Film formation kinetics significantly impact molecular processability and power conversion efficiency (PCE) of organic solar cells. Here, two ternary random copolymerization polymers are reported, D18âN-p and D18âN-m, to modulate the aggregation ability of D18 by introducing trifluoromethyl-substituted pyridine unit at para- and meta-positions, respectively. The introduction of pyridine unit significantly reduces material aggregation ability and adjusts the interactions with acceptor L8-BO, thereby leading to largely changed film formation kinetics with earlier phase separation and longer film formation times, which enlarge fiber sizes in blend films and improve carrier generation and transport. As a result, D18âN-p with moderate aggregation ability delivers a high PCE of 18.82% with L8-BO, which is further improved to 19.45% via interface engineering. Despite the slightly inferior small area device performances, D18âN-m shows improved solubility, which inspires to adjust the ratio of meta-trifluoromethyl pyridine carefully and obtain a polymer donor D18âN-m-10 with good solubility in nonhalogenated solvent o-xylene. High PCEs of 13.07% and 12.43% in 1 cm2 device and 43 cm2 module fabricated with slot-die coating method are achieved based on D18âN-m-10:L8-BO blends. This work emphasizes film formation kinetics optimization in device fabrication via aggregation ability modulation of polymer donors for efficient devices.
Background: Post-stroke aphasia (PSA) is one of the most devastating symptoms after stroke, yet limited treatment options are available. Prolonged intermittent theta burst stimulation (piTBS) is a promising therapy for PSA. However, its efficacy remains unclear. Therefore, we aim to investigate the efficacy of piTBS over the left supplementary motor area (SMA) in improving language function for PSA patients and further explore the mechanism of language recovery. Methods: This is a randomized, double-blinded, sham-controlled trial. A total of 30 PSA patients will be randomly allocated to receive either piTBS stimulation or sham stimulation for 15 sessions over a period of 3 weeks. The primary outcome is the Western Aphasia Battery Revised (WAB-R) changes after treatment. The secondary outcomes include The Stroke and Aphasia Quality of Life Scale (SAQOL-39 g), resting-state electroencephalogram (resting-state EEG), Event-related potentials (ERP), brain derived neurotrophic factor (BDNF). These outcome measures are assessed before treatment, after treatment, and at 4-weeks follow up. This study was registered in Chinese Clinical Trial Registry (No. ChiCTR23000203238). Discussion: This study protocol is promising for improving language in PSA patients. Resting-state EEG, ERP, and blood examination can be used to explore the neural mechanisms of PSA treatment with piTBS. Clinical trial registration: https://www.chictr.org.cn/index.html, ChiCTR2300074533.
BACKGROUND: A wide range of connexins are situated between normal-normal cells, cancer-cancer cells, and cancer-normal cells. Abnormalities in connexin expression are typically accompanied by cancer development; however, no systematic studies have examined the role of Gap Junction Protein Beta 3 (GJB3) in the context of tumor progression and immunity, especially when considering a broad range of cancer types. METHODS: In this study, data on GJB3 expression were gathered from Genotype-Tissue Expression, Cancer Cell Line Encyclopedia, and The Cancer Genome Atlas databases. Then, we analyzed the relationship between GJB3 expression and tumor characteristics. In vitro experiments using colony formation, EdU, CCK8, transwell migration assays, immunohistochemistry and western blot were performed to investigate the function of GJB3 in tumor progression of various cell lines. A drug sensitivity analysis of GJB3 was performed using the Genomics of Drug Sensitivity in Cancer database. RESULT: Our findings demonstrate that GJB3 is widely expressed in various cancers and correlates significantly with disease stages, patient survival, immunotherapy response, and pharmaceutical guidance. Additionally, GJB3 plays a role in different cancer pathways, as well as in different immune and molecular subtypes of cancer. Co-expression of GJB3 with immune checkpoint genes was observed. Further experiments showed that knockdown of GJB3 inhibited the PI3K/AKT pathway and resulted in reduced proliferation, migration, and viability of different cancer cells. CONCLUSION: Overall, GJB3 shows potential as a molecular biomarker and therapeutic target for various cancers, particularly lung adenocarcinomas, mesothelioma, pancreatic adenocarcinoma. Thus, GJB3 may represent a new therapeutic target for a wide range of cancers.
BACKGROUND: In poultry, the smooth transition of follicles from the preovulatory-to-postovulatory phase impacts egg production in hens and can benefit the poultry industry. However, the regulatory mechanism underlying follicular ovulation in avians is a complex biological process that remains unclear. RESULTS: Critical biochemical events involved in ovulation in domestic chickens (Gallus gallus) were evaluated by transcriptomics, proteomics, and in vitro assays. Comparative transcriptome analyses of the largest preovulatory follicle (F1) and postovulatory follicle (POF1) in continuous laying (CL) and intermittent laying (IL) chickens indicated the greatest difference between CL_F1 and IL_F1, with 950 differentially expressed genes (DEGs), and the smallest difference between CL_POF1 and IL_POF1, with 14 DEGs. Additionally, data-independent acquisition proteomics revealed 252 differentially abundant proteins between CL_F1 and IL_F1. Perivitelline membrane synthesis, steroid biosynthesis, lysosomes, and oxidative phosphorylation were identified as pivotal pathways contributing to ovulation regulation. In particular, the regulation of zona pellucida sperm-binding protein 3, plasminogen activator, cathepsin A, and lactate dehydrogenase A (LDHA) was shown to be essential for ovulation. Furthermore, the inhibition of LDHA decreased cell viability and promoted apoptosis of ovarian follicles in vitro. CONCLUSIONS: This study reveals several important biochemical events involved in the process of ovulation, as well as crucial role of LDHA. These findings improve our understanding of ovulation and its regulatory mechanisms in avian species.
Kidney Clear Cell Carcinoma (KIRC), the predominant form of kidney cancer, exhibits a diverse therapeutic response to Immune Checkpoint Inhibitors (ICIs), highlighting the need for predictive models of ICI efficacy. Our study has constructed a prognostic model based on 13 types of Programmed Cell Death (PCD), which are intertwined with tumor progression and the immune microenvironment. Validated by analyses of comprehensive datasets, this model identifies seven key PCD genes that delineate two subtypes with distinct immune profiles and sensitivities to anti-PD-1 therapy. The high-PCD group demonstrates a more immune-suppressive environment, while the low-PCD group shows better responses to PD-1 treatment. In particular, TOP2A emerged as crucial, with its inhibition markedly reducing KIRC cell growth and mobility. These findings underscore the relevance of PCDs in predicting KIRC outcomes and immunotherapy response, with implications for enhancing clinical decision-making.
Heavy metal copper (Cu) will inevitably impact the marine macroalgae Gracilariopsis lemaneiformis (G. lemaneiformis), which is a culture of economic importance along China's coastline. In this study, the detoxification mechanism of Cu stress on G. lemaneiformis was revealed by assessing physiological indicators in conjunction with transcriptome and metabolome analyses at 1 d after Cu stress. Our findings revealed that 25 µM Cu stimulated ROS synthesis and led to the enzymatic oxidation of arachidonic acid residues. This process subsequently impeded G. lemaneiformis growth by suppressing photosynthesis, nitrogen metabolism, protein synthesis, etc. The entry of Cu ions into the algae was facilitated by ZIPs and IRT transporters, presenting as Cu2+. Furthermore, there was an up-regulation of Cu efflux transporters HMA5 and ABC family transporters to achieve compartmentation to mitigate the toxicity. The results revealed that G. lemaneiformis elevated the antioxidant enzyme superoxide dismutase and ascorbate-glutathione cycle to maintain ROS homeostasis. Additionally, metabolites such as flavonoids, 3-O-methylgallic acid, 3-hydroxy-4-keto-gama-carotene, and eicosapentaenoic acid were up-regulated compared with the control, indicating that they might play roles in response to Cu stress. In summary, this study offers a comprehensive insight into the detoxification mechanisms driving the responses of G. lemaneiformis to Cu exposure.
Copper , Metabolome , Transcriptome , Copper/toxicity , Copper/metabolism , Metabolome/drug effects , Seaweed/metabolism , Seaweed/genetics , Rhodophyta/metabolism , Rhodophyta/genetics , Rhodophyta/drug effects , Reactive Oxygen Species/metabolism , Gene Expression Profiling , Stress, Physiological , Oxidative Stress/drug effects , Metabolomics/methods
Cnaphalocrocis medinalis granulovirus (CnmeGV), belonging to Betabaculovirus cnamedinalis, can infect the rice pest, the rice leaf roller. In 1979, a CnmeGV isolate, CnmeGV-EP, was collected from Enping County, China. In 2014, we collected another CnmeGV isolate, CnmeGV-EPDH3, at the same location and obtained the complete virus genome sequence using Illumina and ONT sequencing technologies. By combining these two virus isolates, we updated the genome annotation of CnmeGV and conducted an in-depth analysis of its genome features. CnmeGV genome contains abundant tandem repeat sequences, and the repeating units in the homologous regions (hrs) exhibit overlapping and nested patterns. The genetic variations within EPDH3 population show the high stability of CnmeGV genome, and tandem repeats are the only region of high genetic variation in CnmeGV genome replication. Some defective viral genomes formed by recombination were found within the population. Comparison analysis of the two virus isolates collected from Enping showed that the proteins encoded by the CnmeGV-specific genes were less conserved relative to the baculovirus core genes. At the genomic level, there are a large number of SNPs and InDels between the two virus isolates, especially in and around the bro genes and hrs. Additionally, we discovered that CnmeGV acquired a segment of non-ORF sequence from its host, which does not provide any new proteins but rather serves as redundant genetic material integrated into the viral genome. Furthermore, we observed that the host's transposon piggyBac has inserted into some virus genes. Together, dsDNA viruses could acquire non-coding genetic material from their hosts to expand the size of their genomes. These findings provide new insights into the evolution of dsDNA viruses.
Background: Extensive observational studies have reported an association between inflammatory factors and autism spectrum disorder (ASD), but their causal relationships remain unclear. This study aims to offer deeper insight into causal relationships between circulating inflammatory factors and ASD. Methods: Two-sample bidirectional Mendelian randomization (MR) analysis method was used in this study. The genetic variation of 91 circulating inflammatory factors was obtained from the genome-wide association study (GWAS) database of European ancestry. The germline GWAS summary data for ASD were also obtained (18,381 ASD cases and 27,969 controls). Single nucleotide polymorphisms robustly associated with the 91 inflammatory factors were used as instrumental variables. The random-effects inverse-variance weighted method was used as the primary analysis, and the Bonferroni correction for multiple comparisons was applied. Sensitivity tests were carried out to assess the validity of the causal relationship. Results: The forward MR analysis results suggest that levels of sulfotransferase 1A1, natural killer cell receptor 2B4, T-cell surface glycoprotein CD5, Fms-related tyrosine kinase 3 ligand, and tumor necrosis factor-related apoptosis-inducing ligand are positively associated with the occurrence of ASD, while levels of interleukin-7, interleukin-2 receptor subunit beta, and interleukin-2 are inversely associated with the occurrence of ASD. In addition, matrix metalloproteinase-10, caspase 8, tumor necrosis factor-related activation-induced cytokine, and C-C motif chemokine 19 were considered downstream consequences of ASD. Conclusion: This MR study identified additional inflammatory factors in patients with ASD relative to previous studies, and raised a possibility of ASD-caused immune abnormalities. These identified inflammatory factors may be potential biomarkers of immunologic dysfunction in ASD.
Autism Spectrum Disorder , Genome-Wide Association Study , Mendelian Randomization Analysis , Polymorphism, Single Nucleotide , Humans , Autism Spectrum Disorder/genetics , Autism Spectrum Disorder/blood , Autism Spectrum Disorder/immunology , Genetic Predisposition to Disease , White People/genetics , Biomarkers/blood , Inflammation/genetics , Inflammation/blood , Inflammation Mediators/blood , Inflammation Mediators/metabolism , Male , Female , Cytokines/blood , Cytokines/genetics , Europe
BACKGROUNDS & AIMS: Given its ability to inhibit HBV replication, Interferon alpha (IFN-α) treatment has been confirmed to be effective in managing Chronic Hepatitis B (CHB). However, its underlying mechanisms are incompletely understood. METHODS: Herein, we investigated the antiviral properties of IFN-α by introducing IFN-α expression plasmids into a well-established HBV Hydrodynamic Injection (HDI) mouse model and examined the impact of IFN-α or hepcidin treatment on macrophages derived from THP-1 cells. The cytokine profiles were analyzed using the cytometry microsphere microarray technology, and flow cytometry was used to analyze the polarization of macrophages. Additionally, the IL-6/JAK2/STAT3 signaling pathway and the hepcidin-ferroportin axis were analyzed to better understand the macrophage polarization mechanism. RESULTS: As evidenced by the suppression of HBV replication, injection of an IFN-α expression plasmid and supernatants of IFN-α-treated macrophages exerted anti-HBV effects. The IFN-α treatment up-regulated IL-6 in mice with HBV replication, as well as in IFN-α-treated HepG2 cells and macrophages. Furthermore, JAK2/STAT3 signaling and hepcidin expression was promoted, inducing iron accumulation via the hepcidin-ferroportin axis, which caused the polarization of M1 macrophages. Furthermore, under the effect of IFN-α, IL-6 silencing or blockade downregulated the JAK2/STAT3 signaling pathway and hepcidin, implying that increased hepcidin expression under IFN-α treatment was dependent on the IL-6/JAK2/STAT3 pathway. CONCLUSION: The IL-6/JAK2/STAT3 signaling pathway is activated by IFN-α which induces hepcidin expression. The resulting iron accumulation then induces the polarization of M1 macrophages via the hepcidin-ferroportin axis, yielding an immune response which exerts antiviral effects against HBV replication.
Polyaniline (PANI) has been widely used as a cathode in aqueous zinc-ion batteries (AZIBs) because of its attractive conductivity and energy storage capability. However, the extensive application of PANI is limited by spontaneous deprotonation and slow diffusion kinetics. Herein, an 18-crown-6-functionalised PANI pseudorotaxane (18C6@PANI) cathode is successfully developed through a facile template-directed polymerisation reaction. The 18C6@PANI cathode exhibits a high specific capacity of 256 mAh g-1 at 0.2 A/g, excellent rate performance of 134 mAh g-1 at 6 A/g and outstanding cycle stability at a high current density of 3 A/g over 10,000 cycles. Experimental and theoretical analyses demonstrate the formation of the -N-Zn-O- structure. The abundant supramolecular channels in pseudorotaxane, induced by crown ether functional groups, are beneficial for achieving superior cyclability and rate capability. These encouraging results highlight the potential for designing more efficient PANI-based cathodes for high-performance AZIBs.
Hydrogen, which is a novel biomedical molecule, is currently the subject of extensive research involving animal experiments and in vitro cell experiments, and it is gradually being applied in clinical settings. Hydrogen has been proven to possess anti-inflammatory, selective antioxidant, and antiapoptotic effects, thus exhibiting considerable protective effects in various diseases. In recent years, several studies have provided preliminary evidence for the protective effects of hydrogen on spinal cord injury (SCI). This paper provides a comprehensive review of the potential molecular biology mechanisms of hydrogen therapy and its application in treating SCI, with an aim to better explore the medical value of hydrogen and provide new avenues for the adjuvant treatment of SCI.
Hydrogen , Spinal Cord Injuries , Spinal Cord Injuries/drug therapy , Spinal Cord Injuries/metabolism , Hydrogen/pharmacology , Hydrogen/chemistry , Humans , Animals , Antioxidants/pharmacology , Antioxidants/chemistry , Neuroprotective Agents/pharmacology , Neuroprotective Agents/chemistry , Apoptosis/drug effects , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/chemistry
Effective deep-dewatering is crucial for wastewater sludge management. Currently, the dominant methods focus on promoting cell lysis to release intracellular water, but these techniques often lead to secondary pollution and require stringent conditions, limiting their practical use. This study explores an innovative method using a commercially available complex quaternary ammonium salt surfactant, known as G-agent. This agent remarkably reduces the sludge water content from 98.6 % to 56.8 % with a low dosage (50 mg/g DS) and under neutral pH conditions. This approach surpasses Fenton oxidation in terms of dewatering efficiency and avoids the necessity for cell lysis and bound water release, thereby reducing the risk of secondary pollution in the filtrate, including heavy metals, nitrogen, phosphorus, and other contaminants. The G-agent plays a significant role in destabilizing flocs and enhancing flocculation during the conditioning and initial dewatering stages, effectively reducing the solid-liquid interfacial affinity of the sludge. In the compression filtration stage, the agent's solidification effect is crucial in forming a robust skeleton that improves pore connectivity within the filter cake, leading to increased water permeability, drainage performance and water flow-out efficiency. This facilitates deep dewatering of sludge without cell lysis. The study reveals that the G-agent primarily improves water flow-out efficiency rather than water flowability, indicating that cell lysis and bound water release are not indispensable prerequisites for sludge deep-dewatering. Furthermore, it presents an encouraging prospect for overcoming the limitations associated with conventional sludge deep-dewatering processes.
Triple negative breast cancer (TNBC) is insensitive to conventional targeted therapy and endocrine therapy, and is characterized by high invasiveness and high recurrence rate. This study aimed to explore the role and mechanism of RHOXF2 and HOXC13 on the malignant progression of TNBC. RT-qPCR and western blot were used to detect RHOXF2 and HOXC13 expression in TNBC cells. The proliferation, colony formation, invasion, migration, apoptosis and cell cycle of TNBC cells after transfection were analyzed by CCK-8 assay, colony formation assay, transwell assay, wound healing assay and flow cytometry analysis. Co-Immunoprecipitation and GST pull-down assays were used to analyze the combination between RHOXF2 and HOXC13. ChIP-PCR and luciferase reporter gene assay were used to examine the regulation of H3K27ac on RHOXF2. Besides, the expression of Ki67 and cleaved Caspase3 in tumor tissues of nude mice was determined by immunofluorescence. Results revealed that RHOXF2 and HOXC13 expression was increased in TNBC cells. RHOXF2 knockdown suppressed the proliferation, invasion and migration, as well as induced G0/G1 cell cycle arrest and apoptosis of TNBC cells. Besides, RHOXF2 could bind to HOXC13 and RHOXF2 knockdown suppressed HOXC13 expression in TNBC cells. Furthermore, HOXC13 overexpression reversed the impacts of RHOXF2 downregulation on the proliferation, invasion, migration, G0/G1 cell cycle arrest and apoptosis of TNBC cells. In addition, RHOXF2 silencing limited the tumor volume in nude mice, which was reversed by HOXC13 overexpression. Moreover, RHOXF2 knockdown interfered with Wnt2/ß-catenin pathway in vitro and in vivo by binding to HOXC13. Importantly, H3K27ac acetylation could activate the expression of RHOXF2 promoter region. In conclusion, RHOXF2 activated by H3K27ac functioned as a tumor promoter in TNBC via mediating Wnt2/ß-catenin pathway by binding to HOXC13, which provided promising insight into exploration on TNBC therapy.
BACKGROUND: Blood pressure variability (BPV) is a risk factor for poor kidney function independent of blood pressure (BP) in chronic kidney disease (CKD). Little is known about the association between kidney function decline and BPV in hypertensive patients without CKD. METHODS: A post-hoc analysis of the Systolic Blood Pressure Intervention Trial (SPRINT) was performed. BPV was measured as standard deviation (SD) and average real variability (ARV). Cox proportional hazard models were employed to explore the relationship between BPV and incident CKD and albuminuria. RESULTS: A total of 5700 patients were included, with a mean age of 66.4âyears old. During a median of 3.29âyears follow-up, 150 (2.6%) patients developed CKD and 222 (7.2%) patients developed albuminuria. Patients were divided into four groups according to the quartiles of BPV. Compared with SBPV Q1, the incidence of CKD was higher in SBPV Q2-Q4; hazard ratios and 95% confidence interval were 1.81 (1.07-3.04), 1.85 (1.10-3.12) and 1.90 (1.13-3.19), respectively. The association between incident CKD and albuminuria with DBPV was less significant than SBPV. Similar results were found when measuring BPV as ARV and SD. No interaction was detected in BP-lowering strategy and SBPV on incident CKD and albuminuria (Pâ>â0.05). CONCLUSION: This study found that BPV was a risk factor for incident CKD and albuminuria in patients without CKD, especially SBPV. Although intensive BP control increased the risk of CKD, the association between SBPV and kidney function decline did not differ between the two treatment groups. REGISTRATION: URL: https://clinicaltrials.gov/, Unique identifier: NCT01206062.
Additive manufacturing of conductive layers on a dielectric substrate has garnered significant interest due to its promise to produce printed electronics efficiently and its capability to print on curved substrates. A considerable challenge encountered is the conductive layer's potential peeling due to inadequate adhesion with the dielectric substrate, which compromises the durability and functionality of the electronics. This study strives to facilitate the binding force through dielectric substrate surface modification using concentrated sulfuric acid and ultraviolet (UV) laser treatment. First, polyetheretherketone (PEEK) and nanoparticle silver ink were employed as the studied material. Second, the surface treatment of PEEK substrates was conducted across six levels of sulfuric acid exposure time and eight levels of UV laser scanning velocity. Then, responses such as surface morphology, roughness, elemental composition, chemical bonding characteristics, water contact angle, and surface free energy (SFE) were assessed to understand the effects of these treatments. Finally, the nanoparticle silver ink layer was deposited on the PEEK surface, and the adhesion force measured using a pull-off adhesion tester. Results unveiled a binding force of 0.37 MPa on unmodified surface, which escalated to 1.99 MPa with sulfuric acid treatment and 2.21 MPa with UV laser treatment. Additionally, cross-approach treatment investigations revealed that application sequence significantly impacts results, increasing binding force to 2.77 MPa. The analysis further delves into the influence mechanism of the surface modification on the binding force, elucidating that UV laser and sulfuric acid surface treatment methods hold substantial promise for enhancing the binding force between heterogeneous materials in the additive manufacturing of electronics.
BACKGROUND: The discovery of antimicrobial ingredients from natural products could be an effective way to create novel fungicides. Rubia cordifolia L., a traditional Chinese herb, may have antimicrobial effects on plant pathogens according to our previous screening study. RESULTS: Rubia cordifolia L. extracts had moderate inhibitory effects on apple Valsa canker (Valsa mali) and tomato grey mould (Botrytis cinerea) at a concentration of 10 mg mL-1. With the use of bioguided isolation methods, eight compounds (1-8) were obtained, including the new compound 2,2,6-trimethyl-6-(4-methylphenyl)-tetrahydropyrano- 3-ol (7), and seven quinone derivatives. Two compounds, mollugin (1) and 1,3,6-trihydroxy-2-methylanthraquinone (6), were found to exhibit outstanding antifungal activities against V. mali and Phytophthora capsici Leon. The half maximal effective concentration (EC50) of compound 1 and compound 6 against V. mali were 79.08 and 81.78 µg mL-1, respectively, and the EC50 of compound 6 against P. capsici was 4.86 µg mL-1. Compound 1 also showed excellent activity against tobacco mosaic virus (TMV). The inactive, inductive, protective and curative activities against TMV were 84.29%, 83.38%, 86.81%, and 60.02%, respectively, at a concentration of 500 µg mL-1, which were all close to or greater than that of the positive control (100 µg mL-1 chitosan oligosaccharide, COS). CONCLUSION: Mollugin and 1,3,6-trihydroxy-2-methylanthraquinone are potentially valuable active compounds that lay a foundation for research on botanical fungicide products derived from R. cordifolia L. and provide lead structures for quinone derivative synthesis and structural modification. © 2024 Society of Chemical Industry.
BACKGROUND: The goal was to study the difference of virological, immunologic, and inflammatory indicators between Epstein-Barr associated infectious mononucleosis (EBV-IM) and EBV associated hemophagocytic lymphohistiocytosis (EBV-HLH) and to explore the evaluation indicators for monitoring the therapeutic efficacy of EBV-HLH. METHODS: Twenty children with EBV-IM (IM group) and 10 children with EBV-HLH (HLH group) were selected. Virology indicators were detected; the absolute count of lymphocyte, and lymphocyte subsets were detected; the levels of immunoglobulin and ferritin were assayed. RESULTS: Compared to the IM group, the HLH group showed a decrease in EBV-specific VCA-IgM antibody levels (U = 29.0, p = 0.006) and an increase in EBV-specific NA-IgG antibody levels (U = 17.0, p = 0.001), while there was no significant difference in EB-DNA loads (t = 0.417, p = 0.680). The counts of lymphocytes, and various lymphocyte subsets in the HLH group were lower than those in the IM group. Inflammatory markers in the HLH group were significantly higher than those in IM group. Dynamic monitoring of virological, immunological, and inflammatory indicators in HLH patients during treatment showed that EBV DNA gradually decreased in patients with good prognosis. Inflammatory indicators significantly decreased and returned to normal, lymphocyte count significantly increased and returned to normal during treatment. However, patients with poor prognosis showed rebound increase in EBV DNA and inflammatory indicators in the later stage of treatment, while lymphocyte count further decreased with the recurrence of the disease. CONCLUSIONS: Exhausted and damaged immune function in host by persistent stimulation of EB viral antigen is one of the main pathogeneses of EB-HLH. Lymphocyte count and serum ferritin level are effective indicators to monitor the therapeutic efficacy during the treatment to HLH.
Epstein-Barr Virus Infections , Herpesvirus 4, Human , Infectious Mononucleosis , Lymphohistiocytosis, Hemophagocytic , Humans , Child , Male , Female , Child, Preschool , Herpesvirus 4, Human/immunology , Lymphohistiocytosis, Hemophagocytic/immunology , Lymphohistiocytosis, Hemophagocytic/diagnosis , Lymphohistiocytosis, Hemophagocytic/virology , Lymphohistiocytosis, Hemophagocytic/blood , Infectious Mononucleosis/immunology , Infectious Mononucleosis/blood , Infectious Mononucleosis/virology , Infectious Mononucleosis/diagnosis , Epstein-Barr Virus Infections/immunology , Epstein-Barr Virus Infections/virology , Epstein-Barr Virus Infections/blood , DNA, Viral/blood , Inflammation/immunology , Antibodies, Viral/blood , Antibodies, Viral/immunology , Viral Load , Ferritins/blood , Lymphocyte Count , Adolescent , Infant , Lymphocyte Subsets/immunology
Importance: Overweight and obesity affect 340 million adolescents worldwide and constitute a risk factor for poor mental health. Understanding the association between body mass index (BMI) and mental health in adolescents may help to address rising mental health issues; however, existing studies lack comprehensive evaluations spanning diverse countries and periods. Objective: To estimate the association between BMI and mental health and examine changes over time from 2002 to 2018. Design, Setting, and Participants: This was a repeated multicountry cross-sectional study conducted between 2002 and 2018 and utilizing data from the Health Behaviour in School-aged Children (HBSC) survey in Europe and North America. The study population consisted of more than 1 million adolescents aged 11 to 15 years, with all surveyed children included in the analysis. Data were analyzed from October 2022 to March 2023. Main Outcomes and Measures: Mental health difficulties were measured by an 8-item scale for psychological concerns, scoring from 0 to 32, where a higher score reflects greater psychosomatic issues. BMI was calculated using weight divided by height squared and adjusted for age and sex. Data were fitted by multilevel generalized additive model. Confounders included sex, living with parents, sibling presence, academic pressure, the experience of being bullied, family affluence, screen time, and physical activity. Results: Our analysis of 1â¯036â¯869 adolescents surveyed from 2002 to 2018, with a mean (SD) age of 13.55 (1.64) years and comprising 527â¯585 girls (50.9%), revealed a consistent U-shaped association between BMI and mental health. After accounting for confounders, adolescents with low body mass and overweight or obesity had increased psychosomatic symptoms compared to those with healthy weight (unstandardized ß, 0.14; 95% CI, 0.08 to 0.19; unstandardized ß, 0.27; 95% CI, 0.24 to 0.30; and unstandardized ß, 0.62; 95% CI, 0.56 to 0.67, respectively), while adolescents with underweight had fewer symptoms (unstandardized ß, -0.18; 95% CI, -0.22 to -0.15). This association was observed across different years, sex, and grade, indicating a broad relevance to adolescent mental health. Compared to 2002, psychosomatic concerns increased significantly in 2006 (unstandardized ß, 0.19; 95% CI, 0.11 to 0.26), 2010 (unstandardized ß, 0.14; 95% CI, 0.07 to 0.22), 2014 (unstandardized ß, 0.48; 95% CI, 0.40 to 0.56), and 2018 (unstandardized ß, 0.82; 95% CI, 0.74 to 0.89). Girls reported significantly higher psychosomatic concerns than boys (unstandardized ß, 2.27; 95% CI, 2.25 to 2.30). Compared to primary school, psychosomatic concerns rose significantly in middle school (unstandardized ß, 1.15; 95% CI, 1.12 to 1.18) and in high school (unstandardized ß, 2.12; 95% CI, 2.09 to 2.15). Conclusions and Relevance: Our study revealed a U-shaped association between adolescent BMI and mental health, which was consistent across sex and grades and became stronger over time. These insights emphasize the need for targeted interventions addressing body image and mental health, and call for further research into underlying mechanisms.
BACKGROUND: Aquaporin-8 (AQP8) is involved in impacting glioma proliferation and can effect tumour growth by regulating Intracellular reactive oxygen species (ROS) signalling levels. In addition to transporting H2O2, AQP8 has been shown to affect ROS signaling, but evidence is lacking in gliomas. In this study, we aimed to investigate how AQP8 affects ROS signaling in gliomas. MATERIALS AND METHODS: We constructed A172 and U251 cell lines with AQP8 knockdown and AQP8 rescue by CRISPR/Cas9 technology and overexpression of lentiviral vectors. We used CCK-8 and flow cytometry to test cell proliferation and cycle, immunofluorescence and Mito-Tracker CMXRos to observe the distribution of AQP8 expression in glioma cells, Amplex and DHE to study mitochondria release of H2O2, mitochondrial membrane potential (MMP) and NAD+/NADH ratio to assess mitochondrial function and protein blotting to detect p53 and p21 expression. RESULT: We found that AQP8 co-localised with mitochondria and that knockdown of AQP8 inhibited the release of H2O2 from mitochondria and led to increased levels of ROS in mitochondria, thereby impairing mitochondrial function. We also discovered that AQP8 knockdown resulted in suppression of cell proliferation and was blocked at the G0/G1 phase with increased expression of mitochondrial ROS signalling-related p53/p21. CONCLUSIONS: This finding provides further evidence for mechanistic studies of AQP8 as a prospective target for the treatment of gliomas.
Scutebarbatine B (SBT-B) is a neo-clerodane diterpenic compound isolated from Scutellaria barbata D. Don (S. barbata), which has been reported to exhibit inhibitory P-glycoprotein (P-gp) property in MCF-7/ADR cells. However, its metabolism and molecular mechanism of reversal multidrug resistance (MDR) in breast cancer remains unclear. This study investigated the metabolite profile of SBT-B in rats by UHPLC-Q-Orbitrap-MS/MS, and explored its mechanism of reversal MDR through network pharmacology and molecular docking studies. A total of 16 Phase I metabolites and 2 Phase II metabolites were identified, and 18 metabolites were all newly discovered metabolites as novel compounds. The metabolic pathway of SBT-B mainly includes oxidization, reduction, hydrolysis, acetylation and glycination. Meanwhile, network pharmacology analyses showed that SBT-B mainly regulated p27 phosphorylation during cell cycle progression, p53 signaling pathway, influence of Ras and Rho proteins on G1 to S Transition. Molecular docking studies revealed that SBT-B exhibits the potential to inhibit P-gp expression by selectively binding to GLN721 and ALA981 residue sites at the interface of P-gp. In addition, SBT-B exhibits moderate binding affinity with CDK2 and E2F1. This study illustrated the major metabolic pathways of SBT-B in vivo, clarified detailed information on SBT-B metabolites in rats, and uncovered the potential mechanism of SBT-B reversal MDR in breast cancer, providing new insights for the development of P-gp inhibitors.
