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Clarifying the reaction pathways at the solid-water interface and in bulk water solution is of great significance for the design of heterogeneous catalysts for selective oxidation of organic pollutants. However, achieving this goal is daunting because of the intricate interfacial reactions at the catalyst surface. Herein, we unravel the origin of the organic oxidation reactions with metal oxide catalysts, revealing that the radical-based advanced oxidation processes (AOPs) prevail in bulk water but not on the solid catalyst surfaces. We show that such differing reaction pathways widely exist in various chemical oxidation (e.g., high-valent Mn3+ and MnOX) and Fenton and Fenton-like catalytic oxidation (e.g., Fe2+ and FeOCl catalyzing H2O2, Co2+ and Co3O4 catalyzing persulfate) systems. Compared with the radical-based degradation and polymerization pathways of one-electron indirect AOP in homogeneous reactions, the heterogeneous catalysts provide unique surface properties to trigger surface-dependent coupling and polymerization pathways of a two-electron direct oxidative transfer process. These findings provide a fundamental understanding of catalytic organic oxidation processes at the solid-water interface, which could guide the design of heterogeneous nanocatalysts.
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Developing heterogeneous catalysts with atomically dispersed active sites is vital to boost peroxymonosulfate (PMS) activation for Fenton-like activity, but how to controllably adjust the electronic configuration of metal centers to further improve the activation kinetics still remains a great challenge. Herein, we report a systematic investigation into heteroatom-doped engineering for tuning the electronic structure of Cu-N4 sites by integrating electron-deficient boron (B) or electron-rich phosphorus (P) heteroatoms into carbon substrate for PMS activation. The electron-depleted Cu-N4/C-B is found to exhibit the most active oxidation capacity among the prepared Cu-N4 single-atom catalysts, which is at the top rankings of the Cu-based catalysts and is superior to most of the state-of-the-art heterogeneous Fenton-like catalysts. Conversely, the electron-enriched Cu-N4/C-P induces a decrease in PMS activation. Both experimental results and theoretical simulations unravel that the long-range interaction with B atoms decreases the electronic density of Cu active sites and down-shifts the d-band center, and thereby optimizes the adsorption energy for PMS activation. This study provides an approach to finely control the electronic structure of Cu-N4 sites at the atomic level and is expected to guide the design of smart Fenton-like catalysts.
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Electroencephalography (EEG) has demonstrated significant value in diagnosing brain diseases. In particular, brain networks have gained prominence as they offer additional valuable insights by establishing connections between EEG signal channels. While brain connections are typically delineated by channel signal similarity, there lacks a consistent and reliable strategy for ascertaining node characteristics. Conventional node features such as temporal and frequency domain properties of EEG signals prove inadequate for capturing the extensive EEG information. In our investigation, we introduce a novel adaptive method for extracting node features from EEG signals utilizing a distinctive task-induced self-supervised learning technique. By amalgamating these extracted node features with fundamental edge features constructed using Pearson correlation coefficients, we showed that the proposed approach can function as a plug-in module that can be integrated to many common GNN networks (e.g., GCN, GraphSAGE, GAT) as a replacement of node feature selections module. Comprehensive experiments are then conducted to demonstrate the consistently superior performance and high generality of the proposed method over other feature selection methods in various of brain disorder prediction tasks, such as depression, schizophrenia, and Parkinson's disease. Furthermore, compared to other node features, our approach unveils profound spatial patterns through graph pooling and structural learning, shedding light on pivotal brain regions influencing various brain disorder prediction based on derived features.
Subject(s)
Brain Diseases , Electroencephalography , Neural Networks, Computer , Supervised Machine Learning , Humans , Electroencephalography/methods , Brain Diseases/diagnostic imaging , Brain Diseases/physiopathology , Signal Processing, Computer-Assisted , Adult , Brain/diagnostic imaging , Brain/physiopathology , Male , FemaleABSTRACT
The controllable construction of complex metal-organic coordination polymers (CPs) merits untold scientific and technological potential, yet remains a grand challenge of one-step construction and modulating simultaneously valence states of metals and topological morphology. Here, a thiocyanuric acid (TCA)-triggered strategy is presented to one-step rapid synthesis a double-crystalline Prussian blue analogue hetero-superstructure (PBA-hs) that comprises a Co3[Fe(CN)6]2 cube overcoated with a KCo[Fe(CN)6] shell, followed by eight self-assembled small cubes on vertices. Unlike common directing surfactants, TCA not only acts as a trigger for the fast growth of KCo[Fe(CN)6] on the Co3[Fe(CN)6]2 phase resulting in a PBA-on-PBA hetero-superstructure, but also serves as a flange-like bridge between them. By combining experiments with simulations, a deprotonation-induced electron transfer (DIET) mechanism is proposed for formation of second phase in PBA-hs, differing from thermally and photo-induced electron transfer processes. To prove utility, the calcined PBA-hs exhibits enhanced oxygen evolution reaction performance. This work provides a new method to design of novel CPs for enriching chemistry and material science. This work offers a practical approach to design novel CPs for enriching chemistry and material science.
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Folic acid (FA) has been widely engineered to promote the targeted delivery of FA-modified nanoparticles (NPs) by recognizing the folate receptor α (FRα). However, the efficacy of FA-targeted therapy significantly varied with the abundance of FRα and natural immunoglobulin levels in different tumors. Therefore, a sequential therapy of dexamethasone (Dex)-induced FRα amplification and immunosuppression combined with FA-functionalized doxorubicin (DOX) micelles to synergistically suppress tumor proliferation was proposed in this study. In brief, a pH/reduction-responsive FA-functionalized micelle (FCSD) was obtained by grafting FA, derivatization-modified cholesterol, and 2,3-dimethylmaleic anhydride onto a chitosan oligosaccharide. The obtained FCSD/DOX NPs can effectively deliver DOX in tumors, and their targeting efficiency can be further improved with Dex pretreatment to decrease the immunoglobulin M (IgM) content in serum and amplify FRα levels on the surface of M109 cells. After internalization, charge reversal and disulfide bond breakage of FCSD vectors under the stimulation of tumor extracellular pH (pHe) and intracellular glutathione (GSH) would contribute to the disintegration of vectors and the rapid release of DOX. The sequential therapy that combined Dex pretreatment and targeted chemotherapy by FCSD/DOX NPs demonstrated superior tumor suppression compared with monotherapy, which is expected to provide a potential strategy for FRα-positive lung cancer patients.
Subject(s)
Lung Neoplasms , Nanoparticles , Humans , Drug Carriers/chemistry , Lung Neoplasms/drug therapy , Folic Acid/chemistry , Doxorubicin , Micelles , Nanoparticles/chemistry , Dexamethasone , Drug Delivery Systems , Hydrogen-Ion ConcentrationABSTRACT
Overconfidence, a widely observed cognitive bias, has been linked to increased gambling motivations and behaviors. However, previous studies have largely overlooked overconfidence under a social comparison context, known as overplacement, i.e., the tendency of individuals to believe that they are better than their similar peers. In the present study, we tested the effect of overplacement on gambling motivations and behaviors though a Pilot Survey of Chinese college students (N = 129) and a Field Survey of Chinese Macao casino gamblers (N = 733). Our results revealed a double-edged sword effect of overplacement: Serving as a risk factor, evaluating one self's earning ability as higher than others was linked to more gambling motivations (ß = 0.18, p = .005) and frequency (ß = 0.18, p = .004); Serving as a protective factor, evaluating oneself as happier than others was linked to less gambling motivations (ß = - 0.32, p < .001) and problem behaviors (ß = - 0.26, p < .001). These findings expand the relationship between overconfidence and gambling from a cognitive bias perspective to a social comparison perspective. Our study not only revealed a typical profile of gambling motivations and behaviors among different demographic groups in Chinese casino gamblers, but also highlighted the importance of considering social factors in the study of the psychological mechanisms of gambling.
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PURPOSE: This paper explores the causes of paediatric inguinal hernia (PIH) recurrence after single-port laparoscopic percutaneous extraperitoneal closure (SPLPEC). METHOD: From January 2015 to December 2020, the clinical data of 3480 children with PIHs who underwent SPLPEC were retrospectively reviewed, including 644 children who underwent SPLPEC with a homemade single-hook hernia needle from January 2015 to December 2016 and 2836 children who underwent the SPLPEC with a double-hook hernia needle and hydrodissection from January 2017 to December 2020. There were 39 recurrences (including communicating hydrocele) during the 2-5 years of follow-up. The findings of redo-laparoscopy were recorded and correlated with the revised video of the first operation to analyse the causes of recurrence. RESULT: Thirty-three males and 6 females experienced recurrence, and 8 patients had a unilateral communicating hydrocele. The median time to recurrence was 7.1 months (0-38). There were 20 cases (3.11%) in the single-hook group and 19 cases (0.67%) in the double-hook group. Based on laparoscopic findings, recurrence most probably resulted from multiple factors, including uneven tension of the ligation (10 cases), missing part of the peritoneum (14 cases), loose ligation (8 cases), broken knot (5 cases), and knot reaction (2 cases). All children who underwent repeat SPLPEC were cured by double ligations or reinforcement with medial umbilical ligament. CONCLUSION: The main cause of recurrence is improper ligation. Tension-free and complete PIH ligation are critical to the success of surgery, which requires avoiding the peritoneum skip area and the subcutaneous and muscular tissues. Redo-laparoscopic surgery was suitable for the treatment of recurrent inguinal hernia (RIH). For giant hernias, direct ligation of the internal ring incorporating the medial umbilical ligament (DIRIM) may be needed.
Subject(s)
Hernia, Inguinal , Laparoscopy , Testicular Hydrocele , Male , Female , Child , Humans , Infant , Hernia, Inguinal/etiology , Hernia, Inguinal/surgery , Retrospective Studies , Treatment Outcome , Herniorrhaphy/methods , Laparoscopy/methods , Testicular Hydrocele/surgery , RecurrenceABSTRACT
BACKGROUND: Accurately identifying patients with axillary pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) in breast cancer patients remains challenging. PURPOSE: To compare the feasibility of shear wave elastography (SWE) performed on breast tumors and axillary lymph nodes (LNs) in predicting the axillary status after NAC. MATERIALS AND METHODS: This prospective study included a total of 319 breast cancer patients with biopsy-proven positive node who received NAC followed by axillary lymph node dissection from 2019 to 2022. The correlations between shear wave velocity (SWV) and pathologic characteristics were analyzed separately for both breast tumors and LNs after NAC. We compared the performance of SWV between breast tumors and LNs in predicting the axillary status after NAC. Additionally, we evaluated the performance of the most significantly correlated pathologic characteristic in breast tumors and LNs to investigate the pathologic evidence supporting the use of breast or axilla SWE. RESULTS: Axillary pCR was achieved in 51.41% of patients with node-positive breast cancer. In breast tumors, there is a stronger correlation between SWV and collagen volume fraction (CVF) (r = 0.52, p < 0.001) compared to tumor cell density (TCD) (r = 0.37, p < 0.001). In axillary LNs, SWV was weakly correlated with CVF (r = 0.31, p = 0.177) and TCD (r = 0.29, p = 0.213). No significant correlation was found between SWV and necrosis proportion in breast tumors or axillary LNs. The predictive performances of both SWV and CVF for axillary pCR were found to be superior in breast tumors (AUC = 0.87 and 0.85, respectively) compared to axillary LNs (AUC = 0.70 and 0.74, respectively). CONCLUSION: SWE has the ability to characterize the extracellular matrix, and serves as a promising modality for evaluating axillary LNs after NAC. Notably, breast SWE outperform axilla SWE in determining the axillary status in breast cancer patients after NAC.
Subject(s)
Axilla , Breast Neoplasms , Elasticity Imaging Techniques , Lymph Nodes , Lymphatic Metastasis , Neoadjuvant Therapy , Humans , Breast Neoplasms/drug therapy , Breast Neoplasms/diagnostic imaging , Breast Neoplasms/pathology , Female , Elasticity Imaging Techniques/methods , Middle Aged , Prospective Studies , Adult , Lymph Nodes/diagnostic imaging , Lymph Nodes/pathology , Lymphatic Metastasis/diagnostic imaging , Aged , Feasibility Studies , Lymph Node Excision , Chemotherapy, AdjuvantABSTRACT
To investigate the quality differences between the seeds and husks of Amomum villosum and explore the rationality of using the seeds without husks, this study determined the content of protocatechuic acid, vanillic acid, epicatechin, quercitrin, volatile oil, water extract, and ethanol extract. The 2,2-diphenyl-1-picrylhydrazyl(DPPH), 2,2-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)(ABTS), and hydroxyl radical scavenging activities were determined to evaluate the antioxidant activities of seeds and husks. The quality differences between the seeds and husks were assessed through orthogonal partial least squares-discriminant analysis(OPLS-DA) and analytic hierarchy process(AHP) combined with the entropy weight method(EWM). Significant differences(P<0.05) were observed in all 10 indicators between the seeds and husks. The levels of epicatechin, quercetin, and volatile oil were higher in the seeds, whereas those of protocatechuic acid, vanillic acid, water extract, and ethanol extract were higher in the husks. The seeds showed stronger scavenging ability against DPPH and ABTS radicals, while the husks showed a stronger scavenging effect on hydroxyl radicals. OPLS-DA significantly discriminated between the seeds and husks. Furthermore, volatile oil, water extract, DPPH radical scavenging rate, quercitrin, ABTS radical scavenging rate, hydroxyl radical scavenging rate, and vanillic acid were selected as the main differential indicators by variable importance in projection(VIP). Comprehensive scores calculated by AHP combined with EWM indicated that the seeds were superior to husks in terms of overall quality. However, there are still some dominant components and a certain antioxidant effect in the husks. Therefore, it is suggested to using Amomi Fructus with a certain amount of husks or utilizing the husks for other purposes.
Subject(s)
Amomum , Benzothiazoles , Catechin , Hydroxybenzoates , Oils, Volatile , Sulfonic Acids , Hydroxyl Radical , Vanillic Acid , Antioxidants/chemistry , Water , Ethanol , Oils, Volatile/chemistryABSTRACT
The hollow sandwich core-shell micro-nanomaterials are widely used in materials, chemistry, and medicine, but their fabrication, particularly for transition metal phosphides (TMPs), remains a great challenge. Herein, a general synthesis strategy is presented for binary TMPs hollow sandwich heterostructures with vertically interconnected nanosheets on the inside and outside surfaces of polyhedron FeCoPx /C, demonstrated by a variety of transition metals (including Co, Fe, Cd, Mn, Cu, Cr, and Ni). Density functional theory (DFT) calculation reveals the process and universal mechanism of layered double hydroxide (LDH) growth on Prussian blue analog (PBA) surface in detail for the first time, which provides the theoretical foundations for feasibility and rationality of the synthesis strategy. This unique structure exhibits a vertical nanosheet-shell-vertical nanosheet configuration combining the advantages of sandwich, hollow and vertical heterostructures, effectively achieving their synergistic effect. As a proof-of-concept of their applications, the CoNiPx @FeCoPx /C@CoNiPx hollow sandwich polyhedron architectures (representative samples) show excellent catalytic performance for the oxygen evolution reaction (OER) in alkaline electrolytes. This work provides a general method for constructing hollow-sandwich micro-nanostructures, which provides more ideas and directions for design of micro-nano materials with special geometric topology.
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OBJECTIVE: Pancreatic cancer is an aggressive malignancy with high mortality, and cancer cell stemness and related drug resistance are considered important contributors to its poor prognosis. The objective of this study was to identify regulatory targets associated with the maintenance of pancreatic cancer stemness. MATERIALS AND METHODS: Pancreatic tumor samples were collected from patients at Sun Yat-sen University Cancer Center, followed by immunofluorescence analysis. Pancreatic cancer cell lines with Interleukin-20 receptor subunit beta (IL20RB) overexpression and knockdown were established, and clonal formation, spheroid formation and side population cell analysis were conducted. The effects of IL20RB knockdown on the tumor-forming ability of pancreatic cancer cells and chemotherapy resistance in vivo were explored. RESULTS: IL20RB expression was significantly upregulated in pancreatic cancer tissues, and was correlated with unfavorable prognosis. The IL20RB receptor promotes stemness and chemoresistance in both in vitro and in vivo models of pancreatic cancer. Mechanistically, IL20RB enhances the stemness and chemoresistance of pancreatic cancer by promoting STAT3 phosphorylation, an effect that can be counteracted by a STAT3 phosphorylation inhibitors. Additionally, Interleukin-19 derived from the microenvironment is identified as the primary ligand for IL20RB in mediating these effects. CONCLUSION: Our findings demonstrate that IL20RB plays a crucial role in promoting stemness in pancreatic cancer. This discovery provides a potential therapeutic target for this lethal disease.
Subject(s)
Drug Resistance, Neoplasm , Pancreatic Neoplasms , Humans , Cell Line, Tumor , Signal Transduction , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/metabolism , Prognosis , Neoplastic Stem Cells/pathology , Tumor MicroenvironmentABSTRACT
The study is one of the first prevalence studies of gambling and problem gambling among casino patrons in Macao. It aims to identify the demographic profile of gamblers and evaluate the extent of problem gambling among casino patrons. Using a convenience sampling approach, over 6,000 people were intercepted in the proximity of casinos and were invited to answer a structured questionnaire anonymously and voluntarily. Among these people 1,352 respondents indicated that they gambled in casinos at least once in the past 12 months. Over 90% (1,228) of the respondents reported that they gambled in Macao's casinos and slot lounges. The three most popular forms of casino gambling were baccarat, Sic Bo, and slot machines. The monthly median expenditure on gambling was HKD 1,845 with a range from HKD 2 to HKD 375,175. The prevalence rates for problem gambling and pathological gambling were 15.1% and 7.1%, respectively. Implications of the study's findings are given.
Subject(s)
Gambling , Humans , Gambling/psychology , Macau/epidemiology , Surveys and Questionnaires , PrevalenceABSTRACT
Casino gaming is considered as an entertainment but it may cause financial and psychological burdens to some individuals and their families. Therefore, casino operators have established and deployed responsible gaming policy and practice to mitigate such negative effects. This study explores whether and how responsible gaming policy and practice influences people's casino gaming intention and behavior. Data were collected from 644 Chinese adults in Macao. Results showed that responsible gaming policy and practice significantly influenced people's attitude towards casino gaming (as a legal activity and hobby), subjective norm (for disapproval of casino gaming), and perceived behavior control (for not engaging in casino gaming). Casino gaming intention was positively affected by attitude and negatively affected by subjective norm and perceived behavior control. Casino gaming behavior was positively affected by intention and negatively affected by perceived behavior control. As a whole, responsible gaming policy and practice had a small, negative but significant indirect effect on casino gaming behavior. Implications of the study were given.
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This study investigated the knowledge, thoughts, and attitudes of oncology nurses in China regarding fertility preservation for male cancer patients of childbearing age, and for offering counseling or oncofertility services for the men in their care. Data was collected from 18 oncology nurses in Southwest China through voluntary self-report and in-depth interviews. The qualitative interview data were analyzed using a descriptive phenomenology method based on the lived experience of the nurses. The interviewees commonly reported 6 main concerns regarding fertility preservation (FP): their insufficient knowledge and inadequate nursing education; the importance of offering such services to cancer patients; legal vulnerability if FP information is withheld from patients; the role of the nurse in counseling; and barriers to discussing FP in practice. Nurses had a positive attitude toward FP, but most had no practical role in routinely informing male patients of their options, and the nurses believed that discussion of FP was outside their scope of practice. This study offers insight into the perceptions of oncology nurses in a developing country regarding the provision of FP services for adult male cancer patients. These results lead us to recommend that local fertility nurses should be given new training regarding FP. Furthermore, nurse-led clinics are desirable. Future research should focus on the effectiveness of nurse participation in FP counseling and referral, and how to improve the professional confidence of oncology nurses for addressing FP issues.
Subject(s)
Fertility Preservation , Infertility , Neoplasms , Adult , Humans , Male , Fertility Preservation/psychology , Attitude of Health Personnel , Neoplasms/psychology , CounselingABSTRACT
Pediatric acute hyperextension spinal cord injury (SCI) named as PAHSCI by us, is a special type of thoracolumbar SCI without radiographic abnormality and highly related to back-bend in dance training, which has been increasingly reported. At present, it has become the leading cause of SCI in children, and brings a heavy social and economic burden. Both domestic and foreign academic institutions and dance education organizations lack a correct understanding of PAHSCI and relevant standards, specifications or guidelines. In order to provide standardized guidance, the expert team formulated this guideline based on the principles of science and practicability, starting from the diagnosis, differential diagnosis, etiology, admission evaluation, treatment, complications and prevention. This guideline puts forward 23 recommendations for 14 related issues.
Subject(s)
Spinal Cord Injuries , Child , Humans , Spinal Cord Injuries/diagnosis , Spinal Cord Injuries/therapy , Spinal Cord Injuries/complications , Spinal CordABSTRACT
The present study aimed to investigate the inhibitory effect and mechanism of Isodon terricolous-medicated serum on lipopolysaccharide(LPS)-induced hepatic stellate cell(HSC) activation. LPS-induced HSCs were divided into a blank control group, an LPS model group, a colchicine-medicated serum group, an LPS + blank serum group, an I. terricolous-medicated serum group, a Toll-like receptor 4(TLR4) blocker group, and a TLR4 blocker + I. terricolous-medicated serum group. HSC proliferation was detected by methyl thiazolyl tetrazolium(MTT) assay. Enzyme-linked immunosorbent assay(ELISA) was used to measure type â collagen(COL â ), COL â ¢, transforming growth factor-ß1(TGF-ß1), intercellular adhesion molecule-1(ICAM-1), α-smooth muscle actin(α-SMA), vascular cell adhesion molecule-1(VCAM-1), cysteinyl aspartate-specific proteinase-1(caspase-1), and monocyte chemotactic protein-1(MCP-1). Real-time PCR(RT-PCR) was used to detect mRNA expression of TLR4, IκBα, and NOD-like receptor thermal protein domain associated protein 3(NLRP3), nuclear factor-κB(NF-κB) p65, gasdermin D(GSDMD), and apoptosis-associated speck-like protein containing a CARD(ASC) in HSCs. Western blot(WB) was used to detect the protein levels of TLR4, p-IκBα, NF-κB p65, NLRP3, ASC, and GSDMD in HSCs. The results showed that I. terricolous-medicated serum could inhibit the proliferation activity of HSCs and inhibit the secretion of COL â , COL â ¢, α-SMA, TGF-ß1, caspase-1, MCP-1, VCAM-1, and ICAM-1 in HSCs. Compared with the LPS model group, the I. terricolous-medicated serum group, the colchicine-medicated serum group, and the TLR4 blocker group showed down-regulated expression of p-IκBα, NLRP3, NF-κB p65, GSDMD, and ASC, and up-regulated expression of IκBα. Compared with the TLR4 blocker group, the TLR4 blocker + I. terricolous-medicated serum group showed decreased expression of TLR4, p-IκBα, NLRP3, NF-κB p65, GSDMD, and ASC, and increased expression of IκBα. In conclusion, I. terricolous-medicated serum down-regulates HSC activation by inhibiting the TLR4/NF-κB/NLRP3 signaling pathway.
Subject(s)
Isodon , NF-kappa B , NF-kappa B/genetics , NF-kappa B/metabolism , Hepatic Stellate Cells , Transforming Growth Factor beta1/metabolism , NF-KappaB Inhibitor alpha/metabolism , Intercellular Adhesion Molecule-1/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/genetics , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Toll-Like Receptor 4/genetics , Toll-Like Receptor 4/metabolism , Vascular Cell Adhesion Molecule-1/metabolism , Lipopolysaccharides/pharmacology , Signal Transduction , Colchicine/metabolism , Colchicine/pharmacology , CaspasesABSTRACT
The purpose of this study is to investigate whether chrysin reduces cerebral ischemia-reperfusion injury(CIRI) by inhi-biting ferroptosis in rats. Male SD rats were randomly divided into a sham group, a model group, high-, medium-, and low-dose chrysin groups(200, 100, and 50 mg·kg~(-1)), and a positive drug group(Ginaton, 21.6 mg·kg~(-1)). The CIRI model was induced in rats by transient middle cerebral artery occlusion(tMCAO). The indexes were evaluated and the samples were taken 24 h after the operation. The neurological deficit score was used to detect neurological function. The 2,3,5-triphenyl tetrazolium chloride(TTC) staining was used to detect the cerebral infarction area. Hematoxylin-eosin(HE) staining and Nissl staining were used to observe the morphological structure of brain tissues. Prussian blue staining was used to observe the iron accumulation in the brain. Total iron, lipid pero-xide, and malondialdehyde in serum and brain tissues were detected by biochemical reagents. Real-time quantitative polymerase chain reaction(RT-qPCR), immunohistochemistry, and Western blot were used to detect mRNA and protein expression of solute carrier fa-mily 7 member 11(SLC7A11), transferrin receptor 1(TFR1), glutathione peroxidase 4(GPX4), acyl-CoA synthetase long chain family member 4(ACSL4), and prostaglandin-endoperoxide synthase 2(PTGS2) in brain tissues. Compared with the model group, the groups with drug intervention showed restored neurological function, decreased cerebral infarction rate, and alleviated pathological changes. The low-dose chrysin group was selected as the optimal dosing group. Compared with the model group, the chrysin groups showed reduced content of total iron, lipid peroxide, and malondialdehyde in brain tissues and serum, increased mRNA and protein expression levels of SLC7A11 and GPX4, and decreased mRNA and protein expression levels of TFR1, PTGS2, and ACSL4. Chrysin may regulate iron metabolism via regulating the related targets of ferroptosis and inhibit neuronal ferroptosis induced by CIRI.
Subject(s)
Brain Ischemia , Ferroptosis , Reperfusion Injury , Rats , Male , Animals , Rats, Sprague-Dawley , Signal Transduction , Brain Ischemia/drug therapy , Brain Ischemia/genetics , Brain Ischemia/metabolism , Cyclooxygenase 2/metabolism , RNA, Messenger , Cerebral Infarction , Reperfusion Injury/drug therapy , Reperfusion Injury/genetics , Reperfusion Injury/metabolism , Malondialdehyde , Infarction, Middle Cerebral ArteryABSTRACT
OBJECTIVE: To explore the protective effect of human urine-derived stem cell exosomes (hUSC-Exos) on radiation-induced salivary gland (SG) injuries in Sprague Dawley rats. METHODS: Fresh adult urine was collected, and primary hUSCs were isolated and identified. The hUSCs were hypoxia-pretreated with 1% oxygen for 24 h and then transferred to a normoxic culture environment for 24 h. The hUSC-Exos were collected and identified for exosomes. A radiation-induced injury model was established in the rats, and exosomes were introduced by local injection in the SG and tail vein. The submandibular gland was excised for morphological observation 1 week later. Immunohistochemical detection of the glandular tissue was conducted by α-smooth muscle actin (a-SMA), stem cell growth factor receptor (c-Kit) staining, and periodic acid-Schiff staining. Qualitative polymerase chain reaction and western blot analysis were adopted to detect the gene and protein expression of Wnt3a, GSK3ß, and Axin. RESULTS: In both the normoxic and hypoxic hUSC-Exo groups, microvesicular structures with bilayer membranes of approximately 80 nm in diameter were detected, and the expressions of CD9 and CD63 were detected by nanoflow cytometry. Compared with the control group, in the radiation-induced injury model group, the expression of a-SMA was significantly higher, the expression of c-Kit was significantly lower, and the expressions of Wnt3a, GSK3ß, and Axin were significantly upregulated; the differences were statistically significant (p < 0.05). Compared with the model group, in the normoxic and hypoxic hUSC-Exo groups, the expression of a-SMA was significantly decreased, the expression of c-Kit was significantly increased, and the expressions of Wnt3a, GSK3ß, and Axin were significantly upregulated; the differences were statistically significant (p < 0.05). CONCLUSION: Hypoxia-pretreated hUSC-Exos could repair radiation-induced SG injuries by activating the Wnt3a/GSK3ß pathway to suppress the expressions of a-SMA and c-Kit.
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The dramatic increase in obesity is putting people under increasing pressure. Lipase inhibitors, as a kind of effective anti-obesity drug, have attracted more and more researchers' attention in recent years because of their advantages of acting on the intestinal tract and having no side effects on the central nervous system. In this study, lipase inhibitor Fu Brick Theophylline (FBT) was screened based on enzyme molecular dynamics, and the inhibition mechanism of lipase inhibitors on obesity was analyzed and discussed at the cellular level and animal model level. We found that FBT had high inhibition effects of lipase with an IC50 of 1.02~0.03 µg/mL. Firstly, the laboratory used 3T3-L1 proadipocytes as models, flow cytometry was used to detect the effects of FBT on the cycle, apoptosis and intracellular ROS activity of proadipocytes. To study the contents of triglyceride, total cholesterol, related metabolites and related gene and protein expression in adipocytes. The results showed that FBT could reduce ROS production and inflammatory factor mRNA expression during cell differentiation. Secondly, by establishing the animal model of high-fat feed ob nutritional obese mice, the morphological observation and gene expression analysis of body weight, fat rate, adipocyte and hepatocyte metabolism of FBT obese mice were further discussed. It was proven that FBT can effectively reduce the degree of fatty liver, prevent liver fibrosis and fat accumulation, and improve the damage of mitochondrial membrane structure. This study provides a theoretical basis for the screening and clinical treatment of lipase inhibitors.
Subject(s)
Lipase , Theophylline , 3T3-L1 Cells , Adipose Tissue/metabolism , Animals , Diet, High-Fat/adverse effects , Humans , Mice , Mice, Obese , Obesity/drug therapy , Obesity/etiology , Obesity/metabolism , Reactive Oxygen Species , Tea/chemistryABSTRACT
S-RNase plays vital roles in the process of self-incompatibility (SI) in Rutaceae plants. Data have shown that the rejection phenomenon during self-pollination is due to the degradation of pollen tube RNA by S-RNase. The cytoskeleton microfilaments of pollen tubes are destroyed, and other components cannot extend downwards from the stigma and, ultimately, cannot reach the ovary to complete fertilisation. In this study, four S-RNase gene sequences were identified from the 'XiangShui' lemon genome and ubiquitome. Sequence analysis revealed that the conserved RNase T2 domains within S-RNases in 'XiangShui' lemon are the same as those within other species. Expression pattern analysis revealed that S3-RNase and S4-RNase are specifically expressed in the pistils, and spatiotemporal expression analysis showed that the S3-RNase expression levels in the stigmas, styles and ovaries were significantly higher after self-pollination than after cross-pollination. Subcellular localisation analysis showed that the S1-RNase, S2-RNase, S3-RNase and S4-RNase were found to be expressed in the nucleus according to laser confocal microscopy. In addition, yeast two-hybrid (Y2H) assays showed that S3-RNase interacted with F-box, Bifunctional fucokinase/fucose pyrophosphorylase (FKGP), aspartic proteinase A1, RRP46, pectinesterase/pectinesterase inhibitor 51 (PME51), phospholipid:diacylglycerol acyltransferase 1 (PDAT1), gibberellin receptor GID1B, GDT1-like protein 4, putative invertase inhibitor, tRNA ligase, PAP15, PAE8, TIM14-2, PGIP1 and p24beta2. Moreover, S3-RNase interacted with TOPP4. Therefore, S3-RNase may play an important role in the SI of 'XiangShui' lemon.