Topographic and Surgical Risk Factors for Early Myopic Regression between Small Incision Lenticule Extraction and Laser In Situ Keratomileusis.

Our objective was to evaluate the topographic and surgical factors of early myopic regression between laser in situ keratomileusis (LASIK) and small-incision lenticule extraction (SMILE). A retrospective case-control study was conducted, and 368 and 92 eyes were enrolled in the LASIK and SMILE groups via propensity score matching (PSM). Visual acuity, refractive status, axial length, and topographic/surgical parameters were collected. Multiple linear regression was applied to the yield coefficient and the 95% confidence interval (CI) of the parameters. The cumulative incidence of early myopic regression was higher in the LASIK group (p < 0.001). In the SMILE group, a lower central corneal thickness (CCT) thinnest value and a higher corneal cylinder associated with early myopic regression were observed; meanwhile, in the LASIK group, a lower CCT thinnest value, a higher steep corneal curvature, a larger optic zone, and a lower flap thickness related to early myopic regression were observed (all p < 0.05). In the SMILE group, a higher CCT difference correlated with early myopic regression was observed compared to the LASIK group (p = 0.030), and higher steep corneal curvature and lower cap/flap thickness (both p < 0.05) correlated with early myopic regression were observed in the LASIK group compared to the SMILE group. In conclusion, CCT differences significantly influence early myopic regression in the SMILE group; meanwhile, corneal curvature and flap thickness affect early myopic regression principally in the LASIK group.

Structural Factors That Determine the Amylolytic Properties of Starch-Lipid Complexes.

Structural factors that determine the amylolysis of starch-lipid complexes have remained unclear. Understanding the relationship between the structure and amylolysis of starch-lipid complexes is important for the design and preparation of complexes with predictable digestibility. In this study, the multiscale structures and amylolytic properties of complexes formed under different conditions between debranched high-amylose starch (DHAMS) and lauric, myristic, palmitic, and stearic acids were investigated. Higher complexing temperatures facilitated the formation of DHAMS-fatty acid (FA) complexes, especially the more stable type II crystallites. Longer complexing times also promoted the formation of complexes and the type II crystallites, except for DHAMS-lauric acid (LA). Molecular dynamics simulations showed that the binding free energy for the formation of DHAMS-LA complexes (10 kJ/mol) was lower than those for the other three DHAMS-FA complexes (20-50 kJ/mol), accounting for the lower stability of DHAMS-LA complexes at longer complexing times. The rate and extent of enzymatic digestion of the DHAMS-FA complexes were much lower in comparison to those of gelatinized HAMS. Correlation analyses showed that the rate and extent of enzymic digestion of DHAMS-FA complexes were mainly determined by the degree of crystallite perfection of the complexes.

Refraction and topographic risk factors for early myopic regression after small-incision lenticule extraction surgery.

We sought to evaluate the topographic risk factors for early myopic regression after small-incision lenticule extraction (SMILE). A retrospective case‒control study was conducted, and individuals who underwent SMILE surgery were enrolled. Among them, 406 and 14 eyes were categorized into the nonregression and regression groups, respectively. The preoperative and postoperative parameters in the two groups were collected, including spherical refraction (SE), axial length (AXL) and topographic data. A generalized linear model was adopted to analyze the difference in each parameter between the two groups. After 6 months, UCVA decreased in the regression group, and SE increased in the regression group (both P < 0.05). The increase in the CCT at the thinnest point (P = 0.044), flat corneal curvature (P = 0.012) and TCRP (P = 0.001) were significantly greater in the regression group. Regarding the risk factors for myopic regression, preoperative SE, preoperative sphere power, preoperative AXL, preoperative flat corneal curvature, preoperative SA, early postoperative SE, early postoperative sphere power, early postoperative AXL and early postoperative CCT difference were significantly greater in the regression group (all P < 0.05). The SE, sphere power, AXL, preoperative flat corneal curvature, preoperative SA, and postoperative CCT difference correlate with early myopic regression after SMILE.

Photocatalytic Generation of H2O2 Via a Hydrogen-Abstraction Pathway by Bi2.15WO6 under Visible Light.

Photocatalytic technology is a popular research area for converting solar energy into environmentally friendly chemicals and is considered the greenest approach for producing H2O2. However, the corresponding reactive oxygen species (ROS) and pathway involved in the photocatalytic generation of H2O2 by the Bi2.15WO6-glucose system are still not clear. Quenching experiments have established that neither •OH nor h+ contribute to the formation of H2O2, and show that the formed surface superoxo (≡Bi-OO•) and peroxo (≡Bi-OOH) species are the predominant ROS in H2O2 generation. In addition, various characterizations indicate the enhanced electron-transfer on the surface of Bi2.15WO6 with increasing contents of glucose via the ligand-to-metal charge transfer pathway, confirming H-transfer from glucose to ≡Bi-OO• or ≡Bi-OOH. The increased production of H2O2 with decreasing bond dissociation energy (BDEO-H) values of various phenolic compounds again supports the H-transfer mechanism from phenolic compounds to ≡Bi-OO• and then to ≡Bi-OOH. DFT calculations further reveal that on the Bi2.15WO6 surface, oxygen is sequentially reduced to ≡Bi-OO• and ≡Bi-OOH, while H-transfer from H2O or glucose to ≡Bi-OO• and ≡Bi-OOH, resulting in the production of H2O2. The lower energy barrier of H-transfer from adsorbed glucose (0.636 eV) than that from H2O (1.157 eV) indicates that H-transfer is more favorable from adsorbed glucose. This work gives new insight into the photocatalytic generation of H2O2 by Bi2.15WO6 in the presence of glucose/phenolic compounds via the H-abstraction pathway.

New Insight into the Effects of Endogenous Protein and Lipids on the Enzymatic Digestion of Starch in Sorghum Flour.

The effects of endogenous lipids and protein in sorghum flour on starch digestion were studied following the depletion of lipids and/or protein and after the reconstitution of separated fractions. The removal of protein or lipids moderately increases the digestibility of starch in raw (uncooked) sorghum flour to values close to those for purified starch. Rapid Visco Analyzer data (as a model for the cooking process) show that cooked sorghum flours with lipids have a lower starch digestibility than those without lipids after RVA processing, due to the formation of starch-lipid complexes as evidenced by their higher final viscosity and larger enthalpy changes. Additionally, the formation of a starch-lipid-protein ternary complex was identified in cooked sorghum flour, rather than in a reconstituted ternary mixture, according to the unique cooling stage viscosity peak and a greater enthalpy of lipid complexes. After heating, the sorghum flour showed a lower digestibility than the depleted flours and the reconstituted flours. The results indicate that the natural organization of components in sorghum flour is an important factor in facilitating the interactions between starch, lipids, and protein during RVA processing and, in turn, reducing the starch digestion.

A novel method for quantifying the short-range order in non-crystalline starch by Raman spectroscopy.

A quantitative method was developed to characterize the short-range order in non-crystalline starch by Raman spectroscopy. The Raman spectra of three forms of non-crystalline starches (just-gelatinized starch, which was heated to the point of having just lost its long-range order but still retaining essentially all of its short-range order, gelatinized starch and amorphous starch) were resolved into subspectra to calculate the short-range ordered phases. By deducting the spectra of amorphous starch using a subtraction technique, the areas of subspectra for short-range ordered phases in just-gelatinized and gelatinized starches were obtained. The ratio of the area for short-range ordered phases in gelatinized starch relative to that in just-gelatinized starch was negatively correlated with water content for gelatinization. Based on this, we propose that this ratio of areas provides a quantitative measure for assessing the short-range order in non-crystalline starch. This study provides an alternative and simpler method to an X-ray diffraction protocol proposed previously.

The influence of short-range molecular order in gelatinized starch on the formation of starch-lauric acid complexes.

A model system of gelatinized wheat starch (GWS) and lauric acid (LA) was used to examine the effect of residual short-range molecular order in GWS on the formation of starch-lipid complexes. The extent of residual short-range molecular order, as determined by Raman spectroscopy, decreased with increasing water content or heating duration of gelatinization. The enthalpy changes, crystallinity, short-range molecular order and the in vitro enzymic digestion of GWS-LA complexes increased initially to a maximum and then declined as the short-range molecular order in GWS decreased, showing that there was an optimal amount of residual short-range molecular order in GWS for maximizing GWS-LA complexes formation. Below this optimum amount, the limited disruption of short-range molecular order may constrain the mobility of amylose chains for complexation with LA, whereas with excessive disruption above this amount the amylose chains may be too disorganized or entangled to form complexes with LA. The susceptibility of GWS-LA complexes to enzymatic hydrolysis was influenced by both long- and short-range structural order, and to a lesser extent the amounts of complexes. This study showed clearly the role of short-range molecular order in gelatinized starch in influencing the formation of GWS-LA complexes.

Topographic and surgical risk factors for high postoperative residual astigmatism after small incision lenticule extraction in patients with different degrees of myopia: a retrospective cohort study.

BACKGROUND: To evaluate the possible topographic and surgical risk factors for high postoperative residual astigmatism in patients who undergo small-incision lenticule extraction (SMILE) surgery and have different myopia degrees. METHODS: A retrospective cohort study was conducted, and patients who underwent SMILE surgery were enrolled. A total of 80 and 150 eyes from 40 to 75 individuals, respectively, were selected as the low myopia and high myopia groups. The demographic data, visual acuity, refraction, topographic parameters and surgical settings were recorded. Multiple linear regression with interaction tests were performed to survey the risk factors for high postoperative residual astigmatism in each group. RESULTS: Five (6.25%) and 9 (6.00%) eyes presented with high postoperative residual astigmatism in the low myopia and high myopia groups, respectively, but these differences were not significant (P = 0.569). A steep corneal curvature was correlated with a greater risk of high postoperative residual astigmatism in the low myopia group (P = 0.015), while a higher degree of cycloplegic cylinder power, steeper corneal curvature, greater topographic cylinder power, smaller optic zone and longer incision length were associated with a high rate of postoperative residual astigmatism in the high myopia group (all P < 0.05). In addition, the interaction effects of cycloplegic and topographic cylinder power and longer incision length on the incidence of high postoperative residual astigmatism development were more evident in the high myopia group than in the low myopia group (all P < 0.05). CONCLUSIONS: A steep corneal curvature correlates with a high risk of high postoperative residual astigmatism after SMILE surgery, and a higher degree of cycloplegic and topographic cylinder and longer incision are associated with high postoperative residual astigmatism in individuals with high myopia.

Molecular Mechanisms Underlying the Effects of Small Intestinal Fermentation on Enhancement of Prebiotic Characteristics of Cellulose in the Large Intestine.

Knowledge about the prebiotic characteristics of cellulose by in vitro fermentation is not complete due to the neglect of small intestinal fermentation. This study investigated the effects of small intestinal fermentation on the prebiotic characteristics of cellulose in the large intestine and potential mechanisms through an approach of combined in vivo small intestinal fermentation and in vitro fermentation. The structural similarity between cellulose in feces and after processing by the approach of this study confirmed the validity of the approach employed. Results showed that small intestinal fermentation of cellulose increased both acetate and propionate content and enriched Corynebacterium selectively. Compared to in vitro fermentation after in vitro digestion of cellulose, the in vitro fermentation of cellulose after in vivo small intestinal fermentation produced higher contents of acetate and propionate as well as the abundance of probiotics like Ruminococcaceae_UCG-002, Blautia, and Bifidobaterium. The changes in the structural features of cellulose after in vivo small intestinal fermentation were more obvious than those after in vitro digestion, which may account for the greater production of short-chain fatty acids (SCFAs) and the abundance of probiotics. In summary, small intestinal fermentation enhanced the prebiotic characteristics of cellulose in the large intestine by predisrupting its structure.

Electroencephalogram-based machine learning models to predict neurologic outcome after cardiac arrest: A systematic review.

AIM OF THE REVIEW: The primary aim of this systematic review was to investigate the most common electroencephalogram (EEG)-based machine learning (ML) model with the highest Area Under Receiver Operating Characteristic Curve (AUC) in two ML categories, conventional ML and Deep Neural Network (DNN), to predict the neurologic outcomes after cardiac arrest; the secondary aim was to investigate common EEG features applied to ML models. METHODS: Systematic search of medical literature from PubMed and engineering literature from Compendex up to June 2, 2023. One reviewer screened studies that used EEG-based ML models to predict the neurologic outcomes after cardiac arrest. Four reviewers validated that the studies met selection criteria. Nine variables were manually extracted. The top-five common EEG features were calculated. We evaluated each study's risk of bias using the Quality in Prognosis Studies guideline. RESULTS: Out of 351 identified studies, 17 studies met the inclusion criteria. Random Forest (RF) (n = 7) was the most common ML model in the conventional ML category (n = 11), followed by Convolutional Neural Network (CNN) (n = 4) in the DNN category (n = 6). The AUCs for RF ranged between 0.8 and 0.97, while CNN had AUCs between 0.7 and 0.92. The top-three commonly used EEG features were band power (n = 12), Shannon's Entropy (n = 11), burst-suppression ratio (n = 9). CONCLUSIONS: RF and CNN were the two most common ML models with the highest AUCs for predicting the neurologic outcomes after cardiac arrest. Using a multimodal model that combines EEG features and electronic health record data may further improve prognostic performance.

Cloning and gene functional analysis study of dynamin-related protein GeDRP1E gene in Gastrodia elata / 药学学报

The gene GeDRP1E encoding dynamin-related protein 1E in Gastrodia elata was cloned by specific primers which were designed based on the transcriptome data of G. elata. Bioinformatics analysis on GeDRP1E gene was carried out by using ExPASy, ClustalW, MEGA, etc. Positive transgenic Arabidopsis plant and potato minituber were obtained with the genetic transformation system of Arabidopsis and potato. The plant height and seed setting rate of transgenic Arabidopsis, and agronomic characters, such as size, weight and starch content of potato minituber of transgenic potato were tested and analyzed. And GeDRP1E gene function was preliminarily investigated. The results showed that the open reading frame of GeDRP1E gene was 1 899 bp in length and 632 amino acids residues were encoded, with a relative molecular weight of 69.90 kDa and a molecular formula of C3079H4973N883O933S19. It was predicted that the theoretical isoelectric point was 7.27, the instability coefficient was 43.34, and the average hydrophilicity index was -0.259, which was indicative of an unstable hydrophilic protein. GeDRP1E has no transmembrane structure and signal peptide, and was localized in the cytoplasm. The phylogenetic tree showed that GeDRP1E was highly homologous with DRP1E proteins of other plant species, among which GeDRP1E had the highest homology with DcDRP1E (XP_020689662.1) in Dendrobium candidum, reaching 90.05%. GeDRP1E plant expression vector pCambia1300-35Spro-GeDRP1E was constructed by double digests, and Arabidopsis complementary mutant and potato overexpression strain of GeDRP1E gene were obtained by Agrobacterium-mediated gene transformation. Compared with the Arabidopsis AtDRP1E mutant, the height and seed setting rate of the GeDRP1E complementation mutant were rescued. The minituber of GeDRP1E overexpression potato had larger size, heavier weight and higher starch content, comparing to wild-type potato. It was preliminarily induced that GeDRP1E was involved in mitochondrial morphology regulation, which related to the growth and development of Arabidopsis plants and potato miniature. The research results laid a foundation for further elucidating the molecular mechanisms underlying the growth and development of G. elata tuber development.

Toxic effects of permethrin on HMC3 microglia and its associated mechanism / 环境与职业医学

Background Permethrin is a commonly used pyrethroid insecticide and has been found to be potentially neurotoxic. Microglia are innate immune cells in the central nervous system and are involved in the development of a range of neurodegenerative diseases. Objective To observe possible toxic effects of permethrin on human microglia clone 3 (HMC3) in vitro and explore associated mechanism. Methods HMC3 were treated with 0, 10, 25, and 55 μmol·L−1 permethrin for 72 h. Cell cycle and apoptosis were measured using flow cytometry. Cyclin-dependent kinase 1 (CDK1), cyclin-dependent kinase inhibitor 1A (CDKN1A), cyclin B2 (CCNB2), cellular tumor antigen p53 (p53), factor-related apoptosis (FAS), caspase 3 (CASP3), and H2A histone family member X (H2AX) were detected by quantitative real-time PCR (qPCR). The differential genes and enrichment pathways of HMC3 after 0 and 25 μmol·L−1 permethrin treatment was analyzed by RNA sequencing. HMC3 was treated by 0, 10, 25, and 55 μmol· L−1 permethrin for 72 h. The content of nitric oxide (NO) in the supernatant was detected using Griess reagent. The secretion level of interleukin-6 (IL-6) was detected by enzyme linked immunosorbent assay (ELISA). The mRNA expression levels of mitogen-activated protein kinase (MAPK) pathway (including MAPK1, MAPK8, and MAPK14), interleukin-1β (IL-1β), IL-6, and matrix metalloproteinase (MMP) families (including MMP1, MMP2, MMP3, and MMP9) were detected by qPCR. The protein expressions of phosphorylated p38 mitogen-activated protein kinase (p-p38), phosphorylated extracellular signal-regulated kinase (p-ERK), IL-1β, IL-6, and MMP1 were detected by Western blot. Results HMC3 was arrested in G2/M phase after 0, 10, 25, and 55 μmol·L−1 permethrin treatment for 72 h, of which there was a statistically significant difference between the 55 μmol·L−1 permethrin treatment group and the control group (P<0.01), and the mRNA expression of CDKN1A was up-regulated according to the qPCR (P<0.05). There was no statistically significant difference in the proportions of apoptosis between the groups (P＞0.05). The RNA sequencing showed that the differential genes were enriched in the MAPK pathway, and the mRNA expressions of MAPK1, MAPK8, and MAPK14 were up-regulated after the permethrin treatment at 55 μmol·L−1 compared to the control group by qPCR (P<0.05). The Western blot revealed that, compared to the control group, the levels of p-p38 and p-ERK were increased after the 10 μmol·L−1 permetrin treatment (P<0.05), the p-ERK level was increased after the 25 μmol·L−1 permetrin treatment (P<0.05), and the p-p38 level was up-regulated after the 55 μmol·L−1 permetrin treatment (P<0.05). The secretion of NO in the supernatant of HMC3 increased after permetrin treatment compared to the control group (P<0.05), the mRNA and protein expressions and the secretion of IL-6 showed an upward trend, the mRNA and protein expressions of IL-1β were up-regulated (P<0.05), and the mRNA and protein expressions of MMP1 were up-regulated in the 25 and 55 μmol·L−1 permethrin groups (P<0.05). Conclusion Permethrin inhibits HMC3 cell proliferation in vitro, induces cell cycle arrest, activates MAPK pathway, and promotes the expression of inflammatory factors IL-1β and MMP1, which may be one of the mechanism of neurotoxicity induced by permethrin.

Effects and mechanism of polysaccharides from Hedyotis diffusa on isoniazid-induced liver injury / 中国药房

OBJECTIVE To investigate the effects and mechanism of polysaccharides from Hedyotis diffusa （HDP） on isoniazid （INH）-induced liver injury. METHODS Healthy transgenic zebrafish with liver-specific fluorescence were divided into normal group， model group （4 mmol/L INH）， HDP low-concentration group （4 mmol/L INH+50 mg/mL HDP） and HDP high- concentration group （4 mmol/L INH+100 mg/mL HDP）. After grouping treating， the liver fluorescence area， fluorescence intensity and pathological changes of liver tissue were observed. Human liver L02 cells were divided into normal group， model group （4 mmol/L INH）， HDP low-concentration group （4 mmol/L INH+2 mg/mL HDP）， and HDP high-concentration group （4 mmol/L INH + 4 mg/mL HDP）. After grouping treating， the cell viability was detected， and the levels of alanine transaminase （ALT）， aspartate transaminase （AST）， and the content of glutathione （GSH） as well as the expression levels of silent information regulator 1 （Sirt1）， nuclear factor-erythroid 2-related factor 2 （Nrf2）， heme oxygenase-1 （HO-1） and quinone oxidoreductase 1 （NQO1） proteins were detected. RESULTS Compared with the model group， the HDP low- and high-concentration groups showed varying degrees of increase in the fluorescence area and fluorescence intensity （except for HDP low-concentration group） of zebrafish liver （P＜0.05 or P＜0.01）， and the characteristics of liver injury and necrosis had been improved to varying degrees. Compared with model group， the survival rate of L02 cells， the content of GSH （except for HDP low-concentration group）， the protein expression levels of Sirt1 （except for HDP low-concentration group）， Nrf2， NQO1， HO-1 （except for HDP low-concentration group） were significantly increased in HDP low- and high-concentration groups （P＜0.05 or P＜0.01）， and the levels of ALT and AST （except for HDP low-concentration group） were significantly decreased （P＜0.05）； the number of survival cells significantly increased， while the number of damaged or dead cells significantly decreased. CONCLUSIONS HDP has a potential protective effect against INH-induced liver injury， the mechanism of which may be associated with activating Sirt1/Nrf2 signaling pathway， improving mitochondrial function and enhancing antioxidant capacity.

Effects of comprehensive intervention on 24 h activity behavior among obese students in vocational colleges / 中国学校卫生

Objective@#To explore the effects of comprehensive intervention measures targeting physical activity, sedentary, sleep and other behaviors on 24 h activity behavior of obese students in vocational colleges, so as to provide a more tailored empirical basis for intervening obese students in vocational colleges.@*Methods@#A quasi experimental design using parallel controlled, randomized grouping was conducted from January to March 2023. A total of 79 first year obese students from a vocational college in Wuxi City were selected as the intervention group (41 students) and the control group (38 students). From April to June, 2023, the control group received no intervention, while the intervention group adopted an information based and behavioral intervention approach to comprehensively intervene in 24 h physical activity, sedentary, sleep and other behaviors (120 minutes each day for 8 weeks).Wherein, information based intervention mainly used paper leaflets and social and learning software to accurately push intervention information, and behavioral intervention mainly concentrated 1 hour of physical exercise and multiple activity behavior requirements every day with the triaxial accelerometer to feedback the objective data of physical activity. Subsequently, from June to July, 2023, a one week post test and follow up survey were conducted respectively.Bouchard diary in physical activity, Weekly questionnaire and triaxial accelerometer were used to record the 24 h activity behavior of both groups of students. T-test and repeated measurement analysis of variance were used to compare the differences of 24 h activity component index time between two groups before and after intervention and examine the changes within each group.@*Results@#Before and after intervention, there was no significant difference in the time of each component index of 24 h activity behavior in the control group. However, repeated measures analysis of variance between the intervention group and the control group revealed statistically significant interaction differences in physical activity, sedentary behavior, sleep and other index time were statistically significant(pre-test and post test: F =6.45, 4.66 ,7.21,7.88; pre-test,post-test and follow up test: F =5.37,5.12,5.43,5.29; P <0.01). During the followup period, compared with the post-test data [(313.25±54.15, 601.88±65.47, 462.83±42.86, 61.92±18.53)min/d], the time of each component (physical activity, sedentary behavior, sleep, other) of the 24 h activity behavior of students in the intervention group rebounded [(298.52± 60.27 , 613.69±68.55, 442.33±45.26, 85.28±20.57)min/d], but it was better than the pre-test data [(230.45±67.42, 720.32±105.63, 369.78±32.31, 119.29±22.17)min/d], and the difference was statistically significant( F =42.46,39.45,33.41,59.43, P <0.01). During the intervention period, the physical activity, sedentary and sleep duration indicators of the intervention group students showed fluctuating patterns in the 4th and 5th weeks.@*Conclusions@#The comprehensive intervention on 24 h activity behavior among obese students in vocational colleges shows significant effectiveness, but its sustainability is insufficient. Considering the characteristics of obese students in vocational colleges, personalized intervention measures should be provided to increase physical activity and sleep time and reduce static activity time, in order to promote students to develop a healthy lifestyle.

Erratum: Author correction to "Tumor-microenvironment activated duplex genome-editing nanoprodrug for sensitized near-infrared titania phototherapy" Acta Pharm Sin B (2022) 4224-4234

[This corrects the article DOI: 10.1016/j.apsb.2022.06.016.].

Urolithin C alleviates pancreatic ß-cell dysfunction in type 1 diabetes by activating Nrf2 signaling.

AIMS: Type 1 diabetes (T1D) is an autoimmune disorder that destroys insulin-generating pancreatic ß-cells. Preserving pancreatic ß-cell function is important for treating T1D. Our study aims to explore the mechanism underlying urolithin C (UC)-mediated regulation of ß-cell function. METHODS: Non-obese diabetic (NOD) mice were administrated with UC to evaluate UC-mediated protection of T1D. The inflammation of the pancreas islets was examined by hematoxylin and eosin staining. Glucose-stimulated insulin secretion (GSIS) assay and oral glucose tolerance test were applied to evaluate the progression of T1D. MIN6 cells were treated with TNF-α, IL-1ß and IFN-γ in the presence of UC. Cell viability was analyzed by CCK-8. Cell apoptosis, proliferation and DNA fragmentation were examined by Annexin V-FITC and PI staining, EdU incorporation and comet assays. Keap1, Nrf2, HO-1 and NQO1 were examined by western blot. Immunofluorescence staining was applied to detect Nrf2 and insulin. RESULTS: UC administration significantly reduced diabetes incidence, attenuated insulitis, elevated insulin levels and GSIS and reduced blood glucose and AUC in NOD mice. Cytokine treatment suppressed MIN6 cell viability and proliferation but enhanced apoptosis and DNA damage, and these detrimental effects were relieved by UC treatment. Furthermore, UC administration inhibited Keap1 expression and promoted the expression of Nrf2, HO-1 and NQO1 in NOD mice. Nrf2 signaling has been reported to be implicated in preventing the onset of diabetes, and HO-1 and NQO1 are phase II antioxidant enzymes that are regulated by Nrf2 signaling. Cytokine treatment upregulated Keap1 and downregulated Nrf2, HO-1 and NQO1 in MIN6 cells, but it was reversed by UC. The nuclear translocation of Nrf2 was prevented by cytokine treatment, but UC promoted its nuclear translocation. UC-mediated upregulation of Nrf2, HO-1 and NQO1, decreased cell apoptosis and increased proliferation and insulin secretion were abolished by silencing of Nrf2. CONCLUSION: UC improves pancreatic ß-cell function by activating Nrf2 signaling, thereby alleviating T1D progression.

Ferroptosis: A potential target of macrophages in plaque vulnerability.

Plaque vulnerability has been the subject of several recent studies aimed at reducing the risk of stroke and carotid artery stenosis. Atherosclerotic plaque development is a complex process involving inflammation mediated by macrophages. Plaques become more vulnerable when the equilibrium between macrophage recruitment and clearance is disturbed. Lipoperoxides, which are affected by iron levels in cells, are responsible for the cell death seen in ferroptosis. Ferroptosis results from lipoperoxide-induced mitochondrial membrane toxicity. Atherosclerosis in ApoE(-/-) mice is reduced when ferroptosis is inhibited and iron intake is limited. Single-cell sequencing revealed that a ferroptosis-related gene was substantially expressed in atherosclerosis-modeled macrophages. Since ferroptosis can be regulated, it offers hope as a non-invasive method of treating carotid plaque. In this study, we discuss the role of ferroptosis in atherosclerotic plaque vulnerability, including its mechanism, regulation, and potential future research directions.

Reimagining the Rheumatology Fellowship Interview: Using Participatory Design-Thinking Process to Create a More Applicant-Centered Experience.

OBJECTIVE: Design thinking is a creative problem-solving process used to better understand users' needs and experiences so that a product or service can be improved. Its emphasis on empathy, iterative prototyping, and participatory collaboration make it an ideal methodology for innovation in medical education. We apply this framework to the virtual rheumatology fellowship interview process so that interviews can become more applicant centered. METHODS: This educational quality improvement project uses a design-thinking framework to identify opportunities and challenges for rheumatology fellowship applicants. The investigators use the 5-step process (Empathize, Define, Ideate, Prototype, Test) and incorporate rapid qualitative analysis of semistructured interviews to innovate the interview experience. The iterative and collaborative nature of this process has empowered participants to codesign an applicant-centered interview experience. RESULTS: Interviews with fellowship applicants (n = 9), fellow physicians (n = 4), and faculty members (n = 3) identified three major dynamics of the interview process: (1) Is it a safe environment to ask questions? (2) How do I exchange information effectively? and (3) How do I fit all these data into the bigger picture? Creative brainstorming techniques at a series of three workshops yielded four prototypes emphasizing customization, hybridization, facilitation, and preparation. A finalized applicant-centered interview template was devised in preparation for the 2023-2024 application season. CONCLUSION: Design thinking has yielded insights into three important dynamics that drive applicant experiences. These insights allow for a redesign of processes so that virtual interviews can be more applicant centered. This framework allows for further iterations and modifications as the needs of applicants and programs evolve over time.