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Since the outbreak of monkeypox (mpox) in 2022, widespread concern has been placed on imposing an urgent demand for specific vaccines that offer safer and more effective protection. Using an efficient and scalable circular RNA (circRNA) platform, we constructed four circRNA vaccines that could induce robust neutralizing antibodies as well as T cell responses by expressing different surface proteins of mpox virus (MPXV), resulting in potent protection against vaccinia virus (VACV) in mice. Strikingly, the combination of the four circular RNA vaccines demonstrated the best protection against VACV challenge among all the tested vaccines. Our study provides a favorable approach for developing MPXV-specific vaccines by using a circular mRNA platform and opens up novel avenues for future vaccine research.
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Anticorpos Neutralizantes , Monkeypox virus , RNA Circular , Vaccinia virus , Animais , Camundongos , Vaccinia virus/genética , Vaccinia virus/imunologia , RNA Circular/genética , Anticorpos Neutralizantes/imunologia , Monkeypox virus/imunologia , Monkeypox virus/genética , Anticorpos Antivirais/imunologia , Vacínia/prevenção & controle , Vacínia/imunologia , Mpox/prevenção & controle , Mpox/imunologia , Vacinas Virais/imunologia , Vacinas Virais/genética , Humanos , Modelos Animais de Doenças , Feminino , Linfócitos T/imunologia , Linfócitos T/metabolismoRESUMO
Modeling dynamic interactions among network components is crucial to uncovering the evolution mechanisms of complex networks. Recently, spatio-temporal graph learning methods have achieved noteworthy results in characterizing the dynamic changes of inter-node relations (INRs). However, challenges remain: The spatial neighborhood of an INR is underexploited, and the spatio-temporal dependencies in INRs' dynamic changes are overlooked, ignoring the influence of historical states and local information. In addition, the model's explainability has been understudied. To address these issues, we propose an explainable spatio-temporal graph evolution learning (ESTGEL) model to model the dynamic evolution of INRs. Specifically, an edge attention module is proposed to utilize the spatial neighborhood of an INR at multi-level, i.e., a hierarchy of nested subgraphs derived from decomposing the initial node-relation graph. Subsequently, a dynamic relation learning module is proposed to capture the spatio-temporal dependencies of INRs. The INRs are then used as adjacent information to improve the node representation, resulting in comprehensive delineation of dynamic evolution of the network. Finally, the approach is validated with real data on brain development study. Experimental results on dynamic brain networks analysis reveal that brain functional networks transition from dispersed to more convergent and modular structures throughout development. Significant changes are observed in the dynamic functional connectivity (dFC) associated with functions including emotional control, decision-making, and language processing.
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In supramolecular materials, multiple weak binding groups can act as a single collective unit when confined to a localized volume, thereby producing strong but dynamic bonds between material building blocks. This principle of multivalency provides a versatile means of controlling material assembly, as both the number and the type of supramolecular moieties become design handles to modulate the strength of intermolecular interactions. However, in materials with building blocks significantly larger than individual supramolecular moieties (e.g., polymer or nanoparticle scaffolds), the degree of multivalency is difficult to predict or control, as sufficiently large scaffolds inherently preclude separated supramolecular moieties from interacting. Because molecular models commonly used to examine supramolecular interactions are intrinsically unable to examine any trends or emergent behaviors that arise due to nanoscale scaffold geometry, our understanding of the thermodynamics of these massively multivalent systems remains limited. Here we address this challenge via the coassembly of polymer-grafted nanoparticles and multivalent polymers, systematically examining how multivalent scaffold size, shape, and spacing affect their collective thermodynamics. Investigating the interplay of polymer structure and supramolecular group stoichiometry reveals complicated but rationally describable trends that demonstrate how the supramolecular scaffold design can modulate the strength of multivalent interactions. This approach to self-assembled supramolecular materials thus allows for the manipulation of polymer-nanoparticle composites with controlled thermal stability, nanoparticle organization, and tailored meso- to microscopic structures. The sophisticated control of multivalent thermodynamics through precise modulation of the nanoscale scaffold geometry represents a significant advance in the ability to rationally design complex hierarchically structured materials via self-assembly.
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Peptides and proteins encoded by noncanonical open reading frames (ORFs) of circRNAs have recently been recognized to play important roles in disease progression, but the biological functions and mechanisms of these peptides and proteins are largely unknown. Here, we identified a potential coding circular RNA, circTRIM1, that was upregulated in doxorubicin-resistant TNBC cells by intersecting transcriptome and translatome RNA-seq data, and its expression was correlated with clinicopathological characteristics and poor prognosis in patients with TNBC. CircTRIM1 possesses a functional IRES element along with an 810 nt ORF that can be translated into a novel endogenously expressed protein termed TRIM1-269aa. Functionally, we demonstrated that TRIM1-269aa, which is involved in the biological functions of circTRIM1, promoted chemoresistance and metastasis in TNBC cells both in vitro and in vivo. In addition, we found that TRIM1-269aa can be packaged into exosomes and transmitted between TNBC cells. Mechanistically, TRIM1-269aa enhanced the interaction between MARCKS and calmodulin, thus promoting the calmodulin-dependent translocation of MARCKS, which further initiated the activation of the PI3K/AKT/mTOR pathway. Overall, circTRIM1, which encodes TRIM1-269aa, promoted TNBC chemoresistance and metastasis by enhancing MARCKS translocation and PI3K/AKT/mTOR activation. Our investigation has yielded novel insights into the roles of protein-coding circRNAs and supported circTRIM1/TRIM1-269aa as a novel promising prognostic and therapeutic target for patients with TNBC.
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Resistencia a Medicamentos Antineoplásicos , Proteínas Associadas aos Microtúbulos , Substrato Quinase C Rico em Alanina Miristoilada , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , RNA Circular , Serina-Treonina Quinases TOR , Fatores de Transcrição , Neoplasias de Mama Triplo Negativas , Animais , Feminino , Humanos , Camundongos , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/genética , Regulação Neoplásica da Expressão Gênica , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/genética , Proteínas de Membrana/metabolismo , Proteínas de Membrana/genética , Metástase Neoplásica , Fosfatidilinositol 3-Quinases/metabolismo , Prognóstico , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Circular/genética , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Proteínas com Motivo Tripartido/metabolismo , Proteínas com Motivo Tripartido/genética , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/metabolismo , Proteínas Associadas aos Microtúbulos/genética , Proteínas Associadas aos Microtúbulos/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Calmodulina/metabolismo , Substrato Quinase C Rico em Alanina Miristoilada/metabolismoRESUMO
Molecular-assisted breeding is an effective way to improve targeted agronomic traits. dep1 (dense and erect panicle 1) is a pleiotropic gene that regulates yield, quality, disease resistance, and stress tolerance, traits that are of great value in rice (Oryza sativa L.) breeding. In this study, a colorimetric LAMP (loop-mediated isothermal amplification) assay was developed for the detection of the dep1 allele and tested for the screening and selection of the heavy-panicle hybrid rice elite restorer line SHUHUI498, modified with the allele. InDel (Insertion and Deletion) primers (DEP1_F and DEP1_R) and LAMP primers (F3, B3, FIP, and BIP) for genotyping were designed using the Primer3 Plus (version 3.3.0) and PrimerExplore (version 5) software. Our results showed that both InDel and LAMP markers could be used for accurate genotyping. After incubation at a constant temperature of 65 °C for 60 min with hydroxynaphthol blue (HNB) as a color indicator, the color of the LAMP assay containing the dep1 allele changed to sky blue. The SHUHUI498 rice line that was detected in our LAMP assay displayed phenotypes consistent with the dep1 allele such as having a more compact plant architecture, straight stems and leaves, and a significant increase in the number of effective panicles and spikelets, demonstrating the effectiveness of our method in screening for the dep1 allele in rice breeding.
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Testosterone levels sharply rise during the transition from childhood to adolescence and these changes are known to be associated with changes in human brain structure. During this same developmental window, there are also robust changes in the neural oscillatory dynamics serving verbal working memory processing. Surprisingly, whereas many studies have investigated the effects of chronological age on the neural oscillations supporting verbal working memory, none have probed the impact of endogenous testosterone levels during this developmental period. Using a sample of 89 youth aged 6-14 years-old, we collected salivary testosterone samples and recorded magnetoencephalography during a modified Sternberg verbal working memory task. Significant oscillatory responses were identified and imaged using a beamforming approach and the resulting maps were subjected to whole-brain ANCOVAs examining the effects of testosterone and sex, controlling for age, during verbal working memory encoding and maintenance. Our primary results indicated robust testosterone-related effects in theta (4-7 Hz) and alpha (8-14 Hz) oscillatory activity, controlling for age. During encoding, females exhibited weaker theta oscillations than males in right cerebellar cortices and stronger alpha oscillations in left temporal cortices. During maintenance, youth with greater testosterone exhibited weaker alpha oscillations in right parahippocampal and cerebellar cortices, as well as regions across the left-lateralized language network. These results extend the existing literature on the development of verbal working memory processing by showing region and sex-specific effects of testosterone, and are the first results to link endogenous testosterone levels to the neural oscillatory activity serving verbal working memory, above and beyond the effects of chronological age.
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Magnetoencefalografia , Memória de Curto Prazo , Testosterona , Humanos , Masculino , Memória de Curto Prazo/fisiologia , Feminino , Adolescente , Criança , Encéfalo/fisiologia , Saliva/química , Saliva/metabolismo , Mapeamento Encefálico , Caracteres SexuaisRESUMO
In future regenerative medicine, far-infrared radiation (FIR) may be an essential component of optical therapy. Many studies have confirmed or validated the efficacy and safety of FIR in various diseases, benefiting from new insights into FIR mechanisms and the excellent performance of many applications. However, the lack of consensus on the biological effects and therapeutic parameters of FIR limits its practical applications in the clinic. In this review, the definition, characteristics, and underlying principles of the FIR are systematically illustrated. We outline the therapeutic parameters of FIR, including the wavelength range, power density, irradiation time, and distance. In addition, the biological effects, potential molecular mechanisms, and preclinical and clinical applications of FIR are discussed. Furthermore, the future development and applications of FIR are described in this review. By applying optimal therapeutic parameters, FIR can influence various cells, animal models, and patients, eliciting diverse underlying mechanisms and offering therapeutic potential for many diseases. FIR could represent a superior alternative with broad prospects for application in future regenerative medicine.
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BACKGROUND: Major depressive disorder (MDD) was a prevalent mental condition that may be accompanied by decreased excitability of left frontal pole (FP) and abnormal brain connections. An 820 nm tPBM can induce an increase in stimulated cortical excitability. The purpose of our study was to establish how clinical symptoms and time-varying brain network connectivity of MDD were affected by transcranial photobiomodulation (tPBM). METHODS: A total of 11 patients with MDD received 820 nm tPBM targeting the left FP for 14 consecutive days. The severity of symptoms was evaluated by neuropsychological assessments at baseline, after treatment, 4-week and 8-week follow-up; 8-min transcranial magnetic stimulation combined electroencephalography (TMS-EEG) was performed for five healthy controls and five patients with MDD before and after treatment, and time-varying EEG network was analyzed using the adaptive-directed transfer function. RESULTS: All of scales scores in the 11 patients decreased significantly after 14-day tPBM (p < .01) and remained at 8-week follow-up. The time-varying brain network analysis suggested that the brain regions with enhanced connection information outflow in MDD became gradually more similar to healthy controls after treatment. CONCLUSIONS: This study showed that tPBM of the left FP could improve symptoms of patients with MDD and normalize the abnormal network connections.
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Transtorno Depressivo Maior , Terapia com Luz de Baixa Intensidade , Humanos , Transtorno Depressivo Maior/terapia , Projetos Piloto , Eletroencefalografia , Estimulação Magnética TranscranianaRESUMO
High heritability and strong correlation have been observed in breast and ovarian cancers. However, their shared genetic architecture remained unclear. Linkage disequilibrium score regression (LDSC) and heritability estimation from summary statistics (ρ-HESS) were applied to estimate heritability and genetic correlations. Bivariate causal mixture model (MiXeR) was used to qualify the polygenic overlap. Then, stratified-LDSC (S-LDSC) was used to identify tissue and cell type specificity. Meanwhile, the adaptive association test called MTaSPUsSet was performed to identify potential pleiotropic genes. The Single Nucleotide Polymorphisms (SNP) heritability was 13% for breast cancer and 5% for ovarian cancer. There was a significant genetic correlation between breast and ovarian cancers (rg=0.21). Breast and ovarian cancers exhibited polygenic overlap, sharing 0.4 K out 2.8 K of causal variants. Tissue and cell type specificity displayed significant enrichment in female breast mammary, uterus, kidney tissues, and adipose cell. Moreover, the 74 potential pleiotropic genes were identified between breast and ovarian cancers, which were related to the regulation of cell cycle and cell death. We quantified the shared genetic architecture between breast and ovarian cancers and shed light on the biological basis of the co-morbidity. Ultimately, these findings facilitated the understanding of disease etiology.
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Técnicas Biossensoriais , Imagem Óptica , Técnicas Biossensoriais/métodos , Humanos , AnimaisRESUMO
Initial indications propose that repetitive transcranial magnetic stimulation (rTMS) could mitigate clinical manifestations in patients with autism spectrum disorder (ASD). Nevertheless, the precise mechanisms responsible for these therapeutic and behavioral outcomes remain elusive. We examined alterations in effective connectivity induced by rTMS using concurrent transcranial magnetic stimulation and electroencephalography (TMS-EEG) in children with ASD. TMS-EEG data were acquired from 12 children diagnosed with ASD both before and following rTMS treatment. The rTMS intervention regimen included delivering 5-s trains at a frequency of 15 Hz, with 10-min intervals between trains, targeting the left parietal lobe. This was conducted on each consecutive weekday over 3 weeks, totaling 15 sessions. The dynamic EEG network analysis revealed that following the rTMS intervention, long-range feedback connections within the brains of ASD patients were strengthened (e.g., frontal to parietal regions, frontal to occipital regions, and frontal to posterior temporal regions), and short-range connections were weakened (e.g., between the bilateral occipital regions, and between the occipital and posterior temporal regions). In alignment with alterations in network connectivity, there was a corresponding amelioration in fundamental ASD symptoms, as assessed through clinical scales post-treatment. According to our findings, people with ASD may have increased long-range frontal-posterior feedback connection on application of rTMS to the parietal lobe.
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Large bone defects caused by congenital deformities and acquired accidents are increasing day by day. A large number of patients mainly rely on artificial bone for repair. However, artificial bone cannot fully imitate the structure and composition of human bone, resulting in a large gap with autologous bone function. Therefore, this article proposes a continuous preparation method for inorganic/organic biphasic composite gradient biomimetic bulk bone scaffolds. First, a controllable gradient hybrid forming platform for inorganic/organic dual-phase biomaterials was constructed, and the feeding control strategy was studied to achieve precise control of the feeding of sodium alginate/gelatin composite organic materials and hydroxyapatite inorganic materials. The speed is, respectively, sent from the corresponding feeding nozzle to the mixing chamber to realize the uniform mixing of the biphasic material and the extrusion of the composite material, and the inorganic/organic biphasic composite gradient biomimetic bone scaffold with gradual structure and composition is prepared. Second, to prove the superiority of the preparation method, the physicochemical and biological properties of the prepared scaffolds were evaluated. The test results showed that the morphological characteristics of the biphasic composite gradient bone scaffold showed good microscopic porosity and the structure and composition showed gradients. The mechanical properties are close to that of human bone tissue and in vitro cell experiments show that the scaffold has good biocompatibility and bioactivity. In conclusion, this article provides a new type of bone scaffold preparation technology and equipment for the field of tissue engineering, which has research value and application prospects.
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The development of innovative multi-emission sensors for the rapid and accurate detection of contaminants is both vital and challenging. In this study, utilizing two rigid ligands (H3ICA and H4BTEC), a series of water-stable bimetallic organic frameworks (EuTb-MOFs) were synthesized. Luminescent investigations have revealed that EuTb-MOF-1 exhibits prominent multiple emission peaks, attributed to the distinctive fluorescence characteristics of Eu(III) and Tb(III) ions. Therefore, EuTb-MOF-1 efficiently recognized various metal ions and pharmaceutical compounds through 2D decoded maps. Fe3+ and Pb2+ exhibited significant quenching effects on the luminescence of EuTb-MOF-1, which were attributed to the internal filtering effect and the interaction between Lewis basic sites within EuTb-MOF-1 and Pb2+ ions, respectively. Furthermore, EuTb-MOF-1 demonstrated high sensitivity to sulfonamide antibiotics, with detection limits of 0.037 µM for SMZ and 0.041 µM for SDZ, respectively. In addition, EuTb-MOF-1 was immobilized to prepare MOF-based test strips, enabling direct visual detection of sulfonamides as a portable sensor. With excellent water stability, multi-responsive recognition capabilities, and high sensitivity to specific analytes, EuTb-MOF-1 is a promising candidate for environmental contaminant detection in aquatic systems.
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BACKGROUND: The impact of per- and polyfluoroalkyl substances (PFAS) on constipation, as mediated through gastrointestinal absorption and perturbations to the intestinal microecology, remains poorly understood. OBJECTIVE: This study seeks to explain the relationship between PFAS and constipation. METHODS: A total of 2945 adults from the National Health and Nutrition Examination Survey (NHANES) 2005-2010 were included in this study. Constipation was defined using the Bristol Stool Form Scale (BSFS) based on stool consistency. The relationship between PFAS and constipation was evaluated using weighted logistic regression and restricted cubic spline (RCS) analysis, while adjusting for confounding variables. RESULTS: The weighted median concentration of total PFAS (ΣPFAS) was significantly lower in individuals with constipation (19.01 µg/L) compared to those without constipation (23.30 µg/L) (p < 0.0001). Subgroup analysis revealed that the cumulative effect of PFAS was more pronounced in the elderly, men, individuals with obesity, high school education or equivalent, and high-income individuals (p < 0.05). After adjusting for confounding factors, multivariable analysis demonstrated an inverse association between PFOA [OR (95% CI), 0.666(0.486,0.914)] and PFHxS [OR (95% CI), 0.699(0.482,1.015)], and constipation. None of the personal and lifestyle factors showed a significant correlation with this negative association, as confirmed by subgroup analysis and interaction testing (p for interaction > 0.05). The RCS analysis demonstrated a linear inverse relationship between PFAS levels and constipation. CONCLUSION: The findings of this study provide evidence of a significant inverse correlation between serum concentrations of PFAS, particularly PFOA and PFHxS, and constipation.
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Ácidos Alcanossulfônicos , Poluentes Ambientais , Fluorocarbonos , Adulto , Masculino , Humanos , Idoso , Inquéritos Nutricionais , Constipação Intestinal/epidemiologiaRESUMO
Two-dimensional (2D) MXene nanomaterials display great potential for green energy storage. However, as a result of self-stacking of MXene nanosheets and the presence of conventional binders, MXene-based nanomaterials are significantly hindered in their rate capability and cycling stability. We successfully constructed a self-supported stereo-structured composite (TMA-V2CTx/CoV-LDH/NF) by in-situ growing 2D cobalt vanadium layered double hydroxide (CoV-LDH) vertically on 2D few-layered V2CTx MXene nanosheets and interconnecting it with Ni foam (NF) with a self-supported structure to act as a binder-free electrode. In addition to inhibiting CoV-LDH aggregation, the highly conductive V2CTx MXene and CoV-LDH work synergistically to improve charge storage. The specific capacitance of the TMA-V2CTx/CoV-LDH/NF electrode is 2374 F/g (1187 C/g) at 1 A/g. At the same time, the TMA-V2CTx/CoV-LDH/NF exhibits excellent stability, retaining 85.3 % of its specific capacitance at 20 A/g after 10,000 cycles. In addition, the hybrid supercapacitor (HSC) is assembled based on positive electrode (TMA-V2CTx/CoV-LDH/NF) and negative electrode (AC), achieving the maximum energy density of 74.4 Wh kg-1 at 750.3 W kg-1. TMA-V2CTx/CoV-LDH/NF has potential as an electrode material for storing green energy. The research strategy provides a development prospect for the construction of novel V2CTx MXene-based electrode material with self-supported structures.
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Background and objective: Aberrant epigenetic regulation and increased oxidative stress in the placenta play a significant role in placental pathophysiology and fetal programming in preeclampsia, a hypertensive disorder in human pregnancy. The purpose of the study is to investigate if hypermethylation of histone H3K9 occurs in placental trophoblasts from preeclampsia. Methods: Trophoblasts were isolated and cultured from 14 placentas, 7 from normotensive pregnant women and 7 from preeclamptic pregnancies. Methylated H3K9 expression and antioxidant superoxide dismutase expression were determined by Western blot. We also examined consequences of oxidative stress and the downstream effects of histone methyltransferase inhibition on H3K9 expression associated with antioxidant CuZn-SOD and Mn-SOD expression in placental trophoblasts. Results: We found that expression of mono-, di-, and tri-methylation of histone H3 lysine 9 (H3K9me1, H3K9me2 and H3K9me3) was significantly increased, p<0.01, which correlated with downregulation of antioxidant superoxide dismutase CuZn-SOD and Mn-SOD expression, in trophoblasts from preeclamptic placentas compared to those from uncomplicated control placentas. We further demonstrated hypoxia could promote histone H3K9 methylation in placental trophoblasts, and hypoxia-induced upregulation of H3K9me1, H3K9me2 and H3K9me3 expression was reversible when hypoxic condition was removed. In addition, we also uncovered that inhibition of methyltransferase not only prevented hypoxia-induced upregulation of H3K9me1, H3K9me2 and H3K9me3 expression, but also abolished hypoxia-induced downregulation of CuZn-SOD and Mn-SOD expression in placental trophoblasts. Conclusions: These findings are noteworthy and provide further evidence that increased oxidative stress in the intrauterine environment is likely a mechanism to induce aberrant histone modification in placental trophoblasts in preeclampsia. Moreover, CuZn-SOD and Mn-SOD expression/activity are possibly H3K9 methylation-dependent in placental trophoblasts, which further suggest that oxidative stress and aberrant histone modification have significant impact on placental trophoblasts/fetal programming in preeclampsia.
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Histonas , Estresse Oxidativo , Placenta , Pré-Eclâmpsia , Trofoblastos , Humanos , Feminino , Pré-Eclâmpsia/metabolismo , Pré-Eclâmpsia/genética , Pré-Eclâmpsia/patologia , Gravidez , Trofoblastos/metabolismo , Histonas/metabolismo , Adulto , Placenta/metabolismo , Metilação , Superóxido Dismutase/metabolismo , Superóxido Dismutase/genética , Metilação de DNA , Células Cultivadas , Lisina/metabolismoRESUMO
BACKGROUND: Dengue virus (DENV) infection, a common mosquito-borne disease, has been linked to several mental disorders like depression and anxiety. However, the temporal risk of these disorders after DENV infection is not well studied. METHODS: This population-based cohort study encompassed 45,334 recently lab-confirmed dengue patients in Taiwan spanning 2002 to 2015, matched at a 1:5 ratio with non-dengue individuals based on age, gender, and residence (n = 226,670). Employing subdistribution hazard regression analysis, we assessed the immediate (<3 months), intermediate (3-12 months), and prolonged (>12 months) risks of anxiety disorders, depressive disorders, and sleep disorders post DENV infection. Corrections for multiple comparisons were carried out using the Benjamini-Hochberg procedure. RESULTS: A significant increase in depressive disorder risk across all timeframes post-infection was observed (<3 months [aSHR 1.90, 95% CI 1.20-2.99], 3-12 months [aSHR 1.68, 95% CI 1.32-2.14], and >12 months [aSHR 1.14, 95% CI 1.03-1.25]). Sleep disorder risk was higher only during 3-12 months (aSHR 1.55, 95% CI 1.18-2.04). No elevated anxiety disorder risk was found. Subgroup analysis of hospitalized dengue patients showed increased risk of anxiety disorders within 3 months (aSHR 2.14, 95% CI 1.19-3.85) and persistent risk of depressive disorders across all periods. Hospitalized dengue patients also had elevated sleep disorder risk within the first year. CONCLUSION: Dengue patients exhibited significantly elevated risks of depressive disorders in both the short and long term. However, dengue's impact on sleep disorders and anxiety seems to be short-lived. Further research is essential to elucidate the underlying mechanisms.
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Transtornos de Ansiedade , Dengue , Transtorno Depressivo , Transtornos do Sono-Vigília , Humanos , Dengue/epidemiologia , Dengue/complicações , Masculino , Feminino , Taiwan/epidemiologia , Transtornos do Sono-Vigília/epidemiologia , Adulto , Transtornos de Ansiedade/epidemiologia , Estudos de Coortes , Adulto Jovem , Pessoa de Meia-Idade , Adolescente , Transtorno Depressivo/epidemiologia , Fatores de Risco , Criança , Idoso , Pré-EscolarRESUMO
The focus of exploration geochemistry is an accurate interpretation of geochemical data and the precise extraction of anomaly information related to mineralization from complex geological information. However, geochemical data are component data and exhibit a closure effect. Thus, traditional statistical methods cannot adequately reveal and identify the distribution of deep-seated anomaly information. This paper focuses on the Sidaowanzi area in Inner Mongolia and uses multivariate component data analysis methods to process 1:50â¯000 soil geochemical data. Using the Exploratory Data Analysis (EDA) method, the spatial distribution and internal structure characteristics of raw, logarithmic, and isometric logarithmic ratio (ILR) transformed data were compared and, coupled with robust principal component analysis (RPCA) and elemental component biplots, the association between element combinations and mineralization indicated by these three types of data was revealed. The S-A method was used to decompose composite anomalies of the ILR transformed RPCA score data to extract the characteristics of elemental combination anomalies and background distribution, and the Fry analysis method was utilized to analyze the dominant mineralization direction within the area. The results show that (1) data transformed using the ILR eliminated the influence of the closure effect, making the data more uniform on a spatial scale and exhibiting characteristics of an approximately normal distribution. (2) The S-A method was further used to decompose the composite anomaly of the PC1 and PC2 principal component combinations. The screened-out anomaly and background fields can essentially reflect the ore-causing anomalies dominated by Au and Cu-Mo mineralization. Moreover, the extracted anomalies and background information closely align with known mineral deposits (prospects) and can effectively identify weakly retarded geochemical anomaly information. (3) Fry analysis based on geochemical anomalies indicates that the dominant mineralization directions, by an assemblage dominated by Au and Cu-Mo, predominantly occur in the NE, NW, and proximate EW orientations. The combined application of the aforementioned three methods for the quantitative analysis of geochemical data aims to explore a transferable methodological system, providing new insights and approaches for further prediction of mineralization potential.
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BACKGROUND AND STUDY AIMS: Immunotherapy has emerged as a hot topic in cancer treatment in recent years and has also shown potential in the treatment of Helicobacter pylori-associated gastric cancer. However, there is still a need to identify potential immunotherapy targets. MATERIAL AND METHODS: We used the GSE116312 dataset of Helicobacter pylori-associated gastric cancer to identify differentially expressed genes, which were then overlapped with immune genes from the ImmPort database. The identified immune genes were used to classify gastric cancer samples and evaluate the relationship between classification and tumor mutations, as well as immune infiltration. An immune gene-based prognostic model was constructed, and the expression levels of the genes involved in constructing the model were explored in the tumor immune microenvironment. RESULTS: We successfully identified 60 immune genes and classified gastric cancer samples into two subtypes, which showed differences in prognosis, tumor mutations, immune checkpoint expression, and immune cell infiltration. Subsequently, we constructed an immune prognostic model consisting of THBS1 and PDGFD, which showed significant associations with macrophages and fibroblasts. CONCLUSION: We identified abnormal expression of THBS1 and PDGFD in cancer-associated fibroblasts (CAFs) within the tumor immune microenvironment, suggesting their potential as therapeutic targets.