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The devastating COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has made society acutely aware of the urgency in developing effective techniques to timely monitor the outbreak of previously unknown viral species as well as their mutants, which could be even more lethal and/or contagious. Here, we report a fluorogenic sensor array consisting of peptides truncated from the binding domain of human angiotensin-converting enzyme 2 (hACE2) for SARS-CoV-2. A set of five fluorescently tagged peptides were used to construct the senor array in the presence of different low-dimensional quenching materials. When orthogonally incubated with the wild-type SARS-CoV-2 and its variants of concern (VOCs), the fluorescence of each peptide probe was specifically recovered, and the different recovery rates provide a "fingerprint" characteristic of each viral strain. This, in turn, allows them to be differentiated from each other using principal component analysis. Interestingly, the classification result from our sensor array agrees well with the evolutionary relationship similarity of the VOCs. This study offers insight into the development of effective sensing tools for highly contagious viruses and their mutants based on rationally truncating peptide ligands from human receptors.
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Enzima Convertidora de Angiotensina 2 , COVID-19 , Colorantes Fluorescentes , Péptidos , SARS-CoV-2 , Enzima Convertidora de Angiotensina 2/metabolismo , Enzima Convertidora de Angiotensina 2/química , SARS-CoV-2/enzimología , SARS-CoV-2/aislamiento & purificación , Humanos , Péptidos/química , Péptidos/metabolismo , Colorantes Fluorescentes/química , COVID-19/virología , COVID-19/diagnóstico , Técnicas Biosensibles/métodosRESUMEN
Aromatic metalla-annulenes are important aromatic compounds, research into which has been mainly concentrated on metal-benzenes and their lower homologues. Reports on their superior homologs are rare, and this has greatly limited the systematic study of their properties. In this work, a series of osma-dehydro[11]annulenes with good air and thermal stability were prepared in high yields through a simple [10+1] strategy, by incorporating a metal fragment into conjugated ten-carbon chains in a one-pot reaction. They are the first monometallic aromatic metalla-[n]annulenes with the ring size larger than 6, and their Craig-Hückel hybrid aromaticity is supported by various physical and computational parameters. Besides, these complexes show versatile reactivities, not only giving further evidence for their aromaticity, but also demonstrating their physical and chemical properties can easily be regulated. This work enriches the metalla-aromatic chemistry, and provides a new avenue for the synthesis of large metalla-annulenes with different ring sizes.
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Chlorinated polyfluorinated ether sulfonates (Cl-PFESAs) are one kind of replacement chemistry for perfluorooctanesulfonate (PFOS). Recent studies have shown that Cl-PFESAs could interfere with thyroid function in animal models. However, epidemiological evidence on the link between Cl-PFESAs and thyroid function remains scarce. In this study, we focused on two representative legacy perfluoroalkyl substances (PFAS), including PFOS and perfluorooctanoic acid (PFOA), and two PFOS alternatives (6:2 and 8:2 Cl-PFESAs) in the general adult population from a cross-sectional study, the "Isomers of C8 Health Project in China". Three serum thyroid hormones (THs), thyroid stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4), were measured. We fitted generalized linear regression, restricted cubic spline regression, and Bayesian kernel machine regression models to assess associations of individual Cl-PFESAs, legacy PFAS, and PFAS mixtures with THs, respectively. We found individual PFAS and their mixtures were nonlinearly associated with THs. The estimated changes of the TSH level (µIU/mL) at the 95th percentile of 6:2 Cl-PFESA and PFOS against the 5th percentile were -0.74 (95% CI: -0.94, -0.54) and -1.18 (95% CI: -1.37, -0.98), respectively. The present study provided epidemiological evidence for the association of 6:2 Cl-PFESA with thyroid hormone levels in the general adult population.
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Ácidos Alcanesulfónicos , Fluorocarburos , Alcanosulfonatos , Animales , Teorema de Bayes , China/epidemiología , Estudios Transversales , Éter , Éteres , Fluorocarburos/análisis , Glándula Tiroides , Hormonas Tiroideas , TirotropinaRESUMEN
BACKGROUND: To explore the correlation between the volume of putamen and brain cognitive impairment in patients with HIV and to predict the feasibility of early-stage HIV brain cognitive impairment through radiomics. METHOD: Retrospective selection of 90 patients with HIV infection, including 36 asymptomatic neurocognitive impairment (ANI) patients and 54 pre-clinical ANI patients in Beijing YouAn Hospital. All patients received comprehensive neuropsychological assessment and MRI scanning. 3D Slicer software was used to acquire volume of interest (VOI) and radiomics features. Clinical variables and volume of putamen were compared between patients with ANI and pre-clinical ANI. The Kruskal Wallis test was used to analysis multiple comparisons between groups. The relationship between cognitive scores and VOI was compared using linear regression. For radiomics, principal component analysis (PCA) was used to reduce model overfitting and calculations and then a support vector machine (SVM) was used to build a binary classification model. For model performance evaluation, we used an accuracy, sensitivity, specificity and receiver operating characteristic curve (ROC). RESULT: There were no significant differences in clinical variables between ANI group and pre-clinical-ANI group (P>0.05). The volume of bilateral putamen was significantly different between AHI group and pre-clinical group (P<0.05), but there was only a trend in the left putamen between ANI-treatment group and pre-clinical treatment group(P = 0.063). Reduced cognitive scores in Verbal Fluency, Attention/Working Memory, Executive Functioning, memory and Speed of Information Processing were negatively correlated with the increased VOI (P<0.05), but the correlation was relatively low. In diagnosing the ANI from pre-clinical ANI, the mean area under the ROC curves (AUC) were 0.85 ± 0.22, the mean sensitivity and specificity were 63.12 ± 5.51 and 94.25% ± 3.08%. CONCLUSION: The volumes of putamen in patients with ANI may be larger than patients with pre-clinical ANI, the change of the volume of the putamen may have a certain process; there is a relationship between putamen and cognitive impairment, but the exact mechanism is unclear. Radiomics may be a useful tool for predicting early stage HAND in patients with HIV.
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Complejo SIDA Demencia , Putamen , Complejo SIDA Demencia/diagnóstico por imagen , Complejo SIDA Demencia/patología , Complejo SIDA Demencia/fisiopatología , Adulto , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Disfunción Cognitiva , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Pruebas Neuropsicológicas , Putamen/diagnóstico por imagen , Putamen/patología , Interpretación de Imagen Radiográfica Asistida por Computador , Estudios RetrospectivosRESUMEN
BACKGROUND: Hepatocellular carcinoma (HCC) is the most common malignant tumor of the liver, and its morbidity and mortality have been increasing in recent years. The early diagnosis and prompt treatment of small HCC are crucial to improve the prognosis and quality of life of patients. In China, hepatitis B virus infection is the main cause. HCC with a single tumor nodule of ≤ 3 cm in diameter, or HCC with a number of nodules, in which each nodule is ≤ 2 cm in diameter, with a total diameter of ≤ 3 cm, is considered as small HCC. The MRI liver-specific contrast agent can detect small HCC at the early stage. This has important clinical implications for improving the survival rate of patients. MAIN BODY: Gd-EOB-DTPA-enhanced MRI can significantly improve the sensitivity and specificity of the detection of HBV-related small hepatocellular carcinoma, providing an important basis for the clinical selection of appropriate personalized treatment. Gd-EOB-DTPA-enhanced MRI can reflect the degree of HCC differentiation, and the evaluation of HCC on Gd-EOB-DTPA-enhanced MRI would be helpful for the selection of the treatment and prognosis of HCC patients. The present study reviews the progress of the application of Gd-EOB-DTPA in the early diagnosis of small HCC, its clinical treatment, the prediction of the degree of differentiation, and the assessment of recurrence and prognosis of HCC, including the pharmacoeconomics and application limitations of Gd-EOB-DTPA. The value of the application of HCC with the Gd-EOB-DTPA was summarized to provide information for improving the quality of life and prolonging the survival of patients. CONCLUSION: Gd-EOB-DTPA-enhanced MRI has the diagnostic capability for small HCC with a diameter of ≤ 2 cm. This will have a broader application prospect in the early diagnosis of small liver cancer with a diameter of ≤ 1 cm in the future. The relationship between GD-EOB-DTPA-MRI and the degree of HCC differentiation has a large research space, and Gd-EOB-DTPA is expected to become a potential tool for the preoperative prediction and postoperative evaluation of HCC, which would be beneficial for more appropriate treatments for HCC patients.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/diagnóstico por imagen , China , Medios de Contraste , Gadolinio DTPA , Humanos , Neoplasias Hepáticas/diagnóstico por imagen , Imagen por Resonancia Magnética , Recurrencia Local de Neoplasia , Pronóstico , Calidad de VidaRESUMEN
To study the effect of polysaccharides from Polygonatum sibiricum on mRNA and protein expressions of blood lipid metabolism in hyperlipidemic mice. The mice were randomly divided into 6 groups, namely the blank control group, the hyperlipidemia model group, the simvastatin group, and low, middle and high-dose PSP groups (200, 400, 800 mg·kg⻹·d⻹). Each group of the mice was administrated intragastrically for 14 days, respectively. Subsequently, every group of mice, except for the blank control group, was intraperitoneally injected with 75% fresh egg yolk emulsion for establishing the hyperlipidemic mice model. Upon completion of the administration, the contents of TC, TG, LDL-C and HDL-C in serum of each group were investigated in details. In particular, the mRNA expression levels of PPAR-α, PPAR-ß, PPAR-γ, SREBP-1c, IL-6 and TNF-α of the liver tissues were detected by Real-time PCR, and the protein expression levels (including PPAR-α, PPAR-ß, PPAR-γ, SREBP-1c, IL-6, TNF-α) were examined by Western blot. Consequently, the obtained results showed that the contents of the serum TC, TG, LDL-C of low, middle and high-dose PSP groups significantly decreased compared with those of the hyperlipidemia model group. Simultaneously, there were significant differences between middle-dose and high-dose PSP groups (P<0.01). In striking contrast, the contents of serum HDL-C of low, middle and high-dose PSP groups significantly increased, while obvious differences were also observed between middle-dose and high-dose PSP groups (P<0.01). Moreover, middle-dose and high-dose PSR groups could up-regulate the protein and mRNA expressions of PPAR-α, PPAR-ß (P<0.05) compared with those of the hyperlipidemia model group, and down-regulate the expressions of PPAR-γ,SREBP-1c, IL-6 and TNF-α(P<0.05) compared with those of liver tissues of the hyperlipidemia model group. In conclusion, all of the above results suggested that PSP could inhibit the oxidation of the liver lipid, and regulate the expression levels of the corresponding genes and proteins relating to the lipid metabolism, so as to play a critical role for preventing hyperlipidemia.
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Hiperlipidemias/tratamiento farmacológico , Metabolismo de los Lípidos , Polygonatum/química , Polisacáridos/farmacología , Animales , Ratones , Fitoquímicos/farmacología , ARN Mensajero/metabolismo , Distribución AleatoriaRESUMEN
Objective: To investigate the effect of Dahuang-Taoren with different proportion of extraction amount changes of ten kinds of chemical constituents in Rhizoma Rhei. Methods: Uniform method to set different ratio( 1ⶠ5,2ⶠ5,2ⶠ3,1ⶠ1,3ⶠ2,5ⶠ2,5ⶠ1),and set the control group ( Dahuang-Taoren( 1 ⶠ0). HPLC was used to determine the content of ten constituents as gallic acid,( +)-catechin,sennoside B,anthraquinones( aloe-emodin,rhein,emodin,chrysophanol,physcion,chrysophanol-1-O-glucoside,emodin major grape glycoside) in different ratio of drug. Different proportions of Dahuang-Taoren on the extraction amount of ten chemical components in Rhizoma Rhei changes were analyzed. . Results: Compared to the control group, Dahuang-Taoren with different ratio( 5ⶠ1,5ⶠ2,3ⶠ2) in a sample with increasing proportion of Taoren,the extraction amount of ten kinds of constituents of Rhizoma Rhei gradually decreased;Dahuang-Taoren with ratio of 1ⶠ1,ten kinds of constituents in extraction of total amount arrived minimum value. Dahuang-Taoren with different ratio( 2ⶠ3,2ⶠ5,1ⶠ5) in a sample with increasing proportion of Taoren,the extraction amount of gallic acid,( +) catechin,chrysophanol of Rhizoma Rhei increased significantly. Conclusion: There is obvious change in chemical constituents of the extraction amount of Rhizoma Rhei with the change of the ratio in Dahuang-Taoren, and Dahuang-Taoren with the ratio( 2ⶠ3,2ⶠ5,1ⶠ5),the extraction amount of gallic acid,( +)-catechin,sennoside B,aloe-emodin,emodin,chrysophanol,physcion,chrysophanol-1-O-glucoside are significantly higher than control group.
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Medicamentos Herbarios Chinos , Rizoma , Antraquinonas , Cromatografía Líquida de Alta Presión , Emodina/análogos & derivados , Rheum , Extracto de Senna , SenósidosRESUMEN
Whipple's disease is a chronic systemic infectious disease that mainly affects the gastrointestinal tract. In some cases, Tropheryma whipplei can cause infection at the implant site or even throughout the body. In this study, we collected alveolar lavage fluid samples from patients with Tropheryma whipplei from 2020 to 2022, and retrospectively analyzed the clinical data of Tropheryma whipplei positive patients. Patient's past history, clinical manifestations, laboratory examinations, chest CT findings, treatment, and prognosis were recorded. 16 BALFs (70/1725, 4.0 %) from 16 patients were positive for Tropheryma whipplei. 8 patients were male with an average age of 50 years. The main clinical symptoms of patients included fever (9/16), cough (7/16), dyspnea (7/16), and expectoration (5/16), but neurological symptoms and arthralgia were rare. Cardiovascular and cerebrovascular diseases were the most common comorbidity (n=8). The main laboratory characteristics of the patient are red blood cell count, hemoglobin, total protein and albumin below normal levels (11/16), and/or creatinine above normal levels(14/16). Most chest computed tomography mainly show focal or patchy heterogeneous infection (n=5) and pleural effusion (n=8). Among the 6 samples, Tropheryma whipplei was the sole agent, and Klebsiella pneumoniae was the most common detected other pathogens. Metagenomic next-generation sequencing technology has improved the detection rate and attention of Tropheryma whipplei. Further research is needed to distinguish whether Tropheryma whipplei present in respiratory samples is a pathogen or an innocent bystander.
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Líquido del Lavado Bronquioalveolar , Secuenciación de Nucleótidos de Alto Rendimiento , Metagenómica , Tropheryma , Enfermedad de Whipple , Humanos , Masculino , Persona de Mediana Edad , Líquido del Lavado Bronquioalveolar/microbiología , Femenino , Tropheryma/genética , Tropheryma/aislamiento & purificación , Estudios Retrospectivos , Enfermedad de Whipple/diagnóstico , Enfermedad de Whipple/microbiología , Metagenómica/métodos , Anciano , AdultoRESUMEN
OBJECTIVE: To investigate the effectiveness of focused extracorporeal shock wave therapy (FESWT) in treating postpartum sacroiliac joint (SIJ) dysfunction. METHODS: A total of 90 patients with SIJ dysfunction were included and randomly assigned to FESWT, manual therapy (MT), or combination therapy (CT) groups. Pain intensity and Oswestry Disability Index (ODI) score were measured upon admission, after 1 and 2 weeks of treatments. The treatment efficacy and adverse events of each group were also assessed. RESULTS: There were no significant differences among three groups regarding clinical data, pain intensity, and ODI score on admission (all P > 0.05). After 1 week of treatment, FESWT exhibited similar pain intensity and lower ODI score (P < 0.001) compared to MT. After 2 weeks of treatment, the pain and ODI in FESWT were similar with MT. The pain in CT was lower than MT after 1 week, but lower than FESWT after 2 weeks. Furthermore, we identified interaction effects between treatment method and duration in relation to pain intensity (Fgroup*time = 5.352, P = 0.001) and ODI score (Fgroup*time = 5.902, P < 0.001). FESWT group exhibited the highest improvement rate of 66.7%, while CT group achieved the highest cure rate of 73.3%. No adverse events were observed in any of the patients during 2 months follow-up period. CONCLUSIONS: Compared to MT, FESWT mainly reduced the ODI score rather than pain after 1 week of treatment. After 2 weeks, the effect of FESWT in relieving the pain was inferior to the MT.
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Artropatías , Dolor de la Región Lumbar , Manipulaciones Musculoesqueléticas , Femenino , Humanos , Dolor de la Región Lumbar/terapia , Manipulaciones Musculoesqueléticas/métodos , Estudios Prospectivos , Articulación Sacroiliaca , Resultado del TratamientoRESUMEN
Correction for 'Elaborating the interplay between the detecting unit and emitting unit in infrared quantum dot up-conversion photodetectors' by Qiulei Xu et al., Nanoscale, 2023, 15, 8197-8203, https://doi.org/10.1039/D3NR01237A.
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The application of biomarkers to study the molecular composition of soil organic matter (SOM) can be used to analyze the source and degradation of SOM and reveal the stability mechanism of soil organic carbon (SOC) at the molecular level. In order to further clarify the effects of different land use patterns (farmland, grassland, and forest) on the molecular composition of SOM, the changes in molecular composition of organic matter (free lipids, cutin, suberin, and lignin) on a global scale were studied using a meta-analysis method. The results showed that there were significant differences in the molecular composition of organic matter under different land use patterns. The contents of free lipids (n-alkanes, n-alkanols, n-alkanoic acids, and cyclic lipids), cutin, and lignin phenols in forest soil were significantly higher than those in grassland and farmland. There was no significant difference in the content of suberin between grassland and forest soil. The ratio of suberin to cutin in grassland was the highest, with an average of 2.96, and the averages of farmland and forest were 1.68 and 2.21, respectively. The ratio of syringic acid to syringaldehyde (Ad/Al)S and the ratio of vanillic acid to vanillin (Ad/Al)V of farmland soil were the largest, which were 1.25 and 1.58, respectively, and were significantly higher than those in grassland (0.46 and 0.69) and forest (0.78 and 0.7). The results of correlation analysis showed that in farmland soil, suberin was significantly correlated with mean annual precipitation (MAP) and clay; cutin was significantly correlated with clay; and lignin was significantly correlated with mean annual temperature (MAT), MAP, sand, and bulk density. In grassland soil, total free lipids were significantly correlated with MAP and bulk density; suberin and cutin were significantly correlated with MAT and MAP; and lignin was significantly correlated with MAP, pH, sand, and bulk density. However, only lignin was significantly correlated with MAP and sand in forest soils. Overall, the contents of SOC and molecular components in forest soil were higher under the three land use practices, and the contribution of plant roots to SOM in grassland soil was greater. In farmland soil, the degradation of lignin was accelerated due to human farming activities. Future research should focus on the regulation of soil physicochemical properties and climatic conditions on the molecular composition of SOM.
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Acute liver injury (ALI) is a common clinical disease caused by sepsis, metabolic syndrome, hepatitis virus. Macrophage plays an important role in the development of ALI, which is characterized by polarization and inflammatory regulation. The polarization process of macrophages is related to membrane binding proteins and adaptors. Protein 4.1R acts as an adaptor, linking membrane proteins to the cytoskeleton, and is involved in cell activation and cytokine secretion. However, whether protein 4.1R is involved in regulating macrophage polarization and inflammation-induced liver injury remains unknown. In this study, protein 4.1R is identified with the special effect on macrophage M1 polarization. And it is further demonstrated that protein 4.1R deficiency significantly enhance glycolytic metabolism. Mechanistically, the regulation of protein 4.1R on pyruvate kinase M2 (PKM2) plays a key role in glycolysis metabolism. In addition, we found that protein 4.1R directly interacts with toll-like receptor 4 (TLR4), inhibits the activation of the AKT/HIF-1α signaling pathway. In conclusion, protein 4.1R targets HIF-1α mediated glycolysis regulates M1 macrophage polarization, indicating that protein 4.1R is a candidate for regulating macrophage mediated inflammatory response. In conclusion, we have revealed a novel function of protein 4.1R in macrophage polarization and ALI, providing important insights into the metabolic reprogramming, which is important for ALI therapy. We have revealed a novel function of protein 4.1R in macrophage polarization and ALI, providing important insights into the metabolic reprogramming, which is important for ALI therapy.
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Enfermedad Hepática Crónica Inducida por Sustancias y Drogas , Sepsis , Ratones , Animales , Enfermedad Hepática Crónica Inducida por Sustancias y Drogas/metabolismo , Lipopolisacáridos/farmacología , Macrófagos , Glucólisis , Sepsis/metabolismoRESUMEN
PbS quantum dot light-emitting diodes (QLEDs) emitting around 1550 nm promise important applications in optical communications. However, due to insufficient suppression of surface traps for large-size PbS quantum dots (QDs), their performance under large driving current density was not satisfactory. In this work, octanethiol surfactant was added into a PbS QD solution and adsorbed onto the dot surface. As a result, the surface traps and the continuous oxidation of the unprotected (100) facets in PbS QDs were greatly suppressed. Therefore, the PbS QDs with octanethiol doubled their photoluminescence efficiency and showed outstanding stability. The PbS-based QLEDs with benchmark device structure showed a breakthrough high radiance of 18.3 Wâ¯sr-1â¯m-2 with >2000 mA/cm2 driving current density. The efficient passivation of surface traps with octanethiol surfactant and the suppressed coupling between excitons and surface states under large working current were the main reasons for achieving the breakthrough high radiance.
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Acquired immune deficiency syndrome infection can lead to cognitive dysfunction represented by changes in the default mode network. Most recent studies have been cross-sectional and thus have not revealed dynamic changes in the default mode network following acquired immune deficiency syndrome infection and antiretroviral therapy. Specifically, when brain imaging data at only one time point are analyzed, determining the duration at which the default mode network is the most effective following antiretroviral therapy after the occurrence of acquired immune deficiency syndrome. However, because infection times and other factors are often uncertain, longitudinal studies cannot be conducted directly in the clinic. Therefore, in this study, we performed a longitudinal study on the dynamic changes in the default mode network over time in a rhesus monkey model of simian immunodeficiency virus infection. We found marked changes in default mode network connectivity in 11 pairs of regions of interest at baseline and 10 days and 4 weeks after virus inoculation. Significant interactions between treatment and time were observed in the default mode network connectivity of regions of interest pairs area 31/V6.R and area 8/frontal eye field (FEF). L, area 8/FEF.L and caudal temporal parietal occipital area (TPOC).R, and area 31/V6.R and TPOC.L. ART administered 4 weeks after infection not only interrupted the progress of simian immunodeficiency virus infection but also preserved brain function to a large extent. These findings suggest that the default mode network is affected in the early stage of simian immunodeficiency virus infection and that it may serve as a potential biomarker for early changes in brain function and an objective indicator for making early clinical intervention decisions.
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The quantum dot up-conversion device combines an infrared photodetector (PD) and a visible quantum-dot light-emitting diode (QLED) to directly convert infrared targets to visible images. However, large efficiency loss is usually induced by the integration of the detecting unit and the emitting unit. One of the important reasons is the performances of the PD and QLED units restraining each other. We regulated the equilibrium between infrared absorption and visible emission by changing the thicknesses of infrared active layers in up-conversion devices. A good balance could be achieved between the absorption of 980 nm incident light and the out-coupling of the 634 nm emission when the active layer thickness is 140 nm, leading to the best performance of the up-conversion device. As more photogenerated carriers are produced with the increase of infrared illumination intensity, the external quantum efficiency (EQE) of the QLED unit in the up-conversion device remains little changed. This suggests the limited amount of photogenerated holes in the PD unit does not limit the EQE of the QLED unit. However, a PD unit with a high ratio of photogenerated holes trapped near the interconnection decreased the EQE in the QLED unit. This work provides new insights into the interplay between the PD and QLED units in up-conversion devices, which is crucial for their further improvements.
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BACKGROUND: Pediatric antineutrophil cytoplasmic antibody-associated vasculitis (AAV) is a life-threatening systemic vasculitis featured by liability to renal involvement. However, there are few studies on the risk factors and predictive models for renal outcomes of AAV in children. METHODS: Data from 179 AAV children in multiple centers between January 2012 and March 2020 were collected retrospectively. The risk factors and predictive model of end-stage renal disease (ESRD) in AAV were explored. RESULTS: Renal involvement was the most typical manifestation (95.5%), and the crescent was the predominant pathological lesion (84.9%). The estimated glomerular filtration rate (eGFR) was evaluated in 114 patients, of whom 59.6% developed ESRD, and the median time to ESRD was 3.20 months. The eGFR [P = 0.006, odds ratio (OR) = 0.955, 95% confidence interval (CI) = 0.924-0.987] and the percentages of global glomerulosclerosis (pGGS; P = 0.018, OR = 1.060, 95% CI = 1.010-1.112) were independent risk factors for ESRD of renal biopsy. Based on the pGGS and eGFR at renal biopsy, we developed three risk grades of ESRD and one predictive model. The KaplanâMeier curve indicated that renal outcomes were significantly different in different risk grades (P < 0.001). Compared with serum creatinine at baseline, the predictive model had higher accuracy (0.86 versus 0.58, P < 0.001) and a lower coefficient of variation (0.07 versus 0.92) in external validation. CONCLUSIONS: Renal involvement is the most common manifestation of pediatric AAV in China, of which more than half deteriorates into ESRD. The predictive model based on eGFR at renal biopsy and the pGGS may be stable and accurate in speculating the risk of ESRD in AAV children. Supplementary file 2 (MP4 18937 KB).
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Numerous epidemiological studies have investigated the lipid interference effects of legacy PFASs, however, no studies on PFAS alternatives and blood lipids have been published. In this study, we explored the association between Cl-PFESAs, a typical PFASs alternative in China, and blood lipid profiles in 1336 Guangzhou community residents using linear and non-linear regression models. The results showed a deleterious effect of Cl-PFESAs and blood lipids: adjusted estimates (ß) for TC, TG, LDL-C and HDL-C per natural log unit increase of 6:2 Cl-PFESA were 0.029 (95% CI: 0.020, 0.038), 0.075 (95% CI: 0.049, 0.101), 0.035 (95% CI: 0.021, 0.049) and -0.071 (95% CI: -0.084, -0.058), respectively. The association between Cl-PFESAs and dyslipidemia was also positively significant (P < 0.05). Furthermore, a non-linear relationship was observed in Cl-PFESAs and serum lipid levels using a restricted cubic splines (RCS) model. In summary, our research suggested a negative impact of Cl-PFESAs on blood lipid patterns and a possible non-linear association.
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Ácidos Alcanesulfónicos , Fluorocarburos , China/epidemiología , Fluorocarburos/análisis , Lípidos , Proyectos de InvestigaciónRESUMEN
Experimental evidence has shown that per- and polyfluoroalkyl substances (PFAS) alternatives and mixtures may exert hepatotoxic effects in animals. However, epidemiological evidence is limited. This research aimed to explore associations of PFAS and the alternatives with liver function in a general adult population. The study participants consisted of 1,303 adults from a community-based cross-sectional investigation in Guangzhou, China, from November 2018 to August 2019. We selected 13 PFAS with detection rates > 85% in serum samples and focused on perfluorooctane-sulfonic acid (PFOS), perfluorooctanoic acid (PFOA) and their alternatives [6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA), 8:2 Cl-PFESA, and perfluorohexanoic acid (PFHxA)] as predictors of outcome. Six liver function biomarkers (ALB, ALT, AST, GGT, ALP, and DBIL) were chosen as outcomes. We applied regression models with restricted cubic spline function to explore correlations between single PFAS and liver function and inspected the combined effect of PFAS mixtures on liver by applying Bayesian kernel machine regression (BKMR). We discovered positive associations among PFAS and liver function biomarkers except for ALP. For example, compared with the 25th percentile of PFAS concentration, the level of ALT increased by 12.36% (95% CI: 7.91%, 16.98%) for ln-6:2 Cl-PFESA, 5.59% (95% CI: 2.35%, 8.92%) for ln-8:2 Cl-PFESA, 3.56% (95% CI: -0.39%, 7.68%) for ln-PFHxA, 13.91% (95% CI: 8.93%, 19.13%) for ln-PFOA, and 14.25% (95% CI: 9.91%, 18.77%) for ln-PFOS at their 75th percentile. In addition, higher exposed serum PFAS was found to be correlated with greater odds of abnormal liver function. Analysis from BKMR models also showed an adverse association between PFAS mixtures and liver function. The combined effect of the PFAS mixture appeared to be non-interactive, in which PFOS was the main contributor to the overall effect. Our findings provide evidence of associations between PFAS alternatives, PFAS mixtures, and liver function in the general adult population.
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Ácidos Alcanesulfónicos , Contaminantes Ambientales , Fluorocarburos , Ácidos Alcanesulfónicos/análisis , Ácidos Alcanesulfónicos/toxicidad , Teorema de Bayes , China/epidemiología , Estudios Transversales , Contaminantes Ambientales/análisis , Contaminantes Ambientales/toxicidad , Fluorocarburos/análisis , Fluorocarburos/toxicidad , Humanos , Hígado/químicaRESUMEN
Purpose: To investigate the effect of syphilis infection on the microstructure of white matter (WM) in HIV-infected male patients using diffusion tensor imaging (DTI). Methods: Twenty-seven HIV-infected male patients with current syphilis or a history of syphilis (HIV +/syphilis +), twenty-nine HIV-infected male patients without syphilis co-infection (HIV +/syphilis-), and twenty-nine healthy controls (HC) were enrolled. All participants received DTI, and all patients received comprehensive neuropsychological assessment. Tract-based spatial statistics (TBSS) was adopted to analyze the DTI measures: fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD). Correlation analysis was conducted to investigate the relationships between DTI measures and cognitive performance. Results: There were no significant differences in DTI measures between HIV+/syphilis- and HC. Compared with HC, lower FA was found in body of corpus callosum (BCC), splenium of corpus callosum (SCC), genu of corpus callosum (GCC), the bilateral anterior corona radiata (ACR), superior corona radiata (SCR), posterior corona radiata (PCR), and posterior thalamic radiation (PTR) in HIV+/syphilis+ (p < 0.05). Higher RD was found in BCC and SCC (p < 0.05). Compared with HIV+/syphilis-, lower scores were found in complex motor skills (CMS) in HIV+/syphilis+, lower FA was found in BCC, SCC, GCC, the bilateral ACR, SCR, PCR, PTR, cingulate gyrus (CGC), the right inferior fronto-occipital fasciculus (IFO), the retrolenticular part of internal capsule (RLIC), sagittal stratum (SS), external capsule (EC) in HIV+/syphilis+ (p < 0.01). Correlation analysis uncorrected for multiple comparisons showed there was a positive correlation between FA in GCC and CMS, FA in BCC, and CMS in HIV+/syphilis+. Conclusions: Syphilis co-infection can have an additive or synergistic effect on the brain WM in HIV-infected subjects. HIV-infected patients without syphilis should be actively treated to avoid syphilis infection.
RESUMEN
5-Fluorouracil (5-Fu) is an effective anticarcinogenic agent, however, continuous use of 5-Fu may cause severe side effects. The goal of this study was to investigate the effectiveness of Sarcodon aspratus polysaccharides (SATP) in alleviating 5-Fu-induced toxicity in Lewis tumor-bearing mice. Lewis tumor-bearing mice were treated with saline, SATP, 5-Fu or 5-Fu + SATP. The results indicated that compared to the 5-Fu group, the 5-Fu + SATP group showed effective amelioration of the liver, kidney and small intestine injury caused by 5-Fu and decreases in the levels of related biochemical indicators, such as aspartate aminotransferase (AST), alanine aminotransferase (ALT) and urea nitrogen (BUN). Additionally, the combination therapy enhanced the quality of life and immune organ indexes of mice. Further mechanistic studies indicated that the 5-Fu + SATP group showed a decrease in hepatotoxicity caused by 5-Fu via a reduction in the levels of interleukin-1ß (IL-1ß), an increase in the expression of Bcl-2 and decreases in the expression of p-p38, p-JNK and Bax. Collectively, the results indicated that SATP could significantly alleviate the toxicity of 5-Fu in Lewis tumor-bearing mice and showed the hepatoprotective capability of SATP via its effect on the expression levels of inflammatory factors and components of the MAPK/P38/JNK pathway, which shows that it may be a potential adjuvant for the chemotherapeutic drug 5-Fu in cancer treatment.