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Background: Poly-victimization involves more than just counting incidents; it varies in severity and type among adolescents and can change over time. Objective: The aim is to identify latent classes of poly-victimization among children in early adolescence, investigate transition probabilities between these latent categories, and examine the influencing factors. Methods: We used stratified cluster random sampling to select 2275 junior high students from five rural middle schools in Shantou and Jieyang, China, and surveyed them in two waves. Latent Class Analysis (LCA) and Latent Transition Analysis (LTA) identified latent classes of poly-victimization, and multi-factor logistic regression examined factors influencing the probability of students transitioning between these latent classes. Results: LCA identified three categories of poly-victimization: low poly-victimization, group, and high child maltreatment and peer and sibling victimization. The probabilities of remaining in the high child maltreatment and peer and sibling victimization group, transitioning to the transition group, or shifting to the low poly-victimization group were 37.00%, 29.20%, and 33.80%, respectively. Most transition group members remained in the same group, with a conversion probability of 77.10%, followed by transitioning to the low poly-victimization group with a probability of 15.80%. Physically healthy children, compared to those with disabilities or illnesses, were less likely to switch from the low poly-victimization group to the transition group (OR=0.034) or the high child maltreatment and peer and sibling victimization group (OR=0.14). Non-left-behind children, compared to left-behind children, have a higher probability of switching from the high child maltreatment and peer and sibling victimization group to the low poly-victimization group (OR=6.905). Conclusion: The high child maltreatment and peer and sibling victimization group had similar probabilities of transitioning into other categories. Physical illness or disability, as well as being left behind, are significant risk factors for children transitioning from the low-harm group to the high-harm group.
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Aerosol-transmitted viruses possess strong infectivity and can spread over long distances, earning the difficult-to-control title. They cause various human diseases and pose serious threats to human health. Mutations can increase the transmissibility and virulence of the strains, reducing the protection provided by vaccines and weakening the efficacy of antiviral drugs. In this study, we established a manually curated database (termed AVM) to store information on aerosol-transmitted viral mutations (VMs). The current version of the AVM contains 42,041 VMs (including 2613 immune escape mutations), 45 clinical information datasets, and 407 drugs/antibodies/vaccines. Additionally, we recorded 88 human diseases associated with viruses and found that the same virus can target multiple organs in the body, leading to diverse diseases. Furthermore, the AVM database offers a straightforward user interface for browsing, retrieving, and downloading information. This database is a comprehensive resource that can provide timely and valuable information on the transmission, treatment, and diseases caused by aerosol-transmitted viruses (http://www.bio-bigdata.center/AVM).
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Aerossóis , Mutação , Humanos , Antivirais/farmacologia , Bases de Dados Genéticas , Vírus/genética , Vírus/classificação , Vírus/patogenicidade , Viroses/transmissão , Viroses/virologia , Viroses/genética , Bases de Dados Factuais , Curadoria de Dados/métodosRESUMO
BACKGROUND: Poly-victimization (PV) not only threatens physical and mental health but also causes a range of social problems. Left-behind children in rural areas are more likely to experience PV problems. However, there have been fewer studies on PV among rural children, and even fewer intervention studies. OBJECTIVE: The difference-in-differences method was employed to analyze the impact of intervention measures, based on the theory of planned behavior, on PV among left-behind children in rural areas. METHODS: The study subjects were left-behind children from six middle schools in two cities in southern China, who completed the baseline survey from 2020 to 2021. They were divided into a control group and an intervention group, each consisting of 228 cases, based on their schools. Before and after the intervention, the Self-made victimization-related knowledge, attitude, and practice questionnaire, Poly-victimization scale, and Middle school students' coping style scale were used to evaluate the victimization-related KAP(knowledge, attitude, and practice), victimization occurrence, and coping styles of left-behind children, respectively. Stata 15.0 was used to establish a difference-in-differences regression model to analyze the impact of the intervention measures on poly-victimization and coping styles. RESULTS: Mixed Anova revealed that after the intervention, the KAP scores of the intervention group were significantly higher than those of the control group (p < 0.05). After the intervention, the incidence of child victimization in the intervention group dropped to 9.60% (n = 22), lower than in the baseline survey, with a statistically significant difference (p < 0.01). The incidence of PV among children in the intervention group was lower than that in the control group, with the difference being statistically significant (p < 0.01). The net reduction in the incidence of PV among children was 21.20%. After the intervention, the protection rate for preventing PV among children was 73.33%, and the effect index was 3.75. The intervention improved children's coping styles, problem-solving, and help-seeking, while reducing negative coping styles such as avoidance and venting, with the differences being statistically significant (p < 0.05). CONCLUSION: Intervention measures based on the theory of planned behavior reduce the occurrence of PV among left-behind children, and the intervention effects on different types of victimization are also different.
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BACKGROUND: School bullying, a serious problem for the physical and mental health of adolescents, is presently a significant issue in China. It is essential to recognize and comprehend potential risk factors and establish efficient preventive strategies. The purpose of this study was to examine the association between childhood maltreatment and school bullying in adolescents and to assess the mediating role of peer relationships. METHODS: Between March and April 2024, a cross-sectional survey was conducted among 2119 adolescents aged between 12 and 18 years in Guangdong Province, China. Self-report questionnaires were employed to collect data on childhood maltreatment, school bullying, and peer relationships. Subgroup analyses and mediating effects modeling were employed to analyze the data. RESULTS: The results indicated that adolescents who had experienced maltreatment were more at risk of bullying victimization (OR: 2.92, 95% CI: 2.34-3.64, P < 0.001), bullying perpetration (OR: 2.84, 95% CI: 1.99-4.05, P < 0.001), and bully-victimization (OR: 2.93, 95% CI: 1.95-4.41, P < 0.001), compared to adolescents who have not. Sexual abuse showed the most significant connection with all forms of bullying. The mediating effect of peer relationships was found to mediate the association between child maltreatment and bullying behaviour. The results indicated that worse peer relationships may exacerbate the adverse effects of maltreatment experiences and increase the risk of adolescents becoming bullies, either perpetrators or victims of bullying. CONCLUSIONS: Child maltreatment has been identified as one of the most significant influences on bullying behaviour in adolescents. The quality of peer relationships has been demonstrated to play an important role in preventing and reducing the occurrence of bullying. The results underscore the crucial role of early intervention in cases of child maltreatment and the fostering of positive peer relationships in schools.
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Bullying , Maus-Tratos Infantis , Vítimas de Crime , Grupo Associado , Instituições Acadêmicas , Humanos , Bullying/psicologia , Bullying/estatística & dados numéricos , Adolescente , China/epidemiologia , Feminino , Masculino , Estudos Transversais , Maus-Tratos Infantis/psicologia , Maus-Tratos Infantis/estatística & dados numéricos , Criança , Vítimas de Crime/psicologia , Vítimas de Crime/estatística & dados numéricos , Inquéritos e Questionários , Fatores de Risco , Relações Interpessoais , Autorrelato , População do Leste AsiáticoRESUMO
Real-world graphs exhibit increasing heterophily, where nodes no longer tend to be connected to nodes with the same label, challenging the homophily assumption of classical graph neural networks (GNNs) and impeding their performance. Intriguingly, from the observation of heterophilous data, we notice that certain high-order information exhibits higher homophily, which motivates us to involve high-order information in node representation learning. However, common practices in GNNs to acquire high-order information mainly through increasing model depth and altering message-passing mechanisms, which, albeit effective to a certain extent, suffer from three shortcomings: (1) over-smoothing due to excessive model depth and propagation times; (2) high-order information is not fully utilized; (3) low computational efficiency. In this regard, we design a similarity-based path sampling strategy to capture smooth paths containing high-order homophily. Then we propose a lightweight model based on multi-layer perceptrons (MLP), named PathMLP, which can encode messages carried by paths via simple transformation and concatenation operations, and effectively learn node representations in heterophilous graphs through adaptive path aggregation. Extensive experiments demonstrate that our method outperforms baselines on 16 out of 20 datasets, underlining its effectiveness and superiority in alleviating the heterophily problem. In addition, our method is immune to over-smoothing and has high computational efficiency. The source code will be available in https://github.com/Graph4Sec-Team/PathMLP.
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Aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor whose expression regulates immune cell differentiation. Single-cell transcriptomic profiling was used to ascertain the heterogeneity of AHR expression in human B cell subpopulations. We identified a unique population of B cells marked by expression of AHR, CD9, and myeloid genes such as CD14 and CXCL8. Results were confirmed directly in human PBMCs and purified B cells at the protein level. TLR9 signaling induced CD14, CD9, and IL-8 protein expression in CD19+ B cells. CD14-expressing CD9+ B cells also highly expressed AHR and atypical B cell markers such as CD11c and TBET. In patients with active lupus disease, CD14+ and CD9+ B cells are dysregulated, with loss of CD9+ B cells strongly predicting disease severity and demonstrating the relevance of CD9+ B cells in systemic lupus erythematosus and autoimmune disease.
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Background: Advancements in modern medicine have extended human lifespan, but they have also led to an increase in age-related diseases such as Alzheimer's disease (AD) and atherosclerosis (AS). Growing research evidence indicates a close connection between these two conditions. Methods: We downloaded four gene expression datasets related to AD and AS from the Gene Expression Omnibus (GEO) database (GSE33000, GSE100927, GSE44770, and GSE43292) and performed differential gene expression (DEGs) analysis using the R package "limma". Through Weighted gene correlation network analysis (WGCNA), we selected the gene modules most relevant to the diseases and intersected them with the DEGs to identify crosstalk genes (CGs) between AD and AS. Subsequently, we conducted functional enrichment analysis of the CGs using DAVID. To screen for potential diagnostic genes, we applied the least absolute shrinkage and selection operator (LASSO) regression and constructed a logistic regression model for disease prediction. We established a protein-protein interaction (PPI) network using STRING (https://cn.string-db.org/) and Cytoscape and analyzed immune cell infiltration using the CIBERSORT algorithm. Additionally, NetworkAnalyst (http://www.networkanalyst.ca) was utilized for gene regulation and interaction analysis, and consensus clustering was employed to determine disease subtypes. All statistical analyses and visualizations were performed using various R packages, with a significance level set at p<0.05. Results: Through intersection analysis of disease-associated gene modules identified by DEGs and WGCNA, we identified a total of 31 CGs co-existing between AD and AS, with their biological functions primarily associated with immune pathways. LASSO analysis helped us identify three genes (C1QA, MT1M, and RAMP1) as optimal diagnostic CGs for AD and AS. Based on this, we constructed predictive models for both diseases, whose accuracy was validated by external databases. By establishing a PPI network and employing four topological algorithms, we identified four hub genes (C1QB, CSF1R, TYROBP, and FCER1G) within the CGs, closely related to immune cell infiltration. NetworkAnalyst further revealed the regulatory networks of these hub genes. Finally, defining C1 and C2 subtypes for AD and AS respectively based on the expression profiles of CGs, we found the C2 subtype exhibited immune overactivation. Conclusion: This study utilized gene expression matrices and various algorithms to explore the potential links between AD and AS. The identification of CGs revealed interactions between these two diseases, with immune and inflammatory imbalances playing crucial roles in their onset and progression. We hope these findings will provide valuable insights for future research on AD and AS.
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Doença de Alzheimer , Aterosclerose , Biologia Computacional , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Mapas de Interação de Proteínas , Doença de Alzheimer/genética , Doença de Alzheimer/imunologia , Humanos , Aterosclerose/genética , Aterosclerose/imunologia , Biologia Computacional/métodos , Bases de Dados Genéticas , Regulação da Expressão Gênica , TranscriptomaRESUMO
Background: Kurixaluslenquanensis Yu, Wang, Hou, Rao and Yang, 2017 was originally described, based on 14 adult male specimens from Lengquan Village, Mengzi, Yunnan, China. So far, this species is known only from south-eastern Yunnan and information on females of this species is not available. During the field surveys in 2023, two Kurixalus specimens (one female and one male) were collected from central eastern Yunnan (Shilin, Kunming, Yunnan, China). These two specimens were confirmed to be K.lenquanensis by molecular phylogenetic analyses, based on 16S rRNA sequences. New information: A female specimen of K.lenquanensis is described for the first time and morphological variation amongst populations of this species is provided. The diagnosis and distribution of this species are updated.
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The use of agrochemical inputs has significantly enhanced agricultural yields in China; however, their excessive utilization has also caused a range of environmental issues. This paper examines the costs associated with reducing agrochemicals by employing shadow prices, which represent the value of the marginal product of agrochemicals, to further develop cost-effective environmental policy measures for reducing their usage. To this end, the shadow prices of agrochemicals have been assessed by adopting a newly developed convex expectile regression approach and using statistical data from 31 provinces in China spanning from 2005 to 2020. Furthermore, the present study investigates the disparities between shadow prices and market prices for different agrochemicals across various regions in China. The findings suggest that the costs of reducing chemical fertilizers are higher than those of reducing pesticides and plastic films. Moreover, the results indicate that central China exhibits relatively high potential for decreasing agrochemical usage. Finally, these findings can inform the Chinese government's restructuring of producer support and environmental policy in a cost-effective way to mitigate agrochemicals use in the future. Additionally, the research method employed in this study holds potential for extension to other agrochemicals-dependent countries.
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Agricultura , Agroquímicos , China , Agricultura/economia , Fertilizantes , PraguicidasRESUMO
Acrossocheilus fasciatus is a stream-dwelling fish species of the Barbinae subfamily. It is valued for its colorfully striped appearance and delicious meat. This species is also characterized by apparent sexual dimorphism and toxic ovum. Biology and aquaculture researches of A. fasciatus are hindered by the lack of a high-quality reference genome. Here, we report chromosome-level genome assemblies of the male and female A. fasciatus. The HiFi-only genome assemblies for both female and male individuals were 899.13 Mb (N50 length of 32.58 Mb) and 885.68 Mb (N50 length of 33.06 Mb), respectively. Notably, a substantial proportion of the assembled sequences, accounting for 96.15% and 98.35% for female and male genomes, respectively, were successfully anchored onto 25 chromosomes utilizing Hi-C data. We annotated the female assembly as a reference genome and identified a total of 400.62 Mb (44.56%) repetitive sequences, 27,392 protein-coding genes, and 35,869 ncRNAs. The high-quality male and female reference genomes will provide genomic resources for developing sex-specific molecular markers, inform single-sex breeding, and elucidate genetic mechanisms of sexual dimorphism.
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Cromossomos , Genoma , Caracteres Sexuais , Animais , Feminino , Masculino , Cyprinidae/genéticaRESUMO
BACKGROUND: Externalizing problems, internalizing problems, and obesity are among the greatest challenges to adolescent health. However, the moderating and mediating mechanisms that underlie this association remain predominantly unexplored. OBJECTIVES: In this study, we examined the association between body mass index (BMI) and externalizing and internalizing scores in adolescents, tested whether traditional bullying and cyberbullying mediated the association, and explored the moderated role of sex. METHODS: The data came from 1486 adolescents from grade 7, 8, and 10 living in Shantou, China. Information on BMI, traditional bullying, and cyberbullying victimization was obtained through a self-administered questionnaire. The students' externalizing and internalizing scores were evaluated using the Strengths and Difficulties Questionnaire (SDQ). Furthermore, we built two parallel mediation models with sex as a moderating variable. RESULTS: Compared to their peers with normal weight, adolescents with increased BMI reported higher externalizing and internalizing scores. Traditional bullying and cyberbullying were both significant mediators in the two relationships. Sex moderated the pathway from BMI to cyberbullying. But sex did not moderate the relationship between BMI and traditional bullying. CONCLUSIONS: The results highlight that it is imperative for educators to identify students who are subjected to weight-based bullying and provide them with recommendations for effective coping strategies. Meanwhile, both victims of traditional bullying and those affected by cyberbullying should be the focus of prevention and intervention efforts when developing a strategy to improve levels of internalizing and externalizing symptoms among adolescents with increased BMI.
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BACKGROUND: Poly-victimization is more detrimental to adolescents' physical and mental health than is a single type of victimization. However, there has been limited research on the trajectory of poly-victimization among Chinese adolescents. OBJECTIVE: Identify the different developmental trajectories of poly-victimization among Chinese adolescents over time and examine the influencing factors of poly-victimization trajectories. METHODS: Data from four surveys conducted between 2020 and 2022, encompassing a cohort of 319 adolescents who had experienced poly-victimization, were utilized to identify their developmental trajectories via group-based trajectory modeling. Potential influencing factors were screened and compared using ANOVA or chi-square tests, while factors affecting the developmental trajectories of poly-victimization were analyzed through multinomial logistic regression. RESULTS: We identified three poly-victimization trajectories among adolescents: increasing poly-victimization (n = 39, 12.2 %), relieved poly-victimization (n = 228, 71.5 %), and fluctuating poly-victimization (n = 52, 16.3 %). Our findings indicate that boys, and those with poor class grade ranking, a lower level of parental education, lower household economy, smoking, drinking, suicide attempts, and suicide ideation, constitute the primary focus for the prevention and treatment of poly-victimization. CONCLUSION: We identified three poly-victimization trajectories, highlighting a significant heterogeneity in poly-victimization development. Understanding the characteristics of these developmental trajectories is crucial for realizing the dynamics of different poly-victimization subgroups and informing effective interventions.
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Vítimas de Crime , Humanos , Adolescente , Masculino , Feminino , Vítimas de Crime/psicologia , Vítimas de Crime/estatística & dados numéricos , Estudos Longitudinais , China/epidemiologia , Ideação Suicida , Fatores de Risco , Bullying/psicologia , Bullying/estatística & dados numéricos , Tentativa de Suicídio/estatística & dados numéricos , Tentativa de Suicídio/psicologia , População do Leste AsiáticoRESUMO
BACKGROUND: Cardiac hypertrophy is the common pathological process of multiple cardiovascular diseases. However, the molecular mechanisms of cardiac hypertrophy are unclear. Long non-coding RNA (lncRNA), a newly discovered type of transcript that has been demonstrated to function as crucial regulators in the development of cardiovascular diseases. This study revealed a novel regulatory pathway of lncRNA in cardiac hypertrophy. METHODS: The cardiac hypertrophy models were established by transverse aortic constriction (TAC) in mice and angiotensin II (Ang II) in HL-1 cardiomyocytes. Adeno-associated virus 9 (AAV9) in vivo and lncRNA Gm15834 and shRNA plasmids in vitro were used to overexpress and knock down lncRNA Gm15834. The myocardial tissue structure, cardiomyocyte area, cardiac function, protein expressions, and binding of lncRNA Gm15834 and Src-associated substrate during mitosis of 68 KDa (Sam68) were detected by hematoxylin and eosin (HE) staining, immunofluorescence staining, echocardiography, western blot and RNA immunoprecipitation (RIP), respectively. RESULTS: In cardiac hypertrophy models, inhibiting lncRNA Gm15834 could decrease Sam68 expression and nuclear factor kappa-B (NF-κB) mediated inflammatory activities in vivo and in vitro, but overexpressing lncRNA Gm15834 showed the opposite results. RIP experiments validated the binding activities between lncRNA Gm15834 and Sam68. Overexpression of Sam68 could counteract the anti-hypertrophy effects of lncRNA Gm15834 knockdown. Meanwhile, in vivo inhibition of lncRNA Gm15834 could inhibit Sam68 expression, reduce NF-κB mediated inflammatory activity and attenuate cardiac hypertrophy. CONCLUSION: Our study revealed a novel regulatory axis of cardiac hypertrophy, which comprised lncRNA Gm15834/Sam68/NF-κB/inflammation, shedding a new light for identifying therapy target of cardiac hypertrophy in clinic.
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Central Nervous System Germ Cell Tumors (CNS GCTs) represent a subtype of intracranial malignant tumors characterized by highly heterogeneous histology. Current diagnostic methods in clinical practice have notable limitations, and treatment strategies struggle to achieve personalized therapy based on patient risk stratification. Advances in molecular genetics, biology, epigenetics, and understanding of the tumor microenvironment suggest the diagnostic potential of associated molecular alterations, aiding risk subgroup identification at diagnosis. Furthermore, they suggest the existence of novel therapeutic approaches targeting chromosomal alterations, mutated genes and altered signaling pathways, methylation changes, microRNAs, and immune checkpoints. Moving forward, further research is imperative to explore the pathogenesis of CNS GCTs and unravel the intricate interactions among various molecular alterations. Additionally, these findings require validation in clinical cohorts to assess their role in the diagnosis, risk stratification, and treatment of patients.
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PURPOSE: To evaluate the potential efficacy of Triptolide (TP) on cerebral ischemia/reperfusion injury (CIRI) and to uncover the underlying mechanism through which TP regulates CIRI. METHODS: We constructed a middle cerebral artery occlusion/reperfusion (MCAO/R) mouse model to simulate CIRI, and established a lipopolysaccharide (LPS)-stimulated BV-2 cell model to mimic the inflammatory state during CIRI. The neurological deficits score (NS) of mice were measured for assessment of neurologic functions. Both the severity of cerebral infarction and the apoptosis level in mouse brain tissues or cells were respectively evaluated using corresponding techniques. The expression levels of Ionized calcium binding adapter molecule 1 (IBA-1), Inductible Nitric Oxide Synthase (iNOS), Arginase 1 (Arg-1), Tumor necrosis factor-α (TNF-α), Interleukin 1ß (IL-1ß), Cysteine histoproteinase S (CTSS), Fractalkine, chemokine C-X3-C motif receptor 1 (CX3CR1), BCL-2-associated X protein (BAX), and antiapoptotic proteins (Bcl-2) were detected using immunofluorescence, qRT-PCR as well as Western blot, respectively. RESULTS: Relative to the Sham group, treatment with TP attenuated the increased NS, infarct area and apoptosis levels observed in MCAO/R mice. Upregulated expression levels of IBA-1, iNOS, Arg-1, TNF-α and IL-1ß were found in MCAO/R mice, while TP suppressed iNOS, TNF-α and IL-1ß expression, and enhanced Arg-1 expression in both MCAO/R mice and LPS-stimulated BV-2 cells. Besides, TP inhibited the CTSS/Fractalkine/CX3CR1 pathway activation in both MCAO/R mice and LPS-induced BV-2 cells, while overexpression of CTSS reversed such effect. Co-culturing HT-22 cells with TP+LPS-treated BV-2 cells led to enhanced cell viability and decreased apoptosis levels. However, overexpression of CTSS further aggravated HT-22 cell injury. CONCLUSION: TP inhibits not only microglia polarization towards the M1 phenotype by suppressing the CTSS/Fractalkine/CX3CR1 pathway activation, but also HT-22 apoptosis by crosstalk with BV-2 cells, thereby ameliorating CIRI. These findings reveal a novel mechanism of TP in improving CIRI, and offer potential implications for addressing the preventive and therapeutic strategies of CIRI.
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Isquemia Encefálica , Diterpenos , Compostos de Epóxi , Infarto da Artéria Cerebral Média , Fenantrenos , Traumatismo por Reperfusão , Transdução de Sinais , Animais , Masculino , Camundongos , Apoptose/efeitos dos fármacos , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/metabolismo , Quimiocina CX3CL1/efeitos dos fármacos , Quimiocina CX3CL1/metabolismo , Receptor 1 de Quimiocina CX3C/efeitos dos fármacos , Receptor 1 de Quimiocina CX3C/metabolismo , Modelos Animais de Doenças , Diterpenos/farmacologia , Compostos de Epóxi/farmacologia , Infarto da Artéria Cerebral Média/tratamento farmacológico , Infarto da Artéria Cerebral Média/metabolismo , Camundongos Endogâmicos C57BL , Microglia/efeitos dos fármacos , Microglia/metabolismo , Fármacos Neuroprotetores/farmacologia , Fenantrenos/farmacologia , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacosRESUMO
Protocobitis species are typical cave-dwelling fish, exhibiting distinctive morphological adaptations such as colorless body, lack of eyes, and reduced scales and ribs in response to their extreme cave habitats. Distinct from the recorded species, P. anteroventris, P. polylepis, and P. typhlops, a new species, Protocobitis longicostatus sp. nov., is described from Guangxi Zhuang Autonomous Region, China. Protocobitis longicostatus sp. nov. can easily be distinguished from all known congeners by the following characteristics: whole body covered by scales except head, 12 branched caudal fin rays, and long ribs. These species face threats from habitat degradation, hydrological changes, and environmental pollution. Thus, the conservation of cavefish in China has become an urgent issue.
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Cipriniformes , Animais , Cipriniformes/anatomia & histologia , China , Cavernas , Olho , EcossistemaRESUMO
BACKGROUND: The immunopathological mechanisms underlying neurosyphilis remain incompletely elucidated, and the diagnosis of neurosyphilis presents challenges. METHODS: We used an antibody microarray to detect 640 proteins in cerebrospinal fluid (CSF) samples collected from 6 patients with non-neurosyphilis and 10 with neurosyphilis. The levels of CSF CXCL1, CXCL8, G-CSF, LCN2, MMP8, and MMP9 in 46 patients with non-neurosyphilis, 51 with untreated neurosyphilis, and 31 posttreatment for neurosyphilis were quantified using enzyme-linked immunosorbent assay. The associations between the levels of these proteins and clinical parameters in neurosyphilis were evaluated using Spearman analysis, and the diagnostic performance of these proteins in neurosyphilis was assessed using receiver operating characteristic curve. RESULTS: A total of 102 differentially expressed proteins between neurosyphilis and non-neurosyphilis were identified. The levels of significantly elevated neutrophil-associated proteins (CXCL1, CXCL8, G-CSF, LCN2, MMP8, and MMP9) in neurosyphilis positively correlated with white blood cell counts, rapid plasma regain (RPR) titer, and protein concentration in CSF. The combination of CSF CXCL8, MMP9, and LCN2 yielded an area under the curve of 0.92 for diagnosing neurosyphilis, surpassing that of CSF RPR. CONCLUSIONS: CXCL1, CXCL8, G-CSF, LCN2, MMP8, and MMP9 could be associated with central nervous system damage of neurosyphilis. The combination of CSF CXCL8, MMP9, and LCN2 is a promising biomarker for diagnosing neurosyphilis.
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Biomarcadores , Neurossífilis , Humanos , Neurossífilis/líquido cefalorraquidiano , Neurossífilis/diagnóstico , Biomarcadores/líquido cefalorraquidiano , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Idoso , Neutrófilos , Metaloproteinase 9 da Matriz/líquido cefalorraquidiano , Lipocalina-2/líquido cefalorraquidiano , Metaloproteinase 8 da Matriz/líquido cefalorraquidiano , Curva ROCRESUMO
PURPOSE: This study aimed to examine the impact of CA on DN and elucidate its underlying molecular mechanisms of inflammation. METHODS: We fed C57BL/6 mice injected with streptozotocin to induce diabetes. In addition, we stimulated NRK-52E cells with 20 mmol/L d-glucose to mimic the diabetic condition. RESULTS: Our findings demonstrated that CA effectively reduced blood glucose levels, and improved DN in mice models. Additionally, CA reduced kidney injury and inflammation in both mice models and in vitro models. CA decreased high glucose-induced ferroptosis of NRK-52E cells by inducing GSH/GPX4 axis. Conversely, the ferroptosis activator or the PI3K inhibitor reversed positive effects of CA on DN in both mice and in vitro models. CA suppressed PAQR3 expression in DN models to promote PI3K/AKT activity. The PAQR3 activator reduced the positive effects of CA on DN in vitro models. Moreover, CA directly targeted the PAQR3 protein to enhance the ubiquitination of the PAQR3 protein. CONCLUSION: Overall, our study has uncovered that CA promotes the ubiquitination of PAQR3, leading to the attenuation of ferroptosis in DN. This effect is achieved through the activation of the PI3K/AKT signaling pathways by disrupting the interaction between PAQR3 and the P110α pathway. These findings highlight the potential of CA as a viable therapeutic option for the prevention of DN and other forms of diabetes.
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Ácidos Cafeicos , Diabetes Mellitus , Nefropatias Diabéticas , Ferroptose , Succinatos , Animais , Camundongos , Nefropatias Diabéticas/tratamento farmacológico , Inflamação , Camundongos Endogâmicos C57BL , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , UbiquitinaçãoRESUMO
In this study, we isolated lovastatin derivatives, including aculeatiols A-G (1-7) and three known compounds (8-10), from Aspergillus aculeatus. Their structures and absolute configurations were experimentally determined by high-resolution electrospray ionization mass spectrometry, nuclear magnetic resonance spectroscopy, and X-ray diffraction analyses, and the results were corroborated by quantum-chemical calculations. As members of the lovastatin derivatives, aculeatiols A-C (1-3) possess a γ-lactone functional group in the side chain. Compound 6 represents the first example that features an undescribed aromatized heterotetracyclic 6/6/6/6 ring system. Biologically, the lipid-lowering effects of all of these compounds were evaluated by analyzing the free fatty acid-induced intracellular lipid accumulation. In addition, compound 5, which regulated the transcription of genes associated with lipid uptake and synthesis, inhibited the accumulation of lipids.
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Aspergillus , Lovastatina , Aspergillus/química , Lovastatina/farmacologia , Lovastatina/química , Estrutura Molecular , HumanosRESUMO
This study was designed to compare the beneficial effects of paricalcitol combined with or without cinacalcet on calcium and phosphorus metabolism in patients undergoing maintenance hemodialysis (MHD). A total of 140 patients who received MHD in our hospital from March 2021 to March 2022 were randomly divided into a control group (intravenous paricalcitol, n = 70) and a test group (intravenous paricalcitol combined with oral cinacalcet, n = 70). Clinical baseline data and relevant laboratory parameters before treatment were compared. Additionally, calcium, phosphorus, intact parathyroid hormone in serum were measured and compared between the 2 groups before treatment and 1, 2, 3, 4, 5, 6, 9, 10, and 12 months after treatment. As a result, comparison before treatment demonstrated no significant difference in baseline data such as age, sex, and most laboratory parameters between the 2 groups (P > .05), but there was a significant difference in mean corpuscular volume (P < .001). The serum phosphorus level decreased and calcium level increased significantly in the 2 groups after treatment, while the intact parathyroid hormone level showed no significant change within 12 months of treatment (P > .05). In addition, the combined treatment for 6-12 months caused a much lower phosphorus level (P < .05) and higher calcium level (P < .05) than the treatment with paricalcitol alone, and the difference increased with the extension of treatment time. Collectively, paricalcitol combined with cinacalcet, which is more effective than paricalcitol alone, has a positive effect on calcium and phosphorus metabolism in patients receiving MHD.