The effects of advanced glycation end-products on skin and potential anti-glycation strategies.

The advanced glycation end-products (AGEs) are produced through non-enzymatic glycation between reducing sugars and free amino groups, such as proteins, lipids or nucleic acids. AGEs can enter the body through daily dietary intake and can also be generated internally via normal metabolism and external stimuli. AGEs bind to cell surface receptors for AGEs, triggering oxidative stress and inflammation responses that lead to skin ageing and various diseases. Evidence shows that AGEs contribute to skin dysfunction and ageing. This review introduces the basic information, the sources, the metabolism and absorption of AGEs. We also summarise the detrimental mechanisms of AGEs to skin ageing and other chronic diseases. For the potential strategies for counteracting AGEs to skin and other organs, we summarised the pathways that could be utilised to resist glycation. Chemical and natural-derived anti-glycation approaches are overviewed. This work offers an understanding of AGEs to skin ageing and other chronic diseases and may provide perspectives for the development of anti-glycation strategies.

MBL2 polymorphism may be a protective factor of autoimmune thyroid disease susceptibility.

Genetic susceptibility is an essential pathogenetic mechanism in autoimmune thyroid disease (AITD). MBL2 gene polymorphisms have been shown to play a vital role in the pathogenesis of multiple autoimmune disorders, but its contribution to AITD is unclear. The aim of this study was to assess the linkage between MBL2 gene polymorphisms and AITD susceptibility in a Chinese Han population. One thousand seven hundred sixty seven subjects consisting of 965 AITD patients and 802 controls from a Chinese Han population were enrolled in the case-control study. Four common single-nucleotide polymorphisms (SNPs) in the MBL2 gene were tested using high-throughput sequencing technology for sequence-based SNP genotyping. The allele and genotype distribution results showed that the minor alleles of rs198266, rs10824793, and rs4935046 were significantly lower in Hashimoto's thyroiditis (HT) patients than in healthy controls. In further genetic model analysis, the dominant models of rs1982266, rs10824793, and rs4935046 for MBL2 in the AITD group exhibited a lower risk of morbidity. Finally, we discovered that haplotype AAGC was associated with Graves' disease (GD), while AGC was associated with HT. Our study provides strong evidence for a genetic correlation between MBL2 and AITD, and the polymorphism of the MBL2 gene may be a protective factor for AITD, especially for HT. These findings can advance our understanding of the etiology of AITD, as well as provide guidance for prevention and intervention toward AITD.

Social support and vicarious posttraumatic growth among psychological hotline counselors during COVID-19: the role of resilience and cognitive reappraisal.

Background: The COVID-19 pandemic is a serious threat to people's lives and mental health. As a key worker providing psychological assistance services, the purpose of this study was to explore the relationship between social support and vicarious posttraumatic growth of psychological hotline counselors during COVID-19 and its mechanism. Methods: A questionnaire survey was conducted among 241 psychological hotline counselors. Path analysis was conducted through structural equation modeling. Results: The direct path from social support to vicarious posttraumatic growth of psychological hotline counselors was not significant, but the indirect path between them was significant. Social support can influence vicarious posttraumatic growth of psychological hotline counselors through the mediating effects of resilience and cognitive reappraisal as well as the chain mediating effects of these two factors. Conclusions: Social support does not directly stimulate vicarious posttraumatic growth in psychological hotline counselors, but social support can influence counselors' vicarious posttraumatic growth through the role of resilience, cognitive reappraisal, and the chain-mediated effects of psychological resilience and cognitive reappraisal. This encourages hotline counselors to be intentional about applying resources to balance the effects of trauma work on them as they face their clinical work.

High iodine promotes autoimmune thyroid disease by activating hexokinase 3 and inducing polarization of macrophages towards M1.

Autoimmune thyroid disease (AITD), the most common autoimmune disease, includes Graves' disease (GD) and Hashimoto's thyroiditis (HT). Currently, the pathogenesis of AITD is not fully understood. Our study aimed to examine the presence of macrophage polarization imbalance in AITD patients, to investigate whether high iodine can cause macrophage polarization imbalance, and to investigate the role of key genes of metabolic reprogramming in macrophage polarization imbalance caused by high iodine. We synergistically used various research strategies such as systems biology, clinical studies, cell culture and mouse disease models. Gene set enrichment analysis (GSEA) revealed that M1 macrophage hyperpolarization was involved in the pathogenesis of AITD. In vitro and in vivo experiments showed that high iodine can affect the polarization of M1 or M2 macrophages and their related cytokines. Robust rank aggregation (RRA) method revealed that hexokinase 3 (HK3) was the most aberrantly expressed metabolic gene in autoimmune diseases. In vitro and in vivo studies revealed HK3 could mediate macrophage polarization induced by high iodine. In summary, hyperpolarization of M1-type macrophages is closely related to the pathogenesis of AITD. High iodine can increase HK3 expression in macrophages and promote macrophage polarization towards M1. Targeting HK3 can inhibit M1 polarization induced by high iodine.

Hydroxychloroquine use reduces mortality risk in systemic lupus erythematosus: A systematic review and meta-analysis of cohort studies.

OBJECTIVE: Hydroxychloroquine (HCQ) is widely used in patients with systemic lupus erythematosus (SLE), but its effects on the mortality have not reached a definite conclusion. In this systematic review and meta-analysis, we aimed to assess whether HCQ use could reduce the risk of mortality in SLE patients. METHODS: PubMed, Embase, Web of Science, and Cochrane database were searched from inception to April 17, 2022 without language restrictions to explore the relationship between HCQ use and SLE mortality. The relative risk (HR) was pooled using the STATA software. RESULTS: A total of 21 studies with a pooled patient population of 26,037 were included in the study, including 14 studies on the association between HCQ alone and mortality risk and seven studies on the association between HCQ/chloroquine (CQ) and mortality risk. The pooled findings suggested that HCQ significantly reduced the overall mortality risk of SLE (pooled HR 0.46, 95% CI 0.38-0.57, p < 0.001). In subgroup analysis of SLE complications, HCQ use also decreased the risk of death in SLE patients with renal (HR=0.43, 95% CI 0.26-0.70, p = 0.001) and cardiopulmonary involvement (HR=0.37, 95% CI= 0.25-0.54, p < 0.001). In addition, HCQ use was also protective against the risk of mortality in SLE patients in different regions, such as Asia (HR=0.46, 95% CI=0.33-0.64, p < 0.001), Europe (HR= 0.40, 95% CI = 0.22-0.71, p = 0.002), and America (HR=0.52, 95% CI= 0.42-0.64, p < 0.001). CONCLUSION: Our data suggested that HCQ use was associated with a reduced risk of mortality in patients with SLE.

Saikosaponin-d Attenuates Hashimoto's Thyroiditis by Regulating Macrophage Polarization.

Objective: Hashimoto's thyroiditis (HT) is one of the most common clinical autoimmune diseases. Recent studies have found that HT pathogenesis is associated with macrophage polarization. Saikosaponin-d (SSd) is an active component in the Chinese medicine Bupleurum, which has anti-inflammatory and immunomodulatory effects. The purpose of this study was to verify the therapeutic effect of SSd on HT and to investigate the regulatory effect of SSd on macrophage polarization in HT. Methods: Network pharmacology analysis was used to predict the relevant targets and signaling pathways of SSd for HT treatment. The therapeutic effect of SSd on HT model mice and the effect on macrophage polarization were detected by animal experiment. Results: Network pharmacological analysis showed that SSd can alleviate HT against multiple targets such as IL-6 and IL-10 and can act on macrophage polarization-related signaling pathways such as MAPK and JAK-STAT signaling pathways. Animal experiments showed that SSd intervention attenuated the lymphocytic infiltration in thyroid tissues of HT mice (P = 0.044); SSd intervention reduced serum TPOAb antibody level in HT mice (P < 0.001); SSd adjusted M1/M2 imbalance towards M2-type macrophage polarization in the spleen of HT mice (P = 0.003); SSd inhibited the expressions of Th1-type cytokine IFN-γ and Th17-type cytokine IL-17 systemically and locally in the thyroid of HT mice (P < 0.05). Conclusion: SSd treatment can regulate Th1/Th2 and Th17/Treg imbalances and reduce the severity of HT in mice by promoting the polarization of M2 macrophages.

Age-dependent aggregation of ribosomal RNA-binding proteins links deterioration in chromatin stability with challenges to proteostasis.

Chromatin instability and protein homeostasis (proteostasis) stress are two well-established hallmarks of aging, which have been considered largely independent of each other. Using microfluidics and single-cell imaging approaches, we observed that, during the replicative aging of Saccharomyces cerevisiae, a challenge to proteostasis occurs specifically in the fraction of cells with decreased stability within the ribosomal DNA (rDNA). A screen of 170 yeast RNA-binding proteins identified ribosomal RNA (rRNA)-binding proteins as the most enriched group that aggregate upon a decrease in rDNA stability induced by inhibition of a conserved lysine deacetylase Sir2. Further, loss of rDNA stability induces age-dependent aggregation of rRNA-binding proteins through aberrant overproduction of rRNAs. These aggregates contribute to age-induced proteostasis decline and limit cellular lifespan. Our findings reveal a mechanism underlying the interconnection between chromatin instability and proteostasis stress and highlight the importance of cell-to-cell variability in aging processes.

Cytotoxic and inflammatory response of human lung epithelial cells A549 to particles released from dental restorative materials during dry and wet grinding.

OBJECTIVES: The aim was to evaluate the release of particles from dental materials during wet and dry grinding and test their effects on human lung epithelia cells in-vitro. METHODS: Four dental restorative materials were used: two composites [Ceram.x® universal (Dentsply Sirona) and Filtek™ Supreme XTE (3 M)], one ceramic [VITABLOCS® Mark II (VITAy)] and a ceramic-resin material [Lava™ Ultimate (3 M)]. Material samples were ground to powder under standardized wet and dry conditions in an isolated dental room. During grinding, the particle concentrations were measured with LAS and CPC. Baseline values were measured before grinding. The particles' size was evaluated using DLS and SEM. Water was used as control. The cytotoxicity and inflammatory response of the lung cells (A549) after exposure to different concentrations (1, 3, 10, 30, 100, 300 µg/mL) of the generated dust were analyzed with LDH, WST-1 and ELISA. RESULTS: LAS and CPC revealed a high concentration of particles< 10 µm and< 1 µm respectively, into the air. Particles showed high tendency to agglomerate. DLS showed particle size distribution between 150 nm and 18 µm independently of the material composition. All materials induced significant effects (p < 0.05) on the cell membrane integrity and viability of the A549 cells. Only the ceramic particles showed a significant increase in hydroxyl radical formation at low concentrations (p < 0.05), for both wet and dry conditions. All materials except ceramic, induced a significant release of IL-8 in A549 cells at 300 µg / mL (p < 0.05). SIGNIFICANCE: Wet and dry grinding of dental materials result in release of ultrafine and fine particulate matter into the air. The in-vitro findings on the cellular response of lung cells to generated dust indicate a potential risk for human health due inhalation of the released particles. The use of water-cooling seems to be beneficial resulting in reduced release of particles compared to dry grinding.

The Relationship between VEGFC Gene Polymorphisms and Autoimmune Thyroiditis.

Background: Autoimmune thyroid diseases (AITDs), representative autoimmune diseases, mainly consist of Graves' disease (GD) and Hashimoto's thyroiditis (HT). In this passage, we investigated the association between vascular endothelial growth factor C (VEGFC) gene polymorphisms and AITDs. Methods: A total of 1084 patients with AITDs and 794 healthy controls were tested for VEGFC gene genotypes in four single nucleotide polymorphisms (SNPs) by high-throughput sequencing, and the correlation between VEGFC gene polymorphisms and AITDs was statistically analyzed. Results: The genotype distribution of rs3775194 was statistically associated with AITDs compared with the control group. Rs3775194 was associated with AITDs under the overdominant model, both before and after adjusting for confounding factors, while the other three SNPs were not associated with GD and HT. There was a prominent discrepancy between male healthy controls and male AITD patients under overdominant model in rs3775194 and the recessive model in rs11947611. The genotype distribution of rs3775194 was statistically related to male HT. Conclusion: These results reveal the correlation between VEGFC mutation and AITD susceptibility.

Association Between Polymorphisms of IL-23/IL-17 Pathway and Clinical Phenotypes of Autoimmune Thyroid Diseases.

BACKGROUND: Several autoimmune and inflammatory disorders, including autoimmune thyroid diseases (AITD), have been linked to Th17 cells and the IL-23/IL-17 axis. Current data suggest that genetic variation contributes greatly to disease susceptibility to AITD. OBJECTIVES: To study the role of single nucleotide polymorphisms (SNPs) of IL-23/IL-17 pathway in AITD predisposition and test the gene-gene/gene-sex interactions in these loci. METHODS: A total of 1051 patients with AITD, including 657 patients with Graves' disease (GD) and 394 patients with Hashimoto's thyroiditis (HT), and 874 healthy controls were enrolled in this case-control association study. Six SNPs were selected and genotyped by multiplex PCR combined with high-throughput sequencing. Interactions were tested by the general multifactor dimensionality reduction (GMDR) method. RESULTS: Allele C and combinational genotype AC+CC of rs3212227 within IL-23 were significantly associated with GD with goiter (p=0.003 and 0.014, respectively). Allele G and combinational genotype AG+GG of rs4819554 within IL-17RA were significantly related to HT with family history and the severity of HT (p=0.011 and 0.027; p=0.041 and 0.035). Also, allele T and genotype CT+TT of rs9463772 within IL-17F were significantly correlated with the severity of HT (p=0.001 and 0.027, respectively). Moreover, high dimensional gene-sex interaction (IL-23R-IL-23-IL-17RA-IL-17F-sex) was identified in AITD, GD, and HT patients with GMDR analysis. CONCLUSIONS: Our study identified the novel loci and gene-sex interaction in AITD. This evidence, from another perspective, suggests that sex, IL-23/IL-17 pathway, and Th17 cells play an important role in the pathogenesis of AITD.

Effects of college students' mindfulness on depression symptoms during the epidemic prevention and control period: The mediating effect of psychological resilience.

Depression symptoms significantly impact college students' mental health, particularly during the "closed management" period during the spread of COVID-19. Exploring the mechanism that affects college students' depression symptoms can help alleviate the impact of closed management policies on individual mental health and improve their mental health level. The onset of the COVID-19 pandemic resulted in the normalization of epidemic prevention and control in China and the implementation of the dynamic zero-COVID policy. This study used the Five-Factor Mindfulness Questionnaire-Short Form, Psychological Resilience Scale, and Beck Depression Scale to investigate the mindfulness, psychological resilience, and depression symptoms of 1,062 students under closed management conditions at Northwest Normal University. The mindfulness, psychological resilience, and depression status of students in closed management were investigated using an online questionnaire survey. Eight hundred and ten college students (M age = 20.43, SD = 1.67, range = 17-30) were selected to test the model using the structural equation model and bootstrap method. The results showed that the gender differences in mindfulness and psychological resilience were not significant. Gender differences in depression symptoms were significant, and depression symptoms in men were significantly higher than in women. Grade differences in resilience, mindfulness, and depression levels were not significant. Thus, psychological resilience is negatively associated with depressive symptoms. Psychological resilience plays a mediating role between mindfulness and depressive symptoms. This study provides reference and inspiration for improving college students' mental health under epidemic prevention and control circumstances.

Psoriasis Susceptibility 1 Candidate 1 (PSORS1C1) Polymorphism is Associated with Autoimmune Thyroid Disease in a Chinese Han Population.

BACKGROUND: Autoimmune thyroid disease (AITD) is an inherited, complex gene- and immune-related disorder that mainly includes Graves' disease (GD) and Hashimoto's thyroiditis (HT). Psoriasis susceptibility 1 candidate 1 (PSORS1C1) is a susceptibility gene associated with many autoimmune diseases, but its role in an individual's predisposition to AITD is unknown. METHODS: This study included 1065 Chinese Han patients with AITD and 943 matched healthy individuals. The rs3130983, rs3778638, rs3815087, and rs4959053 single nucleotide polymorphisms (SNPs) in PSORS1C1 were determined using multiplex polymerase chain reaction technology. RESULTS: Of the four SNPs, only the distribution of the rs3778638 genotypes was different between the AITD (AA, 2.67%; AG, 19.15%; and GG, 78.18%) and control (AA, 1.52%; AG, 22.2%; and GG, 75.87%) groups (P = .046). An association between rs3778683 and GD was observed (p = .039) but not with HT. No linkage disequilibrium was observed for rs3130983, rs3815087, rs3778638, and rs4959053 in PSORS1C1 among the patients with AITD and controls. CONCLUSION: This study suggests the influence of PSORS1C1 rs3778638 on the susceptibility to GDs, supporting this locus as a common autoimmunity risk factor.

The Influence of College Students' Empathy on Prosocial Behavior in the COVID-19 Pandemic: The Mediating Role of Social Responsibility.

Prosocial behavior has played an irreplaceable role during the COVID-19 pandemic, not only in infection prevention and control, but also in improving individual mental health. The current study was conducted after COVID-19 control was under the stage of Ongoing Prevention and Control in China. Using the Interpersonal Response Scale, Prosocial Tendencies Measure and Big Five Personality Questionnaire. In total, 898 college students participated in the current study (Mage = 19.50, SDage = 1.05, Age range = 16-24). The result showed that against the background of the COVID-19 pandemic, college students' social responsibility partially mediated the relationship between empathy and prosocial behavior. This study provides new insights and inspiration for improving college students' mental health in the context of the pandemic.

A characteristic optical variability time scale in astrophysical accretion disks.

Accretion disks around supermassive black holes in active galactic nuclei produce continuum radiation at ultraviolet and optical wavelengths. Physical processes in the accretion flow lead to stochastic variability of this emission on a wide range of time scales. We measured the optical continuum variability observed in 67 active galactic nuclei and the characteristic time scale at which the variability power spectrum flattens. We found a correlation between this time scale and the black hole mass extending over the entire mass range of supermassive black holes. This time scale is consistent with the expected thermal time scale at the ultraviolet-emitting radius in standard accretion disk theory. Accreting white dwarfs lie close to this correlation, suggesting a common process for all accretion disks.

Study of asymmetric biconical fiber tapers for in-fiber Mach-Zehnder interferometers and applications in single-frequency fiber lasers.

In this paper, asymmetric biconical fiber tapers (ABFTs) for in-fiber Mach-Zehnder interferometers (IFMZIs) are proposed and analyzed to enhance the interference effect. The proposed ABFT-IFMZIs are fabricated, tested, and demonstrated in applications of single-frequency (SF) emissions when incorporated into an all-fiber laser cavity as the frequency selecting component. In comparison with the traditional IFMZIs composed of all symmetric biconical fiber tapers (SBFTs), higher average transmittance and fringe contrast have been demonstrated with the ABFT-based IFMZIs. When applied to the SF fiber laser emission, lower pump threshold and higher slope efficiency have also been confirmed with the ABFT-IFMZI device. The theoretical and experimental results have indicated that the interference effect of IFMZIs can indeed be improved by the designated asymmetry of conical taper angles in ABFTs that can offer an extra flexibility in fiber taper design, fabrication, and applications.

Chlorogenic acid inhibits proliferation in human hepatoma cells by suppressing noncanonical NF-κB signaling pathway and triggering mitochondrial apoptosis.

Chlorogenic acid (CGA), a phenylpropanoid derived from Eucommia ulmoides Oliver, has been shown to exhibit potent cytotoxic and anti-proliferative activities against several human cancers. However, the effects of CGA on hepatocellular carcinoma (HCC) and the underlying mechanisms have not been intensively studied. In this study, the CGA treatment effects on the viability of human hepatoma cells were investigated by MTT assay. Our data showed that CGA could dose-dependently inhibit the activity of human hepatoma cells Hep-G2 and Huh-7, but did not affect the activity and growth of normal human hepatocyte QSG-7701. The genes and pathways influenced by CGA treatment were explored by RNA sequencing and bioinformatics analysis, which identified 323 differentially expressed genes (DEGs) involved in multiple pharmacological signaling pathways such as MAPK, NF-κB, apoptosis and TGF-ß signaling pathways. Further analyses by real-time quantitative PCR, Western blot and flow cytometry revealed that CGA effectually suppressed the noncanonical NF-κB signaling pathway, meanwhile it activated the mitochondrial apoptosis of HCC by upregulation of the BH3-only protein Bcl-2 binding component 3 (BBC3). Our findings demonstrated the potential of CGA in suppressing human hepatoma cells and provided a new insight into the anti-cancer mechanism of CGA.

Memorizing environmental signals through feedback and feedforward loops.

Cells in diverse organisms can store the information of previous environmental conditions for long periods of time. This form of cellular memory adjusts the cell's responses to future challenges, providing fitness advantages in fluctuating environments. Many biological functions, including cellular memory, are mediated by specific recurring patterns of interactions among proteins and genes, known as 'network motifs.' In this review, we focus on three well-characterized network motifs - negative feedback loops, positive feedback loops, and feedforward loops, which underlie different types of cellular memories. We describe the latest studies identifying these motifs in various molecular processes and discuss how the topologies and dynamics of these motifs can enable memory encoding and storage.

Cell-cycle-gated feedback control mediates desensitization to interferon stimulation.

Cells use molecular circuits to interpret and respond to extracellular cues, such as hormones and cytokines, which are often released in a temporally varying fashion. In this study, we combine microfluidics, time-lapse microscopy, and computational modeling to investigate how the type I interferon (IFN)-responsive regulatory network operates in single human cells to process repetitive IFN stimulation. We found that IFN-α pretreatments lead to opposite effects, priming versus desensitization, depending on input durations. These effects are governed by a regulatory network composed of a fast-acting positive feedback loop and a delayed negative feedback loop, mediated by upregulation of ubiquitin-specific peptidase 18 (USP18). We further revealed that USP18 upregulation can only be initiated at the G1/early S phases of cell cycle upon the treatment onset, resulting in heterogeneous and delayed induction kinetics in single cells. This cell cycle gating provides a temporal compartmentalization of feedback loops, enabling duration-dependent desensitization to repetitive stimulations.

A programmable fate decision landscape underlies single-cell aging in yeast.

Chromatin instability and mitochondrial decline are conserved processes that contribute to cellular aging. Although both processes have been explored individually in the context of their distinct signaling pathways, the mechanism that determines which process dominates during aging of individual cells is unknown. We show that interactions between the chromatin silencing and mitochondrial pathways lead to an epigenetic landscape of yeast replicative aging with multiple equilibrium states that represent different types of terminal states of aging. The structure of the landscape drives single-cell differentiation toward one of these states during aging, whereby the fate is determined quite early and is insensitive to intracellular noise. Guided by a quantitative model of the aging landscape, we genetically engineered a long-lived equilibrium state characterized by an extended life span.