Multiple Enzyme-Mimicking CuMOF-Driven Self-Cascading Antioxidant Reaction for Synergistic Electrochemiluminescence Modulation in Ultrasensitive Biosensing.

Developing nanozyme-based free radical scavenging is a promising signal modulation approach for ECL sensing. Nevertheless, the relatively low antioxidant activity and inherent pro-oxidant activity of numerous nanozymes have significantly hindered the development of this strategy. Here a biofunctional copper-based metal-organic framework (CuMOF) with multiple enzyme-mimicking activities was employed for the modulation of the ECL immunosensor, guided by the self-cascade antioxidant reaction. The inherent SOD, CAT, and the capacity to eliminate ·OH endow CuMOF with powerful synergistic antioxidant effects while little pro-oxidant activities were displayed, enabling efficient scavenging of the O2·- produced during the electrochemical oxidation of H2O2. Subsequently, the nanoconfinement effect of the layered double hydroxide was introduced to ensure a steady ECL signal. The suggested ECL immunosensor, using aflatoxin B1 as a proof-of-concept target, demonstrated a detection range spanning from 0.001 pg/mL to 10 ng/mL, with the detection limit calculated to be 0.18 fg/mL. This exceptional achievement greatly broadens the range of possible uses for nanozyme-based radical scavenging modulated ECL analysis.

Evaluating eight indicators for identifying metabolic syndrome in Chinese and American adolescents.

BACKGROUND: Early intervention and diagnosis of Metabolic Syndrome (MetS) are crucial for preventing adult cardiovascular disease. However, the optimal indicator for identifying MetS in adolescent remains controversial. METHODS: In total,1408 Chinese adolescents and 3550 American adolescents aged 12-17 years were included. MetS was defined according to the modified version for adolescents based on Adult Treatment Panel III (NCEP-ATP III) criteria. Areas under the curve (AUC) and corresponding 95% confidence interval (95% CI) of 8 anthropometric/metabolic indexes, such as waist circumference (WC), body mass index (BMI), a body shape index (ABSI), waist triglyceride index (WTI), were calculated to illustrate their ability to differentiate MetS. Sensitivity analysis using the other MetS criteria was performed. RESULTS: Under the modified NCEP-ATP III criteria, WTI had the best discriminating ability in overall adolescents, with AUC of 0.922 (95% CI: 0.900-0.945) in Chinese and 0.959 (95% CI: 0.949-0.969) in American. In contrast, ABSI had the lowest AUCs. Results of sensitivity analysis were generally consistent for the whole Chinese and American population, with the AUC for WC being the highest under some criteria, but it was not statistically different from that of WTI. CONCLUSIONS: WTI had relatively high discriminatory power for MetS detection in Chinese and American adolescents, but the performance of ABSI was poor. IMPACT: While many studies have compared the discriminatory power of some anthropometric indicators for MetS, there are few focused on pediatrics. The current study is the first to compare the discriminating ability of anthropometric/metabolic indicators (WC, BMI, TMI, ABSI, WHtR, VAI, WTI, and TyG) for MetS in adolescents. WTI remains the optimal indicator in screening for MetS in adolescents. WC was also a simple and reliable indicator when screening for MetS in adolescents, but the performance of ABSI was poor. This study provides a theoretical basis for the early identification of MetS in adolescents by adopting effective indicators.

Cross-Electrophile Couplings of Benzyl Sulfonium Salts with Thiosulfonates via C-S Bond Activation.

A zinc-mediated cross-electrophile coupling of benzyl sulfonium salts with thiosulfonates via C-S bond cleavage was achieved. The reductive thiolation proceeded well under transition metal-free conditions to afford the desired benzyl sulfides in good yields, exhibiting both broad substrate scope and good functionality tolerance. In addition, the reaction could be applied to the use of selenosulfonate as an effective selenylation agent and be subjected to scale-up synthesis.

Integrative metabolome and transcriptome analysis characterized methyl jasmonate-elicited flavonoid metabolites of Blumea balsamifera.

As a commonly used medicinal plant, the flavonoid metabolites of Blumea balsamifera and their association with genes are still elusive. In this study, the total flavonoid content (TFC), flavonoid metabolites and biosynthetic gene expression patterns of B. balsamifera after application of exogenous methyl jasmonate (MeJA) were scrutinized. The different concentrations of exogenous MeJA increased the TFC of B. balsamifera leaves after 48 h of exposure, and there was a positive correlation between TFC and the elicitor concentration. A total of 48 flavonoid metabolites, falling into 10 structural classes, were identified, among which flavones and flavanones were predominant. After screening candidate genes by transcriptome mining, the comprehensive analysis of gene expression level and TFC suggested that FLS and MYB may be key genes that regulate the TFC in B. balsamifera leaves under exogenous MeJA treatment. This study lays a foundation for elucidating flavonoids of B. balsamifera, and navigates the breeding of flavonoid-rich B. balsamifera varieties.

Nanozyme catalysis pressure-powered intuitive distance variation for portable quantitative detection of H2S with the naked eye.

As a representative gas of food spoilage, the development of rapid hydrogen sulfide (H2S) analysis strategies for food safety control is in great demand. Despite traditional methods for H2S detection possessing great achievements, they are still incapable of meeting the requirement of portability and quantitative detection at the same time. Herein, a nanozyme catalysis pressure-powered sensing platform that enables visual quantification with the naked eye is proposed. In this methodology, Pt nanozyme inherits the catalase-like activity to facilitate the decomposition of H2O2 to O2, which can significantly improve the pressure in the closed container, further pushing the movement of indicator dye. Furthermore, H2S was found to effectively inhibit the catalytic activity of Pt nanozyme, indicating that the catalase-like activity of PtNPs may be regulated by varying concentrations of H2S. Therefore, by utilizing a self-designed pressure-powered microchannel device, the concentration of H2S was successfully converted into a distinct signal variation in distance. The effectiveness of the as-designed sensor in assessing the spoilage of red wine by H2S determination has been demonstrated. It exhibits a strong correlation between the change in dye distance and H2S concentration within the range of 1-250 µM, with a detection limit of 0.17 µM. This method is advantageous as it enhances the quantitative detection of H2S with the naked eye based on the portable pressure-powered sensing platform, as compared to traditional H2S biosensors. Such a pressure-powered distance variation platform would greatly broaden the application of H2S-based detection in food spoilage management.

The Function of Circular RNAs in Myocardial Ischemia-Reperfusion Injury: Underlying Mechanisms and Therapeutic Advancement.

Myocardial ischemia reperfusion injury (MIRI) represents a prevalent and severe cardiovascular condition that arises primarily after myocardial infarction recanalization, cardiopulmonary bypass surgery, and both stable and unstable angina pectoris. MIRI can induce malignant arrhythmias and heart failure, thereby increasing the morbidity and mortality rates associated with cardiovascular diseases. Hence, it is important to assess the potential pathological mechanisms of MIRI and develop effective treatments. The role of circular RNAs (circRNAs) in MIRI has increasingly become a topic of interest in recent years. Moreover, significant evidence suggests that circRNAs play a critical role in MIRI pathogenesis, thereby representing a promising therapeutic target. This review aimed to provide a comprehensive overview of the current understanding of the role of circRNAs in MIRI and discuss the mechanisms through which circRNAs contribute to MIRI development and progression, including their effects on apoptosis, inflammation, oxidative stress, and autophagy. Furthermore, the potential therapeutic applications of circRNAs in MIRI treatment, including the use of circRNA-based therapies and modulation of circRNA expression levels, have been explored. Overall, this paper highlights the importance of circRNAs in MIRI and underscores their potential as novel therapeutic targets.

A combined AIMD and DFT study of the low-energy radiation responses of GaN.

Although GaN is a promising candidate for semiconductor devices, degradation of GaN-based device performance may occur when the device is bombarded by high-energy charged particles during its application in aerospace, astronomy, and nuclear-related areas. It is thus of great significance to explore the influence of irradiation on the microstructure and electronic properties of GaN and to reveal the internal relationship between the damage mechanisms and physical characteristics. Using a combined density functional theory (DFT) and ab initio molecular dynamics (AIMD) study, we explored the low-energy recoil events in GaN and the effects of point defects on GaN. The threshold displacement energies (Eds) significantly depend on the recoil directions and the primary knock-on atoms. Moreover, the Ed values for nitrogen atoms are smaller than those for gallium atoms, indicating that the displacement of nitrogen dominates under electron irradiation and the created defects are mainly nitrogen vacancies and interstitials. The formation energy of nitrogen vacancies and interstitials is smaller than that for gallium vacancies and interstitials, which is consistent with the AIMD results. Although the created defects improve the elastic compliance of GaN, these radiation damage states deteriorate its ability to resist external compression. Meanwhile, these point defects lead the Debye temperature to decrease and thus increase the thermal expansion coefficients of GaN. As for the electronic properties of defective GaN, the point defects have various effects, i.e., VN (N vacancy), Gaint (Ga interstitial), Nint (N interstitial), and GaN (Ga occupying the N lattice site) defects induce the metallicity, and NGa (N occupying the Ga lattice site) defects decrease the band gap. The presented results provide underlying mechanisms for defect generation in GaN, and advance the fundamental understanding of the radiation resistances of semiconductor materials.

A lithium-oxygen battery with a long cycle life in an air-like atmosphere.

Lithium-air batteries are considered to be a potential alternative to lithium-ion batteries for transportation applications, owing to their high theoretical specific energy. So far, however, such systems have been largely restricted to pure oxygen environments (lithium-oxygen batteries) and have a limited cycle life owing to side reactions involving the cathode, anode and electrolyte. In the presence of nitrogen, carbon dioxide and water vapour, these side reactions can become even more complex. Moreover, because of the need to store oxygen, the volumetric energy densities of lithium-oxygen systems may be too small for practical applications. Here we report a system comprising a lithium carbonate-based protected anode, a molybdenum disulfide cathode and an ionic liquid/dimethyl sulfoxide electrolyte that operates as a lithium-air battery in a simulated air atmosphere with a long cycle life of up to 700 cycles. We perform computational studies to provide insight into the operation of the system in this environment. This demonstration of a lithium-oxygen battery with a long cycle life in an air-like atmosphere is an important step towards the development of this field beyond lithium-ion technology, with a possibility to obtain much higher specific energy densities than for conventional lithium-ion batteries.

Hydroxylation of Aryl Sulfonium Salts for Phenol Synthesis under Mild Reaction Conditions.

Hydroxylation of aryl sulfonium salts could be realized by utilizing acetohydroxamic acid and oxime as hydroxylative agents in the presence of cesium carbonate as a base, leading to a variety of structurally diverse hydroxylated arenes in 47-95% yields. In addition, the reaction exhibited broad functionality tolerance, and a range of important functional groups (e.g., cyano, nitro, sulfonyl, formyl, keto, and ester) could be well amenable to the mild reaction conditions.

Washed microbiota transplantation improves renal function in patients with renal dysfunction: a retrospective cohort study.

BACKGROUND: Changes in the gut microbiota composition is a hallmark of chronic kidney disease (CKD), and interventions targeting the gut microbiota present a potent approach for CKD treatment. This study aimed to evaluate the efficacy and safety of washed microbiota transplantation (WMT), a modified faecal microbiota transplantation method, on the renal activity of patients with renal dysfunction. METHODS: A comparative analysis of gut microbiota profiles was conducted in patients with renal dysfunction and healthy controls. Furthermore, the efficacy of WMT on renal parameters in patients with renal dysfunction was evaluated, and the changes in gut microbiota and urinary metabolites after WMT treatment were analysed. RESULTS: Principal coordinate analysis revealed a significant difference in microbial community structure between patients with renal dysfunction and healthy controls (P = 0.01). Patients with renal dysfunction who underwent WMT exhibited significant improvement in serum creatinine, estimated glomerular filtration rate, and blood urea nitrogen (all P < 0.05) compared with those who did not undergo WMT. The incidence of adverse events associated with WMT treatment was low (2.91%). After WMT, the Shannon index of gut microbiota and the abundance of several probiotic bacteria significantly increased in patients with renal dysfunction, aligning their gut microbiome profiles more closely with those of healthy donors (all P < 0.05). Additionally, the urine of patients after WMT demonstrated relatively higher levels of three toxic metabolites, namely hippuric acid, cinnamoylglycine, and indole (all P < 0.05). CONCLUSIONS: WMT is a safe and effective method for improving renal function in patients with renal dysfunction by modulating the gut microbiota and promoting toxic metabolite excretion.

Anemia Is Associated with Disease Severity, Hepatic Complications, and Progression of Wilson Disease: A Retrospective Cohort Study.

INTRODUCTION: Anemia is a common manifestation of chronic liver diseases. It is a predictor of severe disease, a high risk of complications, and poor outcomes in various liver diseases. However, it remains unclear whether anemia serves as a similar indicator in patients with Wilson disease (WD). Therefore, this study aimed to investigate the relationship between anemia and severity, hepatic complications, and the progression of WD. METHODS: Medical data were collected retrospectively from January 1, 2016, to December 31, 2020. Univariate and multivariate analyses were carried out to investigate the relationship between anemia and liver-associated disease severity, hepatic complications, and the progression of WD. RESULTS: A total of 288 WD patients (48 with and 240 without anemia) were enrolled in the study. Multivariate linear regression revealed that WD patients with anemia had significantly higher levels of bilirubin, alanine transaminase, prothrombin time, international normalized ratio, type Ⅳ collagen, and hyaluronic acid and significantly lower levels of albumin, total cholesterol, and high-density lipoprotein-cholesterol (all p < 0.05). Multivariate logistic regression showed that anemia was a risk factor for gastric varices and ascites (all p < 0.05). Fully adjusted Cox regression revealed that anemia was an independent risk factor for advanced Child-Pugh classification (p = 0.034). CONCLUSIONS: Anemia was common in WD patients and was associated with greater disease severity, a higher risk of hepatic complications, and a faster progression.

PDHA1 Alleviates Myocardial Ischemia-Reperfusion Injury by Improving Myocardial Insulin Resistance During Cardiopulmonary Bypass Surgery in Rats.

OBJECTIVE: Cardiopulmonary bypass (CPB) is a requisite technique for thoracotomy in advanced cardiovascular surgery. However, the consequent myocardial ischemia-reperfusion injury (MIRI) is the primary culprit behind cardiac dysfunction and fatal consequences post-operation. Prior research has posited that myocardial insulin resistance (IR) plays a vital role in exacerbating the progression of MIRI. Nonetheless, the exact mechanisms underlying this phenomenon remain obscure. METHODS: We constructed pyruvate dehydrogenase E1 α subunit (PDHA1) interference and overexpression rats and used ascending aorta occlusion in an in vivo model of CPB-MIRI. We devised an in vivo model of CPB-MIRI by constructing rat models with both pyruvate dehydrogenase E1α subunit (PDHA1) interference and overexpression through ascending aorta occlusion. We analyzed myocardial glucose metabolism and the degree of myocardial injury using functional monitoring, biochemical assays, and histological analysis. RESULTS: We discovered a clear downregulation of glucose transporter 4 (GLUT4) protein content expression in the CPB I/R model. In particular, cardiac-specific PDHA1 interference resulted in exacerbated cardiac dysfunction, significantly increased myocardial infarction area, more pronounced myocardial edema, and markedly increased cardiomyocyte apoptosis. Notably, the opposite effect was observed with PDHA1 overexpression, leading to a mitigated cardiac dysfunction and decreased incidence of myocardial infarction post-global ischemia. Mechanistically, PDHA1 plays a crucial role in regulating the protein content expression of GLUT4 on cardiomyocytes, thereby controlling the uptake and utilization of myocardial glucose, influencing the development of myocardial insulin resistance, and ultimately modulating MIRI. CONCLUSION: Overall, our study sheds new light on the pivotal role of PDHA1 in glucose metabolism and the development of myocardial insulin resistance. Our findings hold promising therapeutic potential for addressing the deleterious effects of MIRI in patients.

Insulin reduces pyroptosis-induced inflammation by PDHA1 dephosphorylation-mediated NLRP3 activation during myocardial ischemia-reperfusion injury.

BACKGROUND: Previous studies proved that pyrin domain-containing protein 3 (NLRP3)-induced pyroptosis plays an important role in Myocardial ischemia-reperfusion injury (MIRI). Insulin can inhibit the activation of NLRP3 inflammasome, although the exact mechanism remains unclear. The aim of this study was to determine whether insulin reduces NLRP3-induced pyroptosis by regulating pyruvate dehydrogenase E1alpha subunit (PDHA1) dephosphorylation during MIRI. METHODS: Rat hearts were subject to 30 min global ischemia followed by 60 min reperfusion, with or without 0.5 IU/L insulin. Myocardial ischemia-reperfusion injury was evaluated by measuring myocardial enzymes release, Cardiac hemodynamics, pathological changes, infarct size, and apoptosis rate. Cardiac aerobic glycolysis was evaluated by measuring ATP, lactic acid content, and pyruvate dehydrogenase complex (PDHc) activity in myocardial tissue. Recombinant adenoviral vectors for PDHA1 knockdown were constructed. Pyroptosis-related proteins were measured by Western blotting analysis, immunohistochemistry staining, and ELISA assay, respectively. RESULTS: It was found that insulin significantly reduced the area of myocardial infarction, apoptosis rate, and improved cardiac hemodynamics, pathological changes, energy metabolism. Insulin inhibits pyroptosis-induced inflammation during MIRI. Subsequently, Adeno-associated virus was used to knock down cardiac PDHA1 expression. Knockdown PDHA1 not only promoted the expression of NLRP3 but also blocked the inhibitory effect of insulin on NLRP3-mediated pyroptosis in MIRI. CONCLUSIONS: Results suggest that insulin protects against MIRI by regulating PDHA1 dephosphorylation, its mechanism is not only to improve myocardial energy metabolism but also to reduce the NLRP3-induced pyroptosis.

Smart Contract Vulnerability Detection Based on Deep Learning and Multimodal Decision Fusion.

With the rapid development and widespread application of blockchain technology in recent years, smart contracts running on blockchains often face security vulnerability problems, resulting in significant economic losses. Unlike traditional programs, smart contracts cannot be modified once deployed, and vulnerabilities cannot be remedied. Therefore, the vulnerability detection of smart contracts has become a research focus. Most existing vulnerability detection methods are based on rules defined by experts, which are inefficient and have poor scalability. Although there have been studies using machine learning methods to extract contract features for vulnerability detection, the features considered are singular, and it is impossible to fully utilize smart contract information. In order to overcome the limitations of existing methods, this paper proposes a smart contract vulnerability detection method based on deep learning and multimodal decision fusion. This method also considers the code semantics and control structure information of smart contracts. It integrates the source code, operation code, and control-flow modes through the multimodal decision fusion method. The deep learning method extracts five features used to represent contracts and achieves high accuracy and recall rates. The experimental results show that the detection accuracy of our method for arithmetic vulnerability, re-entrant vulnerability, transaction order dependence, and Ethernet locking vulnerability can reach 91.6%, 90.9%, 94.8%, and 89.5%, respectively, and the detected AUC values can reach 0.834, 0.852, 0.886, and 0.825, respectively. This shows that our method has a good vulnerability detection effect. Furthermore, ablation experiments show that the multimodal decision fusion method contributes significantly to the fusion of different modalities.

[Application of Rat Model of Neurotic Erectile Dysfunction in Experiment].

Erectile dysfunction (ED) refers to the persistent inability to achieve and/or maintain a sufficient erection of the penis to obtain a satisfactory sexual life,which affects the quality of life of the patients and their sexual partners.To decipher the pathophysiological mechanism of ED,researchers have established a variety of animal models and achieved a series of progress.The cavernous nerve (CN) of rodents,anatomically similar to that of humans,is cost-effective,thick,and easy to be identified,which has gradually become the mainstream of animal models.In this paper,we reviewed the modeling methods of the neurological ED caused by bilateral CN injury in rats in recent years,summarized the model evaluation indicators,and discussed the application and progress of ED models in basic experimental research.

The influence of educational and emotional support on e-learning acceptance: An integration of social support theory and TAM.

Flexible education is considered the primary function of e-learning, however, empirical evidence during the COVID-19 pandemic has also demonstrated that students may seek emotional comforts in e-learning to alleviate their negative emotions. This study aims to provide a holistic view of the antecedents of college students' e-learning acceptance by integrating social support theory with the technology acceptance model. Specifically, drawing upon social support theory, this study adopted perceived educational support and perceived emotional support as two driving factors and examined their influences on students' continuous intention in e-learning. The model was empirically validated using survey data from 512 college respondents in China during the first wave of the pandemic. Our results suggested that while perceived educational support exerts a major influence on e-learning acceptance, perceived emotional support also has an important role to play. Besides, the analytics results suggested that the two facets of support had different influencing patterns: perceived educational support has a positive and significant relationship with both perceived ease of use and perceived usefulness, whereas perceived emotional support solely has a significant relationship with perceived ease of use. Additionally, compared with the prior studies, the effect size ( ß ) between perceived ease of use and perceived usefulness is larger in the present study (COVID-19 context). These findings stress the need to better understand the mechanism by which social support influences college students' e-learning acceptance and to make use of various kinds of social supports to enhance perceived ease of use (e.g. human-computer interface), promote perceived usefulness, and ultimately motivate more students' continuance intention in e-learning.

NCAPG promotes tumorigenesis of bladder cancer through NF-κB signaling pathway.

The non-SMC condensin I complex subunit G (NCAPG) is a subunit of the condensin complex, many studies have shown that NCAPG is aberrantly expressed in different tumors and closely associated with poor prognosis, but its role in bladder cancer is unclear. In this paper, we found that NCAPG expression was upregulated in bladder cancer in tumor-related databases, and further verified the expression of NCAPG in bladder cancer tissues as well as bladder cancer cell lines by tissue microarray, qPCR, and WB. Next, we explored the changes in bladder cancer cell proliferation as well as migration after NCAPG knockdown by cell growth curve, colony formation, soft agar assay, and xenograft model. Finally, we examined the changes in downstream signaling pathways after NCAPG knockdown using RNA-Seq, and we found that the NF-κB signaling pathway was inhibited with NCAPG gene knockdown, which was verified by luciferase reporter assay as well as WB. In conclusion, our results illustrate that NCAPG knockdown can inhibit the proliferation of bladder cancer cells through the NF-κB signaling pathway. This finding demonstrates that NCAPG could be a potential target for the treatment of bladder cancer.

Golgi scaffold protein PAQR3 as a candidate suppressor of gastric cardia adenocarcinoma via regulating TGF-ß/Smad pathway.

OBJECTIVES: To investigate the function of PAQR3 in gastric cardia adenocarcinoma (GCA) and understand the possible mechanism of PAQR3 in regulating epithelial-mesenchymal transition (EMT). METHODS: We detected PAQR3 protein in 146 GCA tissues and paired normal adjacent tissues (PNTs) specimens using immunohistochemical analysis, and explored its clinical significance. The expression levels of PAQR3 protein in 20 GCA tissues, their paired PNTs, HGC27, SGC7901, and GES-1 cells were analyzed by Western blot. Wild-type PAQR3 was overexpressed in HGC27 cells. The effects of PAQR3 overexpression on the function of HGC27 cells and its underlying mechanisms were then analyzed through a series of cell and molecular biology experiments. RESULTS: PAQR3 was significantly down-regulated in GCA tissues when compared with paired PNTs (p < 0.0001). The expression level of PAQR3 in GCA tissues was significantly negatively correlated with Helicobacter pylori infection (p = 0.000), venous invasion (p = 0.000), invasion depth (p = 0.000), lymph node metastasis (p = 0.022), tumor stage (p = 0.000), and patient survival (p = 0.009). Downregulation of PAQR3 was highly correlated with increased EMT signature and activated TGF-ß/Smad pathway in GCA tissues. Overexpression of PAQR3 in HGC27 cells negatively regulates its cellular functions, such as cell proliferation and migration, and suppresses EMT. Mechanistically, overexpression of PAQR3 significantly down-regulates the protein expression levels of TGF-1, p-Smad2, and p-Smad3 in HGC27 cells. CONCLUSION: PAQR3 was significantly down-regulated in GCA tissues, HGC27, and SGC7901 cells. PAQR3 significantly inhibits the proliferation, migration, and invasion of HGC27 cells. Mechanistically, PAQR3 can inhibit the EMT process in HGC27 cells by regulating TGF-ß/Smad signaling pathway.

Extracellular Vesicles Isolated From Hypoxia-Preconditioned Adipose-Derived Stem Cells Promote Hypoxia-Inducible Factor 1α-Mediated Neovascularization of Random Skin Flap in Rats.

BACKGROUND: Random flaps are widely used for wound repair. However, flap necrosis is a serious complication leading to the failure of operation. Our previous study demonstrated a great proangiogenic potential of hypoxia-treated adipose-derived stem cells-extracellular vesicles (HT-ASC-EVs). Thus, we aim to evaluate the effect of HT-ASC-EVs in the survival and angiogenesis of random skin flap in rats. METHODS: Adipose-derived stem cells-extracellular vesicles were respectively isolated from adipose-derived stem cell culture medium of 3 donors via ultracentrifugation. The expression of hypoxia-inducible factor 1α (HIF-1α) and proangiogenic potential of HT-ASC-EVs and ASC-EVs were compared by co-culturing with human umbilical vein endothelial cells. Forty male Sprague-Dawley rats were randomly divided into 3 group (n = 10/group). A 9 × 3-cm random skin flap was separated from the underlying fascia with both sacral arteries sectioned on each rat. The survival and angiogenesis of flaps treated by ASC-EVs or HT-ASC-EVs were also compared. Laser Doppler flowmetry and immunohistochemistry were used to evaluate skin perfusion and angiogenesis of skin flaps on postoperative day 7. RESULTS: Hypoxia-treated adipose-derived stem cells-extracellular vesicles further improve the proliferation, migration, tube formation with upregulated HIF-1α, and VEGF expression of human umbilical vein endothelial cells in vitro, compared with ASC-EVs. In vivo, postoperatively injecting HT-ASC-EVs suppressed necrosis rate (29.1 ± 2.8% vs 59.2 ± 2.1%) and promoted the angiogenesis of skin flap including improved skin perfusion (803.2 ± 24.3 vs 556.3 ± 26.7 perfusion unit), increased number of CD31-positive cells, and upregulated expression of HIF-1α in vascular endothelium on postoperative day 7, compared with ASC-EVs. CONCLUSIONS: Intradermal injecting HT-ASC-EVs improve the survival of random skin flap by promoting HIF-1α-mediated angiogenesis in rat model.

Effects of Chicken Serum Metabolite Treatment on the Blood Glucose Control and Inflammatory Response in Streptozotocin-Induced Type 2 Diabetes Mellitus Rats.

Chickens can live healthy without adverse effects despite high blood glucose levels. However, the blood biomolecules responsible for maintaining chronic hyperglycemia are unknown. Here, the effects of chicken serum metabolite treatment on blood glucose control and inflammatory response in streptozotocin (STZ)-induced Type 2 Diabetes Mellitus (T2DM) rats were investigated. First, chicken serum treatment reduced the advanced glycation end-products (AGEs) and blood glucose levels in STZ-induced T2DM rats. Second, insulin/glucose-induced acute hypoglycemic/hyperglycemic chickens and the blood biomolecules were screened via nontargeted ultra-performance liquid chromatography with mass spectroscopy (UPLC-MS), identifying 366 key metabolites, including DL-arginine and taurine, as potential markers for chronic hyperglycemia in chickens. Finally, DL-arginine functions for blood glucose control and inflammatory response were evaluated. We found that DL-arginine reduced the levels of blood glucose and AGEs in STZ-induced T2DM rats. In addition, DL-arginine treatment upregulated the glucose transporter type 4 (GLUT4) expression in the muscles and downregulated the advanced glycation end products receptor-1 (AGER1) expression in the liver and nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) expression in the pancreas and thymus tissues. Overall, these results demonstrate that serum metabolite of DL-arginine could maintain blood glucose homeostasis and suppress the inflammatory response in chickens. Therefore, DL-arginine may be a novel target for developing therapeutic agents to regulate hyperglycemia.