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SARS-CoV-2 ancestral strain-induced immune imprinting poses great challenges to updating vaccines for new variants. Studies showed that repeated Omicron exposures could override immune imprinting induced by inactivated vaccines but not mRNA vaccines, a disparity yet to be understood. Here, we analyzed the immune imprinting alleviation in inactivated vaccine (CoronaVac) cohorts after a long-term period following breakthrough infections (BTI). We observed in CoronaVac-vaccinated individuals who experienced BA.5/BF.7 BTI, the proportion of Omicron-specific memory B cells (MBCs) substantially increased after an extended period post-Omicron BTI, with their antibodies displaying enhanced somatic hypermutation and neutralizing potency. Consequently, the neutralizing antibody epitope distribution encoded by MBCs post-BA.5/BF.7 BTI after prolonged maturation closely mirrors that in BA.5/BF.7-infected unvaccinated individuals. Together, these results indicate the activation and expansion of Omicron-specific naïve B cells generated by first-time Omicron exposure helped to alleviate CoronaVac-induced immune imprinting, and the absence of this process should have caused the persistent immune imprinting seen in mRNA vaccine recipients.
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Severe fever with thrombocytopenia syndrome (SFTS) is a highly fatal disease. Droplet digital polymerase chain reaction (ddPCR) presents unparalleled sensitivity and enables absolute quantification of viral load. In this prospective study, we enrolled 111 patients with SFTS and collected 259 continuous samples. Our findings unveil a robust reverse transcription (RT)-ddPCR method for SFTS with a limit of detection of 2.46 copies/µL (95% CI, 1.50-11.05), surpassing the sensitivity of RT-quantitative polymerase chain reaction at 103.29 copies/µL (95% CI, 79.69-216.35). Longitudinal cohort analysis revealed significantly higher RT-ddPCR detection rates at days 10 to 11, 13 to 14, and ≥15 of the disease course as compared with RT-quantitative polymerase chain reaction (P < .05). Positive RT-ddPCR results were associated with declined platelet and elevated aspartate aminotransferase and lactate dehydrogenase on the same day vs negative RT-ddPCR samples. RT-ddPCR exhibits commendable diagnostic efficacy in SFTS, and it remains detectable in blood samples from patients with an extended disease course. Furthermore, RT-ddPCR correlates with clinical laboratory tests, furnishing valuable reference data for clinical diagnosis.
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OBJECTIVE: To investigate the correlation between glucose and lipid metabolism, renal function, and retinopathy in patients with diabetic retinopathy (DR) based on optical coherence tomography angiography (OCTA). METHODS: A total of 584 diabetic patients who underwent treatment at The Second Affiliated Hospital of Dalian Medical University from March 2022 to June 2023 were retrospectively selected as research participants. They were categorized into a NDR group (n=366) and a DR group (n=218) based on the presence or absence of DR. Relevant indexes of glucose and lipid metabolism, renal function, and OCTA findings were collected. Logistic regression analysis was applied to identify the influencing factors of diabetes mellitus complicated with DR. ROC curves were drawn to examine the diagnostic value of the screened influencing factors for diabetes mellitus complicated with DR. Finally, Spearman correlation coefficients were calculated to examine the relevance between influencing factors and the severity of DR Lesions. RESULTS: Logistic regression showed that high levels of angiography 3 × 3 inner vascular density (IVD_33) and angiography 3 × 3 inner perfusion density (IPD_33) were protective factors for diabetes mellitus complicated with DR, and diabetic peridiabetic vascular disease (DPVD), elevated blood urea nitrogen (BUN), and urea levels were risk factors for diabetes mellitus complicated with DR (all P<0.05). ROC curve displayed that the areas under the curve (AUC) of IVD_33, DPVD, BUN, IPD_33, and Urea in predicting diabetes mellitus with DR were 0.779, 0.705, 0.621, 0.723, and 0.632, respectively. The AUC of combined prediction with OCTA index was higher than that of combined prediction without OCTA index (0.781 VS 0.84, P<0.05). Spearman correlation coefficient displayed that IVD_33 and IPD_33 were negatively correlated with the severity of DR, whereas DPVD and Urea showed a positive correlation (P<0.05). CONCLUSION: Our findings provide valuable insights for the initial clinical assessment of diabetic patients with DR and aid in the early determination of DR severity. Corresponding intervention measures should be formulated as early as possible to remedy patients' outcomes.
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As a widely used brominated flame retardant, the widespread presence of decabromodiphenyl ether (BDE-209) in the natural environment and the toxicity risks it poses are well established, but the recoverability of BDE-209-induced individual injuries remains unknown. Therefore, a 7-day depuration experiment following a 4-day exposure of zebrafish to BDE-209 was conducted to confirm the recoverability and its mode of action. Oxidative stress after depuration was significantly reduced compared with BDE-209 exposure as indicated by the decreased expression level of oxidative stress-related genes and the reduced MDA, Gpx, and GST in zebrafish, indicating a gradual recovery of antioxidant activity. However, BDE-209 inhibition of extracellular matrix (ECM) proteins worsened after depuration. Mechanistically, BDE-209 mediated ECM production and secretion by down-regulating integrin expression. Furthermore, BDE-209 inhibition of collagen synthesis worsened after depuration. Biochemical assays and histopathological observations revealed a same result in zebrafish. Mechanistically, lysine hydroxylation is inhibited thereby affecting collagen synthesis. Interestingly, zebrafish showed arrhythmia after depuration compared to BDE-209 exposure, and abnormal changes in ATPase levels indicated that disturbances in Ca2+ homeostasis contributed to arrhythmia. Collectively, BDE-209-induced interference with ECM production and collagen synthesis persisted after depuration, which will provide new insights for understanding the recovery patterns of individuals under BDE-209 stress.
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Tissues undergo distinct morphogenetic processes to achieve similarly shaped structures. In the heart, cardiomyocytes in both the ventricle and atrium build internal structures for efficient contraction. Ventricular wall formation (trabeculation) is initiated by cardiomyocyte delamination. How cardiomyocytes build the atrial wall is poorly understood. Using longitudinal imaging in zebrafish, we found that at least 25% of the atrial cardiomyocytes elongate along the long axis of the heart. These cell shape changes result in cell intercalation and convergent thickening, leading to the formation of the internal muscle network. We tested factors important for ventricular trabeculation including Nrg/ErbB and Notch signaling and found no evidence for their role in atrial muscle network formation. Instead, our data suggest that atrial cardiomyocyte elongation is regulated by Yap, which has not been implicated in trabeculation. Altogether, these data indicate that distinct cellular and molecular mechanisms build the internal muscle structures in the atrium and ventricle.
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Átrios do Coração , Ventrículos do Coração , Miócitos Cardíacos , Proteínas de Peixe-Zebra , Peixe-Zebra , Animais , Átrios do Coração/metabolismo , Átrios do Coração/citologia , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/citologia , Ventrículos do Coração/metabolismo , Ventrículos do Coração/citologia , Proteínas de Peixe-Zebra/metabolismo , Proteínas de Peixe-Zebra/genética , Transdução de Sinais , Forma Celular , Animais Geneticamente Modificados , Regulação da Expressão Gênica no Desenvolvimento , Morfogênese , Receptores Notch/metabolismoRESUMO
PURPOSE: The objective of this study was to evaluate the diagnostic value of transvaginal contrastenhanced ultrasound (CEUS) in differentiating benign from malignant endometrial lesions and assessing the extent of myometrial invasion. METHODS: A total of 70 patients who underwent surgery for endometrial lesions at the authors' hospital were selected. Transvaginal ultrasound examination and CEUS were performed for quantitative and qualitative analysis. Based on the CEUS results, an International Federation of Gynecology and Obstetrics (FIGO) disease grade was assigned and compared with pathological findings. RESULTS: Postmenopausal vaginal bleeding is a key clinical manifestation of endometrial carcinoma. Among the patients with endometrial carcinoma, compared with normal myometrium, the lesion areas exhibited a greater rate of rise (defined as enhanced intensity divided by enhancement time) and a shorter half-clearance time (P<0.05). These findings suggest that in endometrial carcinoma, the contrast agent displays a "fast-in/fast-out/hyperenhancement" perfusion pattern. In contrast, the characteristic perfusion pattern for benign endometrial lesions is low enhancement (P<0.05). The diagnostic accuracy of CEUS in detecting myometrial invasion was 88% (22 of 25 cases). CONCLUSION: Transvaginal CEUS is a practical and effective diagnostic imaging method for distinguishing between benign and malignant endometrial lesions. It can also be used to evaluate the depth of myometrial invasion in patients with early-stage endometrial carcinoma.
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A simple and efficient method to access 4-selenyl-isocoumarin derivatives through visible-light-promoted selenylation/cyclization of o-(1-alkynyl) benzoates has been developed. This transformation is performed under mild conditions and has the advantages of functional group tolerance and broad substrate scope.
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A series of organoselenium compounds based on the hybridization of artesunate (ART) scaffolds and Se functionalities (-SeCN and -SeCF3) were synthesized. The redox properties of artesunate-SeCN and artesunate-SeCF3 derivatives were conducted by 2, 2-didiphenyl-1-picrylhydrazyl (DPPH), and the results showed that compounds 2c, 2f and 3e have a good free radical scavenging activity. Their cytotoxicity was evaluated against four types of cancer cell lines, SW480 (human colon adenocarcinoma cells), HCT116 (human colorectal adenocarcinoma cells), HepG2 (human hepatocellular carcinoma cells), MCF-7 (human breast cancer cells). The MTT results showed that compared with ART and 5-FU, compound 2c exhibited potent in vitro antiproliferative activity in SW480, HCT116, and MCF-7 cancer cell lines, and was thus chose for further antitumor mechanism investigation. The antitumor mechanism study revealed that compound 2c induced ferroptosis in HCT116 cells by inhibiting the expression of GPX4 protein, accompanying by the up-regulation of intracellular ROS levels. Mitochondria in HCT116 cells exhibit depolarization of mitochondrial membrane potential (MMP) and ultrastructural changes in morphology, which indicated that 2c resulted in mitochondrial dysfunction and ferroptosis. Moreover, 2c could increase the levels of lipid peroxidation and ferrous ion, which further confirm that compound 2c may exert its antitumor effect through ferroptosis. Overall, these results suggest that the artesunate-Se candidates could provide promising new lead derivatives for further potential anticancer drug development.
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Antineoplásicos , Artesunato , Proliferação de Células , Desenho de Fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Ferroptose , Fosfolipídeo Hidroperóxido Glutationa Peroxidase , Humanos , Artesunato/farmacologia , Artesunato/síntese química , Artesunato/química , Antineoplásicos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Ferroptose/efeitos dos fármacos , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/antagonistas & inibidores , Proliferação de Células/efeitos dos fármacos , Relação Estrutura-Atividade , Estrutura Molecular , Relação Dose-Resposta a Droga , Linhagem Celular Tumoral , Espécies Reativas de Oxigênio/metabolismo , Compostos Organosselênicos/farmacologia , Compostos Organosselênicos/química , Compostos Organosselênicos/síntese químicaRESUMO
BACKGROUND: Systemic contact dermatitis (SCD) is an allergic inflammatory skin disease. We report that 3 family members developed SCD after exposing to laundry detergent containing benzalkonium chloride, which is rare. SCD caused by benzalkonium chloride has been reported. However, Similar symptoms in the whole family caused by it have not been reported yet. In our case, a 36-year-old man was diagnosed as SCD, and his symptoms had not controlled after 7 days treatment, until he stopped dressing the clothes washed by the laundry detergent containing benzalkonium chloride. It was interesting that both his wife and the daughter developed SCD successively, and they have not exposed to any haptens besides the benzalkonium chloride in the laundry detergent. METHODS: Dermoscopic examination showed bright-red background, focal branching vessels and white scales. HE staining from the lesion revealed hyperkeratosis and parakeratosis, focal subcorneal microabscess, ocal hyperkeratosis, koilocyte in the epidermis, and erythrocyte extravasation, fibroplasia, hyaline degeneration and scattered aggregates of lymphocytes in the dermis. Then path test was performed 1 month after recovery with benzalkonium chloride 0.05% and 0.1% in petrolatum. RESULTS: Stop the laundry detergent containing benzalkonium chloride. The symptoms had controlled after they stopped the laundry detergent containing benzalkonium chloride. CONCLUSION: The case highlights that benzalkonium chloride with very low concentration and repeated exposure may be an active agent of SCD. It is of the utmost importance to pay close attention to patients presenting with similar symptoms within the family. A thorough examination of the medical history is essential to determine the underlying cause.
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Compostos de Benzalcônio , Detergentes , Humanos , Masculino , Adulto , Compostos de Benzalcônio/efeitos adversos , Detergentes/efeitos adversos , Feminino , Dermatite Alérgica de Contato/diagnóstico , Dermatite Alérgica de Contato/etiologiaRESUMO
BACKGROUND: FMS-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) is a common mutation type in acute myeloid leukemia (AML) and is usually associated with poor patient prognosis. With advancements in molecular diagnostics and the development of tyrosine kinase inhibitors (TKI), the overall survival (OS) of AML patients with FLT3-ITD mutations has been prolonged to some extent, but relapse and drug resistance are still substantial challenges. Ningetinib is a novel TKI against various kinases in relation to tumour pathogenesis and is undergoing clinical trials of lung cancer. In this study, we explored the antitumor activity of ningetinib against AML with FLT3 mutations both in vivo and in vitro. METHODS: Cell proliferation assays were performed in AML cell lines and Ba/F3 cells expressing various FLT3 mutations to validate the antileukemic activity of ningetinib in vitro. Immunoblot assays were used to verify the effect of ningetinib on the FLT3 protein and downstream pathways. Molecular docking and CETSA were used to validate the interaction of ningetinib with target proteins. The survival benefit of ningetinib in vivo was assessed in Ba/F3-FLT3-ITD-, MOLM13, Ba/F3-FLT3-ITD-F691L-, MOLM13-FLT3-ITD-F691L-induced leukemia mouse models. We also used patient-derived primary cells to determine the efficacy of ningetinib. RESULTS: Ningetinib inhibited cell proliferation, blocked the cell cycle, induced apoptosis and bound FLT3 to inhibit its downstream signaling pathways, including the STAT5, AKT and ERK pathways, in FLT3-ITD AML cell lines. In the mouse models with FLT3-ITD and FLT3-ITD-F691L mutation, ningetinib showed superior anti-leukemia activity to existing clinical drugs gilteritinib and quizartinib, significantly prolongating the survival of mice. In addition, ningetinib exhibited activity against patient-derived primary cells harboring FLT3-ITD mutations. CONCLUSION: Overall, our study confirmed the therapeutic role of ningetinib in AML with FLT3-ITD mutations, providing a potential new option for clinically resistant patients.
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Proliferação de Células , Resistencia a Medicamentos Antineoplásicos , Leucemia Mieloide Aguda , Inibidores de Proteínas Quinases , Tirosina Quinase 3 Semelhante a fms , Tirosina Quinase 3 Semelhante a fms/antagonistas & inibidores , Tirosina Quinase 3 Semelhante a fms/genética , Tirosina Quinase 3 Semelhante a fms/metabolismo , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patologia , Humanos , Animais , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Linhagem Celular Tumoral , Inibidores de Proteínas Quinases/farmacologia , Proliferação de Células/efeitos dos fármacos , Camundongos , Ensaios Antitumorais Modelo de Xenoenxerto , Apoptose/efeitos dos fármacos , Mutação , Transdução de Sinais/efeitos dos fármacosRESUMO
Direct construction of gem-difluorinated heterocycles represents a long-standing challenge in organic chemistry. Herein, we developed a transition-metal-free photocatalytic radical addition/cyclization of BrCF2COR with 2-cyanoaryl acrylamides to give gem-difluorinated naphthyridinone scaffolds in moderate to good yields. Furthermore, some natural products were found to be suitable in the reaction system. The easily available substrates, mild reaction conditions, simple operation, and wide functionality tolerance show practical and environmental advantages in this method.
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BACKGROUND: Transurethral holmium laser enucleation of the prostate (HoLEP) has a good therapeutic effect on benign prostatic hyperplasia (BPH). The purpose of this study was to investigate the clinical efficacy of HoLEP in the treatment of high-risk elderly patients with BPH and assess its impact on the inflammatory response, vascular endothelial function and quality of life (QoL). METHODS: Patients at high risk of BPH who were hospitalised in Chengde Central Hospital from February 2021 to December 2022 were retrospectively selected as the study objects, and a total of 100 cases were included. The control group underwent transurethral resection of the prostate, and the observation group underwent HoLEP. Perioperative indexes, urodynamic indexes, QoL 6 months after surgery and incidence of postoperative complications were compared between the two groups. Moreover, serum levels of inflammatory factors and vascular endothelial factors were detected in two groups. RESULTS: We found no significant difference in general data between the two groups of patients (p > 0.05). The operation time, perioperative bleeding, bladder flushing time and hospitalisation time of the observation group were significantly shorter than those of the control group (p < 0.05). On the 7th day after surgery, the serum levels of tumour necrosis factor alpha, interleukin-1ß, interleukin-6, vascular endothelial growth factor, basic fibroblast growth factor and endothelin-1 in the observation group were significantly lower than those in the control group (p < 0.05). Six months after surgery, the maximal urinary flow rate and QoL scores of the patients in the observation group were significantly higher than those of the control group (p < 0.05), and the residual urine volume and International Prostate Symptom Score of observation group were significantly lower than those of the control group (p < 0.05). The incidence of postoperative complications in the observation group was significantly lower than that in the control group (χ2 = 7.440, p = 0.006). CONCLUSIONS: HoLEP can effectively remove hyperplasia of the prostate and reduce the inflammatory response in the patient's body when treating BPH in high-risk elderly patients. It can also regulate the levels of vascular endothelial factors and effectively improve the patient's QoL.
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Lasers de Estado Sólido , Hiperplasia Prostática , Qualidade de Vida , Ressecção Transuretral da Próstata , Humanos , Masculino , Hiperplasia Prostática/cirurgia , Idoso , Ressecção Transuretral da Próstata/métodos , Estudos Retrospectivos , Lasers de Estado Sólido/uso terapêutico , Resultado do Tratamento , Medição de Risco , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Terapia a Laser/métodos , Idoso de 80 Anos ou maisRESUMO
Cervical cancer is one of the most common malignant tumours. Human papillomavirus (HPV) infection is the main cause of this cancer so that it could be prevented by screening and early treatment. Developing reginal screen protocols of maximum public health efficacy requires in-depth understandings of local HPV distribution and consequential cancer risks. Therefore, test results of HPV genotyping, cytology testing (TCT) and colposcopy inspection with biopsy were collected in this retrospective research. Data included by this research involved 63,906 women received screen related tests from Shenzhen Baoan Shiyan People's Hospital and the subsidiary institutes between 2017.01 and 2023.05. 10,238 colposcopies were performed in this period collecting 8,716 samples and 814 high-grade CIN were discovered. Within the 763 high-grade CIN cases with both TCT and HPV testing results, 232 were tested cytologically normal but only 30 were negative in HPV test. Besides, the rates of high-grade CIN observed in coinfection were all lower than the estimated rates generated from related single infection. HPV 52, 58 and 16 were found to be the most common types in Baoan, Shenzhen. The result also suggested that HPV coinfections should not increase risk for cervical cancers.
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Coinfecção , Genótipo , Papillomaviridae , Infecções por Papillomavirus , Neoplasias do Colo do Útero , Humanos , Feminino , Infecções por Papillomavirus/virologia , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/complicações , Neoplasias do Colo do Útero/virologia , Neoplasias do Colo do Útero/epidemiologia , China/epidemiologia , Coinfecção/virologia , Coinfecção/epidemiologia , Adulto , Estudos Retrospectivos , Papillomaviridae/genética , Papillomaviridae/isolamento & purificação , Papillomaviridae/classificação , Pessoa de Meia-Idade , Adulto Jovem , Displasia do Colo do Útero/virologia , Displasia do Colo do Útero/epidemiologia , Colposcopia , Detecção Precoce de Câncer , IdosoRESUMO
The cardiac extracellular matrix (cECM) is fundamental for organ morphogenesis and maturation, during which time it undergoes remodeling, yet little is known about whether mechanical forces generated by the heartbeat regulate this remodeling process. Using zebrafish as a model and focusing on stages when cardiac valves and trabeculae form, we found that altering cardiac contraction impairs cECM remodeling. Longitudinal volumetric quantifications in wild-type animals revealed region-specific dynamics: cECM volume decreases in the atrium but not in the ventricle or atrioventricular canal. Reducing cardiac contraction resulted in opposite effects on the ventricular and atrial ECM, whereas increasing the heart rate affected the ventricular ECM but had no effect on the atrial ECM, together indicating that mechanical forces regulate the cECM in a chamber-specific manner. Among the ECM remodelers highly expressed during cardiac morphogenesis, we found one that was upregulated in non-contractile hearts, namely tissue inhibitor of matrix metalloproteinase 2 (timp2). Loss- and gain-of-function analyses of timp2 revealed its crucial role in cECM remodeling. Altogether, our results indicate that mechanical forces control cECM remodeling in part through timp2 downregulation.
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Matriz Extracelular , Coração , Inibidor Tecidual de Metaloproteinase-2 , Peixe-Zebra , Animais , Peixe-Zebra/embriologia , Peixe-Zebra/metabolismo , Matriz Extracelular/metabolismo , Inibidor Tecidual de Metaloproteinase-2/metabolismo , Inibidor Tecidual de Metaloproteinase-2/genética , Coração/embriologia , Proteínas de Peixe-Zebra/metabolismo , Proteínas de Peixe-Zebra/genética , Contração Miocárdica/fisiologia , Miocárdio/metabolismo , Morfogênese , Átrios do Coração/embriologia , Átrios do Coração/metabolismo , Fenômenos Biomecânicos , Regulação da Expressão Gênica no Desenvolvimento , Ventrículos do Coração/metabolismo , Ventrículos do Coração/embriologiaRESUMO
Understanding the photoluminescence mechanisms of carbon dots (C-dots) is of importance for both fundamental science and their corresponding applications. In this study, we verify the emitting-unit model of C-dots by an upgraded "contrastive analysis" research paradigm. Employing preparative thin-layer chromatography, we recently developed polyamide column chromatography separation techniques, and four kinds of highly correlative C-dots are obtained from a homologous sample made from ortho-aminophenol precursors. Combining comprehensive experimental characterizations, especially the direct evidence from electrospray ionization mass spectrometry, we demonstrate that the photoluminescence of the four C-dots comes from the same polycyclic aromatic hydrocarbon units (named as emitting units) indeed, although these C-dots have substantially different chemical compositions.
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BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease known for its high mortality rate and its correlation with Cytokine Storms (CS). Timely detection of CS is crucial for improving the prognosis of the disease. The objective of this investigation was to develop a model for identifying cytokine storms in the acute phase of SFTS. METHODS: A total of 245 patients diagnosed with SFTS were included in this study between January 2020 and July 2022. Among them, 184 patients were part of the training set, while 61 patients were part of the validation set. Variables identified by LASSO were subsequently included in a multivariate logistic regression analysis to determine independent predictors. Subsequently, a nomogram was then developed to predict the likelihood of CS in SFTS patients. The predictive efficacy and clinical applicability of the nomogram model were further assessed through ROC analysis and the DCA curve. RESULTS: Following LASSO analysis, a total of 11 indicators were included in multivariate logistic regression analysis. The findings indicated that PLT (OR 0.865, P < 0.001), LDH (OR 1.002, P < 0.001), Na+ (OR 1.155, P = 0.005), and ALT (OR 1.019, P < 0.001) serve as independently predictors of CS in the acute phase of SFTS. Furthermore, a nomogram named the PLNA was constructed by integrating these four factors. The PLNA model exhibited favorable predictive accuracy with an AUC of 0.958. Moreover, the PLNA model exhibited excellent clinical applicability in both the training and validation sets, as evidenced by the DCA curve. CONCLUSIONS: The PLNA model, constructed using clinical indicators, can predict the probability of cytokine storm in the acute phase of SFTS patients.
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Síndrome da Liberação de Citocina , Nomogramas , Febre Grave com Síndrome de Trombocitopenia , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Síndrome da Liberação de Citocina/diagnóstico , Síndrome da Liberação de Citocina/imunologia , Febre Grave com Síndrome de Trombocitopenia/diagnóstico , Febre Grave com Síndrome de Trombocitopenia/imunologia , Idoso , Estudos de Coortes , Prognóstico , Adulto , Estudos RetrospectivosRESUMO
Severe fever with thrombocytopenia syndrome (SFTS) virus and hantavirus are categorized under the Bunyavirales order. The severe disease progression in both SFTS and hemorrhagic fever with renal syndrome (HFRS) is associated with cytokine storms. This study aimed to explore the differences in cytokine profiles and immune responses between the two diseases. A cross-sectional, single-center study involved 100 participants, comprising 46 SFTS patients, 48 HFRS patients, and 6 healthy controls. The study employed the Luminex cytokine detection platform to measure 48 cytokines. The differences in cytokine profiles and immune characteristics between the two diseases were further analyzed using multiple linear regression, principal component analysis, and random forest method. Among the 48 cytokines tested, 30 showed elevated levels in SFTS and/or HFRS compared to the healthy control group. Furthermore, there were 19 cytokines that exhibited significant differences between SFTS and HFRS. Random forest analysis suggested that TRAIL and CTACK were predictive of SFTS, while IL2Ralpha, MIG, IL-8, IFNalpha2, HGF, SCF, MCP-3, and PDGFBB were more common with HFRS. It was further verified by the receiver operating characteristic with area under the curve >0.8 and P-values <0.05, except for TRAIL. Significant differences were observed in the cytokine profiles of SFTS and HFRS, with TRAIL, IL2Ralpha, MIG, and IL-8 being the top 4 cytokines that most clearly distinguished the two diseases. IMPORTANCE: SFTS and HFRS differ in terms of cytokine immune characteristics. TRAIL, IL-2Ralpha, MIG, and IL-8 were the top 4 that differed markedly between SFTS and HFRS.
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Citocinas , Febre Hemorrágica com Síndrome Renal , Febre Grave com Síndrome de Trombocitopenia , Humanos , Febre Hemorrágica com Síndrome Renal/imunologia , Febre Hemorrágica com Síndrome Renal/virologia , Febre Hemorrágica com Síndrome Renal/sangue , Citocinas/sangue , Masculino , Febre Grave com Síndrome de Trombocitopenia/imunologia , Febre Grave com Síndrome de Trombocitopenia/virologia , Pessoa de Meia-Idade , Feminino , Estudos Transversais , Adulto , Idoso , Phlebovirus/imunologiaRESUMO
Fatty acids (FA) are an important factor affecting meat quality and human health, and the important role of the solute carrier family 27 member 6 (SLC27A6) in FA metabolism has been demonstrated in several species. However, the expression profile of the SLC27A6 in different tissues and the effect of its polymorphism on FA in sheep are currently unknown. This study aimed to explore the differences in FAs in the longissimus dorsi (LD) of 1,085 Hu sheep, the expression profile of SLC27A6, and confirm the effect of single nucleotide polymorphisms (SNPs) on FA phenotypes. We found that many FA phenotypes differ significantly across different seasons, and winter promoted the deposition of polyunsaturated fatty acids (PUFA). The mRNA expression level of SLC27A6 in the lung was significantly higher than that in the heart, testis, and LD. A total of 16 SNPs were detected in the SLC27A6, and 14 SNPs were successfully genotyped by improved multiplex ligase detection reaction (iMLDR) technology. Correlation analysis showed that 7 SNPs significantly affected at least one FA phenotype. Among them, SNP14 contributes to the selection of lamb with low saturated fatty acid content and high PUFA content. Combined genotypes also significantly affected a variety of beneficial FAs such as C18:3n3, C20:4n6, C22:6n3, and monounsaturated fatty acids. This study suggests that SLC27A6 plays an important role in FA metabolism and SNPs that are significantly associated with FA phenotype could be used as potential molecular markers for later targeted regulation of FA profiles in sheep.
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Ácidos Graxos , Polimorfismo de Nucleotídeo Único , Animais , Ácidos Graxos/metabolismo , Ovinos/genética , Ovinos/metabolismo , Masculino , Genótipo , Fenótipo , Carneiro Doméstico/genética , Proteínas de Transporte de Ácido Graxo/genética , Proteínas de Transporte de Ácido Graxo/metabolismo , Músculo Esquelético/metabolismoRESUMO
The form of soil nitrogen input significantly affects soil CO2 emission. As a new form of nitrogen input, biochar-loaded ammonia nitrogen not only reduces the input of chemical nitrogen fertilizer in farmland but also reduces the cost of environmental treatment. It is of great significance to promote the zero growth of national chemical fertilizer, the prevention and control of farmland non-point source pollution, and the realization of the national goal of "carbon peak" and "carbon neutralization." Through an indoor culture experiment, the effects of different nitrogen input forms on soil carbon emission, enzyme activity, and microbial community were studied through four treatments:no fertilization (CK), single application of chemical nitrogen fertilizer (CF), biochar combined application of chemical nitrogen fertilizer (BF), and biochar-loaded ammonia nitrogen (BN). The results showed that compared with that in CF, BF significantly increased cumulative carbon emissions (66.24 %), whereas BN had no significant difference. It is worth noting that the cumulative carbon emissions were significantly reduced by 35.28 % compared with that in BF and BN. Compared with those in CF and BF, the activities of ß-glucosidase, peroxidase, and polyphenol oxidase treated with BN significantly increased by 20.25 % and 5.20 %, respectively. Compared with that in CF, the BF treatment increased microbial community richness and community diversity, whereas the BN treatment decreased microbial community richness. Compared with that in BF, the relative abundance of Proteobacteria decreased by 11.16 %, and the relative abundance of Actinobacteria and Bacteroidota increased by 8.12 % and 5.83 %, respectively, in which xylosidase activity was the most important soil factor affecting microbial community structure. The relative abundance of Chloroflexi was significantly correlated with cellobiose hydrolase activity, and the relative abundance of Gemmatimonadetes was significantly correlated with ß-glucosidase activity. There was a very significant correlation between the relative abundance of Proteobacteria and cumulative carbon emissions. To summarize, compared with those under biochar combined with chemical nitrogen fertilizer, biochar loaded with ammonia nitrogen significantly reduced cumulative carbon emissions, and its emission reduction effect was better. The results of this study will be beneficial to the landing of the national "double carbon strategy," the healthy development of the biological natural gas industry, the construction of the national green cultivation circular agriculture system, and the realization of the national zero growth strategy of chemical fertilizer.
Assuntos
Amônia , Carbono , Carvão Vegetal , Fertilizantes , Nitrogênio , Microbiologia do Solo , Solo , Carvão Vegetal/química , Solo/química , Microbiota/efeitos dos fármacos , Bactérias/classificação , Bactérias/crescimento & desenvolvimento , Bactérias/efeitos dos fármacos , Dióxido de Carbono/análiseRESUMO
The recent outbreak of mpox epidemic, caused by monkeypox virus (MPXV), poses a new threat to global public health. Here, we initially assessed the preexisting antibody level to the MPXV B6 protein in vaccinia vaccinees born before the end of the immunization program and then identified two monoclonal antibodies (MAbs), hMB621 and hMB668, targeting distinct epitopes on B6, from one vaccinee. Binding assays demonstrate that both MAbs exhibit broad binding abilities to B6 and its orthologs in vaccinia (VACV), variola (VARV) and cowpox viruses (CPXV). Neutralizing assays reveal that the two MAbs showed potent neutralization against VACV. Animal experiments using a BALB/c female mouse model indicate that the two MAbs showed effective protection against VACV via intraperitoneal injection. Additionally, we determined the complex structure of B6 and hMB668, revealing the structural feature of B6 and the epitope of hMB668. Collectively, our study provides two promising antibody candidates for the treatment of orthopoxvirus infections, including mpox.