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The advantage of 3D printing-that is, additive manufacturing (AM) of structural materials-has been severely compromised by their disappointing fatigue properties1,2. Commonly, poor fatigue properties appear to result from the presence of microvoids induced by current printing process procedures3,4. Accordingly, the question that we pose is whether the elimination of such microvoids can provide a feasible solution for marked enhancement of the fatigue resistance of void-free AM (Net-AM) alloys. Here we successfully rebuild an approximate void-free AM microstructure in Ti-6Al-4V titanium alloy by development of a Net-AM processing technique through an understanding of the asynchronism of phase transformation and grain growth. We identify the fatigue resistance of such AM microstructures and show that they lead to a high fatigue limit of around 1 GPa, exceeding the fatigue resistance of all AM and forged titanium alloys as well as that of other metallic materials. We confirm the high fatigue resistance of Net-AM microstructures and the potential advantages of AM processing in the production of structural components with maximum fatigue strength, which is beneficial for further application of AM technologies in engineering fields.
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BACKGROUND: Preeclampsia is a serious disease of pregnancy that lacks early diagnosis methods or effective treatment, except delivery. Dysregulated uterine immune cells and spiral arteries are implicated in preeclampsia, but the mechanistic link remains unclear. METHODS: Single-cell RNA sequencing and spatial transcriptomics were used to identify immune cell subsets associated with preeclampsia. Cell-based studies and animal models including conditional knockout mice and a new preeclampsia mouse model induced by recombinant mouse galectin-9 were applied to validate the pathogenic role of a CD11chigh subpopulation of decidual macrophages (dMφ) and to determine its underlying regulatory mechanisms in preeclampsia. A retrospective preeclampsia cohort study was performed to determine the value of circulating galectin-9 in predicting preeclampsia. RESULTS: We discovered a distinct CD11chigh dMφ subset that inhibits spiral artery remodeling in preeclampsia. The proinflammatory CD11chigh dMφ exhibits perivascular enrichment in the decidua from patients with preeclampsia. We also showed that trophoblast-derived galectin-9 activates CD11chigh dMφ by means of CD44 binding to suppress spiral artery remodeling. In 3 independent preeclampsia mouse models, placental and plasma galectin-9 levels were elevated. Galectin-9 administration in mice induces preeclampsia-like phenotypes with increased CD11chigh dMφ and defective spiral arteries, whereas galectin-9 blockade or macrophage-specific CD44 deletion prevents such phenotypes. In pregnant women, increased circulating galectin-9 levels in the first trimester and at 16 to 20 gestational weeks can predict subsequent preeclampsia onset. CONCLUSIONS: These findings highlight a key role of a distinct perivascular inflammatory CD11chigh dMφ subpopulation in the pathogenesis of preeclampsia. CD11chigh dMφ activated by increased galectin-9 from trophoblasts suppresses uterine spiral artery remodeling, contributing to preeclampsia. Increased circulating galectin-9 may be a biomarker for preeclampsia prediction and intervention.
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Decidua , Galectinas , Macrófagos , Preeclampsia , Remodelación Vascular , Preeclampsia/metabolismo , Preeclampsia/inmunología , Embarazo , Femenino , Animales , Galectinas/metabolismo , Macrófagos/metabolismo , Macrófagos/inmunología , Macrófagos/patología , Ratones , Humanos , Decidua/metabolismo , Decidua/patología , Ratones Noqueados , Útero/metabolismo , Útero/irrigación sanguínea , Modelos Animales de Enfermedad , Receptores de Hialuranos/metabolismo , Receptores de Hialuranos/genética , Estudios Retrospectivos , Ratones Endogámicos C57BL , Antígenos CD11RESUMEN
Dwarfism is an important agronomic trait in fruit breeding programs. However, the germplasm resources required to generate dwarf pear (Pyrus spp.) varieties are limited. Moreover, the mechanisms underlying dwarfism remain unclear. In this study, "Yunnan" quince (Cydonia oblonga Mill.) had a dwarfing effect on "Zaosu" pear. Additionally, the dwarfism-related NAC transcription factor gene PbNAC71 was isolated from pear trees comprising "Zaosu" (scion) grafted onto "Yunnan" quince (rootstock). Transgenic Nicotiana benthamiana and pear OHF-333 (Pyrus communis) plants overexpressing PbNAC71 exhibited dwarfism, with a substantially smaller xylem and vessel area relative to the wild-type controls. Yeast one-hybrid, dual-luciferase, chromatin immunoprecipitation-qPCR, and electrophoretic mobility shift assays indicated that PbNAC71 downregulates PbWalls are thin 1 expression by binding to NAC-binding elements in its promoter. Yeast two-hybrid assays showed that PbNAC71 interacts with the E3 ubiquitin ligase PbRING finger protein 217 (PbRNF217). Furthermore, PbRNF217 promotes the ubiquitin-mediated degradation of PbNAC71 by the 26S proteasome, thereby regulating plant height as well as xylem and vessel development. Our findings reveal a mechanism underlying pear dwarfism and expand our understanding of the molecular basis of dwarfism in woody plants.
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Regulación de la Expresión Génica de las Plantas , Proteínas de Plantas , Plantas Modificadas Genéticamente , Pyrus , Factores de Transcripción , Xilema , Xilema/metabolismo , Xilema/genética , Pyrus/genética , Pyrus/metabolismo , Pyrus/crecimiento & desarrollo , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Nicotiana/genética , Nicotiana/metabolismo , Nicotiana/crecimiento & desarrollo , Regiones Promotoras Genéticas/genética , Complejo de la Endopetidasa Proteasomal/metabolismo , Complejo de la Endopetidasa Proteasomal/genéticaRESUMEN
The development of sepsis can lead to many organ dysfunction and even death. Myocardial injury is one of the serious complications of sepsis leading to death. New evidence suggests that microRNAs (miRNAs) play a critical role in infection myocardial injury. However, the mechanism which miR-208a-5p regulates sepsis-induced myocardial injury remains unclear. To mimic sepsis-induced myocardial injury in vitro, rat primary cardiomyocytes were treated with LPS. Cell viability and apoptosis were tested by CCK-8 and flow cytometry, respectively. The secretion of inflammatory factors was analyzed by ELISA. mRNA and protein levels were detected by RT-qPCR and Western blotting. The interaction among SP1, XIAP and miR-208a-5p was detected using dual luciferase report assay. Ultrasonic analysis and HE staining was performed to observe the effect of miR-208a-5p in sepsis-induced rats. Our findings indicated that miR-208a-5p expression in primary rat cardiomyocytes was increased by LPS. MiR-208a-5p inhibitor reversed LPS-induced cardiomyocytes injury through inhibiting the apoptosis. Furthermore, the inflammatory injury in cardiomyocytes was induced by LPS, which was rescued by miR-208a-5p inhibitor. In addition, downregulation of miR-208a-5p improved LPS-induced sepsis myocardial injury in vivo. Mechanistically, XIAP might be a target gene of miR-208a-5p. SP1 promoted transcription of miR-208a by binding to the miR-208a promoter region. Moreover, silencing of XIAP reversed the regulatory of miR-208a-5p inhibitor on cardiomyocytes injury. To sum up, those findings revealed silencing of miR-208a-5p could alleviate sepsis-induced myocardial injury, which would grant a new process for the treatment of sepsis.
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MicroARNs , Sepsis , Animales , Ratas , Apoptosis , Lipopolisacáridos/farmacología , MicroARNs/metabolismo , Miocitos Cardíacos/metabolismo , Sepsis/complicaciones , Sepsis/genética , Sepsis/metabolismo , Factor de Transcripción Sp1RESUMEN
BACKGROUND: Thrombocytopenia is the major clinical feature associated with the severity of SFTS, but the mechanism by which it occurs remains unclear. METHODS: RNA transcriptome analyses were performed on platelets purified from SFTS patients and SFTSV-infected mice. The functions of differentially expressed genes (DEGs) in the platelets were characterized. ELISA, flow cytometry, and qRT-PCR were used to measure the levels of platelet activation, SFTSV infection in platelets, formation of neutrophil extracellular traps (NETs), transcription of DEGs and percent of platelets undergoing cell death. RESULTS: Enhanced neutrophil activation and interferon (IFN) signaling involved in the viral life cycle were common platelet responses in SFTS, which may consume increasing numbers of platelets. Other functional changes may be associated with different outcomes of SFTS. SFTSV infection led to platelet destruction by pyroptosis, apoptosis, necroptosis, and autophagy. In contrast to SFTS patients, platelets in SFTSV-infected mice mainly play a role in adaptive immunity, and platelet death was not as severe as in humans. CONCLUSIONS: The altered functions of platelets, such as mediating leukocyte activation and undergoing cell death, contribute to thrombocytopenia in SFTS patients. The different mechanisms of thrombocytopenia in mice, suggest that platelet functions should be considered in experimental animal models.
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Non-small-cell lung cancer (NSCLC) is a major cause of worldwide cancer death, posing a challenge for effective treatment. Our previous findings showed that Chinese herbal medicine (CHM) QiDongNing (QDN) could upregulate the expression of p53 and trigger cell apoptosis in NSCLC. Here, our objective was to investigate the mechanisms of QDN-induced apoptosis enhancement. We chose A549 and NCI-H460 cells for validation in vitro, and LLC cells were applied to form a subcutaneous transplantation tumour model for validation in more depth. Our findings indicated that QDN inhibited multiple biological behaviours, including cell proliferation, cloning, migration, invasion and induction of apoptosis. We further discovered that QDN increased the pro-apoptotic BAX while inhibiting the anti-apoptotic Bcl2. QDN therapy led to a decline in adenosine triphosphate (ATP) and a rise in reactive oxygen species (ROS). Furthermore, QDN elevated the levels of the tumour suppressor p53 and the mitochondrial division factor DRP1 and FIS1, and decreased the mitochondrial fusion molecules MFN1, MFN2, and OPA1. The results were further verified by rescue experiments, the p53 inhibitor Pifithrin-α and the mitochondrial division inhibitor Mdivi1 partially inhibited QDN-induced apoptosis and mitochondrial dysfunction, whereas overexpression of p53 rather increased the efficacy of the therapy. Additionally, QDN inhibited tumour growth with acceptable safety in vivo. In conclusion, QDN induced apoptosis via triggering p53/DRP1-mediated mitochondrial fission in NSCLC cells.
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Apoptosis , Carcinoma de Pulmón de Células no Pequeñas , Medicamentos Herbarios Chinos , Dinaminas , Neoplasias Pulmonares , Dinámicas Mitocondriales , Proteína p53 Supresora de Tumor , Animales , Humanos , Ratones , Células A549 , Apoptosis/efectos de los fármacos , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/genética , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Medicamentos Herbarios Chinos/farmacología , Dinaminas/metabolismo , Dinaminas/genética , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/tratamiento farmacológico , Mitocondrias/metabolismo , Mitocondrias/efectos de los fármacos , Dinámicas Mitocondriales/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Proteína p53 Supresora de Tumor/genética , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
This study longitudinally evaluated the immune response in individuals over a year after receiving three doses of an inactivated SARS-CoV-2 vaccine, focusing on reactions to Omicron breakthrough infections. From 63 blood samples of 37 subjects, results showed that the third booster enhanced the antibody response against Alpha, Beta, and Delta VOCs but was less effective against Omicron. Although antibody titres decreased post-vaccination, SARS-CoV-2-specific T-cell responses, both CD4+ and CD8+, remained stable. Omicron breakthrough infections significantly improved neutralization against various VOCs, including Omicron. However, the boost in antibodies against WT, Alpha, Beta, and Delta variants was more pronounced. Regarding T cells, breakthrough infection predominantly boosted the CD8+ T-cell response, and the intensity of the spike protein-specific T-cell response was roughly comparable between WT and Omicron BA.5.
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Anticuerpos Antivirales , Infección Irruptiva , Vacunas contra la COVID-19 , COVID-19 , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Anticuerpos Neutralizantes/inmunología , Anticuerpos Neutralizantes/sangre , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Infección Irruptiva/epidemiología , Infección Irruptiva/inmunología , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , COVID-19/prevención & control , COVID-19/inmunología , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , Inmunización Secundaria , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus/inmunología , Linfocitos T/inmunología , Vacunas de Productos Inactivados/inmunología , Vacunas de Productos Inactivados/administración & dosificaciónRESUMEN
INTRODUCTION: The staging and treatment of axillary nodes in breast cancer have become a focus of research. For breast cancer patients with fine-needle aspiration-or core needle biopsy-confirmed positive nodes, axillary lymph node dissection (ALND) after neoadjuvant chemotherapy (NAC) is still a standard treatment. However, some patients achieve an axillary pathologic complete response (pCR) after NAC. In this study, the authors sought to construct a model to predict axillary pCR in patients with positive axillary lymph nodes (cN+) breast cancer. METHODS: Data from patients with pathologically proven cN+ breast cancer treated with NAC followed by ALND between January 2010 and April 2019 at the Peking University Cancer Hospital were reviewed. Axillary lymph node status was assessed using ultrasonography before and after NAC. The patient cohort was assigned to the construction and internal validation cohorts according to admission time. A nomogram was constructed based on the significant factors associated with axillary pCR. The predictive performance of the model was externally validated using data from Peking University First Hospital. RESULTS: This study included 953 and 267 patients from Peking University Cancer Hospital and Peking University First Hospital, respectively. In the construction cohort, 39.7% (238 of 600) of patients achieved axillary pCR after NAC. The result of multivariate logistic regression analysis showed that tumor grade, clinical nodal response, NAC regimen, tumor pCR, lymphovascular invasion, and tumor biologic subtype were significant independent predictors of ypN0 (p < 0.05). The areas under the receiver operating characteristic curves for the construction, validation, and independent testing cohorts were 0.87 (95% confidence interval [CI], 0.84-0.90), 0.83 (95% CI, 0.79-0.87), and 0.84 (0.79-0.89), respectively. CONCLUSIONS: A nomogram was constructed to predict the pCR of axillary lymph nodes after NAC for breast cancer. Validation of both the internal and external cohorts achieved good predictive performance, indicating that the model has preliminary clinical application prospects.
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Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Nomogramas , Terapia Neoadyuvante , Respuesta Patológica Completa , Metástasis Linfática/patología , Ganglios Linfáticos/patología , Escisión del Ganglio Linfático , Ultrasonografía , Axila/patología , Biopsia del Ganglio Linfático CentinelaRESUMEN
BACKGROUND: Previous studies involving risk-benefit analysis of trastuzumab deruxtecan (DS-8201) have indicated the benefit of this treatment, although it may increase the risk of interstitial lung disease (ILD) and/or pneumonitis in certain patients. This study aimed to assess the safety of DS-8201. METHODS: A search was done for relevant articles in four electronic databases: PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov. All reports published up until November 2, 2022, were included, and study types were restricted to clinical trials; the last search was then updated to January 10, 2023. We also assessed the quality of the literature with the Cochrane Handbook for Systematic Reviews of Interventions and the Methodological Index for Non-Randomized Studies tool, and then performed a meta-analysis with R version 4.2.1. RESULTS: A total of 1428 patients reported in 13 articles were included in this study. The analysis revealed that the most common all-grade treatment-emergent adverse events (TEAEs) were nausea and fatigue. The most common TEAE of grade 3 or above (grade ≥3) was neutropenia. The incidences of ILD and/or pneumonitis for all-grade and grade ≥3 TEAEs were 12.5% and 2.2%, respectively. CONCLUSIONS: This comprehensive summary of the incidence of TEAEs associated with DS-8201 in clinical trials provides an important guide for clinicians. The most common TEAEs were gastrointestinal reactions and fatigue; meanwhile, the most common grade ≥3 TEAE was hematological toxicity. ILD and/or pneumonitis were specific adverse drug reactions associated with DS-8201, of which physicians should be particularly aware for their higher morbidity and rates of grade ≥3 TEAEs.
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Enfermedades Pulmonares Intersticiales , Neumonía , Trastuzumab , Humanos , Antineoplásicos Inmunológicos/efectos adversos , Antineoplásicos Inmunológicos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Camptotecina/análogos & derivados , Inmunoconjugados/efectos adversos , Inmunoconjugados/uso terapéutico , Enfermedades Pulmonares Intersticiales/inducido químicamente , Neumonía/inducido químicamente , Neumonía/epidemiología , Trastuzumab/efectos adversos , Trastuzumab/uso terapéuticoRESUMEN
Interface passivation is a key method for improving the efficiency of perovskite solar cells, and 2D/3D perovskite heterojunction is the mainstream passivation strategy. However, the passivation layer also produces a new interface between 2D perovskite and fullerene (C60), and the properties of this interface have received little attention before. Here, the underlying properties of the 2D perovskite/C60 interface by taking the 2D TEA2PbX4 (TEA = C6H10NS; X = I, Br, Cl) passivator as an example are systematically expounded. It is found that the 2D perovskite preferentially exhibits (002) orientation with the outermost surface featuring an oriented arrangement of TEACl, where the thiophene groups face outward. The outward thiophene groups further form a strong π-π stacking system with C60 molecule, strengthening the interaction force with C60 and facilitating the creation of a superior interface. Based on the vacuum-assisted blade coating, wide-bandgap (WBG, 1.77 eV) perovskite solar cells achieved impressive records of 19.28% (0.09 cm2) and 18.08% (1.0 cm2) inefficiency, respectively. This research not only provides a new understanding of interface processing for future perovskite solar cells but also lays a solid foundation for realizing efficient large-area devices.
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OBJECTIVES: The objective of this study was to investigate the dynamic profiles of myocardial injury biomarkers and their association with mortality in patients with severe fever with thrombocytopenia syndrome (SFTS). DESIGN: A retrospective cohort study. SETTINGS: Union Hospital in Wuhan, China. PATIENTS: A total of 580 patients with SFTS, observed between May 2014 and December 2021, were included in the final analysis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: In total, 580 patients with SFTS were enrolled in the study, comprised of 469 survivors and 111 nonsurvivors, with a 21-day fatality rate of 19.1%. The elevation of troponin I (TnI) was observed in 61.6% patients (357/580) with SFTS upon admission, and 68.4% patients (397/580) developed an abnormal TnI level during hospitalization. Multivariate logistic regression identified age, viral load, platelet count, creatinine level, and TnI level as potential risk factors for mortality in patients with SFTS. The results of restricted cubic splines revealed that when the TnI level (baseline TnI: 1.55 [lg (ng/L+1)], peak value: TnI 1.90 [lg (ng/L+1)]) exceeded a certain threshold, the predicted mortality of patients with SFTS increased alongside the rise in TnI levels. Mortality rate surpassed 40% among patients with SFTS with TnI greater than or equal to 10 times the upper limit of normal at admission (43.8%) or during hospitalization (41.7%). Older age, a history of cardiovascular disease, and higher d-dimer levels were potential risk factors for elevated TnI levels in patients with SFTS. CONCLUSIONS: Elevated TnI levels were prevalent among patients with SFTS and were strongly associated with an increased risk of mortality.
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The bacterial type II toxin-antitoxin (TA) system is a rich genetic element that participates in various physiological processes. Aeromonas veronii is the main bacterial pathogen threatening the freshwater aquaculture industry. However, the distribution of type II TA system in A. veronii was seldom documented and its roles in the life activities of A. veronii were still unexplored. In this study, a novel type II TA system AvtA-AvtT was predicted in a fish pathogen Aeromonas veronii biovar sobria with multi-drug resistance using TADB 2.0. Through an Escherichia coli host killing and rescue assay, we demonstrated that AvtA and AvtT worked as a genuine TA system, and the predicted toxin AvtT actually functioned as an antitoxin while the predicted antitoxin AvtA actually functioned as a toxin. The binding ability of AvtA with AvtT proteins were confirmed by dot blotting analysis and co-immunoprecipitation assay. Furthermore, we found that the toxin and antitoxin labelled with fluorescent proteins were co-localized. In addition, it was found that the transcription of AvtAT bicistronic operon was repressed by the AvtAT protein complex. Deletion of avtA gene and avtT gene had no obvious effect on the drug susceptibility. This study provides first characterization of type II TA system AvtA-AvtT in aquatic pathogen A. veronii.
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Aeromonas veronii , Proteínas Bacterianas , Sistemas Toxina-Antitoxina , Aeromonas veronii/genética , Aeromonas veronii/metabolismo , Sistemas Toxina-Antitoxina/genética , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Toxinas Bacterianas/metabolismo , Toxinas Bacterianas/genética , Operón , Escherichia coli/genética , Escherichia coli/metabolismo , Escherichia coli/efectos de los fármacos , Antitoxinas/genética , Antitoxinas/metabolismo , Regulación Bacteriana de la Expresión GénicaRESUMEN
INTRODUCTION: Cognitive dysfunction due to reduced neuronal transmission in the brain is a major emerging complication in diabetes. However, recent neuroimaging studies have demonstrated non-linear changes including hyperactivity in the hippocampus during the early stage of diabetes. This study aimed to determine the changes in neuronal activity at a single-cell level in hippocampal CA1 pyramidal neurons in the early stage of streptozotocin-induced type 1 diabetes in mice. METHODS: Whole-cell patch-clamp recordings from acute brain slices were performed in mice over 4 consecutive weeks following the induction of hyperglycaemia using streptozotocin. In addition, microdialysate was collected from CA1 area while the mice were in an arousal state. The concentrations of glutamate and GABA in the microdialysate were then measured using ultra-performance liquid chromatography with mass spectrometry. RESULTS: CA1 neurons in streptozotocin-induced diabetic mice exhibited higher membrane potentials (p = 0.0052), higher frequency of action potentials (p = 0.0052), and higher frequency of spontaneous excitatory post-synaptic currents (p = 0.037) compared with controls during the second week after hyperglycaemia was established. No changes in electrophysiological parameters were observed during the first, the third, and the fourth week. Moreover, the diabetic mice had higher extracellular glutamate concentration in CA1 area compared with controls (p = 0.021) during the second week after the initiation of diabetes. No change in the extracellular GABA concentration was observed. CONCLUSION: Our study demonstrated a temporary state of neuronal hyperactivity at the single-cell level in the hippocampal CA1 region during the early stage of diabetes. This neuronal hyperactivity might be related to altered glutamate metabolism and provide clues for future brain-target intervention.
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Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 1 , Hiperglucemia , Ratones , Animales , Estreptozocina/toxicidad , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Experimental/metabolismo , Hipocampo/metabolismo , Neuronas , Transmisión Sináptica/fisiología , Ácido Glutámico/metabolismo , Ácido gamma-Aminobutírico/metabolismo , Hiperglucemia/metabolismoRESUMEN
CuII metalations of carbaporphyrins 1-4 gave the corresponding CuII complexes 1-Cu, 2-Cu, 3-Cu, and 4-Cu with varying degrees of distortions in CuII square-planar coordination. Upon treatment with Cu(OAc)2, 1-Cu was inert but 2-Cu and 3-Cu gave the respective O-atom-inserted complexes 2-OCu and 3-OCu. Further, 3-Cu and 4-Cu were converted to meso-methoxynickel(II) porphyrins 3-OMe and 4-OMe, respectively, via treatment with Cu(OAc)2 in methanol. meso-Hydroxynickel(II) porphyrin 3-OH was obtained by the treatment of 3-OCu by acetic acid. The treatment of 4-Cu with Cu(OAc)2 in the presence of acetic acid gave 5,15-diketoporphyrinogen 4-O. CuII complexes of carbaporphyrins became more reactive with an increased distortion in CuII square-planar coordination.
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OBJECTIVE: Our aim was to compare the PIK3CA mutation status in matched primary and recurrent tumors of hormone receptor positive/human epidermal growth factor receptor 2 negative (HR+/HER2-) breast cancer (BC) to gain insight into the optimization of patient selection and detection time for PIK3CA-targeted therapy. METHODS: The data were from 3035 patients with BC diagnosed at the Breast Disease Center, Peking University First Hospital, between January 2008 and December 2017. Matched primary and recurrent samples were profiled using amplification-refractory mutation system-polymerase chain reaction covering 11 mutational hotspots in PIK3CA. RESULTS: PIK3CA mutations were detected in 54.3% primary tumors and 48.6% corresponding recurrences. PIK3CA mutation was detected in 37.5% cases in the locoregional recurrent group and 40.0% of distant metastasis, without a statistical difference. Besides, PIK3CA mutations were concordant in 88.6% of the matched pairs. For patients treated with neoadjuvant chemotherapy, 100% concordance was observed. However, PIK3CA mutation was neither correlated with clinicopathological features nor associated with clinical outcomes. CONCLUSIONS: Mutations in PIK3CA in HR+/HER2- BC generally progressed to recurrent tumors. The high concordance rate of PIK3CA mutation status between primary tumors and corresponding recurrences suggests that the detection of primary tumors could be a substitute approach when recurrent samples are not easily obtainable.
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BACKGROUND: We reported a rare case of combined Giardiasis, sepsis, and DIC in a Tibetan Chinese male in this study. METHODS: Multiple fecal routine examinations, blood routine examination, blood culture, coagulation screening, and biochemical tests were done after August 1st, 2022. RESULTS: The child had intermittent diarrhea. Giardia cysts were found in his stool mounts. Sepsis, disseminated intravascular coagulation, fever with blood routine decreasing, low proteinemia, hyperlactemia and hypocalcemia were also found in this case. CONCLUSIONS: It is suggested that improving the resistance, immunity, and personal hygiene is particularly important for children from remote ethnic minority areas of China.
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Giardiasis , Sepsis , Niño , Humanos , Masculino , Giardiasis/complicaciones , Giardiasis/diagnóstico , Tibet , Etnicidad , Grupos Minoritarios , China/epidemiología , Sepsis/diagnósticoRESUMEN
KEY MESSAGE: This study provided a non-destructive detection method with Vis-NIR hyperspectral imaging combining with physio-biochemical parameters in Helianthus annuus in response to Orobanche cumana infection that took insights into the monitoring of sunflower weed. Sunflower broomrape (Orobanche cumana Wallr.) is an obligate weed that attaches to the host roots of sunflower (Helianthus annuus L.) leading to a significant reduction in yield worldwide. The emergence of O. cumana shoots after its underground life-cycle causes irreversible damage to the crop. In this study, a fast visual, non-invasive and precise method for monitoring changes in spectral characteristics using visible and near-infrared (Vis-NIR) hyperspectral imaging (HSI) was developed. By combining the bands sensitive to antioxidant enzymes (SOD, GR), non-antioxidant enzymes (GSH, GSH + GSSG), MDA, ROS (O2-, OH-), PAL, and PPO activities obtained from the host leaves, we sought to establish an accurate means of assessing these changes and conducted imaging acquisition using hyperspectral cameras from both infested and non-infested sunflower cultivars, followed by physio-biochemical parameters measurement as well as analyzed the expression of defense related genes. Extreme learning machine (ELM) and convolutional neural network (CNN) models using 3-band images were built to classify infected or non-infected plants in three sunflower cultivars, achieving accuracies of 95.83% and 95.83% for the discrimination of infestation as well as 97.92% and 95.83% of varieties, respectively, indicating the potential of multi-spectral imaging systems for early detection of O. cumana in weed management.
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Helianthus , Imágenes Hiperespectrales , Orobanche , Helianthus/parasitología , Orobanche/fisiología , Imágenes Hiperespectrales/métodos , Espectroscopía Infrarroja Corta/métodos , Hojas de la Planta/parasitología , Hojas de la Planta/metabolismo , Enfermedades de las Plantas/parasitología , Antioxidantes/metabolismo , Malezas , Interacciones Huésped-ParásitosRESUMEN
The trend of aging of the global population is becoming more and more significant, and the incidence of age-related diseases continues to rise.This phenomenon makes the problem of aging gradually attracted wide attention of the society, and gradually developed into an independent research field.As a vital defense mechanism of the human body, the immune system changes significantly during the aging process.Age-induced changes in the body's immune system are considered harmful and are commonly referred to as immune aging, which may represent the beginning of systemic aging.Immune cells, especially T cells, are the biggest influencers and participants in age-related deterioration of immune function, making older people more susceptible to different age-related diseases.More and more evidence shows that T cells play an important role in the change of human tissue structure after aging, which fundamentally affects the health and survival of the elderly.In this review, we discuss the general characteristics of age-related T cell immune alterations and the possible effects of aging T cells in various tissue structures in the human body.
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PURPOSE: Women are at high risk of stress, anxiety, and depression during the postpartum but the ways in which these different types of psychological distress are related to cortisol regulation is not clear. We examined the distinct association of each type of distress with women's average cortisol level, cortisol awakening response (CAR), cortisol decline across the day (diurnal slope), and overall amount of cortisol secretion across the day (AUCG). METHODS: At 6 months postpartum, a diverse group of 58 women completed measures of depression, anxiety, perceived stress, and life stressors. Each woman provided 4 salivary samples for cortisol assay from waking to bedtime on each of 2 consecutive days. Linear regressions were used to examine associations of stress, anxiety and depression to each of the 4 cortisol measures, controlling for number of stressful life events. RESULTS: Depressive symptoms were associated with less of a rise in the CAR (ß = -.46, p = 0.01), steeper diurnal slope (ß = .51, p = 0.006), and higher average cortisol level (ß = .42, p = .01). Women who met the clinical cutoff for an anxiety disorder had lower overall cortisol output (ß = -.29, p = 0.03). Stress was not related to any cortisol metric. CONCLUSIONS: Findings suggest that stress is less associated with cortisol alterations in the postpartum than are more severe types of psychological distress. Anxiety and depression may have distinct and opposite profiles of cortisol dysregulation. Results indicate that mental health assessment is critical even in the later postpartum so that interventions can be initiated to reduce emotional suffering and the risk of impaired cortisol regulation.
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Ansiedad , Depresión , Hidrocortisona , Periodo Posparto , Saliva , Estrés Psicológico , Humanos , Femenino , Hidrocortisona/análisis , Hidrocortisona/metabolismo , Adulto , Estrés Psicológico/metabolismo , Estrés Psicológico/psicología , Saliva/química , Periodo Posparto/psicología , Ansiedad/psicología , Ansiedad/metabolismo , Depresión/psicología , Depresión/metabolismo , Ritmo Circadiano/fisiología , Depresión Posparto/psicología , Depresión Posparto/metabolismo , Adulto JovenRESUMEN
BACKGROUND: While financial toxicity (FT) is prevalent in patients with cancer, young and middle-aged patients with stroke are also affected by FT, which can exacerbate their physical and psychological challenges. Understanding the patient's experience and response measures can further understand the impact of FT on patients with stroke, to help alleviate FT. However, little is known concerning the experience of patients with stroke with FT or their coping strategies. Therefore, this study aimed to describe the experiences of FT in young and middle-aged patients with stroke and their coping strategies. METHODS: A phenomenological method was utilized. Semi-structured interviews were conducted with 21 young and middle-aged stroke patients (aged 18-59) between October 2022 and March 2023. The participants were recruited from a tertiary hospital in Shanghai, China. The research team used NVivo 12.0 software. Giorgi's phenomenological analysis method was used to analyse the interview data. RESULTS: The interview results were divided into two categories in terms of patients' experiences of FT and their coping strategies. Nine subthemes were constructed. The experience category included four subthemes: (1) taking on multifaceted economic pressure, (2) dual choice of treatment, (3) decline in material living standards, and (4) suffering from negative emotions such as anxiety and depression. The coping strategy category included five subthemes: (1) reducing expenses, (2) improving living habits, (3) proactive participation in medical decision-making, (4) making a job position choice, and (5) seeking social support. CONCLUSIONS: FT in young and middle-aged patients with stroke, which affected their physical and mental health, led them to implement strategies for dealing with FT. The Chinese government needs to broaden the reach of health insurance coverage and advance the fairness of healthcare policies. Healthcare professionals must pay active attention to FT in such patients in terms of strengthening their health education and considering their needs and preferences. Patients need to improve their sense of self-efficacy, actively reintegrate into society, and adhere to rehabilitation and treatment. Individuals at a high risk of stroke are recommended to purchase health insurance. Multifaceted efforts are needed to reduce the impact of FT in young and middle-aged patients with stroke.