GnT-V-mediated aberrant N-glycosylation of TIMP-1 promotes diabetic retinopathy progression.

BACKGROUND: Vascular endothelial growth factor (VEGF) signaling pathway plays an important role in the progression of diabetic retinopathy (DR). The glycosylation modification process of many key functional proteins in DR patients is abnormal. However, the potential involvement of abnormal N-glycoproteins in DR progression remains unclear. METHODS: Glycoproteomic profiling of the vitreous humor was performed. The level of protein and N-glycoprotein was confirmed by Western blot and Lectin blot, respectively. The cell viability and migration efficiency were detected by CCK-8 and Transwell assay. Flow cytometry was conducted to analyze the level of cell apoptosis and reactive oxygen specie. Malondialdehyde, superoxide dismutase activity and VEGF content were detected by Enzyme linked immunosorbent assays. The interaction of metalloproteinase 1 (TIMP-1) with N-acetylglucosamine transferase V (GnT-V) was detected by GST pull-down. Hematoxylin and eosin staining and choroidal and retinal flat mount stained with fluorescein isothiocyanate-Dextran assay were used for functional research in vivo. RESULTS: We found that N-glycosylation was up-regulated in DR rats and high glucose (HG)-induced human retinal pigment epithelium cell line ARPE-19. HG-induced inhibited the viability of ARPE-19 cells and promoted cell apoptosis and oxidative stress (OS), but these effects were reversed with kifunensine treatment, GnT-V knockdown and TIMP-1 mutation. Additionally, GnT-V binds to TIMP-1 to promote N-glycosylation of TIMP-1. Over-expression of GnT-V inhibited the viability of ARPE-19 cells and promoted cell apoptosis, OS and VEGF release, which these effects were reversed with TIMP-1 mutation. Interestingly, over-expression of GnT-V promoted retinal microvascular endothelial cells (RMECs) angiogenesis but was revered with TIMP-1 mutation, which was terminally boosted by VEGF-A treatment. Finally, knockdown of GnT-V relieved DR progression. CONCLUSION: The findings indicate that GnT-V can promote RMECs angiogenesis and ARPE-19 cells injury through activation VEGF signaling pathway by increasing TIMP-1 N-glycosylation level, which provides a new theoretical basis for the prevention of DR.

Comparison of the efficacy and safety of ciprofol and propofol in sedating patients in the operating room and outside the operating room: a meta-analysis and systematic review.

BACKGROUND: As a new type of intravenous anesthetic, ciprofol has the advantages of fast onset of action, fast recovery and high clearance rate. This study aimed to investigate the effectiveness and safety of ciprofol versus traditional propofol for anesthesia and sedation in and out of the operating room. METHODS: We searched the literature in PubMed, Web of Science, Cochrane Library, and Embase databases from January 2021 to December 2023. All clinical studies comparing the sedative effects of propofol and ciprofol, both inside and outside the operating room, were included in our trial. The main outcome measures were induction time and incidence of injection-site pain. Data are merged using risk ratio and standardized mean difference with 95% confidence interval. Subgroup analysis, meta-regression, sensitivity analysis, and publication bias were performed. The study protocol was prospectively registered with PROSPERO (CRD42023447747). RESULTS: A total of 15 randomized, controlled trials involving 2002 patients were included in this study. Compared with propofol, ciprofol has a longer induction time in the operating room but a shorter induction time in non-operating room settings. Ciprofol can effectively reduce the risk of injection-site pain and respiratory depression both inside and outside the operating room. In addition, the risk of drug-related hypotension induced with ciprofol in the operating room is lower, but the awakening time is also longer. Meta-regression analysis showed that neither age nor BMI were potential sources of heterogeneity. Funnel plot, egger and begg tests showed no significant publication bias. Sensitivity analyzes indicate that our results are robust and reliable. CONCLUSION: Ciprofol has absolute advantages in reducing the risk of injection-site pain and respiratory depression, both in and outside operating room. Intraoperative use of ciprofol reduces the risk of drug-related hypotension and may also reduce the risk of intraoperative physical movements. However, ciprofol may have longer induction and awakening time than propofol.

Drought Stress Induced Different Response Mechanisms in Three Dendrobium Species under Different Photosynthetic Pathways.

Many Dendrobium species, which hold a high status and value in traditional Chinese medicine, grow on barks and rocks in the wild, often encountering harsh environments and facing droughts. However, the molecular mechanisms underlying the shift in the photosynthetic pathway induced by drought remain unclear. To address this issue, three Dendrobium species with different photosynthetic pathways were selected for sequencing and transcriptome data analysis after drought treatment. The findings included 134.43 GB of sequencing data, with numerous Differentially Expressed Genes (DEGs) exhibiting different response mechanisms under drought stress. Gene Ontology (GO)-KEGG-based enrichment analysis of DEGs revealed that metabolic pathways contributed to drought tolerance and alterations in photosynthetic pathways. Phosphoenolpyruvate Carboxylase (PEPC) was subjected to phylogenetic tree construction, sequence alignment, and domain analysis. Under drought stress, variations were observed in the PEPC gene structure and expression among different Dendrobium species; the upregulation of Dc_gene2609 expression may be caused by dof-miR-384, which resulted in the shift from C3 photosynthesis to CAM, thereby improving drought tolerance in Dendrobium. This study revealed the expression patterns and roles of PEPC genes in enhancing plant drought tolerance and will provide an important basis for in-depth research on Dendrobium's adaptation mechanisms in arid environments.

Genomic and Expression Analysis of Cassava (Manihot esculenta Crantz) Chalcone Synthase Genes in Defense against Tetranychus cinnabarinus Infestation.

Cassava is susceptible to mites, especially Tetranychus cinnabarinus. Secondary metabolism products such as flavonoids play an important role as antimicrobial metabolites protecting plants against biotic stressors including fungal, pathogen, bacterial, and pest defense. The chalcone synthase (CHS) is the initial step of the phenylpropanoid pathway for producing flavonoids and is the gatekeeper of the pathway. Until recently, the CHS genes family has not been systematically studied in cassava. Thirty-nine CHS genes were identified from the cassava genome database. Based on phylogenetic and sequence composition analysis, these CHSs were divided into 3 subfamilies. Within the same subfamily, the gene structure and motif compositions of these CHS genes were found to be quite conserved. Duplication events, particularly segmental duplication of the cassava CHS genes, were identified as one of the main driving force of its expansion. Various cis-elements contained in the promoter might regulate the gene expression patterns of MeCHS. Protein-protein interaction (PPI) network analysis showed that MeCHS1 and MeCHS10 protein are more closely related to other family members. The expression of MeCHS genes in young leaves was higher than that in other tissues, and their expression varies even within the same tissue. Coincidentally, these CHS genes of most LAP subclasses were highly expressed in young leaves. The verified MeCHS genes showed consistent with the real-time reverse transcription quantitative PCR (RT-qPCR) and proteomic expression in protected and affected leaves respectively, indicating that these MeCHS genes play crucial roles in the response to T. cinnabarinus. This study is the first to comprehensively expatiate the information on MeCHS family members. These data will further enhance our understanding both the molecular mechanisms and the effects of CHS genes. In addition, the results will help to further clarify the effects on T. cinnabarinus and provide a theoretical basis for the potential functions of the specific CHS gene in resistance to mites and other biotic stress.

Assessing usability of intelligent guidance chatbots in Chinese hospitals: Cross-sectional study.

Objective: This study aimed to assessing usability of intelligent guidance chatbots (IGCs) in Chinese hospitals. Methods: A cross-sectional study based on expert survey was conducted between August to December 2023. The survey assessed the usability of chatbots in 590 Chinese hospitals. One-way ANOVA was used to analyze the impact of the number of functions, human-like characteristics, number of outpatients, and staff size on the usability of the IGCs. Results: The results indicate that there are 273 (46.27%) hospitals scoring above 45 points. In terms of function development, 581(98.47%) hospitals have set the number of functions between 1 and 5. Besides, 350 hospitals have excellent function implementation, accounting for 59.32%. In terms of the IGC's human-like characteristic, 220 hospitals have both an avatar and a nickname. Results of One-way ANOVA show that, the number of functions(F = 202.667, P < 0.001), human-like characteristics(F = 372.29, P < 0.001), staff size(F = 9.846, P < 0.001), and the number of outpatients(F = 5.709, P = 0.004) have significant impact on the usability of hospital IGCs. Conclusions: This study found that the differences in the usability of hospital IGCs at various levels of the number of functions, human-like characteristics, number of outpatients, and staff size. These findings provide insights for deploying hospital IGCs and can inform improvements in patient's experience and adoption of chatbots.

Effectiveness of Escape Room in Medical Education: A Systematic Review and Meta-Analysis.

The primary goal of this meta-analysis is to explore the five factors of knowledge, teamwork, learning satisfaction, anxiety, and interprofessional ability to determine the value of escape rooms in medical education. Up to January 2023, we searched ScienceDirect, Scopus, PubMed, Embase, Web of Science, CNKI, and the Cochrane Library for pertinent works in either English or Chinese. The Risk of Bias 2 (RoB 2) tool and Newcastle-Ottawa Scale (NOS) were used to assess the quality of studies. Subgroup and sensitivity analyses were used to assess statistical heterogeneity, and I2 was used to measure it. Overall, escape rooms had a more significant positive effect than traditional learning on knowledge (standardized mean difference [SMD]: 0.84; 95% confidence interval [CI]: 0.36-1.33), teamwork (SMD: 4.91; 95% CI: 4.58-5.24), learning satisfaction (MD: 0.36; 95% CI: 0.08-0.64), and interprofessional ability (SMD: 1.04, 95% CI: 0.81-1.27). Moreover, the impact of escape rooms on anxiety also had significant effects (SMD: -8.23, 95% CI: -11.64 to -4.82). Escape rooms affect medical students' knowledge, teamwork, learning satisfaction, interprofessional ability, and anxiety. The findings of this study can be used as evidence that escape rooms is a more effective method than traditional teaching for improving active learning.

The association of sun-cured tobacco and cigarette use with global cognitive function, verbal fluency and memory in patients with chronic obstructive pulmonary disease: A cross-sectional study.

INTRODUCTION: Some elderly people in China prefer sun-cured tobacco to cigarettes, and the composition of sun-cured tobacco and cigarettes is inconsistent. The influence of cigarettes on the cognitive function of COPD patients has been widely reported, but the research on sun-cured tobacco is relatively rare. Our study explored the association of sun-cured tobacco and cigarette use with cognitive decline in COPD patients. METHODS: This was a cross-sectional study. A total of 401 COPD patients were included, and 190, 103, and 108 participants were included in non-smoking, cigarette-smoking, and sun-cured tobacco groups, respectively. We evaluated the global cognitive function using the Beijing version of the Montreal Cognitive Assessment, verbal fluency function using an animal fluency test, and memory function using ten unrelated words. RESULTS: The participants of both cigarette-smoking (AOR=11.18; 95% CI: 1.28- 97.5) and sun-cured tobacco (AOR=10.46; 95% CI: 1.14-96.4) groups were more likely to develop mild cognitive impairment compared to the non-smoking group. The mean z scores of global cognitive function, verbal fluency, and memory were lower in cigarette-smoking and sun-cured tobacco groups than those in a non-smoking group; Multivariable linear regression showed that global cognitive function (ß= -0.61; 95% CI: -1.04 - -0.18; and ß= -0.48; 95% CI: -0.91 - -0.05) and verbal fluency (ß= -0.79; 95% CI: -1.33 - -0.26; and ß= -0.69; 95% CI: -1.23 - -0.16) of the sun-cured tobacco group and the cigarette-smoking group were significantly lower than those of the non-smoking group when adjusting for demographic and disease-related characteristics. However, there was no significant difference between the cigarette-smoking and sun-cured tobacco groups in global cognitive function, verbal fluency, and memory. CONCLUSIONS: Compared with non-smokers, the use of cigarettes and sun-cured tobacco may damage the cognitive function of COPD patients, especially in global cognitive function and verbal fluency.

Relationship between bedtime, nighttime sleep duration, and anxiety symptoms in preschoolers in China.

Background: Sleep problems in preschoolers are becoming increasingly prominent, and the association between sleep status and anxiety symptoms has attracted growing attention. However, studies investigating the relationship between bedtime and nighttime sleep duration in preschoolers and their anxiety symptoms remain scant. We used the large sample data from the Longhua Cohort Study of Children in Shenzhen, China (LCCS) to analyze the association between bedtime and sleep in preschoolers and their anxiety symptoms. Methods: A cross-sectional study of 69,138 preschoolers in Longhua District, Shenzhen, China was conducted in 2022. Data on sociodemographic characteristics of families, bedtime, nighttime sleep duration of preschoolers, and their anxiety symptoms (measured by the Spence Preschool Children Anxiety Scale) were collected through a structured questionnaire completed by the parents. Using binary logistic regression models, the relationship between bedtime, nighttime sleep duration, and childhood anxiety symptoms was examined. Results: The bedtimes of preschoolers were concentrated between 21:01-22:00 (52.41%). Among the preschoolers, 38.70% had bedtimes later than 22:00, and 75.49% had insufficient nighttime sleep duration. The positive screening rate for anxiety symptoms among preschoolers was 3.50%. After adjusting for confounding factors using binary logistic regression models, compared with preschoolers with bedtime ≤21:00, The OR (95%CI) values of anxiety in preschoolers with bedtime ≥23:01, 22:01-23:00 and 21:01-22:00 were 2.86 (2.21-3.69), 1.51 (1.27-1.79) and 1.48 (1.26-1.76), respectively. Compared with those with sufficient nighttime sleep duration, the OR (95%CI) of children with nighttime sleep duration less than 9 h was 1.36 (1.23-1.51). Conclusion: An association exists between bedtime and nighttime sleep duration in preschoolers and their anxiety symptoms. Preschoolers with 21:00 for bedtime and a nighttime sleep duration of 10 h may have lower anxiety symptoms. These findings support the importance of adequate sleep for preventing anxiety symptoms in children.