The multifaceted role of autophagy in skin autoimmune disorders: a guardian or culprit?

Autophagy is a cellular process that functions to maintain intracellular homeostasis via the degradation and recycling of defective organelles or damaged proteins. This dynamic mechanism participates in various biological processes, such as the regulation of cellular differentiation, proliferation, survival, and the modulation of inflammation and immune responses. Recent evidence has demonstrated the involvement of polymorphisms in autophagy-related genes in various skin autoimmune diseases. In addition, autophagy, along with autophagy-related proteins, also contributes to homeostasis maintenance and immune regulation in the skin, which is associated with skin autoimmune disorders. This review aims to provide an overview of the multifaceted role of autophagy in skin autoimmune diseases and shed light on the potential of autophagy-targeting therapeutic strategies in dermatology.

Unveiling the dynamics of self-regulated learning in project-based learning environments.

Project-based learning (PBL) has been found to exert a positive influence on learners' academic achievements, while also fostering their intrinsic motivation and playing a crucial role in nurturing sustainable learning capacities. Understanding individual differences in self-regulated learning (SRL) within project-based foreign language learning can guide language teachers in delivering personalized instruction. This study utilized a blended learning management system to collect and analyze data on SRL from 95 learners enrolled in a project-based College English course. Through microanalysis, latent profile analysis (LPA), and epistemic network analysis (ENA), the study identified distinct learner profiles and traced their developmental trajectories in project-based language learning. The findings revealed that PBL facilitates the occurrence of SRL behaviors and strengthens connections across different regulation phases. Notably, learners with diverse profiles displayed variations in their SRL epistemic network structures and developmental trajectories. These results highlight the dynamic nature of SRL within the PBL context, underscoring the significance of considering individual differences and supporting learners' evolving self-regulatory behaviors and strategies throughout their engagement in PBL activities. To enhance SRL in PBL, educators are encouraged to provide scaffolding support, promote help-seeking behaviors, and implement interventions targeting metacognitive processes and reflective practices.

Determining the phosphorus release curve for Sunphase HT phytase in nursery pig diets.

A total of 280 pigs (DNA 241 × 600, initially 10.4 ±â€…0.24 kg) were used in a 21-d study to determine the available P (aP) release curve for Sunphase HT phytase (Wuhan Sunhy Biology Co., Ltd., Wuhan, P.R. China) when fed diets with a high phytate concentration. On day 21 post-weaning, considered day 0 of the study, pigs were blocked by average pen body weight (BW) and randomly allotted to 1 of 7 dietary treatments with 5 pigs per pen and 8 pens per treatment. Dietary treatments were derived from a single basal diet, and ingredients including phytase, monocalcium P, limestone, and sand were added to create the treatment diets. Treatments included three diets with increasing (0.11%, 0.19%, and 0.27%) aP from monocalcium P, or four diets with increasing phytase (250, 500, 1,000, or 2,000 phytase unit (FTU)/kg) added to the diet formulated to 0.11% aP. All diets were corn-soybean meal-canola meal-based and were formulated to contain 1.24% SID Lys, a 1.10:1 total calcium-to-phosphorus ratio, and a calculated 0.32% phytate P. Prior to the beginning of the study, all pigs were fed a diet containing 0.11% aP from days 18 to 21 post-weaning. At the conclusion of the study, 1 pig, closest to the mean weight of each pen, was euthanized, and the right fibula, 10th rib, and metacarpal were collected to determine bone ash and density. After cleaning, bones were submerged in ultra-purified water under a vacuum for 4 h and then weighed to calculate the density (Archimedes principle). For bone ash, bones were processed using the non-defatted method. From days 0 to 21, increasing aP from monocalcium P increased (linear, P ≤ 0.014) average daily gain (ADG), gain-to-feed (G:F), and final BW. Pigs fed increasing phytase had increased (linear, P ≤ 0.045) ADG, final BW, and plasma inositol concentration as well as improved (quadratic, P = 0.023) G:F. For bone characteristics, pigs fed increasing aP from inorganic P had a linear improvement (P ≤ 0.019) in fibula bone ash weight and percentage bone ash, rib bone ash weight and bone density, and all metacarpal bone properties, with a quadratic response (P ≤ 0.030) for fibula bone density and rib percentage ash. Additionally, pigs fed increasing phytase had increased (P < 0.05) bone ash weight, percentage bone ash, and bone density in either a linear or quadratic fashion depending on the bone analyzed. The available P release curve generated for Sunphase HT phytase for percentage bone ash combining values from the right fibula, 10th rib, and metacarpal is aP release, % = (0.360 × FTU) ÷ (2,330.250 + FTU).

Association between glycolipids and risk of obstructive sleep apnea: A population-based study.

Background: This study aimed to investigate the associations between multiple glycolipid biomarkers and the risk of obstructive sleep apnea (OSA). Methods: Participants (10,286) aged from 35 to 74 years old were included in this cross-sectional study from the baseline survey of the Guangzhou Heart Study. OSA was ascertained using both Berlin Questionnaire and STOP-BANG Questionnaire. Fasting blood samples were collected from each participant; fasting blood glucose (FBG) and serum concentrations of high-density lipoprotein cholesterol (HDL-CH), low-density lipoprotein cholesterol (LDL-CH), total cholesterol (TC), and triglyceride (TG) were determined. Odds ratio (OR) with 95% confidence interval (CI) was calculated using the multivariate logistic regression model after adjustment for covariates. Results: Of the participants included, 15.56% were categorized into the pre-OSA group, and 8.22% into the OSA group. When comparing the highest with the lowest quartiles, HDL-HC was associated with a 22% (OR: 0.78, 95% CI: 0.65-0.94) and 41% (OR: 0.59, 95% CI: 0.45-0.78) reduced risk of pre-OSA and OSA, triglyceride was associated with a 32% (OR 1.32, 95% CI 1.08-1.60) and a 56% (OR 1.56, 95% CI 1.18-2.07) increased risk of pre-OSA and OSA, and FBG was associated with a 1.37-fold (95% CI 1.13-1.67) risk of pre-OSA and 1.38-fold (95% CI 1.03-1.85) risk of OSA. A significant exposure-response trend was observed for HDL-HC, TG, and FBG with both OSA and Pre-OSA (all p < 0.05). No significant association of LDL-CH and TC with the risk of both pre-OSA and OSA was observed. Conclusion: The findings suggest that serum HDL-CH was inversely associated with OSA risk, while elevated serum TG and FBG could increase the risk of OSA. Healthy glycolipid metabolism warrants more attention in the field of OSA prevention.

Novel lipid indicators and the risk of type 2 diabetes mellitus among Chinese hypertensive patients: findings from the Guangzhou Heart Study.

BACKGROUND: Data are limited on whether several easily measured indices are independent predictors of type 2 diabetes mellitus (T2DM) in hypertensive patients. This study aimed to assess the association of hypertriglyceridemic-waist phenotype, triglyceride glucose (TyG) index, lipid accumulation product (LAP), and visceral adiposity index (VAI) with T2DM risk in hypertensive patients. METHODS: This cross-sectional study included 5321 hypertensive patients from the baseline survey of the Guangzhou Heart Study. Face-to-face questionnaire survey, physical examination, and fasting blood sample collection were completed for all subjects. Odds ratio (OR) with 95% confidence interval (95% CI) were calculated by using the logistic regression model. The potential nonlinear relationship was examined using restricted cubic spline regression. RESULTS: The prevalence of T2DM was 19.98% among hypertensive patients. After adjusting for confounders, participants with elevated triglyceride levels and enlarged waist circumference (HTGW) were associated with a 2.57-fold risk of T2DM (OR 2.57, 95% CI 2.05, 3.23). When comparing with subjects within the lowest quartile of the indices, those in the highest quartile of TyG, LAP, and VAI were associated with 5.35-fold (95% CI 4.33, 6.64), 2.65-fold (95% CI 2.11, 3.34), and 2.17-fold (95% CI 1.77, 2.67) risk of T2DM after adjusting for confounders. Every 1-unit increment of TyG, LAP, and VAI was associated with 81%, 38%, and 31% increased risk of T2DM, respectively. The nonlinear association was observed for TyG, LAP, and VAI (all P Non-linear < 0.001). CONCLUSIONS: The results found that among hypertensive patients, HTGW and a higher level of TyG, LAP, and VAI were associated with an elevated risk of T2DM. The findings suggested that HTGW, TyG, LAP, and VAI may serve as simple and effective tools for T2DM risk assessment in the prevention and management of main chronic diseases.

Identification and Validation of Autophagy-Related Genes in Vitiligo.

Vitiligo is a common depigmented disease with unclear pathogenesis. Autophagy is crucial for maintaining cellular homeostasis and has been linked to a variety of autoimmune disorders; however, there have been no reports exploring the involvement of autophagy-related genes (ARGs) in vitiligo using bioinformatics methodologies. In this study, RNA-sequencing technology was used to identify the differentially expressed genes (DEGs) and the Human Autophagy Database (HADb) was overlapped to identify differentially expressed autophagy-related genes (DEARGs) in stable non-segmental vitiligo (NSV). Bioinformatics analyses were conducted with R packages and Ingenuity Pathways Analysis (IPA). DEARGs were further confirmed with qRT-PCR. Critical autophagy markers were detected with Western blotting analysis. We identified a total of 39 DEARGs in vitiligo lesions. DEARGs-enriched canonical pathways, diseases and bio functions, upstream regulators, and networks were discovered. qRT-PCR confirmed the significant increases in FOS and RGS19 in vitiligo lesions. Lower microtubule-associated protein 1 light chain (LC3) II/LC3I ratio and higher sequestosome 1 (SQSTM1, p62) expression were found in vitiligo lesions. In conclusion, this study provided a new insight that autophagy dysregulation appeared in stable vitiligo lesions and might be involved in the etiology of vitiligo by taking part in multiple pathways and bio functions.

Insights Into the MYB-Related Transcription Factors Involved in Regulating Floral Aroma Synthesis in Sweet Osmanthus.

As an important member of the MYB transcription factor (TF) family, the MYB-related TFs play multiple roles in regulating the synthesis of secondary metabolites and developmental processes, as well as in response to numerous biotic and abiotic stressors in plants. However, little is known regarding their roles in regulating the formation of floral volatile organic compounds (VOCs). In this study, we conducted a genome-wide analysis of MYB-related proteins in sweet osmanthus; 212 OfMYB-related TFs were divided into three distinct subgroups based on the phylogenetic analysis. Additionally, we found that the expansion of the OfMYB-related genes occurred primarily through segmental duplication events, and purifying selection occurred in all duplicated gene pairs. RNA-seq data revealed that the OfMYB-related genes were widely expressed in different organs of sweet osmanthus, and some showed flower organ/development stage-preferential expression patterns. Here, three OfMYB-related genes (OfMYB1R70/114/201), which were expressed nuclearly in floral organs, were found to be significantly involved in regulating the synthesis of floral VOCs. Only, OfMYB1R201 had transcriptional activity, thus implying that this gene participates in regulating the expression of VOC synthesis related genes. Remarkably, the transient expression results suggested that OfMYB1R70, OfMYB1R114, and OfMYB1R201 are involved in the regulation of VOC synthesis; OfMYB1R114 and OfMYB1R70 are involved in accelerating ß-ionone formation. In contrast, OfMYB1R201 decreases the synthesis of ß-ionone. Our results deepen our knowledge of the functions of MYB-related TFs and provide critical candidate genes for the floral aroma breeding of sweet osmanthus in the future.

Altered expression of ferroptosis markers and iron metabolism reveals a potential role of ferroptosis in vitiligo.

Oxidative stress is one of the triggering factors for vitiligo, which leads to melanocyte (MC) destruction in vitiligo lesions. Ferroptosis, which is characterized by iron-dependent increase in oxidative stress and lipid peroxidation, has been widely explored in numerous diseases, whereas whether ferroptosis plays a role in MC loss of vitiligo remains to be elucidated. Quantitative real-time PCR and western blot analysis were used to determine the expression of ferroptosis markers in vitiligo patients. Immunonephelometry and electrochemiluminescence were performed to analyze iron status. Reactive oxygen species (ROS), Fe2+ , and lipid ROS were assessed by flow cytometry. The expression of ferroptosis markers was significantly altered in the epidermis of vitiligo patients. Iron deficiency was revealed in the blood of patients. Erastin reduced cell viability and led to oxidative stress, iron overload as well as lipid peroxide accumulation in human epidermal MCs in vitro. Altered expression of ferroptosis markers and inhibition of melanin synthesis in MCs were induced by erastin, which was attenuated by N-acetyl-L-cysteine (NAC) pretreatment or post-treatment in vitro. In conclusion, ferroptosis might take place during the process of vitiligo. Erastin could induce ferroptosis in human epidermal MCs and NAC could protect MCs from ferroptosis in vitro.

The fate of melanocyte: Mechanisms of cell death in vitiligo.

Loss of melanocytes (MCs) is the most notable feature of vitiligo. Hence, it is critical to clarify the mechanisms of MC destruction in vitiligo. Apoptosis is most widely studied cell death pathways in vitiligo. In addition, the other two forms of cell death, conventional necrosis and autophagy seem to be involved in the death of vitiligo MCs under certain situations. Moreover, new types of regulated cell death including necroptosis, pyroptosis, and ferroptosis may also participate in the pathogenesis of vitiligo. Anoikis is likely to be connected with the death of detached MCs, which is provoked specifically by loss of anchorage. Primary phagocytosis, later called phagoptosis can execute death of viable cells, probably partly responsible for the loss of MCs in vitiligo. In this review, we aim to summarize the latest insights into various forms of MC death in vitiligo and discuss the corresponding mechanisms.