Endosymbionts of citrus leafminer Phyllocnistis citrella Stainton among different citrus orchards in China.

Endosymbionts regulate the behavior of pest species, which could provide insights into their control. The citrus leafminer (Phyllocnistis citrella Stainton) is a widely distributed pest associated with diseases of citrus, especially of young trees. Here, we determined the endosymbiont composition of P. citrella in citrus orchards across China. The resulting dataset comprised average 50,430 high-quality reads for bacterial 16S rRNA V3-V4 regions of endosymbionts from 36 P. citrella larvae sampled from 12 citrus orchards across China. The sequencing depth and sampling size of this dataset were sufficient to reveal most of the endosymbionts of P. citrella. In total, 2,875 bacterial amplicon sequence variants were obtained; taxonomic analysis revealed a total of 372 bacterial genera, most of which were Proteobacteria phylum with Undibacterium being the most abundant genus. This dataset provides the first evidence of P. citrella endosymbionts that could support the development of pest management approaches in citrus orchards.

CBX3 antagonizes IFNγ/STAT1/PD-L1 axis to modulate colon inflammation and CRC chemosensitivity.

As an important immune stimulator and modulator, IFNγ is crucial for gut homeostasis and its dysregulation links to diverse colon pathologies, such as colitis and colorectal cancer (CRC). Here, we demonstrated that the epigenetic regulator, CBX3 (also known as HP1γ) antagonizes IFNγ signaling in the colon epithelium by transcriptionally repressing two critical IFNγ-responsive genes: STAT1 and CD274 (encoding Programmed death-ligand 1, PD-L1). Accordingly, CBX3 deletion resulted in chronic mouse colon inflammation, accompanied by upregulated STAT1 and CD274 expressions. Chromatin immunoprecipitation indicated that CBX3 tethers to STAT1 and CD274 promoters to inhibit their expression. Reversely, IFNγ significantly reduces CBX3 binding to these promoters and primes gene expression. This antagonist effect between CBX3 and IFNγ on STAT1/PD-L1 expression was also observed in CRC. Strikingly, CBX3 deletion heightened CRC cells sensitivity to IFNγ, which ultimately enhanced their chemosensitivity under IFNγ stimulation in vitro with CRC cells and in vivo with a syngeneic mouse tumor model. Overall, this work reveals that by negatively tuning IFNγ-stimulated immune genes' transcription, CBX3 participates in modulating colon inflammatory response and CRC chemo-resistance.

An Intermolecular Hydroarylation of Unactivated Arylcyclopropane via Re2O7/HFIP-Mediated Ring Opening.

In this paper, we describe a Re2O7-mediated ring-opening arylation of unactivated arylcyclopropane because of its functionalization with various arenes via Friedel-Crafts-type reactivity. This protocol allows facile access to functionalized 1,1-diaryl alkanes and is characterized by a broad substrate scope, mild reaction conditions, high efficiency, and high atom economy. Both density functional theory calculations and deuterium labeling experiments were carried out to justify the indispensable role of HFIP in this transformation and pointed to Re2O7-mediated ring opening being the rate-determining step.

D-A Conjugated Polymer/CdS S-Scheme Heterojunction with Enhanced Interfacial Charge Transfer for Efficient Photocatalytic Hydrogen Generation.

Owing to the improved charge separation and maximized redox capability of the system, Step-scheme (S-scheme) heterojunctions have garnered significant research attention for efficient photocatalysis of H2 evolution. In this work, an innovative linear donor-acceptor (D-A) conjugated polymer fluorene-alt-(benzo-thiophene-dione) (PFBTD) is coupled with the CdS nanosheets, forming the organic-inorganic S-scheme heterojunction. The CdS/PFBTD (CP) composite exhibits an impressed hydrogen production rate of 7.62 mmol g-1  h-1 without any co-catalysts, which is ≈14 times higher than pristine CdS. It is revealed that the outstanding photocatalytic performance is attributed to the formation of rapid electron transfer channels through the interfacial Cd─O bonding as evidenced by the density functional theory (DFT) calculations and in situ X-ray photoelectron spectroscopy (XPS) analysis. The charge transfer mechanism involved in S-scheme heterojunctions is further investigated through the photo-irradiated Kelvin probe force microscopy (KPFM) analysis. This work provides a new point of view on the mechanism of interfacial charge transfer and points out the direction of designing superior organic-inorganic S-scheme heterojunction photocatalysts.

Gut microbiota alteration and its association with immune function in post-COVID-19 patients.

To reveal the variation of gut microbiota and its association with immune function in cured patients with coronavirus 2019 (COVID-19) disease, gut microbiota of patients discharged from hospital for 20 ~ 23 months and healthy volunteers was analyzed by high throughput 16S rRNA sequencing. The diversity and abundance were compared, and the correlation with immunity factors was investigated, and changes in the content of 6 genera microorganisms with proportion higher than 0.1% were revealed in patients with COVID-19 disease: reduced content of Subdoligranulum, Haemophilus, Coprococcus, Eubacterium vertriosum group, and Lachnospiraceae ND3007 group and increased content of Hungatella. NK cells were negatively correlated to Subdoligranulum, while CD8 cells were positively correlated to Subdoligranulum but negative to Hungatella. IL-8 concentration was negatively correlated to Subdoligranulum, Haemophilus, Coprococcus, Eubacterium vertriosum group, and Lachnospiraceae ND3007 group but positively to Hungatella, while IL-1ß concentration was negatively correlated to Haemophilus and Eubacterium ventriosum group but positively to Hungatella. The variation of probiotics and potential pathogenic bacteria implies a higher risk in diseases and inflammation, and the modulation of the gut microbiota may help the healing of COVID-19 patients.

The 100 Most-Cited Randomised Controlled Trials in Orthodontics: A Bibliometric Study.

INTRODUCTION AND AIM: Randomised controlled trials (RCTs) are recognised as the highest level of original evidence and provide essential evidence for dentists to practice evidence-based dentistry. By analysing the top 100 most-cited RCT reports in orthodontics, this study aimed to determine popular research topics, key authors, countries, journals, and their impacts. METHODS: A comprehensive search was performed in the Web of Science (WoS) electronic database to identify the top 100 most-cited RCT reports in orthodontics. Publication and citation data were retrieved and further analysed and visualised using R Biblioshiny. The primary themes of the 100 articles were also determined. Additionally, the correlation between number of years since publication and citation counts was examined. RESULTS: The top 100 most-cited RCT reports were published between 1992 and 2018, contributed by 419 authors across 22 journals, with an average citation count of 93.48. The US led with the highest number of publications (28) and citations (2552), followed by the UK (22 and 2061) and Australia (8 and 912). Notably, 20 of the top 24 authors with at least 4 publications are from the UK. The primary focus areas of the articles included early Class II treatment (n = 14), obstructive sleep apnoea (n = 14), demineralisation (n = 12), and pain and quality of life (n = 12). Besides, a positive correlation was found between the number of years since publication and citation counts (P < .001). CONCLUSIONS: The top 100 most-cited RCT reports in orthodontics encompass a wide range of topics with varying focus areas across different time periods. This analysis recognises the contributions of scholars and offers valuable insights into the research trends within the field of orthodontics.

Ferroptosis regulation through Nrf2 and implications for neurodegenerative diseases.

This article provides an overview of the background knowledge of ferroptosis in the nervous system, as well as the key role of nuclear factor E2-related factor 2 (Nrf2) in regulating ferroptosis. The article takes Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS) as the starting point to explore the close association between Nrf2 and ferroptosis, which is of clear and significant importance for understanding the mechanism of neurodegenerative diseases (NDs) based on oxidative stress (OS). Accumulating evidence links ferroptosis to the pathogenesis of NDs. As the disease progresses, damage to the antioxidant system, excessive OS, and altered Nrf2 expression levels, especially the inhibition of ferroptosis by lipid peroxidation inhibitors and adaptive enhancement of Nrf2 signaling, demonstrate the potential clinical significance of Nrf2 in detecting and identifying ferroptosis, as well as targeted therapy for neuronal loss and mitochondrial dysfunction. These findings provide new insights and possibilities for the treatment and prevention of NDs.

Confined In-Situ Encapsulation of Co/C Composites with Increased Heterogeneous Interface Polarization for Enhanced Electromagnetic Performance.

It is an urgent problem to realize reliable microwave absorption materials (MAMs) with low density. To address this issue, a series of controlled experiments w ere carried out, which indicated that the tubular structure enables excellent microwave absorption properties with a lower powder filling rate. This performance is attributable to the combined dielectric and magnetic loss mechanisms provided by Co/C and the interface polarization facilitated by multiple heterogeneous interfaces. Particularly, Co@C nanotubes, benefiting from the enhanced heterointerface polarization due to their abundant specific surface area and the reduced electron migration barrier induced by their 1D stacked structure, effectively achieved a dual enhancement of dielectric loss and polarization loss at lower powder filling ratios. Furthermore, the magnetic coupling effect of magnetic nanoparticle arrays in tubular structures is demonstrated by micromagnetic simulation, which have been few reported elsewhere. These propertied enable Co@C nanotubes to achieve minimum reflection loss and maximum effective absorption broadband values of 61.0 dB and 5.5 GHz, respectively, with a powder filling ratio of 20 wt% and a thickness of 1.94 mm. This study reveals the significance of designing 1D structures in reducing powder filling ratio and matching thickness, providing valuable insights for developing MAMs with different microstructures.

Biomechanical analysis of miniscrew-assisted molar distalization with clear aligners: a three-dimensional finite element study.

BACKGROUND/OBJECTIVES: To compare the biomechanical characteristics of maxillary molar distalization with clear aligners in conjunction with three types of miniscrew anchorage. MATERIALS/METHODS: Three-dimensional (3D) finite element models of maxillary molar distalization with clear aligners and three types of miniscrew anchorage were established, including (A) control group, (B) direct buccal miniscrew anchorage group, (C) direct palatal miniscrew anchorage group, and (D) indirect buccal miniscrew anchorage group. The 3D displacement of maxillary teeth and the principal stress (maximum tensile and compressive stress) on the root and periodontal ligament (PDL) during molar distalization were recorded. RESULTS: The tooth displacement pattern during maxillary molar distalization in the four groups showed similarities, including labial tipping of anterior teeth, mesial and buccal tipping of premolars, and distal and buccal tipping of molars, but with varying magnitudes. Group C exhibited the greatest molar distalization, with the first molar achieving 0.1334 mm of crown distalization. Group D demonstrated a notable buccal crown movement (0.0682 mm) and intrusion (0.0316 mm) of the first premolar. Compared to Groups A and B, Groups C and D showed less labial crown tipping of the central incisor. Group B showed the greatest amount of maxillary incisor intrusion (central incisor: 0.0145 mm, lateral incisor: 0.0094 mm). Moreover, Groups C and D displayed significantly lower levels of compressive and tensile stress in the roots and PDL of the maxillary central and lateral incisors. LIMITATION: Molar distalization is a dynamic process involving sequential tooth movement stages; however, our research primarily examined the tooth movement patterns in the initial aligner. CONCLUSIONS/IMPLICATIONS: The use of miniscrew anchorage, especially direct palatal miniscrew anchorage, may enhance the treatment efficacy of maxillary molar distalization with clear aligners, leading to increased molar distalization, reduced mesial movement of premolars, and minimized labial tipping of anterior teeth.

Single-cell RNA sequencing uncovers the cell type-dependent transcriptomic changes in the retrosplenial cortex after peripheral nerve injury.

The retrosplenial cortex (RSC) is a vital area for storing remote memory and has recently been found to undergo broad changes after peripheral nerve injury. However, little is known about the role of RSC in pain regulation. Here, we examine the involvement of RSC in the pain of mice with nerve injury. Notably, reducing the activities of calcium-/calmodulin-dependent protein kinase type II-positive splenial neurons chemogenetically increases paw withdrawal threshold and extends thermal withdrawal latency in mice with nerve injury. The single-cell or single-nucleus RNA-sequencing results predict enhanced excitatory synaptic transmissions in RSC induced by nerve injury. Local infusion of 1-naphthyl acetyl spermine into RSC to decrease the excitatory synaptic transmissions relieves pain and induces conditioned place preference. Our data indicate that RSC is critical for regulating physiological and neuropathic pain. The cell type-dependent transcriptomic information would help understand the molecular basis of neuropathic pain.

Adverse Crosstalk between Extracellular Matrix Remodeling and Ferroptosis in Basal Breast Cancer.

(1) Background: Breast cancer is a frequent heterogeneous disorder diagnosed in women and causes a high number of mortality among this population due to rapid metastasis and disease recurrence. Ferroptosis can inhibit breast cancer cell growth, improve the sensitivity of chemotherapy and radiotherapy, and inhibit distant metastases, potentially impacting the tumor microenvironment. (2) Methods: Through data mining, the ferroptosis/extracellular matrix remodeling literature text-mining results were integrated into the breast cancer transcriptome cohort, taking into account patients with distant relapse-free survival (DRFS) under adjuvant therapy (anthracyclin + taxanes) with validation in an independent METABRIC cohort, along with the MDA-MB-231 and HCC338 transcriptome functional experiments with ferroptosis activations (GSE173905). (3) Results: Ferroptosis/extracellular matrix remodeling text-mining identified 910 associated genes. Univariate Cox analyses focused on breast cancer (GSE25066) selected 252 individual significant genes, of which 170 were found to have an adverse expression. Functional enrichment of these 170 adverse genes predicted basal breast cancer signatures. Through text-mining, some ferroptosis-significant adverse-selected genes shared citations in the domain of ECM remodeling, such as TNF, IL6, SET, CDKN2A, EGFR, HMGB1, KRAS, MET, LCN2, HIF1A, and TLR4. A molecular score based on the expression of the eleven genes was found predictive of the worst prognosis breast cancer at the univariate level: basal subtype, short DRFS, high-grade values 3 and 4, and estrogen and progesterone receptor negative and nodal stages 2 and 3. This eleven-gene signature was validated as regulated by ferroptosis inductors (erastin and RSL3) in the triple-negative breast cancer cellular model MDA-MB-231. (4) Conclusions: The crosstalk between ECM remodeling-ferroptosis functionalities allowed for defining a molecular score, which has been characterized as an independent adverse parameter in the prognosis of breast cancer patients. The gene signature of this molecular score has been validated to be regulated by erastin/RSL3 ferroptosis activators. This molecular score could be promising to evaluate the ECM-related impact of ferroptosis target therapies in breast cancer.

Trend of blood pressure changes among children from 2012 to 2022: findings from student health surveillance in Eastern China.

OBJECTIVES: The primary objective of this study is to examine the secular trends in blood pressure levels from 2012 to 2022 in eastern China. Additionally, to compare two standards [International Blood Pressure Reference for Children and Adolescents (ICBP) and the National Blood Pressure Reference for Chinese Han Children and Adolescents (CCBP)], we calculate the 95th percentile of blood pressure levels for students in developed regions (ECCBP). Secondly, the study aims to investigate potential contributors to elevated blood pressure, including sex, age, behaviors, and mental health. Lastly, the study seeks to estimate the total population aged 7-18 years with elevated blood pressure in Eastern China based on three references. METHODS: The data used in this study were obtained from the Student Health Surveillance program in Jiangsu Province, which has been collecting data since 2012. Trained project members, skilled nurses, and doctors measured anthropometric variables. Additionally, online student questionnaires were administered in 2017, 2019, and 2021 to collect personal information behavior patterns, and mental health. RESULTS: The study examined blood pressure changes in 123 013 children and adolescents in Eastern China from 2012 to 2022. Significant increases were observed in systolic blood pressure (SBP) and pulse pressure difference. Prevalence of elevated blood pressure followed a similar trend with ECCBP and CCBP, ranging from 17.2%/16.3% (2012-2015) to 11.6%/14.6% (2020-2022). Notably, BP with ICBP showed a significant increase in both prevalence and population, from 12.6% [6 713 679, 95% confidence interval (CI): 6 708 931 to 6 718 427] to 14.5% (7 004 208, 95% CI: 6 999 411 to 7 009 004). The study further emphasizes the significant impact of various risk factors on elevated blood pressure among children and adolescents, particularly the detrimental effect of depression on blood pressure, with the odds ratios (OR) in 2021 being 1.310 (95% CI, 1.290-1.330) for ECCBP, 1.239 (95% CI, 1.223-1.255) for CCBP, and 1.189 (95% CI, 1.176-1.202) for ICBP. CONCLUSION: The study revealed significant changes in the population and prevalence of elevated blood pressure in Eastern China from 2012 to 2022. The findings indicate a decline in the prevalence of elevated blood pressure (referred to as CCBP or ECCBP), while highlighting an increasing trend in elevated blood pressure (referred to as ICBP). Untreated high blood pressure can lead to serious cardiovascular diseases in adulthood, underscoring the importance of early prevention and management, particularly through nonpharmacological methods and regular monitoring for students in Eastern China. Raising awareness among educators, parents, and healthcare providers about the association between mental health and elevated blood pressure is essential.

Artificial intelligence in orthodontics and orthognathic surgery: a bibliometric analysis of the 100 most-cited articles.

BACKGROUND: The application of artificial intelligence (AI) in orthodontics and orthognathic surgery has gained significant attention in recent years. However, there is a lack of bibliometric reports that analyze the academic literature in this field to identify publishing and citation trends. By conducting an analysis of the top 100 most-cited articles on AI in orthodontics and orthognathic surgery, we aim to unveil popular research topics, key authors, institutions, countries, and journals in this area. METHODS: A comprehensive search was conducted in the Web of Science (WOS) electronic database to identify the top 100 most-cited articles on AI in orthodontics and orthognathic surgery. Publication and citation data were obtained and further analyzed and visualized using R Biblioshiny. The key domains of the 100 articles were also identified. RESULTS: The top 100 most-cited articles were published between 2005 and 2022, contributed by 458 authors, with an average citation count of 22.09. South Korea emerged as the leading contributor with the highest number of publications (28) and citations (595), followed by China (16, 373), and the United States (7, 248). Notably, six South Korean authors ranked among the top 10 contributors, and three South Korean institutions were listed as the most productive. International collaborations were predominantly observed between the United States, China, and South Korea. The main domains of the articles focused on automated imaging assessment (42%), aiding diagnosis and treatment planning (34%), and the assessment of growth and development (10%). Besides, a positive correlation was observed between the testing sample size and citation counts (P = 0.010), as well as between the time of publication and citation counts (P < 0.001). CONCLUSIONS: The utilization of AI in orthodontics and orthognathic surgery has shown remarkable progress, particularly in the domains of imaging analysis, diagnosis and treatment planning, and growth and development assessment. This bibliometric analysis provides valuable insights into the top-cited articles and the trends of AI research in this field.

Pattern of lifestyle behaviors and associated risk of being bullied at schools: A latent class analysis of 25,379 adolescents in Jiangsu Province of China.

School bullying is a worldwide problem. Although previous studies examined the association between different lifestyle behaviors and bullying victimization, the complex co-occurrence of these behaviors was not identified, and their association with the risk of being bullied remains unclear. We aimed to identify the behavioral patterns of adolescents and to explore their association with bullying victimization. This cross-sectional study employed data from the "Surveillance for Common Diseases and Health Risk Factors among Students" project implemented in Jiangsu Province of China in 2019, and a total of 25,379 school-enrolled students were included. We used a latent class analysis to identify behavioral patterns and a regression mixture model to explore various demographic characteristics, such as age, sex, and family structure in relation to bullying victimization across different patterns. We considered respondents having targeted behaviors, including smoking, alcohol consumption, illicit drug use, sugar consumption, no fruit consumption, low physical activity, electronic media use, and insufficient sleep. Four behavioral patterns were identified, including the "adolescents without apparent targeted behaviors" (19.65%), "substance and electronic media users" (12.76%), "typical electronic media users" (54.49%), and "typical substance users" (8.10%). The risk of being bullied was the highest in the "substance and electronic media users" (probability: 0.33), tripled that in "adolescents without apparent targeted behaviors" (odds ratio: 3.60, 95% confidence interval: 3.01-4.30). Risk of being bullied was reduced for those "substance and electronic media users" living with a nuclear family. Behavioral patterns and their association with being bullied differ between groups of school-aged adolescents. To better inform decision-making based on the current real-world findings, the implementation of bullying prevention programs could target specific behavioral patterns.

Longitudinal Observation of Immune Response for 23 Months in COVID-19 Convalescent Patients After Infection and Vaccination.

To better understand dynamic changes of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) immune response, a prospective, single-center, cohort study was conducted on longitudinal immune response in 34 COVID-19 convalescent patients over 23 months in Chongqing. Two blood samples from convalescent patients were collected, first sample collected during 10-13 months (M10-13) after infection (pre-SARS-CoV-2 vaccination) and second sample collected during 20-23 months (M20-23) after infection (post-SARS-CoV-2 vaccination). The SARS-CoV-2-specific humoral and cellular immunity were traced by testing total antibody (Ab), anti-nucleocapsid (NP) immunoglobulin M (IgM), anti-NP immunoglobulin G (IgG), and anti-spike (S) IgG Abs, lymphocyte subset count, and Th1 cytokines. Healthy donors (30) were also included in the study as the uninspected healthy controls. Our data showed significant change in mean titer of SARS-CoV-2-specific Ab response from M10-13 to M20-23 included, namely, SARS-CoV-2-specific total Ab as 219 AU/mL increasing to 750.9 AU/mL; anti-NP IgM as 3.5 AU/mL decreasing significantly (p < 0.001) to 0.6 AU/mL; anti-NP IgG as 7.9 AU/mL increasing to 87.1 AU/mL; and anti-S IgG as 499.0 RU/mL increasing to 1,802.3 RU/mL. Our observations suggested that one vaccine dose might have been sufficient for COVID-19 convalescent patients. Larger sample sizes are needed to compare better immune effect of protein subunit vaccine. Besides, compared to healthy donors, patients had decreased CD3+ and CD8+ T lymphocyte counts during two periods. Patients had most cytokines recovered normally within 2 years, but IL-6 level was significantly elevated; however, IL-6 was negatively correlated with IgM and positively correlated with IgG. Changes in cytokines might have been caused by SARS-CoV-2 infection or vaccination. Patients with comorbidities were associated with decreased CD3+ and CD8+ T lymphocytes and lower Ab titers following SARS-CoV-2 vaccination. Vaccination enormously increased humoral immunity beneficial in COVID-19 convalescent patients. Elderly COVID-19 convalescent patients with comorbidities needed more attention.

Cingulate protein arginine methyltransferases 1 regulates peripheral hypersensitivity via fragile X messenger ribonucleoprotein.

The deficit of fragile X messenger ribonucleoprotein (FMRP) leads to intellectual disability in human and animal models, which also leads to desensitization of pain after nerve injury. Recently, it was shown that the protein arginine methyltransferases 1 (PRMT1) regulates the phase separation of FMRP. However, the role of PRMT1 in pain regulation has been less investigated. Here we showed that the downregulation of PRMT1 in the anterior cingulate cortex (ACC) contributes to the development of peripheral pain hypersensitivity. We observed that the peripheral nerve injury decreased the expression of PRMT1 in the ACC; knockdown of the PRMT1 via shRNA in the ACC decreased the paw withdrawal thresholds (PWTs) of naïve mice. Moreover, the deficits of FMRP abolished the effects of PRMT1 on pain sensation. Furthermore, overexpression of PRMT1 in the ACC increased the PWTs of mice with nerve injury. These observations indicate that the downregulation of cingulate PRMT1 was necessary and sufficient to develop peripheral hypersensitivity after nerve injury. Thus, we provided evidence that PRMT1 is vital in regulating peripheral pain hypersensitivity after nerve injury via the FMRP.

Design, methodology, and baseline of eastern China student health and wellbeing cohort study.

Purpose: To describe the study design, methodology, and cohort profile of the Eastern China Student Health and Wellbeing Cohort Study. The cohort baseline includes (1) targeted disease (myopia, obesity, elevated blood pressure, and mental health) and (2) exposures (individual behaviors, environment, metabolomics, and gene and epigenetics). Participants: Annual physical examination, questionnaire-based survey, and bio-sampling have been carried out in the study population. In the first stage (2019-2021), a total of 6,506 students in primary schools are enrolled in the cohort study. Findings to date: Of all the cohort participants, the ratio of male to female is 1.16 among a total of 6,506 student participants, of which 2,728 (41.9%) students are from developed regions and 3,778 (58.1%) students are from developing regions. The initial age of observation is 6-10 years, and they will be observed until they graduate from high school (>18 years of age). (1) Targeted diseases: The growth rates of myopia, obesity, and high blood pressure vary by regions, and for developed regions, the prevalence of myopia, obesity, and elevated blood pressure is 29.2%, 17.4%, and 12.6% in the first year, respectively. For developing regions, the prevalence of myopia, obesity, and elevated blood pressure is 22.3%, 20.7%, and 17.1% in the first year, respectively. The average score of CES-D is 12.9 ± 9.8 in developing regions/11.6 ± 9.0 in developed regions. (2) Exposures: ① The first aspect of individual behaviors: the questionnaire topics include diet, physical exercise, bullying, and family. ② The second aspect of environment and metabolomics: the average desk illumination is 430.78 (355.84-611.56) LX, and the average blackboard illumination is 365.33 (286.83-516.84) LX. Metabolomics like bisphenol A in the urine is 0.734 ng/ml. ③ The third aspect of gene and epigenetics: SNPs (rs524952, rs524952, rs2969180, rs2908972, rs10880855, rs1939008, rs9928731, rs72621438, rs9939609, rs8050136 and so on) are detected. Future plans: Eastern China Student Health and Wellbeing Cohort Study is aiming to focus on the development of student-targeted diseases. For children with student common diseases, this study will focus on targeted disease-related indicators. For children without targeted disease, this study aims to explore the longitudinal relationship between exposure factors and outcomes, excluding baseline confounding factors. Exposure factors include three aspects: (1) individual behaviors, (2) environment and metabolomics, and (3) gene and epigenetics. The cohort study will continue until 2035.

Epitranscriptomic profiling of N4-acetylcytidine-related RNA acetylation in the spinal dorsal horn of rat with cancer-induced bone pain.

Recently, epigenetics involved in the regulation of gene expression has become a research hotspot. This study evaluated N4-acetylcytidine (ac4c) RNA acetylation in the spinal dorsal horn (SDH) of rats with cancer-induced bone pain (CIBP). The ac4C-specific RIP sequencing and NAT10-specific RIP sequencing were performed to identify the differences in ac4C acetylation and gene expression in the SDH between CIBP and sham groups, the relationship with the acetylation-modifying enzyme NAT10, and association analysis was performed. By interfering with the NAT10 expression, the relationship between some up-regulated genes and ac4C acetylation in CIBP was verified. In this study, we demonstrated that bone cancer increases the levels of NAT10 and the overall acetylation, inducing differential ac4C patterns in the SDH of rats. Through verification experiments, it was found that ac4C acetylation of some genes is regulated by NAT10, and differential ac4C patterns in RNA determine the expression of this RNA. We exposed that some CIBP-related gene expression was altered in the SDH of rats, which was regulated by differentially expressed ac4C acetylation.

HP1γ Prevents Activation of the cGAS/STING Pathway by Preserving Nuclear Envelope and Genomic Integrity in Colon Adenocarcinoma Cells.

Chronic inflammatory processes in the intestine result in serious conditions such as inflammatory bowel disease (IBD) and cancer. An increased detection of cytoplasmic DNA sensors has been reported in the IBD colon mucosa, suggesting their contribution in mucosal inflammation. Yet, the mechanisms altering DNA homeostasis and triggering the activation of DNA sensors remain poorly understood. In this study, we show that the epigenetic regulator HP1γ plays a role in preserving nuclear envelope and genomic integrity in enterocytic cells, thereby protecting against the presence of cytoplasmic DNA. Accordingly, HP1 loss of function led to the increased detection of cGAS/STING, a cytoplasmic DNA sensor that triggers inflammation. Thus, in addition to its role as a transcriptional silencer, HP1γ may also exert anti-inflammatory properties by preventing the activation of the endogenous cytoplasmic DNA response in the gut epithelium.

Nuclear modifier YARS2 allele correction restored retinal ganglion cells-specific deficiencies in Leber's hereditary optic neuropathy.

Leber's hereditary optic neuropathy (LHON) is a maternally transmitted eye disease due to the degeneration of retinal ganglion cells (RGCs). Mitochondrial 11778G > A mutation is the most common LHON-associated mitochondrial DNA (mtDNA) mutation. Our recent studies demonstrated some LHON families manifested by synergic interaction between m.11778G > A mutation and YARS2 allele (c.572G > T, p.Gly191Val) encoding mitochondrial tyrosyl-tRNA synthetase. However, the RGC-specific effects of LHON-associated mtDNA mutations remain elusive and there is no highly effective therapy for LHON. Here, we generated patients-derived induced pluripotent stem cells (iPSCs) from fibroblasts derived from a Chinese LHON family (both m.11778G > A and c.572G > T mutations, only m.11778G > A mutation, and control subject). The c.572G > T mutation in iPSC lines from a syndromic individual was corrected by CRISPR/Cas9. Those iPSCs were differentiated into neural progenitor cells and subsequently induced RGC-like cells using a stepwise differentiation procedure. Those RGC-like cells derived from symptomatic individual harboring both m.11778G > A and c.572G > T mutations exhibited greater defects in neuronal differentiation, morphology including reduced area of soma, numbers of neurites and shortened length of axons, electrophysiological properties than those in cells bearing only m.11778G > A mutation. Furthermore, these RGC-like cells revealed more drastic reductions in oxygen consumption rates, levels of mitochondrial ATP and increasing productions of reactive oxygen species than those in other cell models. These mitochondrial dysfunctions promoted the apoptotic process for RGC degenerations. Correction of YARS2 c.572G > T mutation rescued deficiencies of patient-derived RGC-like cells. These findings provide new insights into pathophysiology of LHON arising from RGC-specific mitochondrial dysfunctions and step toward therapeutic intervention for this disease.