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In the exploitation of seawater resources, the transported pipelines are frequently corroded, resulting in economic losses and environmental pollution. The development of corrosion inhibitors is an effective measure to mitigate the corrosion of metals in seawater. In this work, novel chitosan oligosaccharide derivatives (CF) were synthesized as fluorescent eco-friendly corrosion inhibitor by modifying fluorescent monomers. The characterization of CF revealed excellent fluorescence intensity, promising the potential for on-line detection. The inhibition performance of CF on P110 in 3.5 wt% NaCl solution was investigated through experimental evaluation and theoretical analysis. The electrochemical measurements indicated that the corrosion inhibition efficiency was increased from 61.00 % to 91.19 % with the introduction of fluorane. Adsorption isotherm and XPS analysis demonstrated that CF is designed to protect metal by forming the composite film on P110 through physical and chemical adsorption. In addition, theoretical calculations revealed differences in the interaction energies, radial distribution functions and diffusion coefficients of inhibitors on the Fe (110) surface. These theoretical results aligned with the experiments and confirmed the excellent ability of CF in metal corrosion protection from the molecular perspective. This new chitosan derivative provides new possibilities for the development of the green composite inhibitor that allows on-line detection.
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The flavor stability of tea beverages during storage has long been a concern. The study aimed to explore the flavor stability of Longjing green tea beverage using accelerated heat treatment trials, addressing the shortage of lengthy storage trials. Sensory evaluations revealed changes in bitterness, umami, overall harmonization, astringency, and ripeness as treatment duration increased. Accompanied by a decrease in L-values, ΔE and an increase in a and b-values. Seventeen non-volatile metabolites and three volatile metabolites were identified differential among samples by metabolomics, with subsequent correlation analysis indicating associations between sensory attributes and specific metabolites. Umami was linked to epigallocatechin 3,5-digallate and alpha-D-glucopyranose, astringency was correlated with ellagic acid and 1-ethyl-1H-pyrrole. Ripeness showed associations with ellagic acid, 6,7-dihydroxycoumarin, heptanal, and benzaldehyde, and overall harmonization was linked to 6,7-dihydroxycoumarin, ß-myrcene, α-terpineol, and heptanal. A series of verification tests confirmed the feasibility of accelerated heat treatment trials to replace traditional storage trials. These results offer valuable insights into unraveling the complex relationship between sensory and chemical profiles of green tea beverages.
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Calor , Metabolómica , Gusto , Té , Té/química , Humanos , Compuestos Orgánicos Volátiles/análisis , Manipulación de Alimentos/métodos , Masculino , Almacenamiento de Alimentos/métodos , Adulto , Ácido Elágico/análisis , FemeninoRESUMEN
The new genus, Cerogamasus gen. nov., with the type species Cerogamasus tibetensis sp. nov., is established. The new genus is easily distinguished from other genera of Parasitidae because the dorsal idiosoma in both sexes bears more than 40 pairs of setae, of which fewer than 7 pairs of podonotal setae are smooth; the seta z5 of the dorsal hexagon is similar to j5 and j6 in form (pilose or distally pilose) while different in length (z5 longer); the seta al of the palpfemur is pectinate, and al1 and al2 of the palpgenu are entire; the gnathotectum is trispinate; peritrematal shields in females are posteriorly free; and the palptrochanter in males has a pointed ventral protuberance. C. anhuiensis sp. nov., C. guizhouensis sp. nov. and C. multidentatus sp. nov. are described based on adult samples; C. tibetensis sp. nov. is described based on deutonymph and adult samples. Cycetogamasus coreanus Athias-Henriot, 1980, is transferred to Cerogamasus gen. nov. as a new combination.
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Endometrial cancer is the most common gynecological cancer in the developed world. However, the accuracy of current diagnostic methods is still unsatisfactory and time-consuming. Here, we presented an alternate approach to monitoring the progression of endometrial cancer via multiphoton microscopy imaging and analysis of collagen, which is often overlooked in current endometrial cancer diagnosis protocols but can offer a crucial signature in cancer biology. Multiphoton microscopy (MPM) based on the second-harmonic generation and two-photon excited fluorescence was introduced to visualize the microenvironment of endometrium in normal, hyperplasia without atypia, atypical hyperplasia, and endometrial cancer specimens. Furthermore, automatic image analysis based on the MPM image processing algorithm was used to quantify the differences in the collagen morphological features among them. MPM enables the visualization of the morphological details and alterations of the glands in the development process of endometrial cancer, including irregular changes in the structure of the gland, increased ratio of the gland to the interstitium, and atypical changes in the glandular epithelial cells. Moreover, the destructed basement membrane caused by gland proliferation and fusion is clearly shown in SHG images, which is a key feature for identifying endometrial cancer progression. Quantitative analysis reveals that the formation of endometrial cancer is accompanied by an increase in collagen fiber length and width, a progressive linearization and loosening of interstitial collagen, and a more random arrangement of interstitial collagen. Observation and quantitative analysis of interstitial collagen provide invaluable information in monitoring the progression of endometrial cancer. Label-free multiphoton imaging reported here has the potential to become an in situ histological tool for effective and accurate early diagnosis and detection of malignant lesions in endometrial cancer.
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African swine fever (ASF), caused by the African swine fever virus (ASFV), is one of the most important infectious diseases that cause high morbidity and mortality in pigs and substantial economic losses to the pork industry of affected countries due to the lack of effective vaccines. The need to develop alternative robust antiviral countermeasures, especially anti-ASFV agents, is of the utmost urgency. This study shows that fangchinoline (FAN), a bisbenzylisoquinoline alkaloid found in the roots of Stephania tetrandra of the family Menispermaceae, significantly inhibits ASFV replication in porcine alveolar macrophages (PAMs) at micromolar concentrations (IC50 = 1.66 µM). Mechanistically, the infection of ASFV triggers the AKT/mTOR/NF-κB signaling pathway. FAN significantly inhibits ASFV-induced activation of such pathways, thereby suppressing viral replication. Such a mechanism was confirmed using an AKT inhibitor MK2206 as it inhibited AKT phosphorylation and ASFV replication in PAMs. Altogether, the results suggest that the AKT/mTOR pathway could potentially serve as a treatment strategy for combating ASFV infection and that FAN could potentially emerge as an effective novel antiviral agent against ASFV infections and deserves further in vivo antiviral evaluations.
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Virus de la Fiebre Porcina Africana , Antivirales , Bencilisoquinolinas , Macrófagos Alveolares , FN-kappa B , Proteínas Proto-Oncogénicas c-akt , Transducción de Señal , Serina-Treonina Quinasas TOR , Replicación Viral , Animales , Macrófagos Alveolares/virología , Macrófagos Alveolares/efectos de los fármacos , Macrófagos Alveolares/metabolismo , Replicación Viral/efectos de los fármacos , Virus de la Fiebre Porcina Africana/efectos de los fármacos , Virus de la Fiebre Porcina Africana/fisiología , Porcinos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Transducción de Señal/efectos de los fármacos , FN-kappa B/metabolismo , Bencilisoquinolinas/farmacología , Antivirales/farmacología , Fiebre Porcina Africana/virología , Fiebre Porcina Africana/tratamiento farmacológico , Fiebre Porcina Africana/metabolismoRESUMEN
In military and aerospace fields, petrol and aviation kerosene are the preferred fuels for micro power systems due to their reduced carrying load and convenient fuel source. Therefore, n-heptane, an alternative to petrol and aviation paraffin, was chosen as the fuel. A micro quartz glass tube was used as the combustor, and the premixed combustion characteristics of n-heptane/air were investigated using numerical simulations. The method used to improve the internal flow channel includes a built-in cross baffle and scaled backward-facing step. The resulting optimized combustion characteristics, such as internal flow line, wall temperature, CO emission, and wall radiation, have been analyzed. The results indicate that, with a fixed equivalence ratio of 1.0 and a n-heptane mass flow rate of 2.70 mg/s, the built-in cross baffle concentrates and stabilizes the high temperature zone of the flame, resulting in a significant increase in wall temperature. Conversely, the use of the micro tube with scaled backward-facing step creates a reflux zone due to the sudden expansion of the inlet cross-section, which promotes better fuel mixing and flame anchoring. Furthermore, after comparing the output efficiencies of micro tube with different internal structures, it was discovered that enhancing the internal channel of the micro tube is crucial for increasing the wall radiation efficiency.
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Objectives: This study aims to develop 7×7 machine-learning cross-combinatorial methods for selecting and classifying radiomic features used to construct Radiomics Score (RadScore) of predicting the mid-term efficacy and prognosis in high-risk patients with diffuse large B-cell lymphoma (DLBCL). Methods: Retrospectively, we recruited 177 high-risk DLBCL patients from two medical centers between October 2012 and September 2022 and randomly divided them into a training cohort (n=123) and a validation cohort (n=54). We finally extracted 110 radiomic features along with SUVmax, MTV, and TLG from the baseline PET. The 49 features selection-classification pairs were used to obtain the optimal LASSO-LASSO model with 11 key radiomic features for RadScore. Logistic regression was employed to identify independent RadScore, clinical and PET factors. These models were evaluated using receiver operating characteristic (ROC) curves and calibration curves. Decision curve analysis (DCA) was conducted to assess the predictive power of the models. The prognostic power of RadScore was assessed using cox regression (COX) and Kaplan-Meier plots (KM). Results: 177 patients (mean age, 63 ± 13 years,129 men) were evaluated. Multivariate analyses showed that gender (OR,2.760; 95%CI:1.196,6.368); p=0.017), B symptoms (OR,4.065; 95%CI:1.837,8.955; p=0.001), SUVmax (OR,2.619; 95%CI:1.107,6.194; p=0.028), and RadScore (OR,7.167; 95%CI:2.815,18.248; p<0.001) independently contributed to the risk factors for predicting mid-term outcome. The AUC values of the combined models in the training and validation groups were 0.846 and 0.724 respectively, outperformed the clinical model (0.714;0.556), PET based model (0.664; 0.589), NCCN-IPI model (0.523;0.406) and IPI model (0.510;0.412) in predicting mid-term treatment outcome. DCA showed that the combined model incorporating RadScore, clinical risk factors, and PET metabolic metrics has optimal net clinical benefit. COX indicated that the high RadScore group had worse prognosis and survival in progression-free survival (PFS) (HR, 2.1737,95%CI: 1.2983, 3.6392) and overall survival (OS) (HR,2.1356,95%CI: 1.2561, 3.6309) compared to the low RadScore group. KM survival analysis also showed the same prognosis prediction as Cox results. Conclusion: The combined model incorporating RadScore, sex, B symptoms and SUVmax demonstrates a significant enhancement in predicting medium-term efficacy and prognosis in high-risk DLBCL patients. RadScore using 7×7 machine learning cross-combinatorial methods for selection and classification holds promise as a potential method for evaluating medium-term treatment outcome and prognosis in high-risk DLBCL patients.
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BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) ranks among the deadliest types of cancer, and it will be meaningful to search for new biomarkers with prognostic value to help clinicians tailor therapeutic strategies. METHODS: Here we tried to use an advanced optical imaging technique, multiphoton microscopy (MPM) combining second-harmonic generation (SHG) and two-photon excited fluorescence (TPEF) imaging, for the label-free detection of PDAC tissues from a cohort of 149 patients. An automated image processing method was used to extract collagen features from SHG images and the Kaplan-Meier survival analysis and Cox proportional hazards regression were used to assess the prognostic value of collagen signatures. RESULTS: SHG images clearly show the different characteristics of collagen fibers in tumor microenvironment. We gained eight collagen morphological features, and a Feature-score was derived for each patient by the combination of these features using ridge regression. Statistical analyses reveal that Feature-score is an independent factor, and can predict the overall survival of PDAC patients as well as provide well risk stratification. CONCLUSIONS: SHG imaging technique can potentially be a tool for the accurate diagnosis of PDAC, and this optical biomarker (Feature-score) may help clinicians make more approximate treatment decisions.
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Carcinoma Ductal Pancreático , Colágeno , Neoplasias Pancreáticas , Humanos , Carcinoma Ductal Pancreático/diagnóstico por imagen , Carcinoma Ductal Pancreático/patología , Carcinoma Ductal Pancreático/mortalidad , Carcinoma Ductal Pancreático/metabolismo , Pronóstico , Femenino , Masculino , Colágeno/metabolismo , Neoplasias Pancreáticas/diagnóstico por imagen , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/mortalidad , Neoplasias Pancreáticas/diagnóstico , Persona de Mediana Edad , Anciano , Microscopía de Generación del Segundo Armónico/métodos , Biomarcadores de Tumor/metabolismo , Biomarcadores de Tumor/análisis , Estimación de Kaplan-Meier , Microscopía de Fluorescencia por Excitación Multifotónica/métodos , Adulto , Microambiente TumoralRESUMEN
After long-term clinical application, traditional Chinese medicine (TCM) has accumulated rich experience in the stroke treatment. Huang-Qi-Long-Dan Granule (HQLDG) is a TCM formula that has been used in clinical for the treatment of acute ischemic stroke. However, its mechanism against ischemic stroke is still unknown. This study aimed to identify HQLDG's effect against ischemic stroke and explore its underlying mechanism. 16s rRNA sequencing, metabolomics/tryptophan (Trp)-targeted metabolomics analysis and transcriptomic analysis were used to investigate HQLDG underlying therapeutic mechanism. Our results revealed that HQLDG significantly decreased the infarct volume, improved mouse behavior and brain slices pathological staining. In addition, it could ameliorate intestinal barrier damage and regulate tight junction gene expression. 16s rRNA, metabolomics and transcriptomics analysis revealed that HQLDG treatment significantly improved the composition of gut microbiota and Trp metabolism pathway, and further downregulated Th17/IL-17 signaling pathway. HQLDG treatment could significantly decrease serum inflammatory cytokines, IL-17A and IL-22; down-regulate Trp metabolism receptor gene (Ahr), inflammatory cytokines genes (IL-17a, IL-22), and an important coding gene for maintaining the mature Th17 (rorc) in both brain and intestinal tissues. In the contrary, after gut microbiota removal, this effect of HQLDG was impaired. HQLDG treated mouse fecal microbiota transplantation also had positive effect against tMCAO injury. Moreover, AhR inhibitor could decrease IL-17A immunofluorescence. These results suggested that the gut microbiota regulation might be an important intermediate in HQLDG against tMCAO injury. HQLDG might exert anti-ischemic stroke effects through the gut microbiota-Trp metabolism-Th17/IL-17 signaling, which provides new insights into HQLDG-mediated prevention in ischemic stroke.
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Medicamentos Herbarios Chinos , Microbioma Gastrointestinal , Accidente Cerebrovascular Isquémico , Metabolómica , Ratones Endogámicos C57BL , Animales , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Microbioma Gastrointestinal/efectos de los fármacos , Masculino , Accidente Cerebrovascular Isquémico/metabolismo , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Ratones , Triptófano/metabolismo , Astragalus propinquus , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Encéfalo/metabolismo , Encéfalo/efectos de los fármacos , Citocinas/metabolismo , Células Th17/efectos de los fármacos , Células Th17/metabolismo , Infarto de la Arteria Cerebral Media/tratamiento farmacológico , Infarto de la Arteria Cerebral Media/metabolismo , Modelos Animales de Enfermedad , Multiómica , Receptores de Hidrocarburo de Aril , Factores de Transcripción con Motivo Hélice-Asa-Hélice BásicoRESUMEN
Background: Ischemic stroke frequently leads to a condition known as post-stroke cognitive impairment (PSCI). Timely recognition of individuals susceptible to developing PSCI could facilitate the implementation of personalized strategies to mitigate cognitive deterioration. High mobility group box 1 (HMGB1) is a protein released by ischemic neurons and implicated in inflammation after stroke. Circulating levels of HMGB1 could potentially serve as a prognostic indicator for the onset of cognitive impairment following ischemic stroke. Objective: To investigate the predictive value of circulating HMGB1 concentrations in the acute phase of ischemic stroke for the development of cognitive dysfunction at the 3-month follow-up. Methods: A total of 192 individuals experiencing their initial episode of acute cerebral infarction were prospectively recruited for this longitudinal investigation. Concentrations of circulating HMGB1 were quantified using an enzyme-linked immunosorbent assay (ELISA) technique within the first 24 hours following hospital admission. Patients underwent neurological evaluation including NIHSS scoring. Neuropsychological evaluation was conducted at the 3-month follow-up after the cerebrovascular event, employing the Montreal Cognitive Assessment (MoCA) as the primary tool for assessing cognitive performance. Multivariable logistic regression models were employed to investigate the relationship between circulating HMGB1 concentrations and cognitive dysfunction following stroke, which was operationalized as a MoCA score below 26, while controlling for potential confounders including demographic characteristics, stroke severity, vascular risk factors, and laboratory parameters. Results: Of 192 patients, 84 (44%) developed PSCI. Circulating HMGB1 concentrations were significantly elevated in individuals who developed cognitive dysfunction following stroke compared to those who maintained cognitive integrity (8.4 ± 1.2 ng/mL vs 4.6 ± 0.5 ng/mL, respectively; p < 0.001). The prevalence of PSCI showed a dose-dependent increase with higher HMGB1 quartiles. After controlling for potential confounders such as demographic factors (age, gender, and education), stroke severity, vascular risk factors, and laboratory parameters in a multivariable logistic regression model, circulating HMGB1 concentrations emerged as a significant independent predictor of cognitive dysfunction following stroke (regression coefficient = 0.236, p < 0.001). Conclusion: Circulating HMGB1 concentrations quantified within the first 24 hours following acute cerebral infarction are significantly and independently correlated with the likelihood of developing cognitive dysfunction at the 3-month follow-up, even after accounting for potential confounding factors. HMGB1 may be a novel biomarker to identify patients likely to develop post-stroke cognitive impairment for targeted preventive interventions.
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Biomarcadores , Disfunción Cognitiva , Proteína HMGB1 , Accidente Cerebrovascular Isquémico , Humanos , Proteína HMGB1/sangre , Masculino , Femenino , Accidente Cerebrovascular Isquémico/sangre , Accidente Cerebrovascular Isquémico/complicaciones , Disfunción Cognitiva/sangre , Disfunción Cognitiva/etiología , Disfunción Cognitiva/diagnóstico , Anciano , Persona de Mediana Edad , Estudios Prospectivos , Biomarcadores/sangre , Estudios Longitudinales , Anciano de 80 o más Años , Ensayo de Inmunoadsorción EnzimáticaRESUMEN
Zhi-Ke-Bao pills (ZKB), a traditional Chinese medicine preparation composed of 13 herbs, is generally used to treat cough caused by external wind cold, phlegm, etc in clinical applications, and it plays a core role in relieving cough caused by COVID-19 and influenza in China. Till now, the understanding of its chemical constituents was dramatically limited due to its chemical complexity, restricting its clinical application or development. In this work, a developed ultra-high performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF MS) method, a targeted and non-targeted strategy and network pharmacology were used to comprehensively characterize the chemical compositions in ZKB and predict its mechanism against cough. A total of 164 compounds (148 targeted compounds and 16 non-targeted ones) were identified or tentatively characterized in ZKB, including 65 flavonoids, 25 alkaloids, 19 organic acids, 41 saponins, 9 coumarins, 2 phenylpropanoids, 2 anthraquinones, and 1 other types. Among them, 37 compounds were unambiguously identified by comparison to reference standards. Meanwhile, the fragmentation behaviors of five main chemical structure types were also summarized. 309 targets and two core signaling pathways of ZKB against cough were predicted by network pharmacology, including MAPK and PI3K-Akt signaling pathways. It was the first time to characterize the chemical compounds of ZKB and reveal its potential mechanism against cough, providing the material basis for further quality control or pharmacodynamic evaluation of ZKB.
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Tos , Medicamentos Herbarios Chinos , Farmacología en Red , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/análisis , Cromatografía Líquida de Alta Presión/métodos , Tos/tratamiento farmacológico , Humanos , Espectrometría de Masas/métodos , Medicina Tradicional China/métodos , Antitusígenos/farmacología , Antitusígenos/química , Antitusígenos/análisis , Tratamiento Farmacológico de COVID-19 , Alcaloides/análisis , Alcaloides/química , Alcaloides/farmacologíaRESUMEN
[This corrects the article DOI: 10.3389/fpls.2022.887179.].
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[This corrects the article DOI: 10.1016/j.fochx.2022.100203.].
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In this study, we outline a general method for the construction of various (furyl)methyl disulfides from acetyl-masked disulfide nucleophiles and ene-yne-ketones. This protocol is feathered by metal-free, simple experimental conditions, high efficiency, and scalable potential, which make it attractive and practical.
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In this manuscript, a broadband transmitarray antenna (TA) using a metasurface-based element is presented for millimeter-wave communication applications. The metasurface-based TA element adopts a receiver-transmitter configuration: metasurfaces are applied as the receiver and transmitter, and slot-coupled differentially fed striplines are used as the phase compensation. The designed TA element achieves good transmission performance with a more than 360° transmission phase shift range and less than 1-dB transmission insertion loss within a wide frequency range. To verify the proposed TA, a prototype is fabricated based on the conventional printed circuit board (PCB) process, and a pyramid horn is designed as the source. The measured results show that the proposed TA with the differential feed network presents a 1-dB gain bandwidth of 26.2% from 23.5 to 30.5 GHz and a peak gain of 24.5 dBi. The designed TA is a promising alternative for millimeter-wave communications applications because of its high gain, broad bandwidth, low costs, and convenient integration with other circuits.
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BACKGROUND: The histological grade is an important factor in the prognosis of invasive breast cancer and is vital to accurately identify the histological grade and reclassify of Grade2 status in breast cancer patients. METHODS: In this study, data were collected from 556 invasive breast cancer patients, and then randomly divided into training cohort (n = 335) and validation cohort (n = 221). All patients were divided into actual low risk group (Grade1) and high risk group (Grade2/3) based on traditional histological grade, and tumor-infiltrating lymphocyte score (TILs-score) obtained from multiphoton images, and the TILs assessment method proposed by International Immuno-Oncology Biomarker Working Group (TILs-WG) were also used to differentiate between high risk group and low risk group of histological grade in patients with invasive breast cancer. Furthermore, TILs-score was used to reclassify Grade2 (G2) into G2 /Low risk and G2/High risk. The coefficients for each TILs in the training cohort were retrieved using ridge regression and TILs-score was created based on the coefficients of the three kinds of TILs. RESULTS: Statistical analysis shows that TILs-score is significantly correlated with histological grade, and is an independent predictor of histological grade (odds ratio [OR], 2.548; 95%CI, 1.648-3.941; P < 0.0001), but TILs-WG is not an independent predictive factor for grade (P > 0.05 in the univariate analysis). Moreover, the risk of G2/High risk group is higher than that of G2/Low risk group, and the survival rate of patients with G2/Low risk is similar to that of Grade1, while the survival rate of patients with G2/High risk is even worse than that of patients with G3. CONCLUSION: Our results suggest that TILs-score can be used to predict the histological grade of breast cancer and potentially to guide the therapeutic management of breast cancer patients.
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Neoplasias de la Mama , Femenino , Humanos , Neoplasias de la Mama/patología , Linfocitos Infiltrantes de Tumor/patología , Pronóstico , Distribución AleatoriaRESUMEN
The root of Aconitum carmichaelii Debx. (Fuzi) is an herbal medicine used in China that exerts significant efficacy in rescuing patients from severe diseases. A key toxic compound in Fuzi, aconitine (AC), could trigger unpredictable cardiotoxicities with high-individualization, thus hinders safe application of Fuzi. In this study we investigated the individual differences of AC-induced cardiotoxicities, the biomarkers and underlying mechanisms. Diversity Outbred (DO) mice were used as a genetically heterogeneous model for mimicking individualization clinically. The mice were orally administered AC (0.3, 0.6, 0.9 mg· kg-1 ·d-1) for 7 d. We found that AC-triggered cardiotoxicities in DO mice shared similar characteristics to those observed in clinic patients. Most importantly, significant individual differences were found in DO mice (variation coefficients: 34.08%-53.17%). RNA-sequencing in AC-tolerant and AC-sensitive mice revealed that hemoglobin subunit beta (HBB), a toxic-responsive protein in blood with 89% homology to human, was specifically enriched in AC-sensitive mice. Moreover, we found that HBB overexpression could significantly exacerbate AC-induced cardiotoxicity while HBB knockdown markedly attenuated cell death of cardiomyocytes. We revealed that AC could trigger hemolysis, and specifically bind to HBB in cell-free hemoglobin (cf-Hb), which could excessively promote NO scavenge and decrease cardioprotective S-nitrosylation. Meanwhile, AC bound to HBB enhanced the binding of HBB to ABHD5 and AMPK, which correspondingly decreased HDAC-NT generation and led to cardiomyocytes death. This study not only demonstrates HBB achievement a novel target of AC in blood, but provides the first clue for HBB as a novel biomarker in determining the individual differences of Fuzi-triggered cardiotoxicity.
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Proteínas Quinasas Activadas por AMP , Aconitina , Cardiotoxicidad , Histona Desacetilasas , Animales , Ratones , Cardiotoxicidad/metabolismo , Cardiotoxicidad/etiología , Histona Desacetilasas/metabolismo , Proteínas Quinasas Activadas por AMP/metabolismo , Masculino , Humanos , Aconitum/química , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/metabolismo , Medicamentos Herbarios Chinos/farmacologíaRESUMEN
Wild mushroom poisoning is a global public health concern, with mushrooms containing amatoxins being the main cause of fatalities. Mushrooms from the genus Amanita and Galerina contain amatoxins. Here we present a case of wild mushroom poisoning that affected three individuals, resulting in two fatalities. Within 10-15 hours after consumption, they experienced symptoms of gastroenteritis such as vomiting, abdominal pain, and diarrhea. One individual sought medical attention promptly and recovered, while the other two sought medical help nearly two or three days after the onset of symptoms, by which time their conditions had already worsened and led to their deaths. The mushrooms were identified belonging to genus Galerina, and laboratory test revealed variations in toxin levels among mushrooms collected from different parts of the decaying stump. The higher levels of α-amanitin, ß-amanitin, and γ-amanitin were detected near the base of the tree stump, but trace levels of α-amanitin were found near the top of the stump, while ß-amanitin and γ-amanitin were undetectable. This case emphasizes the importance of seeking immediate medical attention when experiencing delayed-onset gastrointestinal symptoms, as it may indicate more severe mushroom poisoning, particularly amatoxin poisoning. Timely and appropriate treatment is equally important. Additionally, consuming different units of the mushrooms in the same incident can lead to varying prognoses due to differences in toxin levels.
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Intoxicación por Setas , Humanos , Intoxicación por Setas/diagnóstico , Intoxicación por Setas/terapia , Alfa-Amanitina , Salud Pública , Amanitinas/análisis , AmanitaRESUMEN
Under transition-metal-free conditions, trisulfide dioxides were used as disulfurating reagents to react with a wide range of amides, affording various substituted N-disulfanyl amides in good yields. Furthermore, the gram-scale experiment has confirmed the practicability of this approach.