Mental Health Literacy Among Urban and Rural Residents of Guangdong Province, China.

Purpose: The study aims to understanding the mental health literacy level of urban and rural residents in Guangdong Province, the first major province in China, and its influencing factors is crucial. Methods: A multi-stage stratified equal-volume random sampling method was adopted in October-December 2022 to select permanent residents aged 18 years and above in Guangdong Province for the questionnaire survey, which consisted of a general demographic information questionnaire and a national mental health literacy questionnaire. Rao-Scott χ²-test with correction based on sampling design, independent samples t-test and binary multivariate logistic regression analysis were performed. Results: A total of 51744 individuals completed the questionnaire, including 31822 urban residents and 19200 rural residents. The rate of achievement of mental health literacy was 13.6% among urban residents, which was significantly higher compared to the rate of 8.6% among rural residents. Logistic regression analysis showed that female, higher education, being mental worker, being a retiree, having a higher monthly household income, maintaining a regular diet, and using electronic products for 2-6 hours per day were protective factors for mental health literacy attainment in urban residents, while having chronic diseases, being a smoker and having a history of drinking were identified as risk factors in urban residents. Among in rural residents, married, younger, higher education, being mental worker and using electronic products for 2-6 hours per day, maintaining a regular diet, and engaging in regular exercise were protective factors for achieving mental health literacy, while previous smoking was a risk factor. Conclusion: The study revealed a low level of mental health literacy among urban and rural residents of Guangdong Province, with a significant disparity between the two areas. These findings highlight the need for continuing efforts to increase the dissemination of mental health knowledge in rural communities and improve levels of mental health literacy.

Assortative mating across nine psychiatric disorders is consistent and persistent over cultures and generations.

Emerging evidence has shown that assortative mating (AM) is a key factor that shapes the landscape of complex human traits. It can increase the overall prevalence of disorders, influence occurrences of comorbidities, and bias estimation of genetic architectures. However, there is lack of large-scale studies to examine the cultural differences and the generational trends of AM for psychiatric disorders. Here, using national registry datasets, we conduct the largest scale of AM analyses on nine psychiatric disorders, with up to 1.4 million mated cases and 6 million matched controls. We performed meta-analyses on AM estimates from Taiwan, Denmark, and Sweden, to examine the potential impact of cultural differences. Generational changes for people born after 1930s were investigated as well. We found that AM of psychiatric disorders are consistent across nations and persistent over generations, with a small proportion of disorders showing generational changes of AM. Our results provide additional insight into the mechanisms of AM across psychiatric disorders and have evident implications on the estimation of the genetic architectures of psychiatric disorders.

Public Awareness of Blindness Caused by Hyaluronic Acid Injection in China: A Questionnaire Survey.

Background: The occurrence of blindness resulting from facial injection is a catastrophic complication that remains a significant safety concern for patients. The aim was to assess public awareness of blindness caused by hyaluronic acid injection. Methods: The Tencent questionnaire platform was used to gather self-reported demographic data, information about injection experience, and factors influencing the understanding of blindness. Additionally, we included an educational section on blindness caused by hyaluronic acid injection and evaluated the respondents' intention to undergo injections. Results: A total of 1000 respondents completed the questionnaire, 15.4% had received filler injections, and 53.7% expressed their consideration of facial filler injections. The majority of respondents (68.3%) reported being aware of the risk of blindness associated with filler injections, with professional health blogs, social media, and news serving as the primary sources of information. Furthermore, 93.4% of the respondents believed that plastic surgeons should discuss the risk of blindness with patients before injection. Conclusions: The majority of the respondents in this study were aware of the possibility of blindness resulting from filler injections. Health blogs, news outlets, and social media platforms are likely the primary channels through which the public obtains information on this topic.

Hippocampal dipeptidyl peptidase 9 bidirectionally regulates memory associated with synaptic plasticity.

INTRODUCTION: Subtypes of the dipeptidyl peptidase (DPP) family, such as DPP4, are reportedly associated with memory impairment. DPP9 is widely distributed in cells throughout the body, including the brain. However, whether DPP9 regulates memory has not yet been elucidated. OBJECTIVES: This study aimed to elucidate the role of DPP9 in memory, as well as the underlying molecular mechanism. METHODS: We performed immunofluorescence on mouse brains to explore the distribution of DPP9 in different brain regions and used AAV vectors to construct knockdown and overexpression models. The effects of changing DPP9 expression on memory were demonstrated through behavioral experiments. Finally, we used electrophysiology, proteomics and affinity purification mass spectrometry (AP-MS) to study the molecular mechanism by which DPP9 affects memory. RESULTS: Here, we report that DPP9, which is found almost exclusively in neurons, is expressed and has enzyme activity in many brain regions, especially in the hippocampus. Hippocampal DPP9 expression increases after fear memory formation. Fear memory was impaired by DPP9 knockdown and enhanced by DPP9 protein overexpression in the hippocampus. According to subsequent hippocampal proteomics, multiple pathways, including the peptidase pathway, which can be bidirectionally regulated by DPP9. DPP9 directly interacts with its enzymatic substrate neuropeptide Y (NPY) in neurons. Hippocampal long-term potentiation (LTP) is also bidirectionally regulated by DPP9. Moreover, inhibiting DPP enzyme activity impaired both LTP and memory. In addition, AP-MS revealed that DPP9-interacting proteins are involved in the functions of dendritic spines and axons. By combining AP-MS and proteomics, DPP9 was shown to play a role in regulating actin functions. CONCLUSION: Taken together, our findings reveal that DPP9 affects the CNS not only through enzymatic activity but also through protein-protein interactions. This study provides new insights into the molecular mechanisms of memory and DPP family functions.

Low mental health literacy is associated with depression and anxiety among adults: a population-based survey of 16,715 adults in China.

BACKGROUND: Mental health literacy is a predictor of health outcomes in psychological distress. However, limited research has explored whether low mental health literacy is associated with recent depression and anxiety. METHODS: We used data from the Guangdong Mental Health Survey, a provincial representative and a population-based survey with a multistage stratified cluster random sampling method. We included adults aged 18 and above living in communities from September to December 2021 in Guangdong, China. Eligible participants were those who completed the mental health literacy questionnaire and assessments for depression and anxiety symptoms. We assessed the proportion of individuals with low mental health literacy by categories of psychological symptoms and whether low mental health literacy was associated with depressive and anxiety symptoms in the general population and subgroups. RESULTS: A total of 16,715 adults were included. We found that individuals with more severe symptoms had a greater proportion of low mental health literacy- it went from 89.4% in participants without depression or anxiety to 96.2% in people who co-occurred with depression and anxiety (x2 = 21.457, P < 0.001). After controlling confounders, low mental health literacy was associated with depression (adjusted Odds Ratio, aOR [95%CI]:2.74 [1.92-4.04]) and anxiety (2.27 [1.49-3.64]) in the total sample, when compared with adequate mental health literacy. CONCLUSIONS: This study found a positive association between low mental health literacy and the presence of depression and anxiety. Tackling inadequate mental health literacy may be a key strategy to promote psychological well-being across the lifespan, especially for young adults.

Transition Metal (Molybdenum)-Doped Drug-like Conformational Nanoarchitectonics with Altered Valence States (Mn2+/Mn4+ and Mo5+/Mo6+) for Augmented Cancer Theranostics.

Despite the advancements in cancer therapy, delivering active pharmaceutical ingredients (APIs) using nanoparticles remains challenging due to the failed conveyance of the required drug payload, poor targeting ability, and poor biodistribution, hampering their clinical translation. Recently, the appropriate design of materials with intrinsic therapeutic functionalities has garnered enormous interest in the development of various intelligent therapeutic nanoplatforms. In this study, we demonstrate the fabrication of transition metal (molybdenum, Mo)-doped manganese dioxide (MnO2) nanoarchitectures, exhibiting diagnostic (magnetic resonance imaging, MRI) and therapeutic (chemodynamic therapy, CDT) functionalities. The facile hydrothermal approach-assisted Mo-doped MnO2 flower-like nanostructures offered tailorable morphologies in altered dimensions, precise therapeutic effects, exceptional biocompatibility, and biodegradability in the tumor microenvironment. The resultant defects due to doped Mo species exhibited peroxidase and oxidase activities, improving glutathione (GSH) oxidation. The two sets of variable valence metal ion pairs (Mn2+/Mn4+ and Mo5+/Mo6+) and their interplay could substantially improve the Fenton-like reaction and generate toxic hydroxyl radicals (•OH), thus achieving CDT-assisted antitumor effects. As inherent T1-MRI agents, these MnO2 nanoparticles displayed excellent MRI efficacy in vitro. Together, we believe that these conformational Mo-doped MnO2 nanoarchitectures with two pairs of variable valence states could potentiate drugless therapy in pharmaceutics.

Nucleos(t)ide analogs to treat patients with positive hepatitis B virus deoxyribonucleic acid and normal alanine transaminase: protocol for an open-label single-center randomized parallel controlled trial.

BACKGROUND: Direct high-quality evidence remains absent on the benefits of HBeAg-negative chronic hepatitis B patients (CHB) with normal alanine transaminase (ALT) and positive HBV DNA after nucleos(t)ide analogs (NAs) treatment. METHODS: This is a single-center, open-label, randomized parallel controlled trial with a follow-up duration of 96 weeks. An estimated 300 patients will be recruited at West China Hospital of Sichuan University, China. After stratified by serum HBV DNA (< 2000 vs. ≥ 2000 IU/ml), eligible patients will be randomized (allocation ratio 1:1) to receive either antiviral therapy (the treatment group) or regular examination alone (the control group). The primary outcomes are rates of virological response and changes in the levels of serum HBV pregenomic RNA (pgRNA) and scores of health-related qualities of life. DISCUSSION: This randomized controlled trial focuses on HBeAg-negative patients with normal ALT, including those of the inactive carrier phase and the grey zone, whose antiviral treatment remains controversial. Additionally, a health-related quality of life scale is introduced to comprehensively estimate the benefit of antiviral treatment apart from virological response and adverse liver events. Meaningfully, the study findings will provide high-quality and direct evidence for optimal clinical management in such populations. TRIAL REGISTRATION: This trial was registered with the Chinese Clinical Trial Registry (ChiCTR2300069391) on 15 March 2023.

Effectiveness of Risk-Adapted Upper Gastrointestinal Cancer Screening in China: Prospective Cohort Study.

Background: Previous studies have proved the effectiveness of endoscopic screening in rural areas; however, long-term, high-quality evidence regarding the effectiveness of risk-adapted upper gastrointestinal cancer (UGC) sequential screening strategies in resource-rich regions is currently lacking. Objective: The objectives were to validate the effectiveness of risk-adapted sequential screening strategies in UGC prevention and control and assess the potential of sequential screening to lower mortality rates. Methods: Based on the Cancer Screening Program in Urban China, a prospective, large-scale cohort study based on population was conducted to recruit individuals from 4 cities in China from 2013-2019. Those identified as having a high risk of UGC according to a validated risk-score model were advised to undergo endoscopy tests. Follow-up outcomes were tracked until June 2021. Incidence of UGC, UGC-related mortality, and all-cause mortality were evaluated between the screened and nonscreened cohorts. Results: The study included 153,079 participants at baseline. In total, 113,916 (74.42%) of the participants were designated as low risk of UGC. The remaining 39,163 (25.68%) participants were deemed to be at high risk of UGC and were offered gastroscopy tests. Among the high-risk participants, 9627 (compliance rate 24.6%) adhered to the gastroscopy tests. Over a median follow-up of 6.05 (IQR 3.06-7.06) years, 622 UGC cases, 180 UGC deaths, and 1958 all-cause death cases were traced. The screened cohort exhibited the highest cumulative incidence of UGC (119.2 per 100,000 person-years), followed by the nonscreened and low-risk cohorts. Obvious reductions in both all-cause mortality and UGC mortality were observed between those who undertook screening (153.7 and 4.7 per 100,000 person-years, respectively) and the nonscreened group (245.3 and 27 per 100,000 person-years, respectively). The screening population showed a significant 36% and 82% reduction in both all-cause mortality (hazard ratio [HR] 0.64, 95% CI 0.49-0.83, P<.001) and UGC mortality (HR 0.18, 95% CI 0.04-0.74, P=.02), respectively, compared to the nonscreened group. Reductions of 35% in all-cause mortality (HR 0.65, 95% CI 0.49-0.86, P=.003) and 81% in UGC mortality (HR 0.19, 95% CI 0.05-0.80, P=.02) were observed in participants aged older than 55 years in the screened group compared to the nonscreened group. The reductions in all-cause mortality and UGC mortality were statistically significant in males (all-cause mortality: HR 0.64, 95% CI 0.47-0.88, P=.005; UGC mortality: HR 0.10, 95% CI 0.01-0.72, P=.02), but significant reductions were not observed in females (all P values were >.05). Conclusions: Our study suggests the significance of one-off risk-adapted UGC screening in reducing both all-cause mortality and UGC mortality, particularly among high-risk individuals, indicating its effectiveness in UGC prevention and management.

Sex- and dose-dependent catalase increase and its clinical impact in a benzoate dose-finding, randomized, double-blind, placebo-controlled trial for Alzheimer's disease.

BACKGROUND: Sex differences in Alzheimer's disease (AD) are gaining increasing attention. Previously research has shown that sodium benzoate treatment can improve cognitive function in AD patients, particularly in the female patients; and 1000 mg/day of benzoate appears more efficacious than lower doses. Catalase is a crucial endogenous antioxidant; and deficiency of catalase is regarded to be related to the pathogenesis of AD. The current study aimed to explore the role of sex and benzoate dose in the change of catalase activity among benzoate-treated AD patients. METHODS: This secondary analysis used data from a double-blind trial, in which 149 CE patients were randomized to receive placebo or one of three benzoate doses (500, 750, or 1000 mg/day) and measured with Alzheimer's disease assessment scale-cognitive subscale. Plasma catalase was assayed before and after treatment. RESULTS: Benzoate treatment, particularly at 1000 mg/day, increased catalase among female patients, but not among male. The increases in the catalase activity among the benzoate-treated women were correlated with their cognitive improvements. In addition, higher baseline catalase activity was associated with more cognitive improvement after benzoate treatment among both female and male patients. CONCLUSIONS: Supporting the oxidative stress theory and sex difference in AD, the finding suggest that sex (female) and benzoate dose co-determine catalase increase in benzoate-treated AD patients and the catalase increment contributes to cognitive improvement of benzoate-treated women. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03752463.

Prenatal and early childhood infections requiring hospitalization and risk of neurodevelopmental disorders in offspring: a population-based birth cohort study in Taiwan.

In utero and early childhood infections have been associated with an increased risk of neurodevelopmental disorders; however, the observed associations may be confounded by familial predispositions. This study examined the neurodevelopmental disorders attributable to maternal infections during pregnancy and early childhood infections during the first year of life, including autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), tic disorders, and mental retardation (MR). We performed population and sibling comparison analyses to account for unmeasured familial confounding factors. We conducted a register-based cohort study with 2,885,662 individuals (comprising 1,864,660 full siblings) born in Taiwan between 2001 and 2018 and followed up until 2021. We employed Cox regression analysis to assess the association between in utero and early childhood infections requiring hospitalization and the subsequent risk of neurodevelopmental disorders. In the population analyses, an offspring exposed to maternal infection had an increased risk for ASD (hazard ratio (HR) = 1.19, 95% confidence interval (CI): 1.13-1.26), ADHD (HR = 1.14, 95% CI: 1.11-1.18), and MR (HR = 1.21, 95% CI: 1.13-1.30). These associations attenuated toward null in the sibling analyses. Individuals exposed to early childhood infection had an increased risk for ASD (HR = 1.13, 95% CI: 1.10-1.16), ADHD (HR = 1.16, 95% CI: 1.15-1.18), tic disorders (HR = 1.12, 95% CI: 1.09-1.15), and MR (HR = 1.64, 95% CI: 1.60-1.69) in the population analyses; these associations were also significant for ASD (HR = 1.14, 95% CI: 1.07-1.21) and MR (HR = 1.52, 95% CI: 1.44-1.62) in the sibling analyses. The association between maternal infection during pregnancy and offspring neurodevelopmental risk is largely due to familial confounding factors. Conversely, infection in early childhood may be attributable to it being a sensitive period and may play a role in the subsequent risk of ASD and MR.

Hybrid modality dual-energy imaging aggregating complementary advantages of kV-CT and MV-CBCT: concept proposal and clinical validation.

OBJECTIVE: Megavoltage cone-beam CT (MV-CBCT) is advantageous in metal artifact reduction during Image-Guided Radiotherapy (IGRT), although it is limited by poor soft tissue contrast. This study proposed and evaluated a novel hybrid modality dual-energy (DE) imaging method combining the complementary advantages of kV-CT and MV-CBCT. Approach: The kV-CT and MV-CBCT images were acquired on a planning CT scanner and a Halcyon linear accelerator respectively. After rigid registration, images of basis materials were generated using the iterative decomposition method in the volumetric images. The decomposition accuracy was quantitatively evaluated on a Gammex 1472 phantom. The performance of contrast enhancement and metal artifact reduction in virtual monochromatic images were evaluated on both phantom and patient studies. Main results: Using the proposed method, the mean percentage errors for RED and SPR were 0.90% and 0.81%, outperforming the clinical single-energy mapping method with mean errors of 1.28% and 1.07%, respectively. The contrasts of soft-tissue insets were enhanced by a factor of 2~3 at 40 keV compared to kV-CT. The standard deviation in the metal artifact area was reduced by ~67%, from 42 HU (kV-CT) to 14 HU (150 keV monochromatic). The head and neck patient test showed that the percent error of soft-tissue RED in the metal artifact area was reduced from 18.1% (HU-RED conversion) to less than 1.0% (the proposed method), which was equivalent to the maximum dosimetric difference of 28.7% based on the patient-specific plan. Significance: Without hardware modification or extra imaging dose, the proposed hybrid modality method enabled kV-MV DE imaging, providing improved accuracy of quantitative analysis, soft-tissue contrast and metal artifact suppression for more accurate IGRT. .

Hydrogen peroxide participates in leaf senescence by inhibiting CHLI1 activity.

KEY MESSAGE: Hydrogen peroxide promoted leaf senescence by sulfenylating the magnesium chelating protease I subunit (CHLI1) in the chlorophyll synthesis pathway, and inhibited its activity to reduce chlorophyll synthesis. Leaf senescence is the final and crucial stage of plant growth and development, during which chlorophyll experiences varying degrees of destruction. It is well-known that the higher ROS accumulation is a key factor for leaf senescence, but whether and how ROS regulates chlorophyll synthesis in the process are unknown. Here, we report that H2O2 inhibits chlorophyll synthesis during leaf senescence via the I subunit of magnesium-chelatase (CHLI1). During leaf senescence, the decrease of chlorophyll content is accompanied by the increase of H2O2 accumulation, as well as the inhibition of catalase (CAT) genes expression. The mutant cat2-1, with increased H2O2 shows an accelerated senescence phenotype and decreased CHLI1 activity compared with the wild type. H2O2 inhibits CHLI1 activity by sulfenylating CHLI1 during leaf senescence. Consistent with this, the chli1 knockout mutant displays the same premature leaf senescence symptom as cat2-1, while overexpression of CHLI1 in cat2-1 can partially restore its early senescence phenotype. Taken together, these results illustrate that CAT2-mediated H2O2 accumulation during leaf senescence represses chlorophyll synthesis through sulfenylating CHLI1, and thus inhibits its activity, providing a new insight into the pivotal role of chlorophyll synthesis as a participant in orchestrating the leaf senescence.

Genome-wide association study reveals the underlying regulatory mechanisms of red blood traits in Anadara granosa.

BACKGROUND: Anadara granosa, commonly known as the blood clam, exhibits the unusual characteristic of having red blood among invertebrates. There is significant individual variation in blood color intensity among blood clams; individuals with vibrant red blood are deemed healthier and exhibit stronger stress resistance. However, the molecular basis underlying these red blood traits (RBTs) remains poorly understood. RESULTS: In this study, we performed genome-wide association studies (GWAS) in a population of 300 A. granosa individuals, focusing on RBTs as measured by hemoglobin concentration (HC), total hemocyte count (THC), and heme concentration (HEME). Our analysis identified 18 single nucleotide polymorphisms (SNPs) correlated with RBTs, subsequently selected 117 candidate genes within a 100 kb flanking region of these SNPs, potentially involved in the RBTs of A. granosa. Moreover, we discovered two haplotype blocks specifically associated with THC and HEME. Further analysis revealed eight genes (Septin7, Hox5, Cbfa2t3, Avpr1b, Hhex, Eif2ak3, Glrk, and Rpl35a) that significantly influence RBTs. Notably, a heterozygous A/T mutation in the 3'UTR of Cbfa2t3 was found to promote blood cell proliferation. These genes suggest that the hematopoietic function plays a significant role in the variability of RBTs in A. granosa. CONCLUSIONS: Our findings reveal a conservation of the regulatory mechanisms of RBTs between blood clams and vertebrates. The results not only provide a scientific basis for selective breeding in blood clams, but also offer deeper insights into the evolutionary mechanisms of RBTs in invertebrates.

Efficacy of magnifying endoscopy combined with narrowband imaging in detection of early gastric cancer: a systematic evaluation and meta-analysis.

OBJECTIVE: To systematically evaluate the diagnostic accuracy of magnifying endoscopy combined with narrowband imaging (ME-NBI) in detecting early gastric cancer (EGC) and to provide a scientific basis for its clinical utility. METHODS: Literature published before May 2024 that utilized ME-NBI for diagnosing EGC was searched across PubMed, EMBASE, The Cochrane Library, Web of Science, and major Chinese databases. Included studies were cohort studies or randomized controlled trials, and their quality was assessed using the QUADAS-2 framework. Meta-analysis was conducted using Stata 17 software to calculate diagnostic indicators such as sensitivity, specificity, and area under the curve (AUC). Heterogeneity was explored through Spearman's correlation coefficient, I2 statistics, subgroup analysis, and meta-regression analysis. Publication bias was assessed with Deeks' funnel plot. RESULTS: Twenty studies involving 7,770 patients and 7,917 lesions were included. The pooled sensitivity of ME-NBI for diagnosing EGC was 0.86 (95% CI: 0.80-0.90), specificity was 0.92 (95% CI: 0.86-0.96), and the AUC was 0.94 (95% CI: 0.91-0.96), demonstrating high diagnostic accuracy. Subgroup analysis revealed lower sensitivity in multicenter studies. Excised samples had similar sensitivity to biopsy samples but differed in specificity. Publication bias was detected (P=0.01), but sensitivity analysis corrected for this, maintaining high combined sensitivity, specificity, and AUC. CONCLUSION: ME-NBI is a highly accurate and reliable diagnostic tool for EGC. Despite have some bias and heterogeneity, this was effectively addressed through sensitivity and subgroup analyses. ME-NBI should be considered a preferred method for EGC screening and diagnosis in clinical practice.

Preoperative C-reactive protein to albumin ratio may be a good prognostic marker in patients undergoing hepatectomy for hepatocellular carcinoma: a meta-analysis.

Background: Systemic inflammatory response represented by C-reactive protein to albumin ratio (CAR) was shown to be associated with long-term outcome in patients with hepatocellular carcinoma (HCC). We conducted a meta-analysis to investigate the prognostic value of preoperative CAR in patients undergoing hepatectomy for HCC. Methods: We searched four databases (PubMed, Embase, Scopus and Cochrane Library) from inception to May 10th, 2024. Studies investigating the prognostic value of preoperative CAR in HCC patients after hepatectomy. The primary endpoints were overall survival (OS) and disease-free survival (DFS). Data from individual studies were aggregated to calculate the pooled hazard ratio (HR) using a random-effects model. Results: A total of 11 studies included 4,066 patients were finally analyzed in the meta-analysis. Overall, the higher preoperative CAR was associated with poorer OS (HR 1.92, 95% CI 1.67 to 2.22, I 2 = 0%) and DFS (HR 1.79, 95% CI 1.59 to 2.02, I 2 = 0%) rate. Furthermore, subgroup analyses indicated that CAR could be a prognostic biomarker for patients with HCC regardless of regions and cut-off value. Conclusion: Our meta-analysis indicates that higher preoperative CAR level is associated with poorer OS and DFS, it may be a good prognostic marker of survival outcomes after hepatectomy in patients with HCC. However, future prospective trials are necessary to validate the conclusion. Systematic review registration: The study protocol was registered in the Open Science Framework (https://osf.io/uavt8).

Identification of immune infiltration and PANoptosis-related molecular clusters and predictive model in Alzheimer's disease based on transcriptome analysis.

This study aims to explore the expression profile of PANoptosis-related genes (PRGs) and immune infiltration in Alzheimer's disease (AD). Based on the Gene Expression Omnibus database, this study investigated the differentially expressed PRGs and immune cell infiltration in AD and explored related molecular clusters. Gene set variation analysis (GSVA) was used to analyze the expression of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes in different clusters. Weighted gene co-expression network analysis was utilized to find co-expressed gene modules and core genes in the network. By analyzing the intersection genes in random forest, support vector machine, generalized linear model, and extreme gradient boosting (XGB), the XGB model was determined. Eventually, the first five genes (Signal Transducer and Activator of Transcription 3, Tumor Necrosis Factor (TNF) Receptor Superfamily Member 1B, Interleukin 4 Receptor, Chloride Intracellular Channel 1, TNF Receptor Superfamily Member 10B) in XGB model were selected as predictive genes. This research explored the relationship between PANoptosis and AD and established an XGB learning model to evaluate and screen key genes. At the same time, immune infiltration analysis showed that there were different immune infiltration expression profiles in AD.

Wnt/Ca2+ pathway inhibits neural differentiation of human dental pulp stem cells in vitro.

Background/purpose: Dental pulp stem cells (DPSCs) have demonstrated significant potential for neuroregeneration. However, a full understanding of the specific mechanism underpinning the neural differentiation of DPSCs is still required. The Wnt signaling is crucial for the development of the embryonic neural system and the maintenance of adult neural homeostasis. This study aimed to investigate the role of the Wnt/Ca2+ pathway in the neural differentiation of human DPSCs (hDPSCs) and its modulation of the Wnt/ß-catenin pathway. Materials and methods: hDPSCs were cultured and divided into the control group and the neurogenic induction group (Neuro group). The mRNA and protein levels of neurogenic markers, Wnt/Ca2+, and Wnt/ß-catenin pathway indicators were determined using Quantitative real-time PCR and Western blotting. After inhibition of the Wnt/Ca2+ pathway using a WNT5A short hairpin RNA (shRNA) plasmid and subsequent neurogenic induction, neurogenic markers and Wnt/ß-catenin pathway indicators in the NC-sh-Neuro group and WNT5A-sh-Neuro group were determined using Quantitative real-time PCR and Western blotting. Results: Compared with the control group, the expression of the Wnt/Ca2+ pathway indicators (WNT5A, Frizzled 2, calmodulin-dependent protein kinase IIa, and nuclear factor of active T cells 1) decreased in the Neuro group. Conversely, the expression of WNT3A, total ß-catenin and active ß-catenin in the Wnt/ß-catenin pathway increased. Moreover, compared with the NC-sh-Neuro group, the WNT5A-sh-Neuro group exhibited a greater level of mature neural differentiation alongside elevated expression of the Wnt/ß-catenin pathway indicators. Conclusion: The Wnt/Ca2+ pathway inhibited neural differentiation of hDPSCs and has a negative effect on the Wnt/ß-catenin pathway in vitro.