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Biomass burning plays an important role in climate-forcing and atmospheric chemistry. The drivers of fire activity over the past two centuries, however, are hotly debated and fueled by poor constraints on the magnitude and trends of preindustrial fire regimes. As a powerful tracer of biomass burning, reconstructions of paleoatmospheric carbon monoxide (CO) can provide valuable information on the evolution of fire activity across the preindustrial to industrial transition. Here too, however, significant disagreements between existing CO records currently allow for opposing fire histories. In this study, we reconstruct a continuous record of Antarctic ice core CO between 1821 and 1995 CE to overlap with direct atmospheric observations. Our record indicates that the Southern Hemisphere CO burden ([CO]) increased by 50% from a preindustrial mixing ratio of ca. 35 ppb to ca. 53 ppb by 1995 CE with more variability than allowed for by state-of-the-art chemistry-climate models, suggesting that historic CO dynamics have been not fully accounted for. Using a 6-troposphere box model, a 40 to 50% decrease in Southern Hemisphere biomass-burning emissions, coincident with unprecedented rates of early 20th century anthropogenic land-use change, is identified as a strong candidate for this mismatch.
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Antimicrobial phototherapy has gained recognition as a promising approach for addressing bacterial biofilms, however, its effectiveness is often impeded by the robust physical and chemical defenses of the biofilms. Traditional antibacterial nanoplatforms face challenges in breaching the extracellular polymeric substances barrier to efficiently deliver photosensitizers deep into biofilms. Moreover, the prevalent hypoxia within biofilms restricts the success of oxygen-reliant phototherapy. In this study, we engineered a soft mesoporous organosilica nanoplatform (SMONs) by incorporating polyethylene glycol (PEG), catalase (CAT), and indocyanine green (ICG), forming SMONs-PEG-CAT-ICG (SPCI). We compared the antimicrobial efficacy of SPCI with more rigid nanoplatforms. Our results demonstrated that unique flexible mechanical properties of SPCI enable it to navigate through biofilm barriers, markedly enhancing ICG penetration in methicillin-resistant Staphylococcus aureus (MRSA) biofilms. Notably, in a murine subcutaneous MRSA biofilm infection model, SPCI showed superior biofilm penetration and pharmacokinetic benefits over its rigid counterparts. The embedded catalase in SPCI effectively converts excess H2O2 present in infected tissues into O2, alleviating hypoxia and significantly boosting the antibacterial performance of phototherapy. Both in vitro and in vivo experiments confirmed that SPCI surpasses traditional rigid nanoplatforms in overcoming biofilm barriers, offering improved treatment outcomes for infections associated with bacterial biofilms. This study presents a viable strategy for managing bacterial biofilm-induced diseases by leveraging the unique attributes of a soft mesoporous organosilica-based nanoplatform. STATEMENT OF SIGNIFICANCE: This research introduces an innovative antimicrobial phototherapy soft nanoplatform that overcomes the inherent limitations posed by the protective barriers of bacterial biofilms. By soft nanoplatform with flexible mechanical properties, we enhance the penetration and delivery of photosensitizers into biofilms. The inclusion of catalase within this soft nanoplatform addresses the hypoxia in biofilms by converting hydrogen peroxide into oxygen in infected tissues, thereby amplifying the antibacterial effectiveness of phototherapy. Compared to traditional rigid nanoplatforms, this flexible nanoplatform not only promotes the delivery of therapeutic agents but also sets a new direction for treating bacterial biofilm infections, offering significant implications for future antimicrobial therapies.
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Antibacterianos , Biopelículas , Catalasa , Verde de Indocianina , Fármacos Fotosensibilizantes , Biopelículas/efectos de los fármacos , Animales , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/farmacocinética , Ratones , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/química , Verde de Indocianina/farmacología , Verde de Indocianina/química , Catalasa/metabolismo , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Staphylococcus aureus Resistente a Meticilina/fisiología , Fototerapia , Polietilenglicoles/química , Polietilenglicoles/farmacología , Nanopartículas/química , Infecciones Estafilocócicas/tratamiento farmacológico , Permeabilidad , Femenino , Ratones Endogámicos BALB CRESUMEN
BACKGROUND: A percentage of total weight loss (%TWL) >20% as the expected weight loss target after metabolic surgery might be insufficient to produce adequate metabolic benefits. OBJECTIVES: This study identified the optimal weight loss target to achieve substantial benefits from metabolic surgery. SETTING: University-affiliated tertiary care center. METHODS: In this retrospective study, participants were categorized into healthy weight (18.5 kg/m2 ≤ body mass index [BMI] < 24 kg/m2), overweight (24 kg/m2 ≤ BMI < 28 kg/m2), and obesity groups (BMI ≥28 kg/m2) according to their BMI 1 year after metabolic surgery. The weight loss and remission of obesity-related comorbidities were evaluated. Ordinal logistic regression analysis was used to identify predictors for achieving healthy weight 1 year postoperatively. RESULTS: Overall, 125 patients (112 sleeve gastrectomies, 13 Roux-en-Y gastric bypasses) were recruited in this study. Forty-two participants achieved healthy weight, 38 were overweight, and 45 had obesity. Type 2 diabetes mellitus and obstructive sleep apnea were relieved in all groups. Individuals who achieved healthy weight showed more improvements in nonalcoholic fatty liver disease, hypertension, and hyperuricemia than those who did not. Preoperative BMI was an independent predictor for the BMI achieved postoperatively, and the optimal cut-off point for achieving healthy weight was 34.9 kg/m2. CONCLUSIONS: Healthy weight was a more stringent target for patients who underwent metabolic surgery than the %TWL. Populations with a preoperative BMI of <34.9 kg/m2 were prone to realize the goal. Additional weight loss interventions could be considered for those with higher preoperative BMIs and enforced within 1 year postoperatively.
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BACKGROUND: Unlike expired sevoflurane concentration, propofol lacks a biomarker for its brain effect site concentration, leading to dosing imprecision particularly in infants. Electroencephalography monitoring can serve as a biomarker for propofol effect site concentration, yet proprietary electroencephalography indices are not validated in infants. The authors evaluated spectral edge frequency (SEF95) as a propofol anesthesia biomarker in infants. It was hypothesized that the SEF95 targets will vary for different clinical stimuli and an inverse relationship existed between SEF95 and propofol plasma concentration. METHODS: This prospective study enrolled infants (3 to 12 months) to determine the SEF95 ranges for three clinical endpoints of anesthesia (consciousness-pacifier placement, pain-electrical nerve stimulation, and intubation-laryngoscopy) and correlation between SEF95 and propofol plasma concentration at steady state. Dixon's up-down method was used to determine target SEF95 for each clinical endpoint. Centered isotonic regression determined the dose-response function of SEF95 where 50% and 90% of infants (ED50 and ED90) did not respond to the clinical endpoint. Linear mixed-effect model determined the association of propofol plasma concentration and SEF95. RESULTS: Of 49 enrolled infants, 44 evaluable (90%) showed distinct SEF95 for endpoints: pacifier (ED50, 21.4 Hz; ED90, 19.3 Hz), electrical stimulation (ED50, 12.6 Hz; ED90, 10.4 Hz), and laryngoscopy (ED50, 8.5 Hz; ED90, 5.2 Hz). From propofol 0.5 to 6 µg/ml, a 1-Hz SEF95 increase was linearly correlated to a 0.24 (95% CI, 0.19 to 0.29; P < 0.001) µg/ml decrease in plasma propofol concentration (marginal R2 = 0.55). CONCLUSIONS: SEF95 can be a biomarker for propofol anesthesia depth in infants, potentially improving dosing accuracy and utilization of propofol anesthesia in this population.
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Anestésicos Intravenosos , Electroencefalografía , Propofol , Humanos , Propofol/sangre , Propofol/administración & dosificación , Lactante , Estudios Prospectivos , Electroencefalografía/efectos de los fármacos , Electroencefalografía/métodos , Anestésicos Intravenosos/sangre , Anestésicos Intravenosos/administración & dosificación , Femenino , Masculino , Biomarcadores/sangre , Relación Dosis-Respuesta a Droga , Determinación de Punto FinalRESUMEN
p62, also known as SQSTM1, has been shown to be closely related to the coronavirus. However, it remains unclear on the relationship between p62 and NIBV infection. Moreover, there are no available antibodies against the chicken p62 protein. Thus, this study aimed to prepare p62 polyclonal antibody and investigate the correlation between the p62 protein and NIBV infection. Here, PET-32a-p62 prokaryotic fusion expression vector was constructed for prokaryotic protein expression, and then p62 polyclonal antibody was prepared by immunizing rabbits. Lastly, these antibodies were then utilized in Western blotting (WB), immunohistochemistry (IHC), and immunofluorescence (IF) assays. The results showed that we successfully prepared chicken p62 polyclonal antibody. Meanwhile, WB and IF demonstrated that the expression of p62 showed a trend of first increase and then decrease after NIBV infection. IHC showed that the expression of p62 in the spleen, lung, kidney, bursa of Fabricius and trachea of chickens infected with NIBV in 11 dpi was significantly higher than that of normal chickens. Taken together, this study successfully prepared a polyclonal antibody for chicken p62 protein and confirmed its application and expression in chickens, as well as the expression of p62 in tissues after NIBV infection.
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Pollos , Infecciones por Coronavirus , Virus de la Bronquitis Infecciosa , Animales , Virus de la Bronquitis Infecciosa/inmunología , Infecciones por Coronavirus/inmunología , Infecciones por Coronavirus/virología , Enfermedades de las Aves de Corral/inmunología , Enfermedades de las Aves de Corral/virología , Proteína Sequestosoma-1/metabolismo , Proteína Sequestosoma-1/inmunología , Proteína Sequestosoma-1/genética , Anticuerpos/inmunología , Conejos , Anticuerpos Antivirales/inmunologíaRESUMEN
SiBCN ceramics based on SiC, BN and Si3N4 structures have good comprehensive properties such as high-temperature resistance, oxidation resistance, creep resistance and long life, which makes it one of the very promising ceramic material systems in military and aerospace fields, etc. In this study, SiBCN ceramics, as well as Si3N4f/BN/SiBCN microcomposites, were prepared by a polymer infiltration pyrolysis method using PBSZ as the polymer precursor. The PBSZ was completely ceramized by pyrolysis at 900 °C. The weight loss and elemental bonding forms of the products after the pyrolysis of the precursors hardly changed from 600 °C to 900 °C. After pyrolysis at 600 °C for 4 h and using the BN coating obtained from twice deposition as the interfacial phase, a more desirable weak interface of fiber/matrix with a binding strength of 21.96 ± 2.01 MPa can be obtained. Si3N4f/BN/SiBCN ceramic matrix microcomposites prepared under the same pyrolysis conditions have a relatively good tensile strength of 111.10 MPa while retaining a weak interface between the fibers and the matrix. The results of the study provide more theoretical and methodological support for the application of new composite structural ceramic material systems.
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Sensory nerves play a crucial role in maintaining bone homeostasis by releasing Semaphorin 3A (Sema3A). However, the specific mechanism of Sema3A in regulation of bone marrow mesenchymal stem cells (BMMSCs) during bone remodelling remains unclear. The tibial denervation model was used and the denervated tibia exhibited significantly lower mass as compared to sham operated bones. In vitro, BMMSCs cocultured with dorsal root ganglion cells (DRGs) or stimulated by Sema3A could promote osteogenic differentiation through the Wnt/ß-catenin/Nrp1 positive feedback loop, and the enhancement of osteogenic activity could be inhibited by SM345431 (Sema3A-specific inhibitor). In addition, Sema3A-stimulated BMMSCs or intravenous injection of Sema3A could promote new bone formation in vivo. To sum up, the coregulation of bone remodelling is due to the ageing of BMMSCs and increased osteoclast activity. Furthermore, the sensory neurotransmitter Sema3A promotes osteogenic differentiation of BMMSCs via Wnt/ß-catenin/Nrp1 positive feedback loop, thus promoting osteogenesis in vivo and in vitro.
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Células Madre Mesenquimatosas , Osteogénesis , Osteogénesis/genética , Semaforina-3A/genética , Retroalimentación , beta Catenina , Ganglios Espinales , Neuropilina-1/genéticaRESUMEN
Polymyxin B (PMB) is considered a last-line treatment for multidrug-resistant (MDR) gram-negative bacterial infections. Model-informed precision dosing with population pharmacokinetics (PopPK) models could help to individualize PMB dosing regimens and improve therapy. However, the external prediction ability of the established PopPK models has not been fully elaborated. This study aimed to systemically evaluate eleven PMB PopPK models from ten published literature based on a new independent population, which was divided into four different populations, patients with liver dysfunction, kidney dysfunction, liver and kidney dysfunction, and normal liver and kidney function. The whole data set consisted of 146 patients with 391 PMB concentrations. The prediction- and simulation-based diagnostics and Bayesian forecasting were conducted to evaluate model predictability. In the overall evaluation process, none of the models exhibited satisfactory predictive ability in both prediction- and simulation-based diagnostic simultaneously. However, the evaluation of the models in the subgroup of patients with normal liver and kidney function revealed improved predictive performance compared to those with liver and/or kidney dysfunction. Bayesian forecasting demonstrated enhanced predictability with the incorporation of two to three prior observations. The external evaluation highlighted a lack of consistency between the prediction results of published models and the external validation dataset. Nonetheless, Bayesian forecasting holds promise in improving the predictive performance of the models, and feedback from therapeutic drug monitoring is crucial in optimizing individual dosing regimens.
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The successful commercialization of algal biophotovoltaics (BPV) technology hinges upon a multifaceted approach, encompassing factors such as the development of a cost-efficient and highly conductive anode material. To address this issue, we developed an environmentally benign method of producing reduced graphene oxide (rGO), using concentrated Chlorella sp. UMACC 313 suspensions as the reducing agent. The produced rGO was subsequently coated on the carbon paper (rGO-CP) and used as the BPV device's anode. As a result, maximum power density was increased by 950% for Chlorella sp. UMACC 258 (0.210 mW m-2) and 781% for Synechococcus sp. UMACC 371 (0.555 mW m-2) compared to bare CP. The improved microalgae adhesion to the anode and improved electrical conductivity of rGO brought on by the effective removal of oxygen functional groups may be the causes of this. This study has demonstrated how microalgal-reduced GO may improve the efficiency of algal BPV for producing bioelectricity.
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BACKGROUND: The prevalence of hyperuricemia in China has been consistently increasing, particularly among the younger generation. The excessive consumption of sugar-sweetened beverages is associated with hyperuricemia. This study examined the knowledge, attitudes, and practices (KAP) of Chinese young adults regarding sugar-sweetened beverage consumption and the correlation with hyperuricemia. METHODS: This cross-sectional investigation was conducted from June 28th, 2023, to July 21st, 2023, and enrolled Chinese young adults. Demographics and KAP were evaluated using a questionnaire (Cronbach's α = 0.787). Factors influencing KAP scores were analyzed using multivariable analyses. RESULTS: A total of 1288 valid questionnaires were analyzed. The median knowledge, attitude, and practice scores were 16 (12,19)/22, 22 (20,24)/30, and 27.5 (23,31.75)/40. The multivariable analysis showed that bachelor's/associate education (OR = 1.912, 95%CI: 1.128-3.239), white collar/employee (OR = 0.147, 95%CI: 0.105-0.206), educator (OR = 0.300, 95%CI: 0.174-0.518), healthcare worker (OR = 0.277, 95%CI: 0.188-0.407), not suffering from hyperuricemia (OR = 0.386, 95%CI: 0.253-0.590), and not having gout (OR = 0.456, 95%CI: 0.282-0.736) were independently associated with knowledge. Age 26-30 (OR = 1.470, 95%CI: 1.052-2.052), age 31-35 (OR = 1.489, 95%CI: 1.097-2.022), age 36-40 (OR = 0.328, 95%CI: 1.010-1.746), age 41-44 (OR = 1.548, 95%CI: 1.091-2.198), and not having hyperuricemia (OR = 0.512, 95%CI: 0.345-0.760) were independently associated with attitude. White collar/employee (OR = 0.386, 95%CI: 0.285-0.521), educator (OR = 0.534, 95%CI: 0.317-0.899), healthcare worker (OR = 0.341, 95%CI: 0.236-0.493), having siblings (OR = 0.725, 95%CI: 0.573-0.917), and not suffering from hyperuricemia (OR = 0.442, 95%CI: 0.296-0.659), were independently associated with practice. CONCLUSION: Chinese young adults display moderate KAP toward sugar-sweetened beverages. Notably, an association was observed between hyperuricemia and each KAP dimension.
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Hiperuricemia , Bebidas Azucaradas , Humanos , Adulto Joven , Adulto , Hiperuricemia/epidemiología , Estudios Transversales , Encuestas y Cuestionarios , China , BebidasRESUMEN
Estimating fire emissions prior to the satellite era is challenging because observations are limited, leading to large uncertainties in the calculated aerosol climate forcing following the preindustrial era. This challenge further limits the ability of climate models to accurately project future climate change. Here, we reconstruct a gridded dataset of global biomass burning emissions from 1750 to 2010 using inverse analysis that leveraged a global array of 31 ice core records of black carbon deposition fluxes, two different historical emission inventories as a priori estimates, and emission-deposition sensitivities simulated by the atmospheric chemical transport model GEOS-Chem. The reconstructed emissions exhibit greater temporal variabilities which are more consistent with paleoclimate proxies. Our ice core constrained emissions reduced the uncertainties in simulated cloud condensation nuclei and aerosol radiative forcing associated with the discrepancy in preindustrial biomass burning emissions. The derived emissions can also be used in studies of ocean and terrestrial biogeochemistry.
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Aqueous zinc-ion hybrid supercapacitors (ZHSCs) have attracted considerable attention because they are inexpensive and safe. However, the inadequate energy densities, power densities, and cycling performance of current ZHSC energy-storage devices are impediments that need to be overcome to enable the further development and commercialization of this technology. To address these issues, in this study, we prepared carbon-based ZHSCs using a series of porous carbon materials derived from Sanhua liquor lees (SLPCs). Among them, the best performance was observed for SLPC-A13, which exhibited excellent properties and a high-surface-area structure (2667 m2 g-1) with abundant micropores. The Zn//SLPC-A13 device was assembled by using 2 mol L-1 ZnSO4, SLPC-A13, and Zn foil as the electrolyte, cathode, and anode, respectively. The Zn//SLPC-A13 device delivered an ultrahigh energy density of 137 Wh kg-1 at a power density of 462 W kg-1. Remarkably, Zn//SLPC-A13 retained 100% of its specific capacitance after 120,000 cycles of long-term charge/discharge testing, with 62% retained after 250,000 cycles. This outstanding performance is primarily attributed to the SLPC-A13 carbon material, which promotes the rapid adsorption and desorption of ions, and the charge-discharge process, which roughens the Zn anode in a manner that improves reversible Zn-ion plating/stripping efficiency. This study provides ideas for the preparation of ZHSC cathode materials.
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BACKGROUND: The aim of this study was to investigate whether using an innervated vascularized iliac bone flap could effectively prevent bone resorption and maintain sensory function in the lower lip. METHODS: In the innervated group, the deep circumflex iliac artery and recipient vessels were anastomosed, with simultaneous microanastomosis of ilioinguinal nerve, mental nerve and inferior alveolar nerve. Conversely, the control group underwent solely vascular anastomosis. CT was utilized to assess bone quality. Sensory recovery of the lower lip was recorded using two-point discrimination and current perception threshold testing. RESULTS: The study comprised a total of 40 subjects, with each group accounting for 20 participants, equally distributed in terms of gender. Hounsfield unit loss was significantly lower in the innervated group (13.26±8.65 %) as compared to the control group (37.98±8.60 %) (P < 0.001). Moreover, two-point discrimination values were lower in the innervated group (15.11±8.39 mm) when compared to the control group (21.44±7.24 mm) (P = 0.02). The current perception threshold values for the innervated group were 176.19 ± 31.89, 64.21 ± 19.23, and 42.29 ± 18.96 in 2kHz, 250Hz, and 5Hz respectively, while in the control group, the current perception threshold values were 204.47 ± 36.99, 82.26 ± 27.29, and 58.89 ± 25.38 in 2kHz, 250Hz, and 5Hz (P =0.02, 0.02, and 0.03, respectively). CONCLUSIONS: The innervated vascularized iliac bone flap represents a safe and effective novel approach to preserving lower lip sensation and preventing bone resorption through functional mandibular reconstruction.
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A variety of commercial platforms are available for the simultaneous detection of multiple cytokines and associated proteins, often employing Ab pairs to capture and detect target proteins. In this study, we comprehensively evaluated the performance of three distinct platforms: the fluorescent bead-based Luminex assay, the proximity extension-based Olink assay, and a novel proximity ligation assay platform known as Alamar NULISAseq. These assessments were conducted on human serum samples from the National Institutes of Health IMPACC study, with a focus on three essential performance metrics: detectability, correlation, and differential expression. Our results reveal several key findings. First, the Alamar platform demonstrated the highest overall detectability, followed by Olink and then Luminex. Second, the correlation of protein measurements between the Alamar and Olink platforms tended to be stronger than the correlation of either of these platforms with Luminex. Third, we observed that detectability differences across the platforms often translated to differences in differential expression findings, although high detectability did not guarantee the ability to identify meaningful biological differences. Our study provides valuable insights into the comparative performance of these assays, enhancing our understanding of their strengths and limitations when assessing complex biological samples, as exemplified by the sera from this COVID-19 cohort.
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COVID-19 , Humanos , COVID-19/diagnóstico , Inmunoensayo/métodos , Citocinas/metabolismo , Suero/metabolismoRESUMEN
BACKGROUND: Neurofibroma type I (NF1) often presents with multiple clinical phenotypes due to mutations of NF1 gene. The aim of this study was to determine the phenotypic and therapeutic relevance of tumor microenvironment in NF1 patients. METHODS: Tumor stem cells (TSCs) from NF1 were isolated and cultured using fluorescence activated cell sorting (FACS) and colony formation experiments. Then, flow cytometry was used to detect the surface markers, osteogenic and adipogenic differentiation were performed as well. Its tumorigenesis ability was confirmed by subcutaneous tumorigenesis in nude mice. Immunohistochemical staining was performed on neurofibroma tissues from the head and trunk with different phenotypes. The expression of BDNF in neurofibroma tissues was detected by Elisa and immunohistochemical staining. Western Blotting was used to detect the expression of p38 MAPK pathway in TSCs. The effect of BDNF neutralizing antibody on the tumorigenesis of TSCs was observed. RESULTS: Herein, we advocate that NF1 contain a new subgroup of mesenchymal-like neurofibroma stem cells (MNSCs). Such colony-forming MNSCs preserved self-renewal, multiple differentiation and tumorigenic capabilities. More interestingly, the MNSCs isolated from neurofibroma tissues of the same patient with different phenotypes presented site-specific capabilities. Moreover, different levels of brain-derived neurotrophic factor (BDNF) in neurofibroma tissues can impact the MNSCs by activating the TrkB/p38 MAPK pathway. Systemic administration of BDNF neutralizing antibodies inhibited MNSCs' characteristics. CONCLUSIONS: We demonstrated that BDNF can modulate MNSCs and thereby controlling different tumor phenotypes between the head and trunk regions. Application of BDNF neutralizing antibodies may inhibit p38 MAPK pathway, therefore providing a promising strategy for managing NF1.
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A variety of commercial platforms are available for the simultaneous detection of multiple cytokines and associated proteins, often employing antibody pairs to capture and detect target proteins. In this study, we comprehensively evaluated the performance of three distinct platforms: the fluorescent bead-based Luminex assay, the proximity extension-based Olink assay, and a novel proximity ligation assay platform known as Alamar NULISAseq. These assessments were conducted on serum samples from the NIH IMPACC study, with a focus on three essential performance metrics: detectability, correlation, and differential expression. Our results reveal several key findings. Firstly, the Alamar platform demonstrated the highest overall detectability, followed by Olink and then Luminex. Secondly, the correlation of protein measurements between the Alamar and Olink platforms tended to be stronger than the correlation of either of these platforms with Luminex. Thirdly, we observed that detectability differences across the platforms often translated to differences in differential expression findings, although high detectability did not guarantee the ability to identify meaningful biological differences. Our study provides valuable insights into the comparative performance of these assays, enhancing our understanding of their strengths and limitations when assessing complex biological samples, as exemplified by the sera from this COVID-19 cohort.
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The blood proteome holds great promise for precision medicine but poses substantial challenges due to the low abundance of most plasma proteins and the vast dynamic range of the plasma proteome. Here we address these challenges with NUcleic acid Linked Immuno-Sandwich Assay (NULISA™), which improves the sensitivity of traditional proximity ligation assays by ~10,000-fold to attomolar level, by suppressing assay background via a dual capture and release mechanism built into oligonucleotide-conjugated antibodies. Highly multiplexed quantification of both low- and high-abundance proteins spanning a wide dynamic range is achieved by attenuating signals from abundant targets with unconjugated antibodies and next-generation sequencing of barcoded reporter DNA. A 200-plex NULISA containing 124 cytokines and chemokines and other proteins demonstrates superior sensitivity to a proximity extension assay in detecting biologically important low-abundance biomarkers in patients with autoimmune diseases and COVID-19. Fully automated NULISA makes broad and in-depth proteomic analysis easily accessible for research and diagnostic applications.
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Proteoma , Proteómica , Humanos , Proteínas Sanguíneas/genética , Anticuerpos , CitocinasRESUMEN
Electroencephalogram (EEG) can be used to assess depth of consciousness, but interpreting EEG can be challenging, especially in neonates whose EEG undergo rapid changes during the perinatal course. EEG can be processed into quantitative EEG (QEEG), but limited data exist on the range of QEEG for normal term neonates during wakefulness and sleep, baseline information that would be useful to determine changes during sedation or anesthesia. We aimed to determine the range of QEEG in neonates during awake, active sleep and quiet sleep states, and identified the ones best at discriminating between the three states. Normal neonatal EEG from 37 to 46 weeks were analyzed and classified as awake, quiet sleep, or active sleep. After processing and artifact removal, total power, power ratio, coherence, entropy, and spectral edge frequency (SEF) 50 and 90 were calculated. Descriptive statistics were used to summarize the QEEG in each of the three states. Receiver operating characteristic (ROC) curves were used to assess discriminatory ability of QEEG. 30 neonates were analyzed. QEEG were different between awake vs asleep states, but similar between active vs quiet sleep states. Entropy beta, delta2 power %, coherence delta2, and SEF50 were best at discriminating awake vs active sleep. Entropy beta had the highest AUC-ROC ≥ 0.84. Entropy beta, entropy delta1, theta power %, and SEF50 were best at discriminating awake vs quiet sleep. All had AUC-ROC ≥ 0.78. In active sleep vs quiet sleep, theta power % had highest AUC-ROC > 0.69, lower than the other comparisons. We determined the QEEG range in healthy neonates in different states of consciousness. Entropy beta and SEF50 were best at discriminating between awake and sleep states. QEEG were not as good at discriminating between quiet and active sleep. In the future, QEEG with high discriminatory power can be combined to further improve ability to differentiate between states of consciousness.
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Background: Inflammatory bowel disease (IBD) is closely related to higher intracellular oxidative stress. Therefore, developing a novel method to scavenge the harmful reactive oxygen species (ROS) and alleviate colon inflammation to treat IBD is a promising strategy. Methods: CeO2@PDA-PEG (CeO2@PP) were synthesized by modifying ceria (CeO2) nanorods with polydopamine (PDA) and polyethylene glycol (PEG). The ROS scavenging ability of CeO2@PP was detected by using flow cytometry and confocal laser scanning microscope (CLSM). The anti-inflammatory ability of CeO2@PP was determined in vitro by treating lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. The biocompatibility of CeO2@PP was evaluated in vivo and in vitro. Moreover, the therapeutic effects of CeO2@PP in vivo were estimated in a dextran sulfate sodium salt (DSS)-induced colitis mouse model. Results: Physicochemical property results demonstrated that PDA and PEG modification endowed CeO2 nanorods with excellent dispersibility and colloidal stability. CeO2@PP maintained superior enzyme-like activity, including superoxide dismutase (SOD) and catalase (CAT), indicating antioxidant ability. Moreover, in vitro results showed that CeO2@PP with PDA promotes LPS-induced RAW 264.7 macrophages into M2-type polarization. In addition, in vitro and in vivo results showed that CeO2@PP have great biocompatibility and biosafety. Animal experiments have shown that CeO2@PP have excellent anti-inflammatory effects against DSS-induced colitis and effectively alleviated intestinal mucosal injury. Conclusion: The nanoplatform CeO2@PP possessed excellent antioxidant and anti-inflammatory properties for scavenging ROS and modulating macrophage polarization, which is beneficial for efficient colitis therapy.
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Colitis , Depuradores de Radicales Libres , Indoles , Nanotubos , Polímeros , Especies Reactivas de Oxígeno , Indoles/química , Indoles/farmacología , Indoles/uso terapéutico , Polímeros/química , Polímeros/farmacología , Polímeros/uso terapéutico , Colitis/tratamiento farmacológico , Colitis/patología , Inflamación/tratamiento farmacológico , Inflamación/patología , Depuradores de Radicales Libres/química , Depuradores de Radicales Libres/farmacología , Depuradores de Radicales Libres/uso terapéutico , Especies Reactivas de Oxígeno/metabolismo , Polaridad Celular , Cerio , Animales , Ratones , Células RAW 264.7 , Masculino , Ratones Endogámicos C57BL , Modelos Animales de EnfermedadRESUMEN
Bone resorption occurs after bone grafting, however, contemporaneous reconstruction of the innervation of the bone graft is a potential treatment to maintain the bone mass of the graft. The innervation of bone is an emerging research topic. To understand the potential molecular mechanisms of bone innervation after bone grafting, we collected normal iliac bone tissue as well as bone grafts with or without innervation from nine patients 1 year after surgery and performed RNA sequencing. We identified differentially expressed genes) from these samples and used the gene ontology and Kyoto Encyclopedia of Genes and Genomes databases for functional enrichment and signaling pathway analysis. In parallel, we established protein-protein interaction networks to screen functional modules. Based on bioinformatic results, we validated in vitro the osteogenic differentiation potential of rat bone marrow mesenchymal stem cells (BMMSCs) after calcitonin gene-related peptide (CGRP) stimulation and the expression of p38 MAPK and Wnt6/ß-catenin pathways during osteogenesis. Our transcriptome analysis of bone grafts reveals functional modules and signaling pathways of innervation which play a vital role in the structural and functional integration of the bone graft. Simultaneously, we demonstrate that CGRP regulates the differentiation of BMMSCs through p38 MAPK and Wnt6/ß-catenin.