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Endothelial dysfunction (ED) serves as the pathological basis for various cardiovascular diseases. Guanosine triphosphate cyclopyrrolone 1 (GCH1) emerges as a pivotal protein in sustaining nitric oxide (NO) production within endothelial cells, yet it undergoes degradation under oxidative stress, contributing to endothelial cell dysfunction. Citronellal (CT), a monoterpenoid, has been shown to ameliorate endothelial dysfunction induced by in atherosclerosis rats. However, whether CT can inhibit the degradation of GCH1 protein is not clear. It has been reported that ubiquitination may play a crucial role in regulating GCH1 protein levels and activities. However, the specific E3 ligase for GCH1 and the molecular mechanism of GCH1 ubiquitination remain unclear. Using data-base exploration analysis, we find that the levels of the E3 ligase Smad-ubiquitination regulatory factor 2 (Smurf2) negatively correlate with those of GCH1 in vascular tissues and HUVECs. We observe that Smurf2 interacts with GCH1 and promotes its degradation via the proteasome pathway. Interestingly, ectopic Smurf2 expression not only decreases GCH1 levels but also reduces cell proliferation and reactive oxygen species (ROS) levels, mostly because of increased GCH1 accumulation. Furthermore, we identify BH 4/eNOS as downstream of GCH1. Taken together, our results indicate that CT can obviously improve vascular endothelial injury in Type 1 diabetes mellitus (T1DM) rats and reverse the expressions of GCH1 and Smurf2 proteins in aorta of T1DM rats. Smurf2 promotes ubiquitination and degradation of GCH1 through proteasome pathway in HUVECs. We conclude that the Smurf2-GCH1 interaction might represent a potential target for improving endothelial injury.

Objective To explore the expression of junctophilin 2(JP2)and fibroblast growth factor 23(FGF23)in a rabbit model of atrial fibrillation mediated-cardiomyopathy(AMC). Methods Rabbit models of atrial fibrillation (AF) were developed through rapid atrial stimulation and then divided into three groups: control group (pacemakers implanted without pacing, n=6), AF group (pacing with ejection fraction decrease ＜10%,n=5), and AMC group (pacing with ejection fraction decrease ≥10%, n=6).Echocardiography was performed to detect left ventricular end-diastolic diameter(LVEDD),left ventricular end-systolic diameter(LVESD) and left ventricular ejection fraction(LVEF). JP2 and FGF23 were detected by ELISA method.Western blot and RT-qPCR were conducted to detect protein and mRNA expression of JP2 and FGF23. Results Left atrial diameter, right atrial diameter and right ventricular diameter increased and LVEF decreased in the AMC group as compared with the control group. AMC group had lower LVEF and larger aorta and right ventricle diameter. Compared with the control group, the expression of FGF23(P＜0.001)and JP2(P＜0.01)in left atrial cardiomyocytes was significantly increased in the AF group, while the expression of JP2 was decreased in the AMC group(P＜0.001).AMC group had lower expression of JP2 and FGF23 compared with AF group. Compared to the control group,plasma concentration of JP2 and FGF23 increased in the AF group and FGF23 plasma concentration increased in the AMC group. Plasma concentration of FGF23 and JP2 was lower in AMC group than that in AF group . Conclusions FGF23 expression increased and JP2 expression decreased as found in the rabbit AMC model.

Previous studies have shown that puerarin plays a key role in protecting humans and animals from cardiovascular diseases. The exact mechanism of the therapeutic effect of puerarin on various cardiovascular diseases (protective effect on cardiomyocytes) is still unclear. In the present study, we identify the role of puerarin in an animal model of experimental heart failure (HF) and explore its underlying mechanisms. The HF rat model is induced by intraperitoneal injection of adriamycin (ADR), and puerarin is administered intragastrically at low, medium, and high concentrations. We demonstrate that puerarin significantly improves myocardial fibrosis and inflammatory infiltration and, as a result, improves cardiac function in ADR-induced HF rats. Mechanistically, we find for the first time that puerarin inhibits overactivated Na+/H+ exchange isoform 1 (NHE1) in HF, which may improve HF by decreasing Na+ and Ca2+ ion concentrations and attenuating mitochondrial damage caused by calcium overload; on the other hand, puerarin inhibits the activation of the p38 pathway in HF, reduces the expressions of TGF-β and proinflammatory cytokines, and suppresses myocardial fibrosis. In conclusion, our results suggest that Puerarin is an effective drug against HF and may play a protective role in the myocardium by inhibiting the activation of p38 and its downstream NHE1.

This study aimed to investigate the teaching effect of the blended BOPPPS based on an online and offline mixed teaching model ("B + BOPPPS") in the course of fermentation engineering in applied universities. The participants were 142 undergraduates majoring from the course of fermentation engineering in Food Science and Engineering in 2019 and 2020 in Huanghuai University, Zhumadian city, Henan province, China. The students in the control group (68 students) were taught in 2019, and the students in the experimental group (74 students) were taught in 2020. The traditional teaching method and "B + BOPPPS" were implemented, respectively. The teaching effect was evaluated using the questionnaire survey of course satisfaction and theoretical knowledge test. The results showed that the scores of the theoretical knowledge test in the experimental group adopting "B + BOPPPS" were significantly higher than those in the control group, and the difference was statistically significant (p < 0.01). The students had a good evaluation of the "B + BOPPPS" in many aspects, which included achieving learning goals, providing in-depth understanding of knowledge points, stimulating interest in learning, training in the ability to analyze and think about problems, and so on. The results suggested that "B + BOPPPS" could stimulate students' interest in learning and improve their subjective initiative. They could also improve students' ability to master and apply knowledge, which was conducive to improving the theoretical teaching quality of the course of fermentation engineering.

Necrolytic migratory erythema (NME) is usually associated with paraneoplastic syndrome caused by functional pancreatic neuroendocrine tumor (PNET). Accurate diagnosis and effective treatment of NET-related NME is challenging due to its rarity and lack of typical clinical symptoms and specific pathological manifestations. Here we report a rare case of PNET with NME as the initial manifestation. 68Ga-DOTA-TATE PET/MR was used to detect the primary pancreatic and metastatic liver tumors. Finally, the patient was diagnosed as PNET via liver biopsy. After four cycles of standard capecitabine plus temozolomide chemotherapy combined with long-acting octreotide, the patient’s skin lesions on both lower extremities improved only slightly, while tumors remained stable and unchanged in size. Then the patient was treated with surufatinib. Two months later, the skin lesions healed completely, and tumors responded significantly. This rare case suggests that surufatinib may be a promising therapy for patients with PNET-associated NME.

X-linked Severe Combined Immunodeficiency (SCID-X1) due to IL2RG mutations is potentially fatal in infancy where 'emergency' life-saving stem cell transplant may only achieve incomplete immune reconstitution following transplant. Salvage therapy SCID-X1 patients over 2 years old (NCT01306019) is a non-randomized, open-label, phase I/II clinical trial for administration of lentiviral-transduced autologous hematopoietic stem cells following busulfan (6 mg/kg total) conditioning. The primary and secondary objectives assess efficacy in restoring immunity and safety by vector insertion site analysis (VISA). In this ongoing study (19 patients treated), we report VISA in blood lineages from first eight treated patients with longer follow up found a > 60-fold increase in frequency of forward-orientated VIS within intron 3 of the High Mobility Group AT-hook 2 gene. All eight patients demonstrated emergence of dominant HMGA2 VIS clones in progenitor and myeloid lineages, but without disturbance of hematopoiesis. Our molecular analysis demonstrated a cryptic splice site within the chicken β-globin hypersensitivity 4 insulator element in the vector generating truncated mRNA transcripts from many transcriptionally active gene containing forward-oriented intronic vector insert. A two base-pair change at the splice site within the lentiviral vector eliminated splicing activity while retaining vector functional capability. This highlights the importance of functional analysis of lentivectors for cryptic splicing for preclinical safety assessment and a redesign of clinical vectors to improve safety.

When the information society has become the mainstream environment, various applications of big data and computers have been popularized in various industries. Multimedia technology has always been a special part of the computer field. In audio, video, image processing, and transmission, multimedia information processing has become the main means to solve the above problems. The performance of this information processing technology is extremely powerful. It can not only process dynamic data but also complete the transmission task in the big data environment. Visual communication design is a way of transmitting information to the masses by using various effects, and it has its advantages in the selection of images, video, text, and other processing technologies. This paper mainly studies the concept, method, and application effect of visual communication design under multimedia information processing. Firstly, the application of multimedia information processing technology in various fields and countries is investigated. Based on the literature analysis and statistics, the advantage tendency of this technology is judged. Starting from the visual functions involved in visual communication, the application effect of the multimedia 3D image processing and rendering communication platform is used. The gray function is used to build the multimedia information processing platform and form a complete and effective evaluation system. Finally, the visual communication design optimized by multimedia processing technology is further analyzed to improve the defects of dynamic images in visual applications and further improve the impact of visual communication design on the masses. The results show that multimedia information processing technology can improve the efficiency of image data processing in visual communication design, and has a good impact on visual communication of dynamic information.