FGF7 and FGF10 Promote Fate Transition of Human Epidermal Cell-derived Organoids to an Eccrine Gland Phenotype.

Rationale: Reconstruction of hair follicles (HFs) and eccrine sweat glands (ESGs) is essential for functional skin regeneration. In skin reconstruction research, we found that foreskin-derived epidermal cells reconstructed HF organoids unidirectionally, but not ESG organoids. Methods: To investigate key genes and pathways influencing the fate of ESG and HF, a transcriptome profiling of ESG placode-containing skin and HF placode-containing skin was employed, and key DEGs were identified and validated by RT-qPCR and immunofluorescence staining in mice and rats. Subsequently, adult human epidermal cell-derived organoids were reconstructed to probe functional roles and mechanisms of FGF7 and FGF10 by series of approaches integrating RT-qPCR, immunofluorescence-staining, WB, apoptosis assay, and pathway interference assay. Results: All members of FGF7 subfamily were among the key DEGs screened, the differential expression of FGF7 and FGF10 and their receptors FGFR1/FGFR2 was verified between ESG placode-containing skin and HF placode-containing skin. In vivo and in vitro Matrigel plug models showed that both FGF7 and FGF10 promoted fate transition of human epidermal cell-derived organoids to ESG phenotype organoids, FGF7 and FGF10 had a synergistic effect, and mainly function through the FGFR1/2-MEK1/2-ERK1/2 pathway. Conclusions: Adult epidermal cells can be manipulated to reconstruct personalized HF and ESG to meet different needs.

Predicting Emotional Experiences through Eye-Tracking: A Study of Tourists' Responses to Traditional Village Landscapes.

This study investigates the relationship between eye-tracking metrics and emotional experiences in the context of cultural landscapes and tourism-related visual stimuli. Fifty-three participants were involved in two experiments: forty-three in the data collection phase and ten in the model validation phase. Eye movements were recorded and the data were analyzed to identify correlations between four eye-tracking metrics-average number of saccades (ANS), total dwell fixation (TDF), fixation count (FC), and average pupil dilation (APD)-and 19 distinct emotional experiences, which were subsequently grouped into three categories: positive, neutral, and negative. The study examined the variations in eye-tracking metrics across architectural, historic, economic, and life landscapes, as well as the three primary phases of a tour: entry, core, and departure. Findings revealed that architectural and historic landscapes demanded higher levels of visual and cognitive engagement, especially during the core phase. Stepwise regression analysis identified four key eye-tracking predictors for emotional experiences, enabling the development of a prediction model. This research underscores the effectiveness of eye-tracking technology in capturing and predicting emotional responses to different landscape types, offering valuable insights for optimizing rural tourism environments and enhancing visitors' emotional experiences.

The NLRP3 inflammasome in burns: a novel potential therapeutic target.

Burns are an underestimated serious injury negatively impacting survivors physically, psychologically and economically, and thus are a considerable public health burden. Despite significant advancements in burn treatment, many burns still do not heal or develop serious complications/sequelae. The nucleotide-binding oligomerization domain-like receptors (NLRs) family pyrin domain-containing 3 (NLRP3) inflammasome is a critical regulator of wound healing, including burn wound healing. A better understanding of the pathophysiological mechanism underlying the healing of burn wounds may help find optimal therapeutic targets to promote the healing of burn wounds, reduce complications/sequelae following burn, and maximize the restoration of structure and function of burn skin. This review aimed to summarize current understanding of the roles and regulatory mechanisms of the NLRP3 inflammasome in burn wound healing, as well as the preclinical studies of the involvement of NLRP3 inhibitors in burn treatment, highlighting the potential application of NLRP3-targeted therapy in burn wounds.

Peripheral CD4+ T helper lymphocytes alterations in major depressive disorder: A systematic review and meta-analysis.

Previous research has shown that patients with major depressive disorder (MDD) develop immune dysfunction. However, the exact alterations of cluster of differentiation (CD)4+ T helper (Th) lymphocytes in MDD remains unclear. This meta-analysis aimed to examine the specific changes in CD4+ Th cells. A comprehensive search of PubMed, EMBASE, Web of Science, and PsycINFO databases was conducted to identify studies investigating CD4+ Th, Th1, Th2, Th17, and T regulatory (Treg) cell counts in the peripheral blood of MDD patients and healthy controls (HCs), covering the period up to June 22, 2024. Our findings revealed that patients with MDD might exhibit higher CD4+ Th cells (SMD=0.26, 95 %CI, 0.02 to 0.50), CD4+/CD8+ cell ratios (SMD=0.51, 95 %CI, 0.14 to 0.89), Th1/Th2 cell ratios (SMD=0.15, 95 %CI, 0.01 to 0.30) and lower Th1 (SMD=-0.17, 95 %CI, -0.30 to -0.03), Th2 (SMD=-0.25, 95 %CI, -0.40 to -0.11), and Treg cells (SMD=-0.69, 95 %CI, -1.27 to -0.11). However, no significant difference was observed in terms of Th17 cells and Th17/Treg cell ratios between MDD patients and the HCs. Heterogeneity was large (I2:18.1-95.2 %), and possible sources of heterogeneity were explored (e.g., age, depression scale, country, and antidepressant use). Our findings indicate that peripheral CD4+ T cells in depressed patients exhibit features of adaptive immune dysfunction, as evidenced by increased CD4+ Th cells and CD4+/CD8+ and decreased Treg cells. These findings offer insights into the underlying mechanism of MDD.

Bidirectional relationship between borderline personality features and depressive symptoms in early adolescence: A school-based cohort study.

Depressive symptoms is a public health concern worldwide, and adolescents may experience more depressive symptoms. Although the relationship between borderline personality features (BPFs) disorder and depressive symptoms has been established, it is unclear whether the longitudinal relationship between them is unidirectional or bidirectional and whether these symptoms are different between boys and girls. In this study, Chinese adolescents (1608 total and separately 972 for boys and 636 girls) were enrolled between September 2019 and September 2021, and we analyzed the data using a cross-lagged model. The results suggested a bidirectional relationship between BPFs and depressive symptoms in boys (ß = 0.191 and 0.117, P < 0.001). However, in girls, depressive symptoms were predicted based on BPFs (ß = 0.225, P < 0.001), whereas BPFs were not predicted based on depressive symptoms (ß = 0.035, P = 0.535). The findings suggest that borderline personality traits and depressive symptoms are only bilaterally associated in girls, which also provides important evidence for the treatment and prevention of adolescent BPFs and depressive symptoms.

Longitudinal trajectories of sleep quality in correlation with maltreatment in early childhood: A cohort of Chinese early adolescents.

BACKGROUND: Child maltreatment may lead to sleep disturbance during the critical period of child development. Our study examined the effect of maltreatment in early childhood on trajectories of sleep quality among early adolescents. METHODS: The study included 1611 participants (mean ± standard deviation age at baseline: 12.5 ± 0.5 years) from a middle school in southeastern China. Of these participants, 60.5 % were males. Information on early childhood maltreatment during pre-seventh grade was obtained through a self-report questionnaire at baseline, and sleep quality was collected at baseline and during follow-up. We used a group-based trajectory model to characterize trajectories of sleep quality. RESULTS: The study identified four trajectories of sleep quality, namely the low sleep score group (25.0 %), the moderate-low sleep score group (51.0 %), the moderate-increasing sleep score (17.0 %), and the high-decreasing sleep score (7.0 %) group. After adjusting for covariates, the findings revealed that emotional abuse and physical abuse were associated with an increased risk of developing new-onset sleep disturbances in early adolescents. Particularly, emotional abuse (incidence rate ratio = 1.71, 95 % confidence interval: 1.08-2.71) significantly increased the risk of belonging to the high-decreasing sleep score group. Moreover, there existed a dose-response relationship between early childhood maltreatment and sleep quality trajectories, with a higher number of maltreatment types in early childhood correlating with a greater risk of belonging to the high-decreasing sleep score group. CONCLUSIONS: The findings of our study provide compelling evidence indicating that specific types and cumulative maltreatment during early childhood contribute to sleep disturbances among early adolescents. The study findings highlight the significance of preventing and reducing early childhood maltreatment to enhance sleep quality during early adolescence.

Vitamin D and suicidality: a Chinese early adolescent cohort and Mendelian randomization study.

AIMS: Previous cross-sectional and case-control studies have proposed that decreased vitamin D levels are positively correlated with the risk of suicidality in adults. However, limited studies have examined the association between vitamin D and suicidality in adolescents. This study aimed to investigate the relationship between serum vitamin D and suicidality risk among early adolescents. METHODS: Data were obtained from a Chinese early adolescent cohort. In this cohort, seventh-grade students from a middle school in Anhui Province were invited to voluntarily participate in the baseline assessments and provide peripheral blood samples (in September 2019). The participants were followed up annually (in September 2020 and September 2021). Serum 25-hydroxyvitamin D [25(OH)D] and vitamin D-related single-nucleotide polymorphisms at baseline were measured in November 2021. Traditional observational and Mendelian randomization (MR) analyses were performed to examine the relationship between serum 25(OH)D at baseline and the risk of baseline and incident suicidality (i.e., suicidal ideation [SI], plans and attempts). RESULTS: Traditional observational analysis did not reveal a significant linear or non-linear association of serum 25(OH)D concentration with the risks of baseline and 2-year incident suicidality in the total sample (P > .05 for all). Sex-stratified analysis revealed a non-linear association between the 25(OH)D concentration and the risk of baseline SI in women (Poverall = .002; Pnon-linear = .001). Moreover, the risk of baseline SI in the 25(OH) insufficiency group was lower than that in the 25(OH) deficiency group in the total sample (odds ratio [OR] = 0.69, 95% confidence interval [CI] = 0.51-0.92, P = .012). This difference remained significant in women (OR = 0.59, 95% CI = 0.40-0.87, P = .008) but not in men (OR = 0.78, 95% CI = 0.53-1.15, P = .205). Additionally, both linear and non-linear MR analyses did not support the causal effect of serum 25(OH)D concentration on the risk of baseline, 1-year and 2-year incident suicidality (P > .05 for all). CONCLUSIONS: This study could not confirm the causal effect of vitamin D on suicidality risk among Chinese early adolescents. Future studies must confirm these findings with a large sample size.

Involvement in bullying and sleep disorders in Chinese early adolescents.

Background: School bullying may cause sleep disorders in early adolescents. Here, we determined the relationship between school bullying (considering all the features of bullying involvement) and sleep disorders, which are the common problems in Chinese early adolescents. Materials and methods: We conducted a questionnaire survey among 5,724 middle school students from Xuancheng, Hefei, and Huaibei cities in Anhui province, China. The self-report questionnaires included the Olweus Bully/Victim Questionnaire and Pittsburgh Sleep Quality Index. We used latent class analysis to identify the potential subgroups of bullying behavior. Logistic regression analysis was used to investigate the association between school bullying and sleep disorders. Results: Active participants in bullying interactions, including the bullies and victims, reported higher levels of sleep disorders compared with the non-active participants [Bully: physical (aOR = 2.62), verbal (aOR = 1.73), relational (aOR = 1.80), and cyber (aOR = 2.08); Victim: physical (aOR = 2.42), verbal (aOR = 2.59), relational (aOR = 2.61), and cyber (aOR = 2.81)]. A dose-response relationship was observed between the number of school bullying types and sleep disorders. In the context of bullying roles, bully-victims had the highest risk of reporting sleep disorders (aOR = 3.07, 95% CI: 2.55-3.69). We identified four potential categories of school bullying behaviors: low involvement in bullying, verbal and relational victims, medium bully-victims, and high bully-victims, and the highest frequency of sleep disorders was observed in the high bully-victims group (aOR = 4.12, 95% CI: 2.94-5.76). Conclusion: Our findings indicate a positive correlation between bullying roles and sleep disorders in early adolescents. Therefore, targeted intervention for sleep disorders should include an evaluation of bullying experiences.

Bidirectional association between sleep quality or duration and aggressive behaviour in early adolescents: A cross-lagged longitudinal study.

BACKGROUND: Several cross-sectional studies have suggested a strongly positive link between sleep and aggressive behaviour; however, longitudinal studies reporting the relationship between sleep and aggressive behaviour are lacking. This study aimed to examine whether a bidirectional relationship exists between sleep quality or duration and aggressive behaviour in early adolescents. METHODS: A total of 1579 early adolescents (60.9 % boys) from the Chinese Early Adolescents Cohort study were included in this study. Data on sleep quality, sleep duration and aggressive behaviour collected at two time points (September 2019 and September 2021) were used, and the bidirectional relationship between sleep quality or duration and aggressive behaviour was examined using a cross-lagged model. RESULTS: The results revealed a bidirectional relationship between low sleep quality and highly aggressive behaviour. A shorter sleep duration did not predict highly aggressive behaviour, whereas only highly aggressive behaviour predicted a shorter sleep duration. CONCLUSIONS: Sleep quality and aggressive behaviour were interrelated over time among adolescents. However, sleep duration did not predict aggressive behaviour, suggesting that sleep quality, instead of sleep duration, should be the primary target for managing aggressive behaviour.

The Relationship Between Child Sexual Abuse and Sexual Dysfunction in Adults: A Meta-Analysis.

Child sexual abuse (CSA) has been recognized as a risk factor for sexual dysfunction and has attracted increasing attention. However, controversies remain regarding related research. The aim is to calculate the pooled effect size estimate for the correlation between CSA and sexual dysfunction in adults by meta-analysis. Five bibliographic databases (PubMed, Cochrane Library, Web of Science, Embase, and PsycINFO) were comprehensively searched to clarify the association between CSA and sexual dysfunction in adults. We used a fixed-effects model to determine the total pooled effect size estimate and reported odds ratios (ORs) and the corresponding 95% confidence intervals (CIs). Subgroup analysis, publication bias analysis, and sensitivity analysis were conducted. Adults who had a history of CSA experienced a higher proportion of sexual dysfunction than adults with no history of CSA (OR = 1.68, 95% CI [1.49, 1.87]). Subgroup analysis showed that women with a history of CSA reported a higher proportion of sexual dysfunction than men with a history of CSA (men: OR = 1.45, 95% CI [1.05, 1.84]; women: OR = 1.62, 95% CI [1.42, 1.83]). The estimates of the effect sizes differed substantially depending on the CSA and sexual dysfunction instruments that were used in each study and the region of each sample. This meta-analysis provides conclusive evidence of an association between CSA and sexual dysfunction in adults. Currently known interventions for the treatment of sexual dysfunction after CSA have only been evaluated in women, so specific interventions should be designed for men CSA survivors who experience sexual impairment.

Psychological Resilience Mediates the Association Between Childhood Maltreatment and Self-Harm Phenotype in Chinese Early Adolescents.

Self-harm (SH) increases significantly in early adolescence with great variability, and childhood maltreatment (CM) contributes to this increase. Understanding the developmental pathway from CM to SH could provide clues for SH prevention. This study used latent class analysis (LCA) to detect the phenotype of SH and explored the role of psychological resilience in the pathway from the CM to SH phenotype among 5724 early adolescents (52.5% male). Three interpretable phenotypes of SH were identified: low SH (57.8%), medium SH (29.0%), and high SH (13.2%). Furthermore, CM was positively associated with the SH phenotype, psychological resilience mediated the association between CM and the SH phenotype (all ps < 0.001), and a larger mediating effect was observed in the medium SH (22.41%). Our findings offer new perspectives that improving psychological resilience can be used as an efficient intervention to reduce the risk of SH among early adolescents who have experienced CM.

A novel prognostic biomarker CD3G that correlates with the tumor microenvironment in cervical cancer.

Cervical cancer (CESC) is the fourth most common and death-causing gynecological cancer, mostly induced by infection of human papillomavirus (HPV). Multiple components of the tumor microenvironment (TME), such as tumor infiltrating immune cells, could be targets of immunotherapy for HPV-related CESC. However, little is known about the TME of CESC until now. Here, we aimed to uncover the pathogenesis as well as to identify novel biomarkers to predict prognosis and immunotherapy efficacy for CESC. Combining the transcriptomic data and clinical characteristics, we identified differentially expressed genes in CESC samples from TCGA database by comparing the two groups with different ImmuneScore and StromalScore. Next, we detected ten key genes based on the PPI network and survival analyses with the univariate Cox regression model. Thereafter, we focused on CD3G, the only gene exhibiting increased RNA and protein expression in tumors by multiple analyses. Higher CD3G expression was associated with better survival; and it was also significantly associated with immune-related pathways through GSEA analysis. Furthermore, we found that CD3G expression was correlated with 16 types of TICs. Single cell RNA-sequencing data of CD3G in lymphocytes subgroup indicated its possible role in HPV defense. Hence, CD3G might be a novel biomarker in prognosis and immunotherapy for CESC patients.

The effect of healthy dietary patterns on male semen quality: a systematic review and meta-analysis.

The incidence of infertility has recently risen. Semen quality is an important male fertility indicator, and dietary factors can affect semen quality. We conducted this systematic review and meta-analysis to determine the effects of healthy dietary patterns on semen quality. A literature search was conducted in 3 databases (Embase, Web of Science and PubMed) on August 21, 2021. The included cross-sectional studies examined the influence of the Mediterranean, Dietary Approaches to Stop Hypertension (DASH), and prudent diet patterns on semen quality parameters; six studies (1244 subjects) were included. By comparing high consumption with low consumption of healthy dietary patterns, the results of the meta-analysis showed significantly higher sperm concentrations (mean difference [MD] = 6.88 × 106 ml-1, 95% confidence interval [CI]: 1.26 × 106 ml-1-12.49 × 106 ml-1; P < 0.05), a significant increase in total sperm count (MD = 16.70 × 106, 95% CI: 2.37 × 106-31.03 × 106; P < 0.05), and a significant increase in progressive sperm motility (MD = 5.85%, 95% CI: 2.59%-9.12%; P < 0.01). The sperm concentration, progressive sperm motility, and total sperm count were significantly higher in men with higher versus lower consumption of healthy dietary patterns. However, the results must be interpreted with caution.

Psychological adjustment mediating the relationship between childhood maltreatment and borderline personality features among Chinese early adolescents.

BACKGROUND: A strong link between childhood maltreatment (CM) and borderline personality features (BPF) has been consistently demonstrated. However, little is known about the role of psychological adjustment (PA) as a mediator of this relationship. The purpose of the study was to explore the mediating role of PA in the CM-BPF linkage in a large sample of early adolescents. METHODS: A total of 5724 students (mean age = 13.5, SD = 1.0) were recruited from three middle schools by using the multistage random cluster sampling method in Anhui Province, China. Participants were required to complete self-report questionnaires regarding CM experience, self-perceived PA and BPF. Mediation analyses were computed via structural equation modelling. RESULTS: CM victimization was positively associated with BPF, and individuals with lower levels of PA were more likely to present with BPF. Mediation analysis showed a significant indirect effect of CM on BPF via PA (effect = 0.047, 95 % CI: 0.035, 0.058). LIMITATION: The cross-sectional design of this study did not allow testing causality. The retrospective investigation of CM history could cause recall bias. CONCLUSIONS: PA partially mediates the relationship between CM and BPF. These findings have important implications for considering PA as a protective factor in this relationship.

Noninvasive isolation of transcervical trophoblast cells for fetal identification.

OBJECTIVE: To identify trophoblastic cells retrieved from the cervix at a gestational age (GA) of 5-9 weeks by a noninvasive modality in fetuses. METHOD: Transcervical cells (TCCs) were noninvasively extracted by a cytobrush using the Papanicolaou sampling method. TCCs were immunostained with antihuman leukocyte antigen (HLA)-G and anticytokeratin (CK)-7 antibodies to identify trophoblastic cells. Maternal finger blood, gestational sacs, and 20 trophoblastic cells collected by a laser-guided microscopic single-cell capture system were examined and compared by short tandem repeat (STR) genotyping. RESULTS: Forty-nine pregnant women with GA of 5-9 weeks and six nonpregnant healthy women were included in the study. Trophoblastic cells were identified in 37 (75.5%) TCC samples, among which 34 (69.4%) were eligible for STR genotyping analysis. No trophoblastic cells were identified in nonpregnant healthy women. The STR genotyping analyses revealed 24 female and 10 male fetuses. TCC trophoblastic cells exhibited the same STR profiles as gestational sac and maternal blood in all samples, which indicated that the TCC trophoblastic cells originated from fetuses. CONCLUSION: This primary study validated that trophoblastic cells from TCCs at GA 5-9 weeks originated from the fetus. Further studies are needed to verify whether this method can be used for early noninvasive prenatal diagnosis and paternity testing.

Differential antigen expression between human eccrine sweat glands and hair follicles/pilosebaceous units.

Eccrine sweat glands and hair follicles are two primary skin appendages that serve different functions. Although the two appendages exhibit unique morphological patterns in adults, it is difficult to distinguish them morphologically in the early stages of development and regeneration. To research and compare the development, differentiation and regeneration between eccrine sweat glands and hair follicles/pilosebaceous units, specific antigen markers must be found first. Human skin samples were fixed, paraffin-embedded, and cut. The expression of K5, K7, K8, K14, K27, K31, K73, AE13, α-smooth muscle actin (α-SMA), epithelial membrane antigen (EMA), carcinoembryonic antigen (CEA), Na+/K+-ATPase α and Na+-K+-2Cl cotransporter 1 (NKCC1) in eccrine sweat glands, hair follicles and sebaceous glands was detected by immunofluorescence staining. The results showed that eccrine sweat glands expressed K5, K7, K8, K14, K31, α-SMA, CEA, EMA, Na+/K+-ATPase α and NKCC1, but did not express K27, K73 or K31. Hair follicles expressed K5, K8, K14, K27, K31, K73, α-SMA and AE13, but did not express K7, CEA, Na+/K+-ATPase α or NKCC1. Sebaceous glands expressed K5, K14, K73, and EMA, but did not express K7, K8, K31, α-SMA, CEA, EMA, Na+/K+-ATPase α or NKCC1. We concluded that K7, CEA, Na+/K+-ATPase and NKCC1 can be used as specific markers for eccrine sweat glands, K27 and AE13 can be used as specific markers for hair follicles, and K73 can be used as a specific marker for pilosebaceous unit. These specific markers may contribute to differentiate between eccrine sweat glands and hair follicle/pilosebaceous units.

Facile crosslinking of polythiophenes by polyethylenimine via ester aminolysis for selective Cu(II) detection in water.

Functionalization of π-conjugated polymers is dispensable for solubilization of the rigid and hydrophobic backbones in water. However, polymer aggregation is always present and leads to issues with complication and reproducibility in spectral properties. Herein, we reported a simple and robust method to make a series of conjugated polymer nanostructures by a crosslinking strategy. In favor of multivalency effect, polythionenes with various chain lengths were functionalized with branched polyethylenimine (PEI) via ester aminolysis reaction under mild conditions. Photophysical studies revealed the conjugated backbones could be well stabilized and dispersed in water. By taking advantage of intermolecular recognition interaction between copper ions and cationic PEI, we applied crosslinked polythiophenes as a nano probe at very low concentration (0.01 mg/mL) to fluorescently detect copper ions with high sensitivity up to 10 nM and selectivity over other metal ions in aqueous solutions, without occurrence of detectable aggregates. The overall performance of our nano probes outperforms reported water-soluble polymers-based probes, particularly in probe availability and manipulation as well as selective copper detection capability.

Cationic Polythiophenes as Gene Delivery Enhancer.

There is urgent demand of easily available and highly effective method to improve transgene performance of polymeric gene carriers at low consumption of delivery materials. We developed biocompatible multicomponent nanocomposites in which small quantities of cationic polythiophenes were engineered into the outer shell of polypeptide/DNA polyplexes without covalent linkages. We revealed the introduction of polythiophenes in small quantities led to multiple outcomes including modulation of polyplex size and zeta potential, increase in polyplex stability, promotion of endolysosome membrane disruption, light-induced generation of reactive oxygen species (ROS), and significant enhancement of gene delivery to tumor cells. The factors such as structural architectures, molecular weights, photosensitizing capability, and percentage composition of polythiophenes were investigated.

A Guiding Evolutionary Algorithm with Greedy Strategy for Global Optimization Problems.

A Guiding Evolutionary Algorithm (GEA) with greedy strategy for global optimization problems is proposed. Inspired by Particle Swarm Optimization, the Genetic Algorithm, and the Bat Algorithm, the GEA was designed to retain some advantages of each method while avoiding some disadvantages. In contrast to the usual Genetic Algorithm, each individual in GEA is crossed with the current global best one instead of a randomly selected individual. The current best individual served as a guide to attract offspring to its region of genotype space. Mutation was added to offspring according to a dynamic mutation probability. To increase the capability of exploitation, a local search mechanism was applied to new individuals according to a dynamic probability of local search. Experimental results show that GEA outperformed the other three typical global optimization algorithms with which it was compared.