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Fusarium solani, as an opportunistic pathogen, can infect individuals with immunosuppression, neutropenia, hematopoietic stem cell transplantation (HSCT), or other high-risk factors, leading to invasive or localized infections. Particularly in patients following allogeneic HSCT, Fusarium solani is more likely to cause invasive or disseminated infections. This study focuses on a pediatric patient who underwent HSCT for severe aplastic anemia. Although initial blood cultures were negative, an abnormality was detected in the 1,3-ß-D-glucan test (G test) post-transplantation. To determine the causative agent, blood samples were subjected to metagenomic next-generation sequencing (mNGS) and blood cultures simultaneously. Surprisingly, the results of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and mNGS differed slightly, with mNGS identifying Nectria haematonectria, while MALDI-TOF MS based on culture showed Fusarium solani. To clarify the results, Sanger sequencing was performed for further detection, and the results were consistent with those of MALDI-TOF MS. Since the accuracy of Sanger sequencing is higher than that of mNGS, the diagnosis was revised to invasive Fusarium solani infection. With advancements in technology, various detection methods for invasive fungi have been developed in recent years, such as mNGS, which has high sensitivity. While traditional methods may be time-consuming, they are important due to their high specificity. Therefore, in clinical practice, it is essential to utilize both traditional and novel detection methods in a complementary manner to enhance the diagnosis of invasive fungal infections.
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The Bin/Amphiphysin/Rvs (BAR) domain protein FAM92A1 is a multifunctional protein engaged in regulating mitochondrial ultrastructure and ciliogenesis, but its physiological role in the brain remains unclear. Here, we show that FAM92A1 is expressed in neurons starting from embryonic development. FAM92A1 knockout in mice results in altered brain morphology and age-associated cognitive deficits, potentially due to neuronal degeneration and disrupted synaptic plasticity. Specifically, FAM92A1 deficiency impairs diverse neuronal membrane morphology, including the mitochondrial inner membrane, myelin sheath, and synapses, indicating its roles in membrane remodeling and maintenance. By determining the crystal structure of the FAM92A1 BAR domain, combined with atomistic molecular dynamics simulations, we uncover that FAM92A1 interacts with phosphoinositide- and cardiolipin-containing membranes to induce lipid-clustering and membrane curvature. Altogether, these findings reveal the physiological role of FAM92A1 in the brain, highlighting its impact on synaptic plasticity and neural function through the regulation of membrane remodeling and endocytic processes.
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Encéfalo , Cognição , Camundongos Knockout , Plasticidade Neuronal , Neurônios , Sinapses , Animais , Encéfalo/metabolismo , Neurônios/metabolismo , Sinapses/metabolismo , Plasticidade Neuronal/fisiologia , Camundongos , Cognição/fisiologia , Membrana Celular/metabolismo , Simulação de Dinâmica Molecular , Humanos , Fosfatidilinositóis/metabolismo , Cardiolipinas/metabolismo , MasculinoRESUMO
Background: CD46 has been revealed to be a key factor in malignant transformation and cancer treatment. However, the clinical significance of CD46 in cervical cancer remains unclear, and this study aimed to evaluate its role in cervical cancer diagnosis and prognosis evaluation. Methods: A total of 180 patients with an initial diagnosis of cervical cancer were enrolled at Taizhou Hospital of Zhejiang Province, China. The plasma levels of soluble CD46 (sCD46) and the expression of membrane-bound CD46 (mCD46) were detected by enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry (IHC), respectively. Results: CD46 was found to be significantly upregulated in cervical cancer tissues vs. normal tissues, while no CD46 staining was detected in paired adjacent noncancerous tissues. CD46 staining was more pronounced in cancer cells than in stromal cells in situ (in tissues). Moreover, the plasma levels of sCD46 were able to some extent discriminate between cancer patients and healthy women (AUC=0.6847, 95% CI:0.6152-0.7541). Analysis of Kaplan-Meier survival curves revealed that patients with low CD46 expression had slightly longer overall survival (OS) than patients with high CD46 expression in the tumor microenvironment, but no significant difference. Univariate Cox regression analysis revealed that CD46 (P=0.034) is an independent risk factor for OS in cervical cancer patients. Conclusion: The present study demonstrated that cervical cancer patients exhibit aberrant expression of CD46, which is closely associated with a poor prognosis, suggesting that CD46 plays a key role in promoting cervical carcinogenesis and that CD46 could serve as a promising potential target for precision therapy for cervical cancer.
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Biomarcadores Tumorais , Proteína Cofatora de Membrana , Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/sangue , Biomarcadores Tumorais/sangue , Pessoa de Meia-Idade , Prognóstico , Adulto , Idoso , Estimativa de Kaplan-MeierRESUMO
Due to the substantial contrast in the output beam quality between the two directions of the semiconductor laser, efficiently coupling the beam directly into the fiber is difficult. In this study, an efficient shaping method based on step multiplexing of misaligned step prisms is proposed and investigated systematically. First, multiple laser stacks eliminate dark areas to improve the beam quality through the full utilization of the transmission and reflection surfaces of the misaligned stepped prisms, which also improves the efficiency of the stepped prisms. It also simultaneously realizes laser wavelength combining based on reflective surface multiplexing without affecting the quality of the beam on the premise of improving the output power. Finally, the whole beam shaping system is completed without using cut-transform-rearranging prisms. The method couples four groups of laser stacks into a single fiber with a fiber diameter of 400 µm and a numerical aperture of 0.22. It can be seen from the computer-simulated model outputs that the final fiber output power can reach 2255.4 W and that the system as a whole has a light-to-light translation rate of 88.1%.
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Objective: The aim of this study was to comprehensively investigate the potential relationship between blood volatile organic compounds (VOCs) and overactive bladder (OAB) risk. Methods: A total of 11,183 participants from the 2007-2020 National Health and Nutrition Examination Survey (NHANES) were included in this cross-sectional study. We used multivariate logistic regression models to investigate the relationship between nine blood VOCs and OAB risk. Restricted cubic spline (RCS) analysis was used to investigate the dose-response relationship between blood VOCs and OAB. In addition, the overall association of blood VOCs with OAB risk was assessed by weighted quantile sum (WQS) regression model. Finally, we conducted subgroup analyses to explore the findings in different high-risk populations. Results: After adjusting for potential confounders, logistic regression analysis revealed that blood 2,5-dimethylfuran (aOR = 2.940, 95% CI: 1.096-7.890, P = 0.032), benzene (aOR = 1.460, 95% CI: 1.044-2.043, P = 0.027) and furan (aOR = 9.426, 95% CI: 1.421-62.500, P = 0.020) were positively independent associated with the risk of OAB. And dose-response risk curves indicated that 2,5-dimethylfuran, benzene and furan in the blood were linearly positive associated with OAB risk. WQS regression analysis showed that exposure to mixed blood VOCs increased the risk of OAB (OR = 1.29, 95% CI: 1.11-1.49), with furans having the greatest weight. In subgroup analyses, we found that OAB was more susceptible to blood VOCs in young and middle-aged, male, non-hypertensive, and alcohol-drinking populations. Conclusions: The results of this study indicate that high exposure to VOCs is independently and positively associated with OAB risk in U.S. adults, particularly 2,5-dimethylfuran, benzene, and furan. In addition, age, gender, hypertension and alcohol consumption may influence the association. Our study provided novel epidemiologic evidence to explore the potential role of environmental pollutants in OAB.
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Inquéritos Nutricionais , Bexiga Urinária Hiperativa , Compostos Orgânicos Voláteis , Humanos , Bexiga Urinária Hiperativa/sangue , Bexiga Urinária Hiperativa/epidemiologia , Estudos Transversais , Masculino , Feminino , Compostos Orgânicos Voláteis/sangue , Pessoa de Meia-Idade , Adulto , Estados Unidos/epidemiologia , Fatores de Risco , Exposição Ambiental/efeitos adversos , Exposição Ambiental/estatística & dados numéricos , Idoso , Modelos LogísticosRESUMO
Contractile actomyosin bundles play crucial roles in various physiological processes, including cell migration, morphogenesis, and muscle contraction. The intricate assembly of actomyosin bundles involves the precise alignment and fusion of myosin II filaments, yet the underlying mechanisms and factors involved in these processes remain elusive. Our study reveals that LUZP1 plays a central role in orchestrating the maturation of thick actomyosin bundles. Loss of LUZP1 caused abnormal cell morphogenesis, migration, and the ability to exert forces on the environment. Importantly, knockout of LUZP1 results in significant defects in the concatenation and persistent association of myosin II filaments, severely impairing the assembly of myosin II stacks. The disruption of these processes in LUZP1 knockout cells provides mechanistic insights into the defective assembly of thick ventral stress fibers and the associated cellular contractility abnormalities. Overall, these results significantly contribute to our understanding of the molecular mechanism involved in actomyosin bundle formation and highlight the essential role of LUZP1 in this process.
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Actomiosina , Movimento Celular , Contração Muscular , Miosina Tipo II , Humanos , Citoesqueleto de Actina/metabolismo , Actomiosina/metabolismo , Contração Muscular/fisiologia , Miosina Tipo II/metabolismo , Miosina Tipo II/genéticaRESUMO
BACKGROUND: Alpha-papillomavirus 9 (α-9) is a member of the human papillomavirus (HPV) α genus, causing 75% invasive cervical cancers worldwide. The purpose of this study was to provide data for effective treatment of HPV-induced cervical lesions in Taizhou by analysing the genetic variation and antigenic epitopes of α-9 HPV E6 and E7. METHODS: Cervical exfoliated cells were collected for HPV genotyping. Positive samples of the α-9 HPV single type were selected for E6 and E7 gene sequencing. The obtained nucleotide sequences were translated into amino acid sequences (protein primary structure) using MEGA X, and positive selection sites of the amino acid sequences were evaluated using PAML. The secondary and tertiary structures of the E6 and E7 proteins were predicted using PSIPred, SWISS-MODEL, and PyMol. Potential T/B-cell epitopes were predicted by Industrial Engineering Database (IEDB). RESULTS: From 2012 to 2023, α-9 HPV accounted for 75.0% (7815/10423) of high-risk HPV-positive samples in Taizhou, both alone and in combination with other types. Among these, single-type-positive samples of α-9 HPV were selected, and the entire E6 and E7 genes were sequenced, including 298 HPV16, 149 HPV31, 185 HPV33, 123 HPV35, 325 HPV52, and 199 HPV58 samples. Compared with reference sequences, 34, 12, 10, 2, 17, and 17 nonsynonymous nucleotide mutations were detected in HPV16, 31, 33, 35, 52, and 58, respectively. Among all nonsynonymous nucleotide mutations, 19 positive selection sites were selected, which may have evolutionary significance in rendering α-9 HPV adaptive to its environment. Immunoinformatics predicted 57 potential linear and 59 conformational B-cell epitopes, many of which are also predicted as CTL epitopes. CONCLUSION: The present study provides almost comprehensive data on the genetic variations, phylogenetics, positive selection sites, and antigenic epitopes of α-9 HPV E6 and E7 in Taizhou, China, which will be helpful for local HPV therapeutic vaccine development.
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Proteínas Oncogênicas Virais , Filogenia , China , Humanos , Proteínas Oncogênicas Virais/genética , Proteínas Oncogênicas Virais/imunologia , Feminino , Proteínas E7 de Papillomavirus/genética , Proteínas E7 de Papillomavirus/imunologia , Alphapapillomavirus/genética , Alphapapillomavirus/imunologia , Epitopos de Linfócito B/imunologia , Epitopos de Linfócito B/genética , Epitopos/imunologia , Epitopos/genética , Epitopos de Linfócito T/imunologia , Epitopos de Linfócito T/genética , Infecções por Papillomavirus/virologia , Sequência de AminoácidosRESUMO
Aldehyde dehydrogenase 2 (ALDH2) plays a critical role in safeguarding cells against acetaldehyde toxicity and is closely linked to human metabolism. Nevertheless, the involvement of ALDH2 in cancer remains enigmatic. This investigation seeks to comprehensively assess ALDH2's significance in pan-cancer. We conducted an all-encompassing analysis of pan-cancer utilizing multiple databases, including TCGA, linkedomicshs, UALCAN, and Kaplan-Meier plotter. We employed diverse algorithms such as EPIC, MCPCOUNTER, TIDTIMER, xCell, MCP-counter, CIBERSORT, quanTIseq, and EPIC to examine the connection between ALDH2 expression and immune cell infiltration. Single-cell sequencing analysis furnished insights into ALDH2's functional status in pan-cancer. Immunohistochemical staining was performed to validate ALDH2 expression in cancer tissues. In a comprehensive assessment, we observed that tumor tissues demonstrated diminished ALDH2 expression levels compared to normal tissues across 16 different cancer types. ALDH2 expression exhibited a significant positive correlation with the infiltration of immune cells, including CD4â +â T cells, CD8â +â T cells, neutrophils, B cells, and macrophages, in various tumor types. Moreover, this study explored the association between ALDH2 and patient survival, examined the methylation patterns of ALDH2 in normal and primary tumor tissues, and delved into genetic variations and mutations of ALDH2 in tumors. The findings suggest that ALDH2 could serve as a valuable prognostic biomarker in pan-cancer, closely linked to the tumor's immune microenvironment.
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Acetaldeído , Aldeído-Desidrogenase Mitocondrial , Neoplasias , Humanos , Aldeído-Desidrogenase Mitocondrial/genética , Aldeído-Desidrogenase Mitocondrial/imunologia , Aldeído-Desidrogenase Mitocondrial/metabolismo , Algoritmos , Biomarcadores , Neoplasias/genética , Prognóstico , Microambiente Tumoral/imunologiaRESUMO
Objective To analyze the correlations between platelet-related parameters and the incidence of anxiety and depression in the patients undergoing peritoneal dialysis(PD),and evaluate the efficacy of the parameters in the diagnosis of anxiety and depression in PD patients. Methods A total of 245 patients undergoing PD in the First Affiliated Hospital of Hebei North University from September 2022 to February 2023 were enrolled.The generalized anxiety scale(GAD-7) and the patient health questionnaire(PHQ-9) were used to evaluate the anxiety and depression of the patients,respectively.The personal information and biochemical indicators of the patients were collected,and the platelet count(PLT),mean platelet volume(MPV),and platelet distribution width(PDW) were measured.Logistic regression was adopted to analyze the relationships of platelet-related parameters with anxiety and depression in PD patients. Results Among the 245 patients undergoing PD,the incidences of anxiety and depression were 15.9% and 38.0%,respectively.There were differences in the dialysis period(Z=-2.358,P=0.018;Z=-3.079,P=0.002),MPV(Z=-4.953,P<0.001;Z=-7.878,P<0.001),and PDW(Z=-4.587,P<0.001;Z=-7.367,P<0.001) between the anxiety group and the non-anxiety group as well as between the depression group and the non-depression group.The correlation analysis showed that MPV(r=0.358,P<0.001;r=0.489,P<0.001) and PDW(r=0.340,P<0.001;r=0.447,P<0.001) were positively correlated with anxiety and depression in the patients undergoing PD.The Logistic regression model showed that MPV(P=0.022,P=0.011),PDW(P=0.041,P=0.018),and dialysis period(P=0.011,P=0.030) were independent risk factors for the anxiety and depressive state in PD patients.The areas under the receiver operating characteristic curve of MPV in the diagnosis of anxiety and depression in PD patients were 0.750 and 0.800,respectively,and those of PDW were 0.732 and 0.780,respectively. Conclusion MPV and PDW have high efficacy in the diagnosis of anxiety and depression associated with PD and can be used as objective indicators to evaluate the anxiety and depression in the patients undergoing PD.
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Ansiedade , Diálise Peritoneal , Humanos , Diálise Peritoneal/efeitos adversos , Hospitais , Modelos Logísticos , Curva ROCRESUMO
Arsenic exposure is a significant risk factor for folate-resistant neural tube defects (NTDs), but the potential mechanism is unclear. In this study, a mouse model of arsenic-induced NTDs was established to investigate how arsenic affects early neurogenesis leading to malformations. The results showed that in utero exposure to arsenic caused a decline in the normal embryos, an elevated embryo resorption, and a higher incidence of malformed embryos. Cranial and spinal deformities were the main malformation phenotypes observed. Meanwhile, arsenic-induced NTDs were accompanied by an oxidant/antioxidant imbalance manifested by elevated levels of reactive oxygen species (ROS) and decreased antioxidant activities. In addition, changes in the expression of autophagy-related genes and proteins (ULK1, Atg5, LC3B, p62) as well as an increase in autophagosomes were observed in arsenic-induced aberrant brain vesicles. Also, the components of the upstream pathway regulating autophagy (AMPK, PKB, mTOR, Raptor) were altered accordingly after arsenic exposure. Collectively, our findings propose a mechanism for arsenic-induced NTDs involving AMPK/PKB-mTORC1-mediated autophagy. Blocking autophagic cell death due to excessive autophagy provides a novel strategy for the prevention of folate-resistant NTDs, especially for arsenic-exposed populations.
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Arsênio , Defeitos do Tubo Neural , Camundongos , Animais , Arsênio/toxicidade , Proteínas Quinases Ativadas por AMP/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Alvo Mecanístico do Complexo 1 de Rapamicina , Antioxidantes , Tubo Neural/metabolismo , Autofagia/fisiologia , Ácido Fólico/efeitos adversos , Defeitos do Tubo Neural/induzido quimicamenteRESUMO
Background: Streptococcus pneumoniae is a common pathogen that colonizes the human upper respiratory tract, causing high morbidity and mortality worldwide. This study aimed to investigate the prevalence status of S. pneumoniae isolated from patients of all ages in Southwest China, including serotype, antibiotic susceptibility and other molecular characteristics, to provide a basis for clinical antibiotic usage and vaccine development. Methods: This study was conducted from January 2018 to March 2022 at West China Hospital, West China Second University Hospital, First People's Hospital of Longquanyi District (West China Longquan Hospital), Meishan Women and Children's Hospital (Alliance Hospital of West China Second University Hospital) and Chengdu Jinjiang Hospital for Women and Children Health. Demographic and clinical characteristics of 263 pneumococcal disease (PD) all-age patients were collected and analyzed. The serotypes, sequence types (STs), and antibiotic resistance of the strains were determined by next-generation sequencing, sequence analysis and the microdilution broth method. Results: The most common pneumococcal serotypes were 19F (17.87%), 19A (11.41%), 3 (8.75%), 23F (6.46%) and 6A (5.70%). Coverage rates for PCV10, PCV13, PCV15, PCV20 and PCV24 were 36.12, 61.98, 61.98, 63.12 and 64.26%, respectively. Prevalent STs were ST271 (12.55%), ST320 (11.79%), ST90 (4.18%), ST876 (4.18%) and ST11972 (3.42%). Penicillin-resistant S. pneumoniae (PRSP) accounted for 82.35 and 1.22% of meningitis and nonmeningitis PD cases, respectively. Resistance genes msrD (32.7%), mefA (32.7%), ermB (95.8%), tetM (97.3%) and catTC (7.6%) were found among 263 isolates. Most isolates showed high resistance to erythromycin (96.96%) and tetracycline (79.85%), with more than half being resistant to SXT (58.94%). A few isolates were resistant to AMX (9.89%), CTX (11.03%), MEN (9.13%), OFX (1.14%), LVX (1.14%) and MXF (0.38%). All isolates were susceptible to vancomycin and linezolid. Conclusion: Our study provides reliable information, including the prevalence, molecular characterization and antimicrobial resistance of S. pneumoniae isolates causing pneumococcal diseases in Southwest China. The findings contribute to informed and clinical policy decisions for prevention and treatment.
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Esophageal squamous cell carcinoma (ESCC) is one of the most lethal malignancies in the world with poor prognosis. Despite the promising applications of immunotherapy, the objective response rate is still unsatisfactory. We have previously shown that Hippo/YAP signaling acts as a powerful tumor promoter in ESCC. However, whether Hippo/YAP signaling is involved in tumor immune escape in ESCC remains largely unknown. Here, we show that YAP directly activates transcription of the "don't eat me" signal CD24, and plays a crucial role in driving tumor cells to avoid phagocytosis by macrophages. Mechanistically, YAP regulates CD24 expression by interacting with TEAD and binding the CD24 promoter to initiate transcription, which facilitates tumor cell escape from macrophage-mediated immune attack. Our animal model data and clinical data show that YAP combined with CD24 in tumor microenvironment redefines the impact of TAMs on the prognosis of ESCC patients which will provide a valuable basis for precision medicine. Moreover, treatment with YAP inhibitor altered the distribution of macrophages and suppressed tumorigenesis and progression of ESCC in vivo. Together, our study provides a novel link between Hippo/YAP signaling and macrophage-mediated immune escape, which suggests that the Hippo-YAP-CD24 axis may act as a promising target to improve the prognosis of ESCC patients. A proposed model for the regulatory mechanism of Hippo-YAP-CD24-signaling axis in the tumor-associated macrophages mediated immune escape.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Animais , Humanos , Transdução de Sinais/fisiologia , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Neoplasias Esofágicas/genética , Evasão da Resposta Imune , Proteínas de Sinalização YAP , Macrófagos/metabolismo , Fagocitose , Linhagem Celular Tumoral , Microambiente Tumoral , Antígeno CD24RESUMO
Iron oxide nanoparticles (Fe3O4 NPs) have attracted great attention due to their extensive applications, which warranted their environmental concerns. Although recent advances have proposed the relevance of Fe3O4 NPs to cardiovascular disease, the intrinsic mechanisms underlying the effects of NPs remain indistinct. ApoE-/- mice were chosen as a long-term exposure model to explore the immanent association between respiratory exposure to Fe3O4 NPs and the development of cardiovascular diseases. Pulmonary exposure to 20 nm and 200 nm Fe3O4 NPS resulted in significant lung injury, and pulmonary histopathological examination displayed inflammatory cell infiltration, septal thickening and alveolar congestion. Intriguingly, liver iron deposition and variations in the hepatic lipid homeostasis were found in Fe3O4 NPs-exposed mice, eventually leading to dyslipidemia, hinting the potential cardiovascular toxicity of Fe3O4 NPs. In addition, we not only found that Fe3O4 NPs exposure increased aortic plaque area, but also increased M1 macrophages in the plaque, which yielding plaque vulnerability in ApoE-/- mice Of note, 20 nm Fe3O4 NPs showed enhanced capability on the progression of atherosclerosis than 200 nm Fe3O4 NPs. This study may propose the potential mechanism for adverse cardiovascular disease induced by Fe3O4 NPs and provide convincing evidence for the safety evaluation of Fe3O4 NPs.
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Doenças Cardiovasculares , Nanopartículas , Placa Aterosclerótica , Camundongos , Animais , Ferro/toxicidade , Doenças Cardiovasculares/patologia , Nanopartículas/toxicidade , Placa Aterosclerótica/patologia , Fígado , Apolipoproteínas E/genética , Homeostase , Nanopartículas Magnéticas de Óxido de FerroRESUMO
BACKGROUND: Toxoplasma gondii (T. gondii) is increasingly considered a risk factor for neurodegenerative diseases. However, there is only limited information on the development of drugs for T. gondii infection. Lentinan from Lentinula edodes is a bioactive ingredient with the potential to enhance anti-infective immunity. The present study aimed to investigate the neuroprotective effect of lentinan on T. gondii-associated cognitive deficits in mice. METHODS: A chronic T. gondii infection mouse model was established by administering 10 cysts of T. gondii by gavage. Lentinan was intraperitoneally administered 2 weeks before infection. Behavioral tests, RNA sequencing, immunofluorescence, transmission electron microscopy and Golgi-Cox staining were performed to assess the effect of lentinan on cognitive deficits and neuropathology in vivo. In vitro, the direct and indirect effects of lentinan on the proliferation of T. gondii tachyzoites were evaluated in the absence and presence of BV-2 cells, respectively. RESULTS: Lentinan prevented T. gondii-induced cognitive deficits and altered the transcriptome profile of genes related to neuroinflammation, microglial activation, synaptic function, neural development and cognitive behavior in the hippocampus of infected mice. Moreover, lentinan reduced the infection-induced accumulation of microglia and downregulated the mRNA expression of proinflammatory cytokines. In addition, the neurite and synaptic ultrastructural damage in the hippocampal CA1 region due to infection was ameliorated by lentinan administration. Lentinan decreased the cyst burden in the brains of infected mice, which was correlated with behavioral performance. In line with this finding, lentinan could significantly inhibit the proliferation of T. gondii tachyzoites in the microglial cell line BV2, although lentinan had no direct inhibitory effect on parasite growth. CONCLUSIONS: Lentinan prevents cognitive deficits via the improvement of neurite impairment and synaptic loss induced by T. gondii infection, which may be associated with decreased cyst burden in the brain. Overall, our findings indicate that lentinan can ameliorate T. gondii-related neurodegenerative diseases.
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Doenças Neurodegenerativas , Toxoplasma , Toxoplasmose , Animais , Camundongos , Lentinano/metabolismo , Lentinano/farmacologia , Toxoplasmose/metabolismo , Encéfalo/patologia , Toxoplasma/genética , Doenças Neurodegenerativas/patologia , CogniçãoRESUMO
Purpose: This study was designed to evaluate the immune protective efficacy of the novel Streptococcus pneumoniae (S. pneumoniae) protein vaccine PiuA-PlyD4 through immunoinformatics prediction and in vitro and in vivo experiments. Methods: In this study, we conducted immunoinformatics prediction and protection analysis on the fusion protein PiuA-PlyD4. The epitope composition of the vaccine was analyzed based on the prediction of B-cell and helper T-cell epitopes. Meanwhile, the molecular docking of PiuA and TLR2/4 was simulated. After immunizing C57BL/6 mice with the prepared vaccine, the biological safety, immunogenicity and conservation were evaluated. By constructing different infection models and from the aspects of adhesion inhibition and cytokines, the protective effect of the fusion protein vaccine PiuA-PlyD4 on S. pneumoniae infection was explored. Results: PiuA-PlyD4 has abundant B-cell and helper T-cell epitopes and shows a high antigenicity score and structural stability. Molecular docking analysis suggested the potential interaction between PiuA and TLR2/4. The specific antibody titer of fusion protein antiserum was as high as (7.81±2.32) ×105. The protective effect of the immunized mice on nasal and lung colonization was significantly better than that of the control group, and the survival rate against S. pneumoniae infection of serotype 3 reached 50%. Cytokine detection showed that the humoral immune response, Th1, Th2 and Th17 cellular immune pathways were all involved in the process. Conclusion: The study indicates that PiuA-PlyD4, whether the results are predicted by immunoinformatics or experimentally validated in vivo and in vitro, has good immunogenicity and immunoreactivity and can provide effective protection against S. pneumoniae infection. Therefore, it can be considered a promising prophylactic vaccine candidate for S. pneumoniae.
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Infecções Pneumocócicas , Vacinas , Animais , Camundongos , Streptococcus pneumoniae , Infecções Pneumocócicas/prevenção & controle , Epitopos de Linfócito T , Imunoinformática , Simulação de Acoplamento Molecular , Receptor 2 Toll-Like , Camundongos Endogâmicos C57BL , Citocinas , Epitopos de Linfócito BRESUMO
The pilus is an extracellular structural part that can be detected in some Streptococcus pneumoniae (S. pneumoniae) isolates (type I pili are found in approximately 30% of strains, while type II pili are found in approximately 20%). It is anchored to the cell wall by LPXTG-like motifs on the peptidoglycan. Two kinds of pili have been discovered, namely, pilus-1 and pilus-2. The former is encoded by pilus islet 1 (PI-1) and is a polymer formed by the protein subunits RrgA, RrgB and RrgC. The latter is encoded by pilus islet 2 (PI-2) and is a polymer composed mainly of the structural protein PitB. Although pili are not necessary for the survival of S. pneumoniae, they serve as the structural basis and as virulence factors that mediate the adhesion of bacteria to host cells and play a direct role in promoting the adhesion, colonization and pathogenesis of S. pneumoniae. In addition, as candidate antigens for protein vaccines, pili have promising potential for use in vaccines with combined immunization strategies. Given the current understanding of the pili of S. pneumoniae regarding the genes, proteins, structure, biological function and epidemiological relationship with serotypes, combined with the immunoprotective efficacy of pilins as protein candidates for vaccines, we here systematically describe the research status and prospects of S. pneumoniae pili and provide new ideas for subsequent vaccine research and development.
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Proteínas de Bactérias , Vacinas , Proteínas de Bactérias/metabolismo , Streptococcus pneumoniae , Fímbrias Bacterianas/metabolismo , Proteínas de Fímbrias/genética , Proteínas de Fímbrias/metabolismo , Polímeros/metabolismoRESUMO
BACKGROUND: Isovaleric acidemia (IVA) is a rare autosomal-recessive metabolic disorder caused by a genetic deficiency of isovaleryl-CoA dehydrogenase (IVD). Deficiency of IVD leads to the accumulation of organic acids; however, the genotype-phenotype relationship has not been well established. METHODS: Two brothers with acute neonatal IVA in a Chinese family were reported, and their clinical manifestations and examination were described. MS/MS and GCMS were used to perform organic acid analysis of blood samples and urine samples, and the patient's blood was sequenced by NGS and Sanger sequencing of the ivd gene. RESULTS: Sequence analysis of the ivd gene identified compound heterozygous mutations in the patient, the c.250T>C (p.W84R) missense mutation (novel) and the c.466-3_466-2 delCAinsGG splicing mutation, which were inherited from their parents. Various bioinformatics prediction algorithms suggest that the p.W84R missense mutation may destabilize the IVD monomer and reduce its ability to bind to substrates. CONCLUSIONS: Both the clinical and genetic features of this family will help us to further expand the knowledge of IVA.
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População do Leste Asiático , Isovaleril-CoA Desidrogenase , Humanos , Recém-Nascido , Masculino , Isovaleril-CoA Desidrogenase/genética , Mutação , Espectrometria de Massas em TandemRESUMO
BACKGROUND: Human papillomavirus (HPV) 33 belongs to the Alphapapillomavirus 9 (α-9 HPV) species group, which also contains types 16, 31, 35, 52, 58 and 67. The purpose of this study was to investigate the genetic variations of HPV33 and to explore its carcinogenicity among women in Taizhou, Southeast China. METHODS: Exfoliated cervical cells were collected for HPV genotyping. Only single HPV33 infection cases were selected, and their E6 and E7 genes were sequenced using the ABI 3730xl sequencer and then analysed using MEGA X. RESULTS: From 2014 to 2020, a total of 185 single HPV33-positive specimens were successfully amplified. We obtained 15 distinct HPV33 E6/E7 variants, which were published in GenBank under accession numbers OQ672665-OQ672679. Phylogenetic analysis revealed that all HPV33 E6/E7 variants belonged to lineage A, of which 75.7% belonged to lineage A1. Compared with CIN1, the proportion of sublineage A1 in CIN2/3 was higher, but there was no significant difference (76.5% vs. 80.6%, P > 0.05). Altogether, 20 single nucleotide substitutions were identified, of which 6 were novel substitutions, including T196G (C30G), A447T, G458T (R117L), G531A, A704A, and C740T. In addition, no significant trends were observed between the nucleotide substitutions of HPV33 E6/E7 variants and the risk of cervical lesions. CONCLUSION: This study provides the most comprehensive data on genetic variations, phylogenetics and carcinogenicity of HPV33 E6/E7 variants in Southeast China to date. The data confirmed that cervical lesions among women in Taizhou are attributable to HPV33, which may be due to the high infection rate of sublineage A1 in the population.
Assuntos
Proteínas Oncogênicas Virais , Infecções por Papillomavirus , Neoplasias do Colo do Útero , Feminino , Humanos , Neoplasias do Colo do Útero/epidemiologia , Filogenia , Infecções por Papillomavirus/epidemiologia , Papillomaviridae/genética , Variação Genética , Nucleotídeos , China/epidemiologia , Proteínas Oncogênicas Virais/genética , Proteínas E7 de Papillomavirus/genéticaRESUMO
The efficient hydrodeoxygenation (HDO) of biomass derivatives to yield specific products is a significant yet challenging task. In the present study, a Cu/CoOx catalyst was synthesized using a facile co-precipitation method, and subsequently used for the HDO of biomass derivatives. Under optimal reaction conditions, the conversion of 5-hydroxymethylfurfural reached 100% with a selectivity of â¼99% to 2,5-diformylfuran. In combination with the experimental results, systematic characterizations revealed that CoOx, as the acid site, tended to adsorb CO bonds, and the metal sites of Cu+ were inclined to adsorb CO bonds and enhance CO bond hydrogenation. Meanwhile, Cu0 was the main active site for 2-propanol dehydrogenation. The excellent catalytic performance could be attributed to the synergistic effects of Cu and CoOx. Further, by optimizing the ratio of Cu to CoOx, the Cu/CoOx catalysts exhibited notable performance in HDO of acetophenone, levulinic acid, and furfural, which verified the universality of the catalysts in the HDO of biomass derivatives.