Aloe-emodin alleviates cerebral ischemia-reperfusion injury by regulating microglial polarization and pyroptosis through inhibition of NLRP3 inflammasome activation.

BACKGROUND: Microglial activation plays a crucial role in injury and repair after cerebral ischemia, and microglial pyroptosis exacerbates ischemic injury. NOD-like receptor protein 3 (NLRP3) inflammasome activation has an important role in microglial polarization and pyroptosis. Aloe-emodin (AE) is a natural anthraquinone compound originated from rhubarb and aloe. It exerts antioxidative and anti-apoptotic effects during cerebral ischemia/reperfusion (I/R) injury. However, whether AE affects microglial polarization, pyroptosis, and NLRP3 inflammasome activation remains unknown. PURPOSE: This study aimed to explore the effects of AE on microglial polarization, pyroptosis, and NLRP3 inflammasome activation in the cerebral infarction area after I/R. METHODS: The transient middle cerebral artery occlusion (tMCAO) and oxygen-glucose deprivation/re-oxygenation (OGD/R) methods were used to create cerebral I/R models in vivo and in vitro, respectively. Neurological scores and triphenyl tetrazolium chloride and Nissl staining were used to assess the neuroprotective effects of AE. Immunofluorescence staining, quantitative polymerase chain reaction and western blot were applied to detect NLRP3 inflammasome activation and microglial polarization and pyroptosis levels after tMCAO or OGD/R. Cell viability and levels of interleukin (IL)-18 and IL-1ß were measured. Finally, MCC950 (an NLRP3-specific inhibitor) was used to evaluate whether AE affected microglial polarization and pyroptosis by regulating the activation of the NLRP3 inflammasome. RESULTS: AE improved neurological function scores and reduced the infarct area, brain edema rate, and Nissl-positive cell rate following I/R injury. It also showed a protective effect on BV-2 cells after OGD/R. AE inhibited microglial pyroptosis and induced M1 to M2 phenotype transformation and suppressed microglial NLRP3 inflammasome activation after tMCAO or OGD/R. The combined administration of AE and MCC950 had a synergistic effect on the inhibition of tMCAO- or OGD/R-induced NLRP3 inflammasome activation, which subsequently suppressed microglial pyroptosis and induced microglial phenotype transformation. CONCLUSION: AE exerts neuroprotective effects by regulating microglial polarization and pyroptosis through the inhibition of NLRP3 inflammasome activation after tMCAO or OGD/R. These findings provide new evidence of the molecular mechanisms underlying the neuroprotective effects of AE and may support the exploration of novel therapeutic strategies for cerebral ischemia.

Expanding the genotypic and phenotypic spectrum associated with TBL1XR1 de novo variants.

BACKGROUND: The TBL1XR1 gene encodes the protein transducin-beta-like 1 receptor1, widely distributed in the pituitary, hypothalamus, white and brown adipose tissue, muscle, and liver. Current evidence suggests that heterozygous TBL1XR1 pathogenic variants can lead to a wide spectrum of phenotypes. This study aims to reveal the clinical phenotype and genetic profiles of de novo TBL1XR1 variations and summarize the relevant clinical and genetic features. METHODS: We analyzed four new cases harboring de novo TBL1XR1 variants and reviewed all reported cases. RESULTS: All probands suffered from global developmental delay. Moreover, patient 1 exhibited susceptibility to startle, patient 2 had hypovitaminosis D, short stature and hyponatremia, and patients 3 and 4 both presented with ASD (Autism spectrum disorder) and short stature. They all had a de novo TBL1XR1 variant (NM_024665.7), c.1184A > G (p.Tyr395Cys), c.1108G > A (p.Asp370Asn), c.1047 + 1G > C, and c.1097C > T (p.Ser366Phe) respectively. In addition, pooled analysis of 51 cases showed that they had speech impairment (38/39), intellectual developmental disorder (28/28), global developmental delay (42/42), and hypotonia (24/27), and some of them had epilepsy (10/22), ASD (13/25), and developmental regression (4/13). CONCLUSIONS: We report four new patients with de novo TBL1XR1 variants and provide a comprehensive overview of 47 previously reported individuals with TBL1XR1 variants, enriching the genotypic and phenotypic spectrum of TBL1XR1-related disease. This report further validates the pathogenicity de novo TBL1XR1 variants.

GmPLP1 negatively regulates soybean resistance to high light stress by modulating photosynthetic capacity and reactive oxygen species accumulation in a blue light-dependent manner.

High light stress is an important factor limiting crop yield. Light receptors play an important role in the response to high light stress, but their mechanisms are still poorly understood. Here, we found that the abundance of GmPLP1, a positive blue light receptor protein, was significantly inhibited by high light stress and mainly responded to high blue light. GmPLP1 RNA-interference soybean lines exhibited higher light energy utilization ability and less light damage and reactive oxygen species (ROS) accumulation in leaves under high light stress, while the phenotype of GmPLP1:GmPLP1-Flag overexpression soybean showed the opposite characteristics. Then, we identified a protein-protein interaction between GmPLP1 and GmVTC2, and the intensity of this interaction was primarily affected by sensing the intensity of blue light. More importantly, overexpression of GmVTC2b improved soybean tolerance to high light stress by enhancing the ROS scavenging capability through increasing the biosynthesis of ascorbic acid. This regulation was significantly enhanced after interfering with a GmPLP1-interference fragment in GmVTC2b-ox soybean leaves, but was weakened when GmPLP1 was transiently overexpressed. These findings demonstrate that GmPLP1 regulates the photosynthetic capacity and ROS accumulation of soybean to adapt to changes in light intensity by sensing blue light. In summary, this study discovered a new mechanism through which GmPLP1 participates in high light stress in soybean, which has great significance for improving soybean yield and the adaptability of soybean to high light.

The contributions of AI in the development of ideological and political perspectives in education.

Opportunities and difficulties have arisen for the educational system as a result of the development of "artificial intelligence" technology. In the era of "artificial intelligence", the main features of ideological and political education in colleges are the development of the intelligence revolution, the development of teaching concepts, and the omnipotence of teaching content, and teaching methods. This study further explores the necessity and development of "artificial intelligence technology" in college ideological and political education through a questionnaire survey, and promotes the organic integration of artificial intelligence and ideological and political education. The results show that [1] College students have positive attitudes toward the application of artificial intelligence in college ideological and political education, and college students are looking forward to the intelligent services and changes brought by artificial intelligence technology in college ideological and political education [2]. According to the results of the questionnaire survey, this paper proposes the development path of college ideological and political education in the era of artificial intelligence, that is, schools and teachers need to improve the transformation of traditional education as well as the construction of contemporary Internet education. This study offers the possibility of interdisciplinary research, expands the scope of ideological and political education research, and provides a reference for front-line teaching to a certain extent.

The Application Effect of Jiawei Sanyu Shengjing Decoction Combined with High Ligation of the Spermatic Vein in Varicocele Male Infertility Patients.

Objective: To analyze the application effect of Jiawei Sanyu Shengjing decoction combined with high ligation of the internal spermatic vein in male infertility patients with varicocele (VC). Methods: 106 male infertility patients with VC treated in our hospital from December 2018 to March 2019 were selected as examples. According to the length of stay, they were divided into the control group and observation group, with 53 cases in each group. High ligation of the internal spermatic vein was performed in both groups. On this basis, the observation group was treated with modified Sanyu Shengjing decoction, and the therapeutic effects of the two groups were compared. Results: The effective rate of 94.34% in the observation group was higher than 79.25% in the control group (P < 0.05). After treatment, the serum index level and sperm deformity rate in the observation group were lower than those in the control group, and the semen density and sperm activity were higher than those in the control group (P < 0.05). Conclusion: The treatment of VC male infertility with modified Sanyu Shengjing decoction combined with high ligation of the internal spermatic vein can effectively improve the number of sperm and reduce the density of semen.

Study on the Efficacy of Electric Acupuncture in the Treatment of Premature Ejaculation Based on Testosterone Level.

Objective: To investigate the clinical efficacy and possible mechanism of electroacupuncture in the treatment of premature ejaculation. Methods: 50 cases of premature ejaculation patients who met the diagnostic criteria were randomly divided into 2 groups with 25 cases in each group. The observation group was treated with electroacupuncture, and the control group was treated with Longdan Xiegan decoction. The treatment period was 4 weeks. Ejaculation latency (IELT), sexual satisfaction score of patients, sexual satisfaction score of partners, testosterone test, and drug safety assessment were performed in all 4 groups before and after treatment. Results: IELT was prolonged in all groups after treatment, the difference was statistically significant (P < 0.05). At the same time, the IELT of the observation group was significantly higher than that of the control group after treatment. Life satisfaction scores of patients and spouses in 2 groups were improved after treatment compared with before treatment, the difference was statistically significant (P < 0.05). After treatment, the satisfaction scores of patients and spouses in the observation group were higher than those in the control group, and the difference was statistically significant (P < 0.05). Before treatment, there was no significant difference in serum testosterone levels among all groups (P > 0.05). Serum testosterone levels in all groups were decreased after treatment compared with before treatment, with statistical significance (P < 0.05). After treatment, the serum testosterone level of the observation group was lower than that of the control group, and the difference was statistically significant (P < 0.05). During the treatment, the adverse reactions in each group disappeared after treatment, and no obvious abnormality was observed in the safety indicators. Conclusion: Electroacupuncture can improve the symptoms of premature ejaculation, which may be related to the regulation of serum testosterone by acupuncture.

Biallelic Mutations in ACACA Cause a Disruption in Lipid Homeostasis That Is Associated With Global Developmental Delay, Microcephaly, and Dysmorphic Facial Features.

OBJECTIVE: We proposed that the deficit of ACC1 is the cause of patient symptoms including global developmental delay, microcephaly, hypotonia, and dysmorphic facial features. We evaluated the possible disease-causing role of the ACACA gene in developmental delay and investigated the pathogenesis of ACC1 deficiency. METHODS: A patient who presented with global developmental delay with unknown cause was recruited. Detailed medical records were collected and reviewed. Whole exome sequencing found two variants of ACACA with unknown significance. ACC1 mRNA expression level, protein expression level, and enzyme activity level were detected in patient-derived cells. Lipidomic analysis, and in vitro functional studies including cell proliferation, apoptosis, and the migratory ability of patient-derived cells were evaluated to investigate the possible pathogenic mechanism of ACC1 deficiency. RNAi-induced ACC1 deficiency fibroblasts were established to assess the causative role of ACC1 deficit in cell migratory disability in patient-derived cells. Palmitate supplementation assays were performed to assess the effect of palmitic acid on ACC1 deficiency-induced cell motility deficit. RESULTS: The patient presented with global developmental delay, microcephaly, hypotonia, and dysmorphic facial features. A decreased level of ACC1 and ACC1 enzyme activity were detected in patient-derived lymphocytes. Lipidomic profiles revealed a disruption in the lipid homeostasis of the patient-derived cell lines. In vitro functional studies revealed a deficit of cell motility in patient-derived cells and the phenotype was further recapitulated in ACC1-knockdown (KD) fibroblasts. The cell motility deficit in both patient-derived cells and ACC1-KD were attenuated by palmitate. CONCLUSION: We report an individual with biallelic mutations in ACACA, presenting global development delay. In vitro studies revealed a disruption of lipid homeostasis in patient-derived lymphocytes, further inducing the deficit of cell motility capacity and that the deficiency could be partly attenuated by palmitate.