Ethyl acetate fraction of Thesium chinense Turcz. alleviates chronic obstructive pulmonary disease through inhibition of ferroptosis mediated by activating Nrf2/SLC7A11/GPX4 axis.

ETHNOPHARMACOLOGICAL RELEVANCE: Thesium chinense Turcz., a traditional Chinese herbal medicine, displays good therapeutic efficiency against respiratory diseases (e.g. pneumonia, pharyngitis) in clinical applications, however, its effects on COPD and the mechanism of action are still unclear. AIM OF THE STUDY: This study aims to investigate the therapeutic effect of the ethyl acetate fraction of Thesium chinense Turcz. (TCEA) on COPD and reveal the underlying mechanism. MATERIALS AND METHODS: A cigarette smoke (CS)-induced mouse COPD model was established, and the efficacy of TCEA was evaluated using peripheral blood testing, HE and Masson staining, qRT-PCR and ELISA assays. TCEA was analyzed for chemical composition by LC-MS/MS and HPLC. Prediction of major signaling pathways and potential targets was performed by network pharmacology. The molecular mechanism of TCEA was explored by immunoblotting, immunofluorescence staining, flow cytometry, and ubiquitination assay. Finally, potential active small molecules in TCEA were identified by molecular virtual screening. RESULTS: TCEA treatment significantly inhibited the secretion of pro-inflammatory factors and attenuated pathological emphysema. The main chemical constituents of TCEA were identified as flavonoids by UPLC-MS/MS. Network pharmacology analysis enriched the Nrf2 signaling pathway closely related to oxidative stress. Our results suggest that TCEA inhibited ferroptosis by activating Nrf2/SLC7A11/GPX4 axis and inhibiting lipid metabolism-related proteins, ACSL4, ALOX5 and COX2 in vivo and in vitro. Noteworthily, the beneficial impact of TCEA on regulation of SLC7A11 and GPX4 vanished after silencing Nrf2. Moreover, Nrf2 ubiquitination was inhibited by TCEA treatment. Finally, several flavonoid active ingredients that may modulate Nrf2 were identified by molecular virtual screening. CONCLUSIONS: TCEA significantly alleviated COPD progression by inhibiting ferroptosis primarily through activation of Nrf2/SLC7A11/GPX4 signaling. Flavonoids are the main active components that exert their effects. These findings shed light on the mechanism of action of TCEA and its potential active components, providing a feasible approach for the treatment of COPD.

Atorvastatin inhibits Lipopolysaccharide (LPS)-induced vascular inflammation to protect endothelium by inducing Heme Oxygenase-1 (HO-1) expression.

PURPOSE: This study aimed to explore the differential effects of varying doses of atorvastatin on antagonizing lipopolysaccharide (LPS)-induced endothelial inflammation based on heme oxygenase 1 (HO-1) expression. METHOD: Vascular endothelial inflammatory injury was induced in 40 Sprague-Dawley rats by intraperitoneal injection of LPS. These rats were randomly divided into control, low-dose atorvastatin, high-dose atorvastatin, and HO-1 blocking groups. Seven days after treatment, all rats were sacrificed, and heart-derived peripheral blood was collected to measure the serum concentrations of bilirubin, alanine aminotransferase (ALT), total cholesterol, malondialdehyde, endothelial cell protein C receptor, endothelin-1, von Willebrand factor, and soluble thrombomodulin. Meanwhile, the number of circulating endothelial cells was determined using flow cytometry. Vascular tissues from descending aorta of rats from each group were extracted to detect the expression level of HO-1. RESULTS: After different doses of atorvastatin intervention, the above inflammatory indices were decreased, and HO-1 expression and ALT concentration were increased in the atorvastatin-treated group of rats compared with the control group. These changes were more pronounced in the high-dose statin group (P < 0.05). Conversely, no significant decrease in the above inflammatory indices and no significant increase in HO-1 expression were observed in rats in the blocking group (P > 0.05). CONCLUSION: For LPS-induced vascular inflammation, high-dose atorvastatin exerts potent anti-inflammatory and vascular endothelial protection effects by inducing HO-1 expression.

Mechanistic Interrogation on Wound Healing and Scar Removing by the Mo4/3B2-x Nanoscaffold Revealed Regulated Amino Acid and Purine Metabolism.

Wound rehabilitation is invariably time-consuming, scar formation further weakens therapeutic efficacy, and detailed mechanisms at the molecular level remain unclear. In this work, a Mo4/3B2-x nanoscaffold was fabricated and utilized for wound healing and scar removing in a mice model, while metabolomics was used to study the metabolic reprogramming of metabolome during therapy at the molecular level. The results showed that transition metal borides, called Mo4/3B2-x nanoscaffolds, could mimic superoxide dismutase and glutathione peroxidase to eliminate excess reactive oxygen species (ROS) in the wound microenvironment. During the therapeutic process, the Mo4/3B2-x nanoscaffold could facilitate the regeneration of wounds and removal of scars by regulating the biosynthesis of collagen, fibers, and blood vessels at the pathological, imaging, and molecular levels. Subsequent metabolomics study revealed that the Mo4/3B2-x nanoscaffold effectively ameliorated metabolic disorders in both wound and scar microenvironments through regulating ROS-related pathways including the amino acid metabolic process (including glycine and serine metabolism and glutamate metabolism) and the purine metabolic process. This study is anticipated to illuminate the potential clinical application of the Mo4/3B2-x nanoscaffold as an effective therapeutic agent in traumatic diseases and provide insights into the development of analytical methodology for interrogating wound healing and scar removal-related metabolic mechanisms.

Functional dyeing of cellulose macromolecule/synthetic fibers two-component fabrics with sustainable microbial prodigiosins.

As an important cellulose macromolecular-based material, cotton/polyamide and cotton/polyester fabrics are widely utilized in the textile and garment field due to their combination of the advantages of both cotton and synthetic fibers, such as excellent breathability, hygroscopicity, and abrasion performance. However, the synthetic dyes used in fabric coloration are derived from non-renewable resources, and the long-time dyeing procedure poses large pollution problems. Herein, microbial prodigiosins fermented by Serratia marcescens were employed for cotton/polyamide and cotton/polyester fabric dyeing and functionalizing. The results demonstrated that the prodigiosins suspension exhibited outstanding stability. Synthetic fibers contributed significantly to the overall color of fabrics and provided good dimensional stability and durability. In contrast, cotton fibers imparted relatively lighter color but played an essential role in enhancing the softness and comfort of fabrics. The dyed fabrics presented bright overall color light with good uniformity. Furthermore, the antibacterial rates of the dyed cotton/polyamide and cotton/polyester fabrics were 87.31 % and 89.70 %, respectively. The UPF values of the dyed cotton/polyamide and cotton/polyester fabrics were recorded as 52.3 and 93.5, respectively. This study provided a novel approach for cleaner functional dyeing of cotton/synthetic fiber two-component fabrics using prodigiosins.

Association between adolescent depression and adult suicidal behavior: A systematic review and meta-analysis.

This meta-analysis aims to estimate the association between adolescent depression and adult suicidal behavior, while systematically evaluating gender differences reported in literature. A random-effects model was used to determine the pooled association, reporting odds ratios (ORs) with corresponding 95 % confidence intervals (CIs). Nine articles comprising over 6084 adolescents together showed that people with a history of depression in adolescence are more likely to gain suicidal behaviors during adulthood (OR = 3.97, 95 % Cl: 2.79, 5.63). Sex-specific analysis indicated that males who experienced depression in adolescence developed a higher incidence of suicidal behavior in adulthood compared to females with a similar history (Males: OR = 3.61, 95 % Cl: 1.02, 12.78; Females: OR = 3.56, 95 % Cl: 1.71, 7.43). Furthermore, suicide attempts emerged as the predominant outcome among various suicidal behaviors (OR = 3.43, 95 % Cl: 1.75, 6.71). This meta-analysis provides robust evidence that depression in adolescence significantly increases the risk of suicidal behavior in adulthood.

Overexpression of cytoplasmic poly(A)-binding protein 1 as a biomarker for the prognosis and selection of postoperative regimen in breast cancer.

PURPOSE: The dysregulation of the cytoplasmic poly(A)-binding protein 1 (PABPC1) is involved in a variety of tumors but little is known about its role in human breast cancer. Therefore, the effect of PABPC1 in the prognosis and regimen selection in breast cancer patients was evaluated. METHODS: A total of 791 cases of invasive breast cancer were included in this study, although only 416 were involved in subsequent analyses after the propensity score matching (PSM) test. PABPC1 expression was detected by immunohistochemistry. The relationship between PABPC1 expression and clinicopathological factors, postoperative regimens, and outcomes was determined. RESULTS: In the total 791 cases, 583 cases were positive for PABPC1, but only 212 (26.8%) showed high PABPC1 expression (PABPC1-HE). The overall survival (OS) and disease-free survival (DFS) of PABPC1-HE patients after PSM were significantly worse than those in patients with PABPC1 low expression (PABPC1-LE), regardless of age, molecular type, tumor size, nodal status, or pStage. Postoperative chemotherapy (CT) increased the OS of PABPC1-HE patients but not that of PABPC1-LE patients. Among patients receiving endocrine therapy, those in the PABPC-LE group had an extended OS, while CT or chemoradiotherapy (CT/CRT) only significantly extended the OS time of PABPC-HE patients. CT/CRT did not significantly extend the survival of PABPC1-LE HER2-positive patients but extended the OS of PABPC1-HE HER2-positive patients. However, the OS of patients treated with CT/CRT + trastuzumab therapy was significantly longer than that of other patients under other therapies in the PABPC1-HE group, suggesting that PABPC1-HE might be sensitive to trastuzumab-based therapy. The multivariate analysis revealed that PABPC1-HE was an independent prognostic factor for both poor OS and DFS in breast cancer except luminal A type. CONCLUSIONS: Our results revealed that PABPC1 might be considered as a biomarker to help in subtyping, as well as in the prognosis and regimen selection of breast cancer patients.

Dual-Site Bridging Mechanism for Bimetallic Electrochemical Oxygen Evolution.

Heterogeneous dual-site electrocatalysts are emerging cutting-edge materials for efficient electrochemical water splitting. However, the corresponding oxygen evolution reaction (OER) mechanism on these materials is still unclear. Herein, based on a series of in-situ spectroscopy experiments and density function theory (DFT) calculations, a new heterogeneous dual-site O-O bridging mechanism (DSBM) is proposed. This mechanism is to elucidate the sequential appearance of dual active sites through in-situ construction (hybrid ions undergo reconstruction initially), determine the crucial role of hybrid dual sites in this mechanism (with Ni sites preferentially adsorbing hydroxyls for catalysis followed by proton removal at Fe sites), assess the impact of O-O bond formation on the activation state of water (inducing orderliness of activated water), and investigate the universality (with Co doping in Ni(P4O11)). Under the guidance of this mechanism, with Fe-Ni(P4O11) as pre-catalyst, the in-situ formed Fe-Ni(OH)2 electrocatalyst has reached a record-low overpotential of 156.4 mV at current density of 18.0 mA cm-2. Successfully constructed Fe-Ni(P4O11)/Ti uplifting the overall efficacy of the phosphate from moderate to superior, positioning it as an innovative and highly proficient electrocatalyst for OER.

CircARAP2 controls sMICA-induced NK cell desensitization by erasing CTCF/PRC2-induced suppression in early endosome marker RAB5A.

Natural killer cells (NK) are the "professional killer" of tumors and play a crucial role in anti-tumor immunotherapy. NK cell desensitization is a key mechanism of tumor immune escape. Dysregulated NKG2D-NKG2DL signaling is a primary driver of this desensitization process. However, the factors that regulate NK cell desensitization remain largely uncharacterized. Here, we present the first report that circular RNA circARAP2 (hsa_circ_0069396) is involved in the soluble MICA (sMICA)-induced NKG2D endocytosis in the NK cell desensitization model. CircARAP2 was upregulated during NK cell desensitization and the loss of circARAP2 alleviated NKG2D endocytosis and NK cell desensitization. Using Chromatin isolation by RNA purification (ChIRP) and RNA pull-down approaches, we identified that RAB5A, a molecular marker of early endosomes, was its downstream target. Notably, transcription factor CTCF was an intermediate functional partner of circARAP2. Mechanistically, we discovered that circARAP2 interacted with CTCF and inhibited the recruitment of CTCF-Polycomb Repressive Complex 2 (PRC2) to the promoter region of RAB5A, thereby erasing histone H3K27 and H3K9 methylation suppression to enhance RAB5A transcription. These data demonstrate that inhibition of circARAP2 effectively alleviates sMICA-induced NKG2D endocytosis and NK cell desensitization, providing a novel target for therapeutic intervention in tumor immune evasion.

OPTICAL COHERENCE TOMOGRAPHY FINDINGS IN PRESUMED VETERINARY ANTHELMINTIC DRUG-INDUCED RETINAL TOXICITY: A Glimpse into Underlying Mechanism.

PURPOSE: To report optical coherence tomography findings of presumed veterinary anthelmintic drugs (VADs)-induced retinal toxicity that may aid in understanding potential pathogenic mechanisms. METHODS: This is a retrospective observational case series analysis of patients with vision abnormalities following the accidental or intentional consumption of veterinary anthelmintic drugs. All cases underwent a thorough ophthalmological examination. Moreover, medical records, as well as the initial and follow-up optical coherence tomography images, were thoroughly scrutinized. RESULTS: Four patients were identified (3 men; mean [range] age, 36.5 [22-52] years). Each patient overdosed on one or two of the following VADs: closantel, triclabendazole, praziquantel, pyrantel pamoate, and niclofolan. The most characteristic optical coherence tomography finding was diffuse, granular, hyperreflective lesions throughout the outer retina, which were initially identified in the ellipsoid zone in two cases. At follow-up, optical coherence tomography exhibited regression of hyperreflective lesions and extensive loss of the outer retinal elements in two patients. In addition, the subfoveal outer retinal layers may be partially preserved. CONCLUSION: Some veterinary anthelmintic drugs could be detrimental to the human retina if overdosed, resulting in visual disturbances. Optical coherence tomography revealed the mitochondria-enriched ellipsoid zone where outer retinal damage first appeared on, implying that these medications may harm the retina by inhibiting mitochondrial energy metabolism, as they do to eliminate parasites.

Sex-specific association of peripheral blood cell indices and inflammatory markers with depressive symptoms in early adolescence.

BACKGROUND: Previous studies have reported the correlation of dysregulated blood cell indices and peripheral inflammatory markers with depression in adults but limited studies have examined this correlation in early adolescents. METHODS: This study used data from the Chinese Early Adolescents Cohort Study, which was conducted in Anhui, China. Students' depression symptoms were repeatedly measured using the Chinese version of the Center for Epidemiological Studies Depression Scale for Children. Students' blood samples were collected in September 2019 and September 2021. The peripheral blood cell counts and inflammatory marker levels were determined using routine blood tests. Multivariable regression models were used to explore the associations between blood cell indices and adolescent depressive symptoms in both the whole sample and the sex-stratified samples. RESULTS: The white blood cell (WBC) count, neutrophil count (NC), platelet (PLT) count, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio, and systemic immune inflammation index (SII) were positively correlated with the severity of depressive symptoms during follow-up. The mean corpuscular volume (MCV), mean hemoglobin (HGB) volume (MCH), and mean corpuscular HGB concentration (MCHC) exhibited negative temporal correlations with depressive symptoms. Additionally, several sex-specific blood cell markers were correlated with depression. Male adolescents with increased red blood cell (RBC) and female adolescents with decreased HGB levels and upregulated WBC, NC, NLR, and SII levels exhibited severe depressive symptoms at follow-up. CONCLUSIONS: These findings suggested the potential usefulness of peripheral blood cell indices in the assessment of depression in early adolescents.

Inconsistency in psychological resilience and social support with mental health in early adolescents: A multilevel response surface analysis approach.

BACKGROUND: Given the high prevalence of adolescent mental health problems, promoting understanding and implementation of protective factors is crucial for prevention and intervention efforts addressing adolescent mental health problems. This study aims to investigate whether consistency and inconsistency in protective factors are associated with adolescent mental health problems and to inform adolescent mental health interventions that target the unique needs of adolescents and promote adolescent mental health. METHODS: We used multistage cluster sampling to conduct psychological resilience, social support, and mental health questionnaires from April to June 2023 among 10,653 Chinese adolescents (52.3 % were boys). Data were analyzed using polynomial regressions with response surface analysis. RESULTS: The higher levels of psychological resilience and social support in adolescents were associated with fewer mental health problems (anxiety: a1 = -1.83, P < 0.001; depression: a1 = -2.44, P < 0.001; and perceived stress: a1 = -1.20, P < 0.001). When the level of psychological resilience was greater than social support, the greater the discrepancy the higher the perceived stress among adolescents (a3 = 1.19, P < 0.001). Moreover, the consistency of psychological resilience and social support had a greater impact on girls' mental health (anxiety: a1 = -1.97, P < 0.001; depression: a1 = -2.71, P < 0.001; perceived stress: a1 = -1.23, P < 0.001). LIMITATIONS: The cross-sectional study design limited the inference of causal relationships between variables. CONCLUSIONS: These results emphasize that adolescents need a balanced development of protective factors and targeted intervention programs for different mental health problems.

Research situation, hot spots, and global trends of melasma therapy: Bibliometric insights and visual analysis from 2000 to 2023.

BACKGROUND: Melasma is a prevalent pigmented disease, yet its pathogenesis remains unclear, posing challenges for effective treatment. Bibliometric analysis, a novel approach to literature research, offers the opportunity to evaluate research trends through qualitative and quantitative methods. This study utilizes bibliometric methods to analyze the existing literature on melasma treatment, examining influential publications, institutions, countries, and authors through statistical analysis. METHODS: In order to retrieve manuscripts related to the topic of melasma treatment, we conducted a search using the search formula: (TS = (melasma or Chloasma or "mask of pregnancy")) AND TS = (treatment or therapy). We searched through the Web of Science Core Collection database, covering publications from 2000 to 2023. VOSviewer, CiteSpace and the Bibliometric online site (https://bibliometric.com/app) were used to conduct this bibliometric analysis. Our analysis focused on various factors including publications, authors co-authorship, institutions, countries, citation analysis, keywords co-occurrence, references co-citation and journal co-citation. RESULTS: A total of 943 articles and 200 reviews were published between 2000 and 2023, accumulating a total of 8628 citations. The average number of citations per item was 18.85, and the average number of citations per year was 292.69. The most prolific author, Sungeun Chang, contributed a total of 9 articles. Cario University emerged as the top research institution. The United States led in terms of article publications with a count of 276. In the past 5 years, the research trends in this field have primarily focused on tranexamic acid and epidermal melasma, as indicated by the burst analysis of publications and keywords. CONCLUSIONS: The United States continues to lead in terms of institutions and research output. The current emphasis is on the meticulous implementation of tranexamic acid and laser therapy. It is crucial to foster enhanced collaboration among countries, institutions, and authors to facilitate improved research.

Treatment of primary nasal tuberculosis with anti-tumor necrosis factor immunotherapy: A case report.

BACKGROUND: Primary nasal tuberculosis (TB) is a rare form of extrapulmonary TB, particularly in patients receiving anti-tumor necrosis factor (TNF) immunotherapy. As a result, its diagnosis remains challenging. CASE SUMMARY: A 58-year-old male patient presented to the ear, nose, and throat department with right-sided nasal obstruction and bloody discharge for 1 month. He was diagnosed with psoriatic arthritis and received anti-TNF immunotherapy for 3 years prior to presentation. Biopsy findings revealed chronic granulomatous inflammation and a few acid-fast bacilli, suggestive of primary nasal TB. He was referred to our TB management department for treatment with oral anti-TB agents. After 9 months, the nasal lesions had disappeared. No recurrence was noted during follow-up. CONCLUSION: The diagnosis of primary nasal TB should be considered in patients receiving TNF antagonists who exhibit thickening and crusting of the nasal septum mucosa or inferior turbinate, particularly when pathological findings suggest granulomatous inflammation.

Involvement of metabotropic glutamate receptors in regulation of immune response in the Pacific oyster Crassostrea gigas.

Metabotropic glutamate receptors (mGluRs) play a pivotal role in the neuroendocrine-immune regulation. In this study, eight mGluRs were identified in the Pacific Oyster Crassostrea gigas, which were classified into three subfamilies based on genetic similarity. All CgmGluRs harbor variable numbers of PBP1 domains at the N-terminus. The sequence and structural features of CgmGluRs are highly similar to mGluRs in other species. A uniformly upregulated expression of CgmGluRs was observed during D-shaped larval stage compared to early D-shaped larval stage. The transcripts of CgmGluRs were detectable in various tissues of oyster. Different CgmGluR exhibited diverse expression patterns response against different PAMP stimulations, among which CgmGluR5 was significantly downregulated under these stimulations, reflecting its sensitivity and broad-spectrum responsiveness to microbes. Following LPS stimulation, the mRNA expression of CgmGluR5 and CgCALM1 in haemocytes was suppressed within 6 h and returned to normal levels by 12 h. Inhibition of CgmGluR5 activity resulted in a significant reduction in CgCALM1 expression after 12 h. Further KEGG enrichment analysis suggested that CgmGluR5 might modulate calcium ion homeostasis and metabolic pathways by regulating CgCALM1. This research delivers the systematic analysis of mGluR in the Pacific Oyster, offering insights into evolutionary characteristics and immunoregulatory function of mGluR in mollusks.

Topological phases and non-Hermitian topology in tunable nonreciprocal cyclic three-mode optical systems.

We propose a method for simulating a 1D non-Hermitian Su-Schrieffer-Heeger model with modulated nonreciprocal hopping using a cyclic three-mode optical system. The current system exhibits different localization of topologically nontrivial phases, which can be characterized by the winding number. We find that the eigenenergies of such a system undergo a real-complex transition as the nonreciprocal hopping changes, accompanied by a non-Bloch parity-time symmetry breaking. We explain this phase transition by considering the evolution of saddle points on the complex energy plan and the ratio of complex eigenenergies. Additionally, we demonstrate that the skin states resulting from the non-Hermitian skin effect possess higher-order exceptional points under the critical point of the non-Bloch parity-time phase transition. Furthermore, we investigate the non-Hermitian skin phase transition by the directional mean inverse participation ratio and the generalized Brillouin zone. This work provides an alternative way to investigate the novel topological and non-Hermitian effects in nonreciprocal optical systems.

Chromosome-level genome assembly of the western flower thrips Frankliniella occidentalis.

The western flower thrips Frankliniella occidentalis (Thysanoptera: Thripidae) is a global invasive species that causes increasing damage by direct feeding on crops and transmission of plant viruses. Here, we assemble a previously published scaffold-level genome into a chromosomal level using Hi-C sequencing technology. The assembled genome has a size of 302.58 Mb, with a contig N50 of 1533 bp, scaffold N50 of 19.071 Mb, and BUSCO completeness of 97.8%. All contigs are anchored on 15 chromosomes. A total of 16,312 protein-coding genes are annotated in the genome with a BUSCO completeness of 95.2%. The genome contains 492 non-coding RNA, and 0.41% of interspersed repeats. In conclusion, this high-quality genome provides a convenient and high-quality resource for understanding the ecology, genetics, and evolution of thrips.

Alantolactone enhances the sensitivity of melanoma to MAPK pathway inhibitors by targeting inhibition of STAT3 activation and down-regulating stem cell markers.

Mitogen-activated protein kinase inhibitors (MAPKi) were the first line drugs for advanced melanoma patients with BRAF mutation. Targeted therapies have significant therapeutic effects; however, drug resistance hinders their long-term efficacy. Therefore, the development of new therapeutic strategies against MAPKi resistance is critical. Our previous results showed that MAPKi promote feedback activation of STAT3 signaling in BRAF-mutated cancer cells. Studies have shown that alantolactone inhibited the activation of STAT3 in a variety of tumor cells. Our results confirmed that alantolactone suppressed cell proliferation and promoted apoptosis by inhibiting STAT3 feedback activation induced by MAPKi and downregulating the expression of downstream Oct4 and Sox2. The inhibitory effect of alantolactone combined with a MAPKi on melanoma cells was significantly stronger than that on normal cells. In vivo and in vitro experiments showed that combination treatment was effective against drug-resistant melanomas. Our research indicates a potential novel combination therapy (alantolactone and MAPKi) for patients with BRAF-mutated melanoma.

Longitudinal and Reciprocal Effects in the Association Between School Bullying and Homicidal Ideation During Early Adolescence.

Several cross-sectional studies indicated a positive association between school bullying and homicidal ideation during early adolescence. However, few longitudinal studies investigated this association. This study examined whether a bi-directional relationship exists within the longitudinal association between bullying victimization or bullying perpetration and homicidal ideation among early adolescents using a Random Intercept Cross-Lagged Panel Model. A total of 1611 early adolescents (39.5% girls; Mage = 12.50 years, SD = 0.50) were recruited from the Chinese Early Adolescents Cohort study. Data on bullying victimization, bullying perpetration, and homicidal ideation collected during three time points (September 2019, September 2020, and September 2021) were used. Bullying victimization showed a significant positive association with homicidal ideation at the between-person level. Bullying victimization and bullying perpetration had a bi-directional relationship with homicidal ideation at the within-person level. Additionally, this study considered the impact of biological sex-based differences and bullying types on adolescents' homicidal ideation. Based on these findings, school bullying might exhibit unique reciprocal associations with homicidal ideation.

Multi-level factors associated with psychological resilience in the face of adverse childhood experiences among Chinese early adolescents.

BACKGROUND: Adverse childhood experiences (ACEs) are pervasive and exert enduring negative effects on health throughout one's life. A better understanding of resilience among adolescents with ACEs exposure is crucial to enhance their mental health; however, comprehensive and multifaceted analyses of its associated factors are limited. OBJECTIVE: This study aimed to investigate multi-level correlates of psychological resilience in Chinese early adolescents exposed to ACEs. PARTICIPANTS AND SETTING: In a sample of 5724 middle school students, 65.5 % (n = 3749; 49.1 % females; Mage = 13.57, SD = 0.96) reported ACEs during their primary school period and were finally included in this study. METHOD: Both linear regression and network models were conducted to explore correlates of capacity- and outcome-oriented resilience at the individual (i.e., five personality traits, emotional release, and loneliness), family (i.e., family support and relationships with the mother and father), and school levels (i.e., peer support, teacher support, and relationships with classmates and teachers). RESULTS: Linear regression analysis revealed that all correlates were associated with capacity- (ß ranged from -0.271 to 0.503, PFDR < 0.001 for all) and outcome-oriented resilience (ß ranged from -0.516 to 0.229, PFDR < 0.001 for all). Similarly, network analysis revealed that neuroticism, conscientiousness, loneliness, emotional release, extraversion, and the relationship with the mother were directly associated with both capacity- (weights ranged from 0.029 to 0.179) and outcome-oriented resilience (weights ranged from 0.024 to 0.396). However, openness, peer and family support, and relationships with classmates and teachers were directly associated with capacity-oriented resilience (weights ranged from 0.020 to 0.201). CONCLUSIONS: This study identified the shared and unique associated factors for capacity- and outcome-oriented resilience in the face of ACEs and demonstrated the complex interactions between these factors, which can guide tailored interventions to enhance resilience among Chinese early adolescents with ACEs exposure. Further longitudinal studies may endeavor to confirm our results.

Systematic investigation of the material basis, effectiveness and safety of Thesium chinense Turcz. and its preparation Bairui Granules against lung inflammation.

BACKGROUND: Thesium chinense Turcz. (Named as Bai Rui Cao in Chinese) and its preparations (e.g., Bairui Granules) have been used to treat inflammatory diseases, such as acute mastitis, lobar pneumonia, tonsillitis, coronavirus disease 2019 (COVID-19), and upper respiratory tract infection. However, the material basis, pharmacological efficiency, and safety have not been illustrated. METHODS: Anti-inflammatory activity-guided isolation of constituents has been performed using multiple column chromatography, and their structures were elucidated by NMR spectroscopy and ECD calculations. The inhibitory effects on lung inflammation and safety of the crude ethanol extract (CE), Bairui Granules (BG), and the purified active constituents were evaluated using lipopolysaccharide (LPS)-stimulated acute lung inflammation (ALI) mice model or normal mice. RESULTS: Seven new compounds (1-7) and fifty-six known compounds (8-63) were isolated from T. chinense, and fifty-four were reported from this plant for the first time. The new flavonoid glycosides 1-2, new fatty acids 4-5, new alkaloid 7 as well as the known constituents including flavonoid aglycones 8-11, lignans 46-54, alkaloids 34 and 45, coumarins 57, phenylpropionic acids 27, and simple aromatic compounds 39, 44 and 58 exhibited anti-inflammatory activity. Network pharmacology analysis indicated that anti-inflammation of T. chinense was attributed to flavonoids and alkaloids by regulating inflammation-related proteins (e.g., TNF, NF-κB, TGF-ß). Furthermore, constituents of T. chinense including kaempferol-3-O-glucorhamnoside (KN, also named as Bairuisu I, 19), astragalin (AG, Bairuisu II, 12), and kaempferol (KF, Bairuisu III, 8), as well as CE and BG could alleviate lung inflammation caused by LPS in mice by preventing neutrophils infiltration and the expression of the genes for pro-inflammatory cytokines NLRP3, caspase-1, IL-1ß, and COX-2. After a 28-day subacute toxicity test, BG at doses of 4.875 g/kg and 9.750 g/kg (equivalent to onefold and twofold the clinically recommended dose) and CE at a dose of 11.138 g/kg (equivalent to fourfold the clinical dose of BG) were found to be safe and non-toxic. CONCLUSIONS: The discovery of sixty-three constituents comprehensively illustrated the material basis of T. chinense. T. chinense and Bairui Granules could alleviate lung inflammation by regulating inflammation-related proteins and no toxicity was observed under the twofold of clinically used doses.