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The metastasis of cancer cells is a principal cause of morbidity and mortality in cancer. The combination of a cytosensor and photothermal therapy (PTT) cannot completely eliminate cancer cells at one time. Hence, this study aimed to design a localized surface plasmonic resonance (LSPR)-based aptasensor for a circuit of cytosensing-PTT (COCP). This was achieved by coating a novel sandwich layer of polydopamine/gold nanoparticles/polydopamine (PDA/AuNPs/PDA) around the Ω-shaped fiber-optic (Ω-FO). The short-wavelength peak of the sandwich layer with strong resonance exhibited a high refractive index sensitivity (RIS). The modification with the T-shaped aptamer endowed FO-LSPR with unique characteristics of time-dependent sensitivity enhancement behavior for a sensitive cytosensor with the lowest limit of detection (LOD) of 13 cells/mL. The long-wavelength resonance peak in the sandwich layer appears in the near-infrared region. Hence, the rate of increased localized temperature of FO-LSPR was 160 and 30-fold higher than that of the bare and PDA-coated FO, indicating strong photothermal conversion efficiency. After considering the localized temperature distribution around the FO under the flow environment, the FO-LSPR-enabled aptasensor killed 77.6% of cancer cells in simulated blood circulation after five cycles of COCP. The FO-LSPR-enabled aptasensor improved the efficiency of the cytosensor and PTT to effectively kill cancer cells, showing significant potential for application in inhibiting cancer metastasis.
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Self-powered photodetectors with bipolar photoresponse characteristics are expected to play a critical role in the field of secure optical communication, artificial neuromorphic systems, and intelligent color sensors. In this work, asymmetric heterojunction devices exhibiting wavelength-dependent bipolar photoresponse with a structure of Glass/FTO/CdSe/Bi2Se3/Au were fabricated. Under a short wavelength light irradiation, the top CdSe absorber generates a high carrier concentration; the excited carriers are quickly separated by the built-in electric field induced by the FTO/CdSe diode, resulting in a negative photocurrent. For light with wavelengths beyond the CdSe absorption edge, it is absorbed by the bottom Bi2Se3 absorber, and a positive photocurrent can be observed. Therefore, based on the bandgap difference between the top CdSe absorber and the bottom Bi2Se3 absorber, combined with the photogenerated carriers separated by asymmetric back-to-back diode, a wavelength-dependent bipolar response is realized. In this work, by employing this structure, the responsivities of -33.3 and 0.3 mA/W were achieved under the illumination of 405 and 830 nm, respectively. This work provides important indications in the preparation and performance optimization for wavelength-dependent bipolar photodetectors.
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Random feature (RF) has been widely used for node consistency in decentralized kernel ridge regression (KRR). Currently, the consistency is guaranteed by imposing constraints on coefficients of features, necessitating that the RFs on different nodes are identical. However, in many applications, data on different nodes vary significantly on the number or distribution, which calls for adaptive and data-dependent methods that generate different RFs. To tackle the essential difficulty, we propose a new decentralized KRR algorithm that pursues consensus on decision functions, which allows great flexibility and well adapts data on nodes. The convergence is rigorously given, and the effectiveness is numerically verified: by capturing the characteristics of the data on each node, while maintaining the same communication costs as other methods, we achieved an average regression accuracy improvement of 25.5% across six real-world datasets.
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Two new carbon skeleton compounds, identified as 2-(1-(3-hydroxy-2,2,6-trimethyl-6-vinyltetrahydro-2H-pyran-3-yl)-2-methylpropoxy)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol named Olerapyran A (1), and (E)-3-(6-acetyl-2-methyl-5-((3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)oxy)cyclooctylidene)butan-2-one named Oleraoctyl (2), were first isolated from Portulaca oleracea L., then their structures were determined using spectroscopic methods, including UHPLC-ESI-QTOF/MS, 1D and 2D NMR. In addition, the activities of Olerapyran A and Oleraoctyl inhibiting nitric oxide (NO) were studied.
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Herein, we show that P-doped Ti3C2Tx MXene nanosheets can effectively catalyze the NO3RR-to-NH3 conversion with a high faradaic efficiency of 95% and a yield rate of 5.39 mg h-1 mgcat.-1. Moreover, the catalyst achieves an impressive high current density of -1200 mA cm-2 at a low potential of -1.51 V, accompanied by an NH3 productivity of 123.5 mg h-1 mgcat.-1. Theoretical calculations further reveal that phosphorous dopants facilitate the adsorption and activation of reactants/intermediates and thus lower the energy barrier.
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Disruption of the extracellular matrix and dysregulation of the balance between Th17 and regulatory T cells are recognized as risk factors for recurrent spontaneous abortion (RSA). However, the interaction between matrix components and the Th17/Treg axis remains poorly elucidated. The result of this study revealed that the absence of type I collagen in the decidua is linked to Th17/Treg imbalance in RSA. Furthermore, we discovered that biomaterial recombinant humanized type I collagen (rhCOLI) promoted T cell differentiation into Tregs by inhibition the Notch1/Hes1 signaling pathway and enhanced the immunosuppressive function of Tregs, as indicated by increased secretion level of IL-10 and TGF-ß. Importantly, this study is the first to demonstrate that rhCOLI can modulate the Th17/Treg imbalance, reduce embryo resorption rates, reshape the immune microenvironment at the maternal-fetal interface, and improve fertility in an RSA mouse model. Collectively, these findings suggest that type I collagen deficiency may contribute to, rather than result from, RSA, and propose a potential intervention for RSA using rhCOLI.
Subject(s)
Collagen Type I , Decidua , Recombinant Proteins , T-Lymphocytes, Regulatory , Th17 Cells , Female , Collagen Type I/metabolism , Animals , Th17 Cells/immunology , Pregnancy , Decidua/immunology , Decidua/metabolism , Mice , Humans , T-Lymphocytes, Regulatory/immunology , Recombinant Proteins/pharmacology , Abortion, Habitual/immunology , Cell Differentiation/drug effectsABSTRACT
The influence of China's "one-child" policy on the mental health of children and adolescents is still unclear. This study examined the associations between number of children and children's mental health using data from the national school children and adolescents survey of China. Mental health was measured using the Achenbach's Child Behavior Checklist (CBCL). Linear regression models were used to explore the relationship between number of children per family and children's mental health. A total of 64,017 students were enrolled, with 68.60â¯% from one-child families. Compared with children from one-child families, those from multiple-children families had significantly higher scores on the total CBLC and each of its subscales (all P<0.001). Analyses suggested children from multiple-child families have a higher risk of mental health problems (total problems on the CBCL: adjusted B=2.217, 95â¯%CI=1.883-2.550, P<0.001). Regular mental health assessments should be implemented and effective interventions should be developed for those in need.
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Electrocatalytic CO2 reduction (ECO2R) has been considered as a promising approach to convert CO2 into valuable chemicals and fuels. CO2 loss in conventional alkaline electrolyzers has been recognized as a major obstacle that compromising the efficiency of the ECO2R system. This review firstly conducts an in-depth assessment of the origin and influence of CO2 loss. On this basis, this work summarizes electrolyzer configurations based on novel material and structure design that are capable of tackling CO2 loss, including acidic electrolyzer, bipolar membrane (BPM) derived electrolyzer, cascade electrolyzer, liquid-phase-anode electrolyzer, and liquid-fed electrolyzer. The design strategies and challenges of these carbon efficient electrolyzers have been deliberated in detail. By comparing and analyzing the advantages and limitations of various electrolyzer designs, this work aims to provide some guidelines for the development of efficient ECO2R technology toward large-scale industrial application.
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PURPOSE: Currently, there is no consensus regarding whether super-elderly (aged > 80 years) patients are suitable candidates for laparoscopic surgery. This study aimed to analyse the short-term outcomes and oncological prognosis of laparoscopic gastrectomy in super-elderly patients with gastric cancer (GC). METHODS: Following PRISMA and AMSTAR-2 guidelines, we searched the Web of Science, Embase, Cochrane Library, and Pubmed databases from inception until May 2024 and performed a meta-analysis. All published studies exploring the surgical outcomes and oncological prognosis of laparoscopic versus open gastrectomy in super-elderly patients with GC were reviewed. Statistical analyses were performed using RevMan 5.3. RESULTS: A total of 1,085 studies were retrieved, eight of which were included in the meta-analysis, comprising 807 patients > 80 years of age with GC. The meta-analysis showed that compared with open gastrectomy, patients with GC > 80 years old who underwent laparoscopic gastrectomy had a longer operative time (weighted mean difference [WMD] = 30.48, p < 0.001), less intraoperative blood loss (WMD = -166.96, P < 0.001), shorter postoperative exhaust time (WMD =-0.83, p < 0.001), shorter length of stay (WMD = -0.78, p < 0.001), fewer overall complications (Odds ratio [OR] = 0.54, p = 0.003), higher 5-year overall survival rate (OR = 1.66, p = 0.03) and disease-specific survival rate (OR = 3.23, p < 0.001). Furthermore, laparoscopic gastrectomy did not significantly affect the number of lymph node dissections, the rate of D2 radical gastrectomy, major postoperative complications, or postoperative pneumonia. CONCLUSIONS: Compared to open gastrectomy, patients with GC aged > 80 years who underwent laparoscopic gastrectomy may have better short-term outcomes. Age should not be a contraindication for minimally invasive surgery.
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BACKGROUND: Chinese giant salamander protein hydrolysates (CGSPH) are beneficial to human health as a result of their high content of amino acids and peptides. However, the formation of bitter peptides in protein hydrolysates (PHs) would hinder their application in food industry. The ultrasound assisted wet-heating Maillard reaction (MR) is an effective way to improve the flavor of PHs. Thus, the effect of ultrasonic assisted wet-heating MR on the structure and flavor of CGSPH was investigated in the present study. RESULTS: The results indicated that the ultrasound assisted wet-heating MR products (MRPs) exhibited a higher degree of graft and more significant changes in the secondary and tertiary structures of CGSPH compared to traditional wet-heating MRPs. Moreover, ultrasound assisted wet-heating MR could significantly increase the content of small molecule peptides and reduce the content of free amino acids of CGSPH, which resulted in more significant changes in flavor characteristics. The changed in flavor properties after MR (especially ultrasound assisted wet-heating MRPs) were mainly manifested by a significant reduction in bitterness, as well as a significant increase in the content of aromatic aldehyde ester compounds such as furan-2-carbaldehyde, butanal, benzaldehyde, furfural, etc. CONCLUSIONS: Ultrasound assisted wet-heating MR between CGSPH and xylose could be a promising way to improve the sensory characteristics of CGSPH. © 2024 Society of Chemical Industry.
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PURPOSE: To summarize the findings of relevant randomized controlled trials (RCTs) and conduct a meta-analysis to investigate the potential effect of aromatase inhibitors on preventing moderate to severe ovarian hyperstimulation syndrome (OHSS) in infertile women undergoing in vitro fertilization (IVF). METHODS: We searched for relevant RCTs in electronic databases, including MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov (from inception to August 2023). In addition, we manually searched the related reviews and reference lists of included studies for further relevant studies. We included RCTs where aromatase inhibitors prescribed either during controlled ovarian stimulation (COS) or in early luteal phase. The meta-analysis was performed using RevMan 5.4.1 software. The primary outcome was the incidence of moderate to severe OHSS. A descriptive analysis was conducted in cases where a meta-analysis was not feasible due to heterogeneity or lack of comparable data. RESULTS: 2858 records were retrieved and 12 RCTs were finally included. Letrozole was administered in the treatment group during COS in seven RCTs, whereas in the early luteal phase in five RCTs. Compared with the control group, the risk of moderate to severe OHSS significantly reduced by 55% in the letrozole group (RR 0.45, 95% CI 0.32 to 0.64, I2 = 0%, 5 RCTs, 494 patients). Moreover, serum estradiol (E2) levels on hCG trigger day significantly decreased with the administration of letrozole during COS (MD -847.23, 95% CI -1398.00 to -296.47, I2 = 93%, 5 RCTs, 374 patients). And serum E2 levels on the 4th, 5th and 7th to 10th day after hCG trigger were also significantly lower than those in the control group when letrozole was administered in the early luteal phase. CONCLUSIONS: Patients with high risk of OHSS probably benefit from letrozole, which has been revealed to reduce the incidence of moderate to severe OHSS by this systematic review. However, the very limited number of participants and the quality of the included studies does not allow to recommend letrozole for the prevention of severe OHSS.
Subject(s)
Aromatase Inhibitors , Fertilization in Vitro , Infertility, Female , Ovarian Hyperstimulation Syndrome , Ovulation Induction , Female , Humans , Pregnancy , Aromatase Inhibitors/administration & dosage , Aromatase Inhibitors/therapeutic use , Fertilization in Vitro/methods , Infertility, Female/prevention & control , Infertility, Female/etiology , Letrozole/therapeutic use , Letrozole/administration & dosage , Ovarian Hyperstimulation Syndrome/prevention & control , Ovarian Hyperstimulation Syndrome/epidemiology , Ovarian Hyperstimulation Syndrome/etiology , Ovulation Induction/methods , Ovulation Induction/adverse effects , Randomized Controlled Trials as TopicABSTRACT
BACKGROUND: Aripiprazole is the most frequently recommended antipsychotic for the treatment of tics in children and adolescents with Tourette's disorder (TD). However, to date, a randomized controlled trial for aripiprazole oral solution has not been conducted despite being widely preferred by children. Therefore, we examined whether aripiprazole oral solution is effective for treating tics. METHODS: All patients received a flexible dose of aripiprazole oral solution (1 mg/mL, range: 2-20 mg) with a starting dose of 2 mg. The target dose for patients weighing < 50 kg was 2, 5, and 10 mg/day, and that for patients weighing ≥ 50 kg was 5, 10, 15, and 20 mg/day. The primary efficacy endpoint was the mean change in the Yale Global Tic Severity Scale-total tic score (YGTSS-TTS) from baseline to week 8. RESULTS: Of the 121 patients enrolled, 59 patients (96.7%) in the aripiprazole group and 53 patients (88.3%) in the placebo group completed the study. The aripiprazole group showed significantly greater improvement in the YGTSS-TTS from baseline to week 8 than the placebo group (least squares mean difference [95% confidence interval (CI)] -5.5 [95% CI - 8.4 to - 2.6]). At week 8, the response rate (i.e., percentage of patients with a Tourette's Syndrome Clinical Global Impression-Improvement score of 1 or 2) of the aripiprazole group (86.4%) was significantly higher than that of the placebo group (56.6%; odds ratio: 3.6, p < 0.001). The incidence of treatment-emergent adverse events (TEAEs) reported in at least one patient was 86.9% in the aripiprazole group and 65.5% in the placebo group. All TEAEs were mild or moderate in severity. No serious adverse events or deaths occurred during the study. CONCLUSIONS: Our findings suggest that aripiprazole oral solution is an effective, well-tolerated, and safe treatment for children and adolescents with TD. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03487783. Registered 4 April 2018.
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BACKGROUND: For patients with rectal cancer, the utilization of temporary ileostomy (TI) has proven effective in minimizing the occurrence of severe complications post-surgery, such as anastomotic leaks; however, some patients are unable to reverse in time or even develop a permanent stoma (PS). We aimed to determine the preoperative predictors associated with TS failure and develop and validate appropriate predictive models to improve patients' quality of life. METHODS: This research included 403 patients with rectal cancer who underwent temporary ileostomies between January 2017 and December 2021. All patients were randomly divided into either the developmental (70%) or validation (30%) group. The independent risk factors for PS were determined using univariate and multivariate logistic regression analyses. Subsequently, a nomogram was constructed, and the prediction probability was estimated by calculating the area under the curve (AUC) using receiver operating characteristic (ROC) analysis. A calibration plot was used to evaluate the nomogram calibration. RESULTS: Of the 403 enrolled patients, 282 were randomized into the developmental group, 121 into the validation group, and 58 (14.39%) had a PS. The development group consisted of 282 patients, of whom 39 (13.81%) had a PS. The validation group consisted of 121 patients, of whom, 19 (15.70%) had a PS; 37 related factors were analyzed in the study. Multivariate logistic regression analysis demonstrated significant associations between the occurrence of PS and various factors in this patient cohort, including tumor location (OR = 6.631, P = 0.005), tumor markers (OR = 2.309, P = 0.035), American Society of Anesthesiologists (ASA) score (OR = 4.784, P = 0.004), T4 stage (OR = 2.880, P = 0.036), lymph node metastasis (OR = 4.566, P = 0.001), and distant metastasis (OR = 4.478, P = 0.036). Furthermore, a preoperative nomogram was constructed based on these data and subsequently validated in an independent validation group. CONCLUSION: We identified six independent preoperative risk factors associated with PS following rectal cancer resection and developed a validated nomogram with an area under the ROC curve of 0.7758, which can assist surgeons in formulating better surgical options, such as colostomy, for patients at high risk of PS.
Subject(s)
Ileostomy , Nomograms , Rectal Neoplasms , Humans , Rectal Neoplasms/surgery , Rectal Neoplasms/pathology , Female , Male , Ileostomy/adverse effects , Retrospective Studies , Middle Aged , Aged , Risk Factors , Surgical Stomas/adverse effects , Quality of Life , ROC Curve , Postoperative Complications/etiology , Postoperative Complications/epidemiology , AdultABSTRACT
This research aimed to devise and assess a mobile game therapy software for children with Attention-Deficit/Hyperactivity Disorder (ADHD), as well as evaluating its suitability and effectiveness in improving the cognitive ability of typically developing children. The study encompassed 55 children diagnosed with ADHD and 55 neurotypical children. Initial assessments involved ADHD-related scales, computerized tests for information processing, and physiological-psychological evaluations. After a 4-week home-based game intervention, participants underwent re-evaluation using baseline measures and provided feedback on treatment satisfaction. Considering the small proportion of study participants who dropped out, data was analyzed using both the Intention-to-Treat (ITT) analysis and the Per-protocol (PP) analysis. The trial was registered at ClinicalTrials.gov (NCT06181747). In ITT analysis, post-intervention analysis using linear mixed models indicated that the ADHD group improved significantly more than the neurotypical group particularly in Continuous Performance Test (CPT) accuracy (B = -23.92, p < 0.001) and reaction time (B = 86.08, p < 0.01), along with enhancements in anti-saccade (B = -10.65, p < 0.05) and delayed-saccade tasks (B = 0.34, p < 0.05). A reduction in parent-rated SNAP-IV scores was also observed (B = 0.43, p < 0.01). In PP analysis, paired-sample t-tests suggested that the ADHD group had significant changes pre- and post-intervention, in terms of CPT Accuracy (t = -7.62, p < 0.01), Anti-saccade task Correct Rate (t = -3.90, p < 0.01) and SNAP-IV scores (t = -4,64, p < 0.01). However, no significant changes post-intervention were observed in the neurotypical group. Survey feedback highlighted a strong interest in the games across both groups, though ADHD participants found the game more challenging. Parents of ADHD children reported perceived benefits and a willingness to continue the game therapy, unlike the neurotypical group's parents. The findings advocated for the integration of serious video games as a complementary tool in ADHD treatment strategies, demonstrating the potential to augment attentional abilities and alleviate clinical symptoms. However, a randomized controlled trial (RCT) is needed to further verify its efficacy.
Subject(s)
Attention Deficit Disorder with Hyperactivity , Feasibility Studies , Video Games , Humans , Attention Deficit Disorder with Hyperactivity/therapy , Attention Deficit Disorder with Hyperactivity/diagnosis , Child , Male , Female , Mobile Applications , Treatment OutcomeABSTRACT
Solid oxide fuel cells utilized with NH3 (NH3-SOFCs) have great potential to be environmentally friendly devices with high efficiency and energy density. The advancement of this technology is hindered by the sluggish kinetics of chemical or electrochemical processes occurring on anodes/catalysts. Extensive efforts have been devoted to developing efficient and durable anode/catalysts in recent decades. Although modifications to the structure, composition, and morphology of anodes or catalysts are effective, the mechanistic understandings of performance improvements or degradations remain incompletely understood. This review informatively commences by summarizing existing reports on the progress of NH3-SOFCs. It subsequently outlines the influence of factors on the performance of NH3-SOFCs. The degradation mechanisms of the cells/systems are also reviewed. Lastly, the persistent challenges in designing highly efficient electrodes/catalysts for low-temperature NH3-SOFCs, and future perspectives derived from SOFCs are discussed. Notably, durability, thermal cycling stability, and power density are identified as crucial indicators for enhancing low-temperature (550 °C or below) NH3-SOFCs. This review aims to offer an updated overview of how catalysts/electrodes affect electrochemical activity and durability, offering critical insights for improving performance and mechanistic understanding, as well as establishing the scientific foundation for the design of electrodes for NH3-SOFCs.
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Introduction: The ligamentum teres hepatis may block the field of vision during totally laparoscopic gastrectomy (TLG), especially in patients with obesity. Aim: We used electrocautery to increase the visual field of TLG by shrinking the ligamentum teres hepatis. This procedure is termed electro-vaporization of the ligamentum teres hepatis (EVLTH). Methods: Patients with body mass index (BMI) ≥24 who underwent total laparoscopic distal gastrectomy (TLDG) or total laparoscopic total gastrectomy (TLTG) between January 2020 and December 2023 were retrospectively enrolled. According to the scope of gastrectomy and whether the patients underwent EVLTH, the patients were divided into the TLDG-EVLTH, TLDG-NEVLTH, TLTG-EVLTH, and TLTG-NEVLTH groups. The clinical characteristics, surgical outcomes, and pathological features were compared between the TLDG-EVLTH and TLDG-NEVLTH groups and the TLTG-EVLTH and TLTG-NEVLTH groups. Results: This study included 65 patients who underwent TLDG (EVLTH: NEVLTH = 29:36) and 32 patients who underwent TLTG (EVLTH:NEVLTH = 15:17). There were no significant differences in clinical characteristics, surgical outcomes, and pathological features between the TLDG-EVLTH and TLDG-NEVLTH groups. However, the operation time in the TLTG-EVLTH group was significantly shorter than that in the TLTG-NEVLTH group, and the difference was statistically significant, although differences in other data were not statistically significant. Conclusions: EVLTH is a simple and safe procedure that reduces the operation time of TLTG in patients who are overweight and enhances the field of vision of TLG.
Subject(s)
Feasibility Studies , Gastrectomy , Laparoscopy , Humans , Gastrectomy/methods , Male , Female , Laparoscopy/methods , Middle Aged , Retrospective Studies , Aged , Electrocoagulation/methods , Stomach Neoplasms/surgery , Operative TimeABSTRACT
Postoperative cognitive dysfunction (POCD) is a neurological complication associated with surgery and anesthesia that is commonly observed in older patients, and it can significantly affect patient prognosis and survival. Therefore, predicting and preventing POCD is important. Regional cerebral oxygen saturation (rSO2) reflects cerebral perfusion and oxygenation, and decreased intraoperative cerebral oxygen saturation has been reported to increase the risk of POCD. In this review, we elucidated the important relationship between the decline in rSO2 and risk of POCD in older patients. We also emphasized the importance of monitoring rSO2 during surgery to predict and prevent adverse perioperative cognitive outcomes. The findings reveal that incorporating intraoperative rSO2 monitoring into clinical practice has potential benefits, such as protecting cognitive function, reducing perioperative adverse outcomes, and ultimately improving the overall quality of life of older adults.
Subject(s)
Cerebrovascular Circulation , Postoperative Cognitive Complications , Humans , Postoperative Cognitive Complications/etiology , Aged , Oxygen Saturation , Brain/metabolism , Quality of Life , Oxygen/metabolism , Oxygen/blood , Cognitive Dysfunction/etiologyABSTRACT
Vascular calcification (VC) increases with age and markedly exacerbates the risk of cardiovascular morbidity and mortality. However, effective pharmaceutical interventions are lacking and the molecular mechanisms linking aging to VC remain elusive. This study explored the role of nuclear factor erythroid 2-related factor 2 (NRF2) in age-associated VC, specifically focusing on vascular smooth muscle cell (VSMC) senescence. Using a chronologically aging mouse model, we noted a significant decline in the expression of NRF2 in the aged mice aortas, coinciding with increased VC. Administering NRF2 activators effectively reduced calcification. By establishing adenine-and vitamin D-induced VC models in VSMC-specific Nrf2 knockout (Nrf2SMCKO) mice, there was an increase in VC with increased VSMC senescence. Aortic rings and primary VSMCs from Nrf2SMCKO mice also showed increased VC under high-phosphate conditions. Furthermore, Nrf2 overexpression inhibited VSMC calcification with decreased VSMC senescence and an osteogenic phenotype, whereas Nrf2 silencing aggravated calcification. Transcriptome RNA-seq analysis of the aortas from Nrf2SMCKO and control mice revealed that inhibitor of DNA binding 2 (Id2) is a core downstream gene of NRF2. Id2 overexpression alleviated NRF2 knockdown-induced VC and VSMC senescence, while silencing Id2 negated the protective effects of NRF2. Moreover, results of a dual luciferase reporter assay indicated that NRF2 promotes the transcriptional activity of the Id2 gene promoter region. This study emphasizes the critical role of age-related NRF2 dysfunction in the nexus between VSMC senescence and VC. The NRF2-ID2 axis in VSMCs has been proposed as a promising therapeutic target for reducing VC and mitigating age-related cardiovascular diseases.
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Electrospun nanofibers have been widely employed in bone tissue engineering for their ability to mimic the micro to nanometer scale network of the native bone extracellular matrix. However, the dense fibrous structure and limited mechanical support of these nanofibers pose challenges for the treatment of critical size bone defects. In this study, we propose a facile approach for creating a three-dimensional scaffold using interconnected electrospun nanofibers containing melatonin (Scaffold@MT). The hypothesis posited that the sponge-like Scaffold@MT could potentially enhance bone regeneration and angiogenesis by modulating mitochondrial energy metabolism. Melatonin-loaded gelatin and poly-lactic-acid nanofibers were fabricated using electrospinning, then fragmented into shorter fibers. The sponge-like Scaffold@MT was created through a process involving homogenization, low-temperature lyophilization, and chemical cross-linking, while maintaining the microstructure of the continuous nanofibers. The incorporation of short nanofibers led to a low release of melatonin and increased Young's modulus of the scaffold. Scaffold@MT demonstrated positive biocompatibility by promoting a 14.2 % increase in cell proliferation. In comparison to the control group, Scaffold@MT significantly enhanced matrix mineralization by 3.2-fold and upregulated the gene expression of osteoblast-specific markers, thereby facilitating osteogenic differentiation of bone marrow mesenchymal stem cells (BMMSCs). Significantly, Scaffold@MT led to a marked enhancement in the mitochondrial energy function of BMMSCs, evidenced by elevated adenosine triphosphate (ATP) production, mitochondrial membrane potential, and protein expression of respiratory chain factors. Furthermore, Scaffold@MT promoted the migration of human umbilical vein endothelial cells (HUVECs) and increased tube formation by 1.3 times compared to the control group, accompanied by an increase in vascular endothelial growth factor (VEGFA) expression. The results of in vivo experiments indicate that the implantation of Scaffold@MT significantly improved vascularized bone regeneration in a distal femur defect in rats. Micro-computed tomography analysis conducted 8 weeks post-surgery revealed that Scaffold@MT led to optimal development of new bone microarchitecture. Histological and immunohistochemical analyses demonstrated that Scaffold@MT facilitated bone matrix deposition and new blood vessel formation at the defect site. Overall, the utilization of melatonin-loaded nanofiber sponges exhibits significant promise as a scaffold that promotes bone growth and angiogenesis, making it a viable option for the repair of critical-sized bone defects.
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OBJECTIVES: To analyze the ability of magnetic resonance (MR) to identify cystic biliary atresia (CBA) and choledochal cyst (CC). METHODS: Infants (≤ 1 year old) who were diagnosed with CBA or CC type I/IV from January 2010 to July 2023 were retrospectively reviewed. Imaging characteristics on MR were compared between the CBA and CC groups. Binary logistic regression and the area under the receiver operating characteristic curve (AUC) were analyzed for the identification of CBA. RESULTS: Sixty-three patients with CBA (median age, 30 days) and 172 patients with CC (median age, 60 days) were included. Gallbladder (GB) wall thickness (cutoff, 1.2 mm) showed 98.4% sensitivity and 100% specificity (AUC, 0.998). MR-triangular cord thickness (MR-TCT) (cutoff, 4.1 mm) showed 100% sensitivity and 95.9% specificity (AUC, 0.986). The bile duct loop visualization showed 96.8% sensitivity and 100% specificity (AUC, 0.984). Proximal bile duct (PBD) diameter (cutoff, 1.3 mm) showed 92.1% sensitivity and 95.3% specificity (AUC, 0.977). Cyst wall thickness (cutoff, 1 mm) showed 77.8% sensitivity and 95.3% specificity (AUC, 0.942). The combination of GB wall thickness > 1.2 mm and MR-TCT > 4.1 mm, GB wall thickness > 1.2 mm and loop visualization, GB wall thickness > 1.2 mm, and cyst wall thickness > 1 mm showed 100% sensitivity and 100% specificity (AUC, 1.000). CONCLUSIONS: Imaging characteristics on MR might be used to identify CBA and CC, and the combination of GB wall thickness and MR-TCT, or loop visualization, or cyst wall thickness, has a perfect diagnostic value. CLINICAL RELEVANCE STATEMENT: Early and accurate differentiation of CBA and CC is essential, but current methods rely on inherently subjective ultrasound. Biliary features on MRI allow for an objective, accurate diagnosis.