.987) for predicting CHF complicated by HUA. GO and KEGG enrichment analyses suggested that the differential expressions of miR-27a-5p and miR-139-3p was associated with the activation of the AMPK-mTOR signaling pathway to activate the autophagic response. We obtained the same conclusion from animal experiment. CONCLUSIONS Upregulated exosomal miR-27a-5p combined with downregulated exosomal miR-139-3p expression can serve as a novel molecular marker for diagnosis of CHF complicated by HUA, and their differential expression may promote autophagy in cardiomyocytes by activating the AMPK-mTOR signaling pathway.
Humans ; Hyperuricemia/diagnosis* ; Heart Failure/genetics* ; MicroRNAs/metabolism* ; Exosomes/metabolism* ; Chronic Disease ; Male ; Female ; Middle Aged ; Animals

OBJECTIVES: To explore the effects of cannabidiol on endoplasmic reticulum stress and neuronal apoptosis in rats with multiple concussions (MCC). METHODS: SD rats were randomized into sham group, MCC group, 1% tween20 (TW) treatment group, and low-dose (10 mg/kg) and high-dose (40 mg/kg) cannabidiol treatment groups. In all but the sham group, MCC models were established using a metal pendulum percussion device, after which the rats received daily intraperitoneal injections of the corresponding agents for 2 weeks. The expressions of PERK, eIF2α, ATF4, CHOP, TRIB3, p-Akt and pro-caspase-3 in the brain tissue of the rats were detected with qRT-PCR, Western blotting and immunofluorescence staining. The core targets of cannabidiol in treatment of traumatic brain injury (TBI) were identified by network pharmacology analysis, and molecular docking was carried out to simulate the interaction of cannabidiol with the factors related to endoplasmic reticulum stress and apoptosis. RESULTS: Compared with the sham-operated rats, the rat models of MCC showed significantly increased mRNA expressions of PERK, eIF2α and CHOP and protein expressions of PERK, eIF2α, ATF4, CHOP, TRIB3, p-AKT and pro-caspase-3 in the cerebral cortex. CBD treatment, especially at the high dose, obviously increased the expression of p-Akt and lowered the expression levels of the other factors tested in the rat models. Network pharmacology analysis indicated interactions of the core targets of CBD with the factors related to endoplasmic reticulum stress and TBI, and molecular docking study showed a high binding energy of CBD with multiple factors pertaining to endoplasmic reticulum stress and apoptosis. CONCLUSIONS MCC induce endoplasmic reticulum stress and apoptosis in rat brain tissues, for which CBD, especially at a high dose, provides neuroprotective effects by inhibiting endoplasmic reticulum stress and cell apoptosis.
Animals ; Endoplasmic Reticulum Stress/drug effects* ; Apoptosis/drug effects* ; Rats, Sprague-Dawley ; Activating Transcription Factor 4/metabolism* ; Transcription Factor CHOP/metabolism* ; Rats ; Eukaryotic Initiation Factor-2/metabolism* ; Signal Transduction/drug effects* ; eIF-2 Kinase/metabolism* ; Cannabidiol/pharmacology* ; Neurons/metabolism* ; Brain Concussion/metabolism* ; Male ; Molecular Docking Simulation

Ursodeoxycholic acid (UDCA) is a naturally occurring, low-toxicity, and hydrophilic bile acid (BA) in the human body that is converted by intestinal flora using primary BA. Solute carrier family 7 member 11 (SLC7A11) functions to uptake extracellular cystine in exchange for glutamate, and is highly expressed in a variety of human cancers. Retroperitoneal liposarcoma (RLPS) refers to liposarcoma originating from the retroperitoneal area. Lipidomics analysis revealed that UDCA was one of the most significantly downregulated metabolites in sera of RLPS patients compared with healthy subjects. The augmentation of UDCA concentration (≥25 μg/mL) demonstrated a suppressive effect on the proliferation of liposarcoma cells. [¹⁵N₂]-cystine and [¹³C₅]-glutamine isotope tracing revealed that UDCA impairs cystine uptake and glutathione (GSH) synthesis. Mechanistically, UDCA binds to the cystine transporter SLC7A11 to inhibit cystine uptake and impair GSH de novo synthesis, leading to reactive oxygen species (ROS) accumulation and mitochondrial oxidative damage. Furthermore, UDCA can promote the anti-cancer effects of ferroptosis inducers (Erastin, RSL3), the murine double minute 2 (MDM2) inhibitors (Nutlin 3a, RG7112), cyclin dependent kinase 4 (CDK4) inhibitor (Abemaciclib), and glutaminase inhibitor (CB839). Together, UDCA functions as a cystine exchange factor that binds to SLC7A11 for antitumor activity, and SLC7A11 is not only a new transporter for BA but also a clinically applicable target for UDCA. More importantly, in combination with other antitumor chemotherapy or physiotherapy treatments, UDCA may provide effective and promising treatment strategies for RLPS or other types of tumors in a ROS-dependent manner.

Ursodeoxycholic acid(UDCA)is a naturally occurring,low-toxicity,and hydrophilic bile acid(BA)in the human body that is converted by intestinal flora using primary BA.Solute carrier family 7 member 11(SLC7A11)functions to uptake extracellular cystine in exchange for glutamate,and is highly expressed in a variety of human cancers.Retroperitoneal liposarcoma(RLPS)refers to liposarcoma originating from the retroperitoneal area.Lipidomics analysis revealed that UDCA was one of the most significantly down-regulated metabolites in sera of RIPS patients compared with healthy subjects.The augmentation of UDCA concentration(≥25 μg/mL)demonstrated a suppressive effect on the proliferation of liposarcoma cells.[15N2]-cystine and[13Cs]-glutamine isotope tracing revealed that UDCA impairs cystine uptake and glutathione(GSH)synthesis.Mechanistically,UDCA binds to the cystine transporter SLC7A11 to inhibit cystine uptake and impair GSH de novo synthesis,leading to reactive oxygen species(ROS)accumulation and mitochondrial oxidative damage.Furthermore,UDCA can promote the anti-cancer effects of ferroptosis inducers(Erastin,RSL3),the murine double minute 2(MDM2)inhibitors(Nutlin 3a,RG7112),cyclin dependent kinase 4(CDK4)inhibitor(Abemaciclib),and glutaminase inhibitor(CB839).Together,UDCA functions as a cystine exchange factor that binds to SLC7A11 for antitumor activity,and SLC7A11 is not only a new transporter for BA but also a clinically applicable target for UDCA.More importantly,in combination with other antitumor chemotherapy or physiotherapy treatments,UDCA may provide effective and promising treatment strategies for RLPS or other types of tumors in a ROS-dependent manner.

AIM:To determine if scutellarin(Scu)provides neuroprotection by reducing neuronal apoptosis in rats subjected to middle cerebral artery occlusion(MCAO)via the inhibition of the JAK2/STAT3 signalling pathway.METHODS:Proteins linked to Scu and ischaemic stroke-induced neuronal apoptosis were identified using the Swiss Tar-get Prediction,PharmMapper,OMIM,and GeneCards databases.Intersecting targets were identified through Venn analy-sis.Protein-protein interaction networks were visualised utilising Cytoscape software,and principal targets were identi-fied.Enrichment analyses of GO functions and KEGG pathways were conducted utilising the Metascape database.Molecu-lar docking of Scu with core targets was performed utilising AutoDock Vina.The neuroprotective effects of Scu were as-sessed in MCAO rats using Zea Longa scoring and the suspension test.JAK2/STAT3 phosphorylation levels and apoptosis-related proteins[cleaved caspase-3(C-caspase-3),caspase-3,Bax,and Bcl-2]were assessed using Western blot and im-munofluorescence staining.The JAK2-specific inhibitor AG490 was employed to further investigate the role of the JAK2/STAT3 signaling pathway.RESULTS:Network pharmacology analysis revealed 832 shared targets,with pathways en-riched in tumor-associated pathways,the JAK/STAT signalling pathway,and the HIF-1 signalling pathway.Molecular docking revealed robust binding affinities of Scu with the ten principal targets.Behavioural assessments utilising Zea Lon-ga scoring and the suspension test demonstrated that Scu markedly enhanced neurological recovery in MCAO rats.Western blot and immunofluorescence analyses demonstrated that phosphorylation levels of JAK2 and STAT3,along with the ex-pression of C-caspase-3,Bax,and Bcl-2,were markedly elevated in the MCAO group relative to the sham group(P<0.05).Post Scu treatment,phosphorylation levels of JAK2 and STAT3,along with C-caspase-3 and Bax expression,were markedly diminished,whereas Bcl-2 expression and fluorescence intensity were substantially increased(P<0.05).In the combined AG490 and Scu treatment group(MCAO+Scu+AG490),the phosphorylation levels of JAK2 and STAT3,as well as the expression of C-caspase-3 and Bax,exhibited no significant difference when compared to the Scu-alone group(P>0.05).Bcl-2 expression and fluorescence intensity were markedly reduced in the combined AG490 and Scu treatment group relative to the Scu-alone group(P<0.05).CONCLUSION:Scu seems to provide neuroprotection in ischaemic stroke by reducing neuronal apoptosis through the inhibition of the JAK2/STAT3 signalling pathway.

Objective:To evaluate the accuracy of a self-developed extraoral scanning system based on photogrammetry technology, and to provide evidence for advancing the development and clinical application evaluation of domestically produced scanning devices.Methods:This research group developed a photogrammetry-based implant extraoral scanning system with customized scan bodies. Two distinct edentulous implant resin models were designed and three-dimensional (3D)-printed by Center of Digital Dentistry, Peking University School and Hospital of Stomatology, containing 6 (Model 1) and 8 (Model 2) abutment analogs respectively. Reference data acquisition was performed using a high-precision denture 3D scanner with scan caps mounted on the analogs. Specialized scan bodies were then mounted on the analogs for 3D positional data acquisition using both the self-developed system (experimental group) and the clinically established system (control group). Each system conducted 10 repeated scans per model. Trueness was assessed through root mean square error (RMSE), linear deviation (LD), and angular deviation (AD) relative to reference data, while precision was determined through intra-group RMSE analysis. Systematic comparisons included inter-group performance on identical models and intra-group variability across different models.Results:For Model 1, the experimental group showed statistically significant advantages over controls in intra-group RMSE [(3.10±0.71) μm vs (4.61±1.51) μm, P<0.001], reference-data RMSE [(21.48±0.60) μm vs (32.50±0.63) μm, P<0.001], linear deviation [23.64 (32.35) μm vs 44.86 (55.73) μm, P<0.001], and angular deviation [0.29° (0.29°) vs 0.23° (0.33°), P<0.001]. In Model 2, significant improvements were observed in intra-group RMSE [(4.47±1.58) μm vs (6.21±2.07) μm, P<0.001], reference-data RMSE [(38.84±0.86) μm vs (43.69±1.34) μm, P<0.001], and linear deviation [37.95 (50.68) μm vs 49.71 (58.89) μm, P<0.001]. Both groups exhibited model-dependent variability, with RMSE of precision and trueness of both groups, linear deviation of experimental group, angular deviation of control group showing statistically significant increases (all P<0.001) corresponding to abutment analog quantity. Conclusions:The self-developed scanning system demonstrates superior accuracy in 3D positional acquisition of abutment analogs compared to the contral group system, with implant number identified as a critical determinant of extraoral scanning accuracy.