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The systemic inflammatory response syndrome (SIRS) represents a self-amplifying cascade of inflammatory reactions and pathophysiological states triggered by infectious or non-infectious factors. The identification of disease targets and differential proteins in the liver (the unique and important immune organ) of SIRS mice treated with the lead compound D1 was conducted using the Genecards database and proteomic analysis, respectively. Subsequently, NOTCH1 was identified as the potential hub target via an intersection analysis between the aforementioned differentially expressed proteins and disease targets. Based on our previous research on the structure-activity relationship, we designed and synthesized a series of SIRS-related derivatives, wherein butyl, halogen, and ester groups were incorporated into benzophenone, aiming at exploring the anti-inflammatory protective action from the perspective of macrophage polarization. Notably, these derivatives exhibited a direct binding capability to the O-glucosylation site (SER496) or its vicinities (such as SER492, VAL485) of NOTCH1 using docking, SPR, DARTS, and CETSA techniques. Mechanistically, derivative D6 exerted anti-inflammatory effects via the dual NOTCH pathway. Firstly, it could inhibit NOTCH1 nuclear transcriptional activity, attenuate the interaction between NICD and RBPJK, concurrently suppress NF-κB and NLRP3 inflammasome (NLRP3, ASC, and cleaved CASP1) activation, and promote NICD (NOTCH1 active fragments) ubiquitination metabolism (the nuclear transcriptional pathway). Secondly, it might possess the ability to increase PGC1α level, subsequently, enhance ATP and MMP levels, mitigate ROS production, increase mitochondrial numbers, and ameliorate mitochondrial inflammatory damage (the mitochondrial pathway). Importantly, the activator Jagged1 could effectively reverse the aforementioned effects, while the inhibitor DAPT exhibited a synergistic effect, suggesting that the nuclear transcriptional regulation and mitochondrial regulation were both in a NOTCH1-dependent manner. Subsequently, it effectively alleviated the inflammatory response and preserved organ function as evidenced by up-regulating M2-type macrophage-related anti-inflammatory cytokines (IL10, TGFß, CD206, and ARG1) and down-regulating M1-type macrophage-related pro-inflammatory cytokines (NO, IL6, IL18, iNOS, TNFα, CD86, and IL1ß). In a word, derivative D6 modulated macrophage polarization and effectively mitigated SIRS by targeting inhibition of the dual NOTCH pathway.
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Hepatocellular carcinoma (HCC) is one of the cancers that seriously threaten human health. Immunotherapy serves as the mainstay of treatment for HCC patients by targeting the programmed cell death protein 1/programmed cell death 1 ligand 1 (PD-1/PD-L1) axis. However, the effectiveness of anti-PD-1/PD-L1 treatment is limited when HCC becomes drug-resistant. Tumor-associated macrophages (TAMs) are an important factor in the negative regulation of PD-1 antibody targeted therapy in the tumor microenvironment (TME). Therefore, as an emerging direction in cancer immunotherapy research for the treatment of HCC, it is crucial to elucidate the correlations and mechanisms between TAMs and PD-1/PD-L1-mediated immune tolerance. This paper summarizes the effects of TAMs on the pathogenesis and progression of HCC and their impact on HCC anti-PD-1/PD-L1 immunotherapy, and further explores current potential therapeutic strategies that target TAMs in HCC, including eliminating TAMs in the TME, inhibiting TAMs recruitment to tumors and functionally repolarizing M2-TAMs (tumor-supportive) to M1-TAMs (antitumor type).
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BACKGROUND: Limb salvage surgery is an important method for treating malignant tumors of the bone involving the adjacent parts of the major joints in children. This technique allows for preservation of limb function, especially in the lower limb. However, the reconstruction of the proximal end of the tibia after removing the tumor mass with a rational scale to preserve the total knee joint and reduce limb length discrepancy presents a challenge. CASE PRESENTATION: We present a case of osteosarcoma of the proximal tibia. After being treated with an extended tumor resection, the proximal tibia of the child was restructured using endoprosthetic replacement with epiphyseal preservation. This procedure preserves the entire articular surface and growth plate of the knee joint of the affected limb and provides a feasible alternative protocol for retaining the function and growth potential of the affected limb. The patient remained disease-free and normal limb motor function was observed during the 3.5 year follow-up since the initial surgery. CONCLUSIONS: Preservation of the epiphysis enabled our patient to perform better limb function after limb-saving surgery as a result of his undamaged knee joint and minimized limb-length discrepancy. We believe that endoprosthetic replacement with preservation of the epiphysis can provide the best strategy for reconstruction after resection of focal malignant tumors in long bones without epiphytic involvement.
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Neoplasias Ósseas , Epífises , Salvamento de Membro , Osteossarcoma , Tíbia , Humanos , Osteossarcoma/cirurgia , Tíbia/cirurgia , Tíbia/diagnóstico por imagem , Neoplasias Ósseas/cirurgia , Epífises/cirurgia , Masculino , Salvamento de Membro/métodos , Criança , Procedimentos de Cirurgia Plástica/métodos , Articulação do Joelho/cirurgia , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/fisiopatologia , Resultado do TratamentoRESUMO
Cobalt substitution for manganese sites in Na0.44MnO2 initiates a dynamic structural evolution process, yielding a composite cathode material comprising intergrown P2 and P3 phases. The novel P2/P3 composite cathode exhibits a reversible phase transition process during Na+ extraction/insertion, showcasing its attractive battery performance in sodium-ion batteries.
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BACKGROUND: The incidence of spontaneous abortion (SA), which affects approximately 15-20% of pregnancies, is the most common complication of early pregnancy. Pathogenic copy number variations (CNVs) are recognized as potential genetic causes of SA. However, CNVs of variants of uncertain significance (VOUS) have been identified in products of conceptions (POCs), and their correlation with SA remains uncertain. RESULTS: Of 189 spontaneous abortion cases, trisomy 16 was the most common numerical chromosome abnormality, followed by monosomy X. CNVs most often occurred on chromosomes 4 and 8. Gene Ontology and signaling pathway analysis revealed significant enrichment of genes related to nervous system development, transmembrane transport, cell adhesion, and structural components of chromatin. Furthermore, genes within the VOUS CNVs were screened by integrating human placental expression profiles, PhyloP scores, and Residual Variance Intolerance Score (RVIS) percentiles to identify potential candidate genes associated with spontaneous abortion. Fourteen potential candidate genes (LZTR1, TSHZ1, AMIGO2, H1-4, H2BC4, H2AC7, H3C8, H4C3, H3C6, PHKG2, PRR14, RNF40, SRCAP, ZNF629) were identified. Variations in LZTR1, TSHZ1, and H4C3 may contribute to embryonic lethality. CONCLUSIONS: CNV sequencing (CNV-seq) analysis is an effective technique for detecting chromosomal abnormalities in POCs and identifying potential candidate genes for SA.
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Aims: Downregulation of nuclear factor erythroid 2-related factor 2 (Nrf2) contributes to doxorubicin (DOX)-induced myocardial oxidative stress, and inhibition of mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) increased Nrf2 protein level in rat heart suffering ischemia/reperfusion, indicating a connection between MALT1 and Nrf2. This study aims to explore the role of MALT1 in DOX-induced myocardial oxidative stress and the underlying mechanisms. Results: The mice received a single injection of DOX (15 mg/kg, i.p.) to induce myocardial oxidative stress, evidenced by increases in the levels of reactive oxidative species as well as decreases in the activities of antioxidative enzymes, concomitant with a downregulation of Nrf2; these phenomena were reversed by MALT1 inhibitor. Similar phenomena were observed in DOX-induced oxidative stress in cardiomyocytes. Mechanistically, knockdown or inhibition of MALT1 notably attenuated the interaction between Nrf2 and MALT1 and decreased the k48-linked ubiquitination of Nrf2. Furthermore, inhibition or knockdown of calcium/calmodulin-dependent protein kinase II (CaMKII-δ) reduced the phosphorylation of caspase recruitment domain-containing protein 11 (CARD11), subsequently disrupted the assembly of CARD11, B cell lymphoma 10 (BCL10), and MALT1 (CBM) complex, and reduced the MALT1-dependent k48-linked ubiquitination of Nrf2 in DOX-treated mice or cardiomyocytes. Innovation and Conclusion: The E3 ubiquitin ligase function of MALT1 accounts for the downregulation of Nrf2 and aggravation of myocardial oxidative stress in DOX-treated mice, and CaMKII-δ-dependent phosphorylation of CARD11 triggered the assembly of CBM complex and the subsequent activation of MALT1.
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Eosinophils account for a significant portion of immune cells in the body. It is well known that eosinophils play a role in the pathogenesis of many diseases. In which the interaction between eosinophils and other immune cells is incompletely understood. The aim of this study is to characterize the immune suppressive functions of eosinophils. In this study, an irway allergy mouse model was established. Eosinophils were isolated from the airway tissues using flow cytometry cell sorting. The RAW264.7 cell line was used to test the immune suppressive functions of eosinophils. We observed that eosinophils had immune suppressive functions manifesting inhibiting immune cell proliferation and cytokine release from other immune cells. The eosinophil's immune suppressive functions were mediated by eosinophil-derived molecules, such as eosinophil peroxidase (EPX) and major basic protein (MBP). The expression of Ras-like protein in the brain 27a (Rab27a) was detected in eosinophils, which controlled the release of MBP and EPX by eosinophils. Eosinophil mediators had two contrast effects on inducing inflammatory responses or rendering immune suppressive effects, depending on the released amounts. Administration of an inhibitor of Rab27a at proper dosage could alleviate experimental airway allergy. To sum up, eosinophils have immune suppressive functions and are also inflammation inducers. Rab27a governs the release of EPX and MBP from eosinophils, which leads to immune suppression or inflammation. Modulation of Rab27a can alleviate airway allergy responses by modulating eosinophil's immune suppressive functions, which has the translational potential for the management of eosinophil-related diseases.
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Peroxidase de Eosinófilo , Eosinófilos , Animais , Eosinófilos/imunologia , Eosinófilos/metabolismo , Camundongos , Células RAW 264.7 , Peroxidase de Eosinófilo/metabolismo , Camundongos Endogâmicos BALB C , Citocinas/metabolismo , Citocinas/imunologia , Modelos Animais de Doenças , Proteína Básica Maior de Eosinófilos/metabolismo , Proteína Básica Maior de Eosinófilos/imunologia , Feminino , Hipersensibilidade/imunologia , Proliferação de Células , Inflamação/imunologiaRESUMO
Deep vein thrombosis (DVT) is one of the common complications after joint replacement, which seriously affects the quality of life of patients. We systematically searched nine databases, a total of eleven studies on prediction models to predict DVT after knee/hip arthroplasty were included, eight prediction models for DVT after knee/hip arthroplasty were chosen and compared. The results of network meta-analysis showed the XGBoost model (SUCRA 100.0%), LASSO (SUCRA 84.8%), ANN (SUCRA 72.1%), SVM (SUCRA 53.0%), ensemble model (SUCRA 40.8%), RF (SUCRA 25.6%), LR (SUCRA 21.8%), GBT (SUCRA 1.1%), and best prediction performance is XGB (SUCRA 100%). Results show that the XGBoost model has the best predictive performance. Our study provides suggestions and directions for future research on the DVT prediction model. In the future, well-designed studies are still needed to validate this model.
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Artroplastia de Quadril , Artroplastia do Joelho , Metanálise em Rede , Complicações Pós-Operatórias , Trombose Venosa , Humanos , Trombose Venosa/etiologia , Artroplastia do Joelho/efeitos adversos , Artroplastia de Quadril/efeitos adversos , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/epidemiologiaRESUMO
Vascular calcification (VC) has a high incidence in patients with chronic kidney disease, which is a worldwide public health problem and presents a heavy burden to society. Hypoxia-inducible factor (HIF)-1α, the active subunit of HIF-1, has been reported to play a vital role in high phosphate-induced VC. However, the underlying mechanism is still undetermined, and effective treatment is unavailable. In the present study, human aortic smooth muscle cells (HASMCs) were cultured under normal or high phosphate media conditions. HIF-1α small interfering RNA and overexpression plasmids were employed to regulate HIF-1α expression. Phosphonoformic acid was employed to restrain the function of type III sodium-dependent phosphate cotransporter 1 (Pit-1). The expression levels of HIF-1α, Pit-1, runt-related transcription factor 2 (Runx2), and smooth muscle 22 alpha (SM22α) were evaluated, and the calcium contents were also examined. Cell growth was assessed using an MTT assay. High phosphate stimulation caused an upregulation in HIF-1α and Pit-1 expression levels and induced calcium depositions in HASMCs. Upregulation of Runx2 expression accompanied by downregulation of SM22α expression was observed in the high phosphate group. Following the suppression of HIF-1α expression, there was a concomitant attenuation in Pit-1 expression, calcium deposition, the alteration of phenotypic transition marker genes, and vice versa. The most serious calcium deposition was noted in HASMCs cultured under high phosphate conditions which were pretreated with a HIF-1α overexpression plasmid. However, when the biological functions of Pit-1 were restrained, the putative serious calcium deposition was not formed even in HASMCs transfected with a HIF-1α overexpression plasmid. The findings confirmed that HIF-1α regulated Pit-1 expression and exerted its pro-calcifying effect through Pit-1, which identified HIF-1α and Pit-1 as therapeutic targets for high phosphate-induced VC.
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Roses are consistently ranked at the forefront in cut flower production. Increasing demands of market and changing climate conditions have resulted in the need to further improve the diversity and quality of traits. However, frequent hybridization leads to highly heterozygous nature, including the allelic variants. Therefore, the absence of comprehensive genomic information leads to them making it challenging to molecular breeding. Here, two haplotype-resolved chromosome genomes for Rosa chinensis 'Chilong Hanzhu' (2n = 14) which is high heterozygous diploid old Chinese rose are generated. An amount of genetic variation (1,605,616 SNPs, 209,575 indels) is identified. 13,971 allelic genes show differential expression patterns between two haplotypes. Importantly, these differences hold valuable insights into regulatory mechanisms of traits. RcMYB114b can influence cyanidin-3-glucoside accumulation and the allelic variation in its promoter leads to differences in promoter activity, which as a factor control petal color. Moreover, gene family expansion may contribute to the abundance of terpenes in floral scents. Additionally, RcANT1, RcDA1, RcAG1 and RcSVP1 genes are involved in regulation of petal number and size under heat stress treatment. This study provides a foundation for molecular breeding to improve important characteristics of roses.
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Mentha canadensis, as a plant with medicinal and culinary uses, holds significant economic value. Jasmonic acid signaling repressor JAZ protein has a crucial role in regulating plant response to adversity stresses. The M. canadensis McJAZ8 gene is cloned and analyzed for protein characterization, protein interactions, and expression patterns, so as to provide genetic resources for molecular breeding of M. canadensis for stress tolerance. This experiment will analyze the protein structural characteristics, subcellular localization, protein interactions, and gene expression of McJAZ8 using bioinformatics, yeast two-hybrid(Y2H), transient expression in tobacco leaves, qRT-PCR, and other technologies. The results show that:(1)The full length of the McJAZ8 gene is 543 bp, encoding 180 amino acids. The McJAZ8 protein contains conserved TIFY and Jas domains and exhibits high homology with Arabidopsis thaliana AtJAZ1 and AtJAZ2.(2)The McJAZ8 protein is localized in the nucleus and cytoplasm.(3)The Y2H results show that McJAZ8 interacts with itself or McJAZ1/3/4/5 proteins to form homologous or heterologous dimers.(4)McJAZ8 is expressed in different tissue, with the highest expression level in young leaves. In terms of leaf sequence, McJAZ8 shows the highest expression level in the fourth leaf and the lowest expression level in the second leaf.(5) In leaves and roots, the expression of McJAZ8 is upregulated to varying degrees under methyl jasmonate(MeJA), drought, and NaCl treatments. The expression of McJAZ8 shows an initial upregulation followed by a downregulation pattern under CdCl_2 treatment. In leaves, the expression of McJAZ8 tends to gradually decrease under CuCl_2 treatment, while in roots, it initially decreases and then increases before decreasing again. In both leaves and roots, the expression of McJAZ8 is downregulated to varying degrees under AlCl_(3 )treatment. This study has enriched the research on jasmonic acid signaling repressor JAZ genes in M. canadensis and provided genetic resources for the molecular breeding of M. canadensis.
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Ciclopentanos , Perfilação da Expressão Gênica , Mentha , Oxilipinas , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Biologia Computacional , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/metabolismo , Filogenia , Estresse Fisiológico/genéticaRESUMO
Mentha canadensis is a traditional Chinese herb with great medicinal and economic value. Abscisic acid(ABA) receptor PYLs have important roles in plant growth and development and response to adversity. The M. canadensis McPYL4 gene was cloned, and its protein characteristics, gene expression, and protein interactions were analyzed, so as to provide genetic resources for genetic improvement and molecular design breeding for M. canadensis resistance. Therefore, the protein characteristics, subcellular localization, gene expression pattern, and protein interactions of McPYL4 were analyzed by bioinformatics analysis, transient expression of tobacco leaves, RT-qPCR, and yeast two-hybrid(Y2H) techniques. The results showed that the McPYL4 gene was 621 bp in length, encoding 206 amino acids, and its protein had the conserved structural domain of SRPBCC and was highly homologous with Salvia miltiorrhiza SmPYL4. McPYL4 protein was localized to the cell membrane and nucleus. The McPYL4 gene was expressed in all tissue of M. canadensis, with the highest expression in roots, followed by leaves, and it showed a pattern of up-regulation followed by down-regulation in leaves 1-8. In both leaves and roots, the McPYL4 gene responded to the exogenous hormones ABA, MeJA, and the treatments of drought, AlCl_3, NaCl, CdCl_2, and CuCl_2. Moreover, McPYL4 was up-regulated for expression in both leaves and roots under the MeJA treatment, as well as in leaves treated with AlCl_3 stress for 1 h, whereas McPYL4 showed a tendency to be down-regulated in both leaves and roots under other treatments. Protein interactions showed that McPYL4 interacted with AtABI proteins in an ABA-independent manner. This study demonstrated that McPYL4 responded to ABA, JA, and several abiotic stress treatments, and McPYL4 was involved in ABA signaling in M. canadensis and thus in the regulation of leaf development and various abiotic stresses in M. canadensis.
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Ácido Abscísico , Mentha , Ácido Abscísico/farmacologia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Folhas de Planta/genética , Folhas de Planta/metabolismo , Clonagem Molecular , Regulação da Expressão Gênica de Plantas , Estresse Fisiológico/genética , SecasRESUMO
Fine particulate matter (PM2.5) has been extensively implicated in the pathogenesis of neurodevelopmental disorders, but the underlying mechanism remains unclear. Recent studies have revealed that PM2.5 plays a role in regulating iron metabolism and redox homeostasis in the brain, which is closely associated with ferroptosis. In this study, the role and underlying mechanism of ferroptosis in PM2.5-induced neurotoxicity were investigated in mice, primary hippocampal neurons, and HT22 cells. Our findings demonstrated that exposure to PM2.5 could induce abnormal behaviors, neuroinflammation, and neuronal loss in the hippocampus of mice. These effects may be attributed to ferroptosis induced by PM2.5 exposure in hippocampal neurons. RNA-seq analysis revealed that the upregulation of iron metabolism-related protein Heme Oxygenase 1 (HO-1) and the activation of mitophagy might play key roles in PM2.5-induced ferroptosis in HT22 cells. Subsequent in vitro experiments showed that PM2.5 exposure significantly upregulated HO-1 in primary hippocampal neurons and HT22 cells. Moreover, PM2.5 exposure activated mitophagy in HT22 cells, leading to the loss of mitochondrial membrane potential, alterations in the expression of autophagy-related proteins LC3, P62, and mTOR, as well as an increase in mitophagy-related protein PINK1 and PARKIN. As a heme-degradation enzyme, the upregulation of HO-1 promotes the release of excess iron, genetically inhibiting the upregulation of HO-1 in HT22 cells could prevent both PM2.5-induced mitophagy and ferroptosis. Furthermore, pharmacological inhibition of mitophagy in HT22 cells reduced levels of ferrous ions and lipid peroxides, thereby preventing ferroptosis. Collectively, this study demonstrates that HO-1 mediates PM2.5-induced mitophagy-dependent ferroptosis in hippocampal neurons, and inhibiting mitophagy or ferroptosis may be a key therapeutic target to ameliorate neurotoxicity following PM2.5 exposure.
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Ferroptose , Heme Oxigenase-1 , Hipocampo , Mitofagia , Neurônios , Material Particulado , Regulação para Cima , Animais , Material Particulado/toxicidade , Ferroptose/efeitos dos fármacos , Mitofagia/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Hipocampo/patologia , Neurônios/efeitos dos fármacos , Neurônios/patologia , Camundongos , Heme Oxigenase-1/metabolismo , Heme Oxigenase-1/genética , Regulação para Cima/efeitos dos fármacos , Masculino , Camundongos Endogâmicos C57BL , Poluentes Atmosféricos/toxicidade , Proteínas de MembranaRESUMO
OBJECTIVE: To study the distribution of pathogenic Aspergillus strains of otomycosis in central China and the identification of their antifungal sensitivity. METHODS: We collected external ear canal secretions clinically diagnosed as otomycosis from April 2020 to January 2023 from the Department of Otolaryngology-Head and Neck Surgery in central China. The pathogenic Aspergillus strains were identified through morphological examination and sequencing. The antifungal sensitivity was performed using the broth microdilution method described in the Clinical Laboratory Standard Institute document M38-A3. RESULTS: In the 452 clinical strains isolated from the external ear canal, 284 were identified as Aspergillus terreus (62.83%), 92 as Aspergillus flavus (20.35%), 55 as Aspergillus niger (12.17%). In antifungal susceptibility tests the MIC of Aspergillus strains to bifonazole and clotrimazole was high,all the MIC90 is > 16 ug/mL. However, most Aspergillus isolates show moderate greatly against terbinafine, itraconazole and voriconazole. CONCLUSION: A. terreus is the most common pathogenic Aspergillus strain in otomycosis in central China. The selected topical antifungal drugs were bifonazole and clotrimazole; the drug resistance rate was approximately 30%. If the infection is persistent and requires systemic treatment, terbinafine and itraconazole can be used. The resistance of Aspergillus in otomycosis to voriconazole should be screened to avoid the systemic spread of infection in immunocompromised people and poor compliance with treatment. However, the pan-azole-resistant strain of Aspergillus should be monitored, particularly in high-risk patients with otomycosis.
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Aspergilose , Otomicose , Humanos , Antifúngicos/farmacologia , Otomicose/epidemiologia , Otomicose/microbiologia , Itraconazol , Voriconazol , Terbinafina , Clotrimazol/farmacologia , Aspergilose/epidemiologia , Aspergilose/microbiologia , Aspergillus , Testes de Sensibilidade MicrobianaRESUMO
Ganglioneuroblastoma (GNB), predominantly observed in children, is an uncommon malignant tumor in adults, with established treatment protocols notably lacking. The present study details the case of a 20-year-old woman who presented with a left adrenal gland mass, identified during a physical examination. Additionally, an unidentified mass was noted near the renal hilum in the preoperative evaluation. Following thorough preoperative preparation, both the primary adrenal gland mass and the renal hilar mass were surgically removed. The procedure concluded successfully. Pathological analysis confirmed that the left adrenal mass was a GNB and identified the renal hilar mass as a metastatic extension. Postoperative examination revealed a new formation at the original surgical site, later verified as a postoperative scar. Through the publication of a case report and extensive literature review, the present study aims to enhance our understanding of this condition, providing valuable diagnostic, therapeutic and post-recovery references for this rare adult disease.
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Objective: In a previous study we have shown that, in the presence of interleukin (IL)-33, repeated, per-nasal challenge of murine airways with Streptococcus pneumoniae (S. pneumoniae) organisms induces human asthma-like airways inflammation. It is not clear, however, whether this effect is unique or manifest in response to other common respiratory pathogens.Methods: To explore this, airways of BALB/c mice were repeatedly challenged per-nasally with formaldehyde-inactivated bacterial bodies in the presence or absence of murine recombinant IL-33. Serum concentrations of S.pneumoniae, Moraxella catarrhalis (M.catarrhalis) and Haemophilus influenzae (H.influenzae) lysates-specific IgE were measured in patients with asthma and control subjects.Results: We showed that in the presence of IL-33, repeated, per-nasal airways exposure to the bodies of these bacteria induced airways hyperresponsiveness (AHR) in the experimental mice. This was accompanied by cellular infiltration into bronchoalveolar lavage fluid (BALF), eosinophilic infiltration and mucous hypertrophy of the lung tissue, with elevated local expression of some type 2 cytokines and elevated, specific IgG and IgE in the serum. The precise characteristics of the inflammation evoked by exposure to each bacterial species were distinguishable.Conclusions: These results suggest that in the certain circumstances, inhaled or commensal bacterial body antigens of both Gram-positive (S. pneumoniae) and Gram-negative (M. catarrhalis and H. influenzae) respiratory tract bacteria may initiate type 2 inflammation typical of asthma in the airways. In addition, we demonstrated that human asthmatic patients manifest elevated serum concentrations of M.catarrhalis- and H.influenzae-specific IgE.
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Antígenos de Bactérias , Asma , Haemophilus influenzae , Imunoglobulina E , Camundongos Endogâmicos BALB C , Streptococcus pneumoniae , Asma/imunologia , Asma/microbiologia , Animais , Camundongos , Streptococcus pneumoniae/imunologia , Haemophilus influenzae/imunologia , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Humanos , Antígenos de Bactérias/imunologia , Feminino , Moraxella catarrhalis/imunologia , Líquido da Lavagem Broncoalveolar/imunologia , Líquido da Lavagem Broncoalveolar/microbiologia , Masculino , Interleucina-33/imunologia , Interleucinas/imunologia , Interleucinas/sangue , Adulto , Pessoa de Meia-IdadeRESUMO
Hole transport materials (HTMs) play a crucial role in achieving efficient perovskite solar cells (PSCs). In this work, an HTM MF-ACD with an asymmetric structure is designed by introducing two different peripheral end groups. The asymmetric feature increases the molecular dipole of MF-ACD, and endows MF-ACD with good stability and film formation properties, higher hole mobility and conductivity. Consequently, the MF-ACD-based PSC shows a high efficiency of 23.1%, which is much higher than that of the symmetric counterpart. The results show that the asymmetric configuration might be a potential choice to develop more efficient HTMs.
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Vegetable oils-based pressure sensitive adhesives (PSAs) are green and sustainable but face unsatisfactory adhesion strengths and are prone to aging during storage and application due to the existence of residual double bonds and massive ester bonds. Nine common antioxidants (tea polyphenol palmitate (TPP), caffeic acid, ferulic acid, gallic acid, butylated hydroxytoluene, tertiary butylhydroquinone, butylated hydroxyanisole, propyl gallate, and tea polyphenols) were grafted into epoxidized soybean oils-PSA (ESO-PSA) system to enhance antiaging properties and adhesion strengths. Results showed ESO-PSAs grafted with caffeic acid, tertiary butylhydroquinone, butylated hydroxyanisole, propyl gallate, tea polyphenols, or TPP didn't occur failure with TPP having best performance. The optimal conditions were ESO reacted with 0.9 % TPP, 70 % rosin ester, and 7.0 % phosphoric acid at 50 °C for 5 min, under which peel strength and loop tack increased to 2.460 N/cm and 1.66 N, respectively, but peel strength residue reduced to 138.09 %, compared with control (0.407 N/cm, 0.43 N, and 1669.99 %). Differential scanning calorimetry and thermogravimetric results showed TPP grafting increased the glass transition temperature of ESO-PSA slightly but improved its thermal stability significantly. Fourier transform infrared spectroscopy and 1H nuclear magnetic resonance results showed TPP, phosphoric acid, and rosin ester all partially participated in the covalently crosslinking polymerization of ESO-PSAs and the rest existed in the network structures in the free form.
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Hidroxianisol Butilado , Ácidos Cafeicos , Ácidos Fosfóricos , Óleo de Soja , Humanos , Masculino , Óleo de Soja/química , Hidroxianisol Butilado/análise , Galato de Propila , Polifenóis , Adesivos/química , Antígeno Prostático Específico , Ésteres , CháRESUMO
The global incidence of Chronic Kidney Disease (CKD) is steadily escalating, with discernible linkage to the intricate terrain of intestinal microecology. The intestinal microbiota orchestrates a dynamic equilibrium in the organism, metabolizing dietary-derived compounds, a process which profoundly impacts human health. Among these compounds, short-chain fatty acids (SCFAs), which result from microbial metabolic processes, play a versatile role in influencing host energy homeostasis, immune function, and intermicrobial signaling, etc. SCFAs emerge as pivotal risk factors influencing CKD's development and prognosis. This paper review elucidates the impact of gut microbial metabolites, specifically SCFAs, on CKD, highlighting their role in modulating host inflammatory responses, oxidative stress, cellular autophagy, the immune milieu, and signaling cascades. An in-depth comprehension of the interplay between SCFAs and kidney disease pathogenesis may pave the way for their utilization as biomarkers for CKD progression and prognosis or as novel adjunctive therapeutic strategies.
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Microbioma Gastrointestinal , Insuficiência Renal Crônica , Humanos , Microbioma Gastrointestinal/fisiologia , Ácidos Graxos Voláteis/metabolismo , Ácidos Graxos Voláteis/uso terapêutico , Biomarcadores , Transdução de Sinais , Insuficiência Renal Crônica/tratamento farmacológicoRESUMO
Accurately obtaining accurate information about the future traffic flow of all roads in the transportation network is essential for traffic management and control applications. In order to address the challenges of acquiring dynamic global spatial correlations between transportation links and modeling time dependencies in multi-step prediction, we propose a spatial linear transformer and temporal convolution network (SLTTCN). The model is using spatial linear transformers to aggregate the spatial information of the traffic flow, and bidirectional temporal convolution network to capture the temporal dependency of the traffic flow. The spatial linear transformer effectively reduces the complexity of data calculation and storage while capturing spatial dependence, and the time convolutional network with bidirectional and gate fusion mechanisms avoids the problems of gradient vanishing and high computational cost caused by long time intervals during model training. We conducted extensive experiments using two publicly available large-scale traffic data sets and compared SLTTCN with other baselines. Numerical results show that SLTTCN achieves the best predictive performance in various error measurements. We also performed attention visualization analysis on the spatial linear transformer, verifying its effectiveness in capturing dynamic global spatial dependency.