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The sensitivity and accuracy of fluorescence probes for biological samples are affected by not only interfering molecule compounds but also the nonspecific adsorption of proteins and other macromolecules. Herein, fluorescence probe based on zwitterionic sulfobetaine methacrylate polymer (PSBMA) as an antibiofouling layer and amino boric acid carbon dots encapsulated in the metal-organic framework UiO-66-NH2 (UiO-66-NH2/BN-CDs) as a target recognition site was designed for the detection of baicalin (BAI). Owing to the introduction of BN-CDs into UiO-66-NH2 with high specific surface area, the prepared UiO-66-NH2/BN-CDs@PSBMA probe exhibited a high adsorption capacity of 78.9 mg g-1, while presented fluorescence enhancing and superior fluorescence selectivity to BAI at excitation and emission wavelengths of 400 and 425 nm, respectively. Connecting PSBMA with good hydrophilicity to UiO-66-NH2, resulted in an anti-protein capacity of over 96.3 %, effectively inhibiting protein interference with the fluorescence signal. By virtue of its good antibiofouling and recognizing capacities, the fluorescence probe exhibited a satisfactory detection range of 10-80 nmol L-1, with a fairly low detection limit of 0.0064 µmol L-1. Using the method to detect BAI in Goji berry, Sophora and Yinhuang oral solution, demonstrating its potential for the accurate and quantitative detection of BAI in complex biological samples.
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Ácidos Borónicos , Carbono , Flavonoides , Colorantes Fluorescentes , Estructuras Metalorgánicas , Puntos Cuánticos , Colorantes Fluorescentes/química , Estructuras Metalorgánicas/química , Ácidos Borónicos/química , Carbono/química , Flavonoides/química , Flavonoides/análisis , Puntos Cuánticos/química , Incrustaciones Biológicas/prevención & control , Polímeros/química , Espectrometría de Fluorescencia/métodos , Límite de Detección , Metacrilatos/química , Adsorción , Betaína/química , Betaína/análogos & derivados , Ácidos FtálicosRESUMEN
Polar stationary phases were prepared by grafting hydrophilic acrylamide (Am) polymer brushes with post modification of carbon dots (CDs) and silicon dots (SiDs) onto SiO2 particles. The prepared stationary phases, SiO2-PAm-CDs, SiO2-PAm-CDs/SiDs, and SiO2-PAm-SiDs, were packed as chromatographic columns, respectively. Using nucleic bases, organic acids, and ß-agonists as target substances to investigate the influence of chromatographic conditions on retention and separation, the packed columns showed the partitioning and adsorption of mixed retention behavior in hydrophilic interaction liquid chromatography mode and successfully separated the polar compounds. Most importantly, under per aqueous liquid chromatography mode (using 100% water as mobile phase), those columns still had good separation ability toward nucleic bases, ß-agonist, and organic acids. Because AM is a temperature-sensitive monomer, the resulting van't Hoff curves exhibited a nonlinear relationship, having temperature-responsive chromatographic characteristic under pure water separation. Hence, building on temperature-sensitive characteristics and pure water of separation conditions, the separation selectivity toward hydrophilic compounds greatly improved. Compared with the commercial hydrophilic columns, the efficiency of our developed column had the superior ability in separation and detection of betaine in Goji berry with the enhanced resolution achieved in the proposed green separation method (just using pure water as mobile phase).
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The ultrasensitive recognition of biomarkers plays a crucial role in the precise diagnosis of diseases. Graphene-based field-effect transistors (GFET) are considered the most promising devices among the next generation of biosensors. GFET biosensors possess distinct advantages, including label-free, ease of integration and operation, and the ability to directly detect biomarkers in liquid environments. This review summarized recent advances in GFET biosensors for biomarker detection, with a focus on interface functionalization. Various sensitivity-enhancing strategies have been overviewed for GFET biosensors, from the perspective of optimizing graphene synthesis and transfer methods, refinement of surface functionalization strategies for the channel layer and gate electrode, design of biorecognition elements and reduction of nonspecific adsorption. Further, this review extensively explores GFET biosensors functionalized with antibodies, aptamers, and enzymes. It delves into sensitivity-enhancing strategies employed in the detection of biomarkers for various diseases (such as cancer, cardiovascular diseases, neurodegenerative disorders, infectious viruses, etc.) along with their application in integrated microfluidic systems. Finally, the issues and challenges in strategies for the modulation of biosensing interfaces are faced by GFET biosensors in detecting biomarkers.
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Biomarcadores , Técnicas Biosensibles , Grafito , Transistores Electrónicos , Técnicas Biosensibles/métodos , Técnicas Biosensibles/instrumentación , Grafito/química , Biomarcadores/análisis , HumanosRESUMEN
ABSTRACT: Glucocorticoids are key components of the standard-of-care treatment regimens for B-cell malignancy. However, systemic glucocorticoid treatment is associated with several adverse events. ABBV-319 is a CD19-targeting antibody-drug conjugate engineered to reduce glucocorticoid-associated toxicities while possessing 3 distinct mechanisms of action (MOA) to increase therapeutic efficacy: (1) antibody-mediated delivery of a glucocorticoid receptor modulator (GRM) payload to activate apoptosis, (2) inhibition of CD19 signaling, and (3) enhanced fragment crystallizable (Fc)-mediated effector function via afucosylation of the antibody backbone. ABBV-319 elicited potent GRM-driven antitumor activity against multiple malignant B-cell lines in vitro, as well as in cell line-derived xenografts and patient-derived xenografts (PDXs) in vivo. Remarkably, a single dose of ABBV-319 induced sustained tumor regression and enhanced antitumor activity compared with repeated dosing of systemic prednisolone at the maximum tolerated dose in mice. The unconjugated CD19 monoclonal antibody (mAb) also displayed antiproliferative activity in a subset of B-cell lymphoma cell lines through the inhibition of phosphoinositide 3-kinase signaling. Moreover, afucosylation of CD19 mAb enhanced Fc-mediated antibody-dependent cellular cytotoxicity. Notably, ABBV-319 displayed superior efficacy compared with afucosylated CD19 mAb in human CD34+ peripheral blood mononuclear cell-engrafted NSG-Tg(Hu-IL15) transgenic mice, demonstrating enhanced antitumor activity when multiple MOAs are enabled. ABBV-319 also showed durable antitumor activity across multiple B-cell lymphoma PDX models, including nongerminal center B-cell diffuse large B-cell lymphoma and relapsed lymphoma after R-CHOP treatment. Collectively, these data support the ongoing evaluation of ABBV-319 in a phase 1 clinical trial.
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Antígenos CD19 , Inmunoconjugados , Receptores de Glucocorticoides , Ensayos Antitumor por Modelo de Xenoinjerto , Humanos , Animales , Antígenos CD19/inmunología , Ratones , Inmunoconjugados/farmacología , Inmunoconjugados/uso terapéutico , Receptores de Glucocorticoides/antagonistas & inhibidores , Anticuerpos Monoclonales Humanizados/farmacología , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/administración & dosificación , Linfoma de Células B/tratamiento farmacológico , Linfoma de Células B/patología , Línea Celular Tumoral , Ratones SCID , Femenino , Maitansina/análogos & derivadosRESUMEN
Importance: Large language models (LLMs) may facilitate the labor-intensive process of systematic reviews. However, the exact methods and reliability remain uncertain. Objective: To explore the feasibility and reliability of using LLMs to assess risk of bias (ROB) in randomized clinical trials (RCTs). Design, Setting, and Participants: A survey study was conducted between August 10, 2023, and October 30, 2023. Thirty RCTs were selected from published systematic reviews. Main Outcomes and Measures: A structured prompt was developed to guide ChatGPT (LLM 1) and Claude (LLM 2) in assessing the ROB in these RCTs using a modified version of the Cochrane ROB tool developed by the CLARITY group at McMaster University. Each RCT was assessed twice by both models, and the results were documented. The results were compared with an assessment by 3 experts, which was considered a criterion standard. Correct assessment rates, sensitivity, specificity, and F1 scores were calculated to reflect accuracy, both overall and for each domain of the Cochrane ROB tool; consistent assessment rates and Cohen κ were calculated to gauge consistency; and assessment time was calculated to measure efficiency. Performance between the 2 models was compared using risk differences. Results: Both models demonstrated high correct assessment rates. LLM 1 reached a mean correct assessment rate of 84.5% (95% CI, 81.5%-87.3%), and LLM 2 reached a significantly higher rate of 89.5% (95% CI, 87.0%-91.8%). The risk difference between the 2 models was 0.05 (95% CI, 0.01-0.09). In most domains, domain-specific correct rates were around 80% to 90%; however, sensitivity below 0.80 was observed in domains 1 (random sequence generation), 2 (allocation concealment), and 6 (other concerns). Domains 4 (missing outcome data), 5 (selective outcome reporting), and 6 had F1 scores below 0.50. The consistent rates between the 2 assessments were 84.0% for LLM 1 and 87.3% for LLM 2. LLM 1's κ exceeded 0.80 in 7 and LLM 2's in 8 domains. The mean (SD) time needed for assessment was 77 (16) seconds for LLM 1 and 53 (12) seconds for LLM 2. Conclusions: In this survey study of applying LLMs for ROB assessment, LLM 1 and LLM 2 demonstrated substantial accuracy and consistency in evaluating RCTs, suggesting their potential as supportive tools in systematic review processes.
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Sesgo , Ensayos Clínicos Controlados Aleatorios como Asunto , Humanos , Reproducibilidad de los Resultados , Lenguaje , Medición de Riesgo/métodosRESUMEN
A method based on novel restricted access materials (RAMs) for the determination of neonicotinoid pesticides in Goji samples using offline and online solid phase extraction (SPE) coupled with high-performance liquid chromatography (LC). RAMs were synthesized using poly(chloromethylstyrene-co-divinylbenzene) (PVBC/DVB) microspheres as substrate, styrene (St) and n-vinylpyrrolidone (NVP) were first copolymerized on the interior to construct adsorption sites, and sulfobetaine methacrylate (SBMA) was then polymerized on the exterior to form exclusion sites via two-step surface initiated-atom transfer polymerization. The prepared PVBC/DVB@poly(St-co-NVP)@poly(SBMA) RAMs could efficiently extract neonicotinoid pesticides and automatically exclude proteins. Under the optimized conditions, the developed methods of offline (magnetic SPE and SPE column) and online extraction coupled with LC both using PVBC/DVB@poly(St-co-NVP)@poly(SBMA) RAMs as the extractant, exhibit a wide linearity, low limits of detection and limit of quantification and good inter-day and intra-day precision with satisfactory recoveries. Among these methods, online extraction coupled with LC based on novel RAMs exhibits clear advantages for the determination of neonicotinoid pesticides in Goji samples has clear advantages, such as simple operation by direct injection, short extraction times, and high accuracy with less human error.
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Plaguicidas , Polímeros , Humanos , Polímeros/química , Plaguicidas/análisis , Adsorción , Extracción en Fase Sólida/métodos , Estireno , Cromatografía Líquida de Alta Presión/métodosRESUMEN
COVID-19 is not only associated with substantial acute liver and kidney injuries, but also with an elevated risk of post-acute sequelae involving the kidney and liver system. We aimed to investigate whether COVID-19 exposure increases the long-term risk of kidney and liver disease, and what are the magnitudes of these associations. We searched PubMed, Embase, Web of Science, ClinicalTrials.gov, and the Living Overview of the Evidence COVID-19 Repository for cohort studies estimating the association between COVID-19 and kidney and liver outcomes. Random-effects meta-analyses were performed to combine the results of the included studies. We assessed the certainty of the evidence using the Grading of Recommendations Assessment, Development and Evaluation approach. Fifteen cohort studies with more than 32 million participants were included in the systematic review COVID-19 was associated with a 35% greater risk of kidney diseases (10 more per 1000 persons; low certainty evidence) and 54% greater risk of liver disease (3 more per 1000 persons; low certainty evidence). The absolute increases due to COVID-19 for acute kidney injury, chronic kidney disease, and liver test abnormality were 3, 8, and 3 per 1000 persons, respectively. Subgroup analyses found no differences between different type of kidney and liver diseases. The findings provide further evidence for the association between COVID-19 and incident kidney and liver conditions. The absolute magnitude of the effect of COVID-19 on kidney and liver outcomes was, however, relatively small.
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COVID-19 , Hepatopatías , SARS-CoV-2 , Humanos , COVID-19/epidemiología , COVID-19/complicaciones , Hepatopatías/epidemiología , Hepatopatías/etiología , Hepatopatías/virología , Enfermedades Renales/epidemiología , Enfermedades Renales/etiología , Enfermedades Renales/virología , Factores de Riesgo , Lesión Renal Aguda/epidemiología , Lesión Renal Aguda/etiología , Lesión Renal Aguda/virologíaRESUMEN
In this study, a developed chromatographic stationary phase combines the high selectivity of mixed-mode retention with a temperature-responsive property to boost separation efficiency. Copolymer brushes were grafted onto silica gels through surface initiated-atom transfer radical polymerization by polymerizing two types of monomer, temperature-responsive vinylcaprolactam (VCl) and quinine (Qun) containing benzopyridine, a tertiary ammonium positive center, and hydroxyl groups. The obtained silica@poly(Qun-co-VCl) stationary phases were packed as a chromatographic column, and the retention behavior of hydrophobic polycyclic aromatics, highly polar nucleosides, charged organic acids and ß-agonists was studied for this column under different separation modes. The ability to separate different types of analyte shows that the silica@poly(Qun-co-VCl) column provides multiple hydrophobic, hydrophilic and electrostatic interactions toward analytes, achieving the separation of various compounds in one column. In addition, temperature-dependent resolution of polycyclic aromatics, nucleosides, organic acids and ß-agonists was investigated using modulation of the column temperature, and the column exhibited adjustable separation selectivity by simply changing the column temperature. These results demonstrate that the grafting of copolymer brushes on a silica surface, consisting of temperature-responsive poly-VCl and multifunctional groups of poly-Qun, is useful as a mixed-mode chromatographic stationary phase for thermally-modulated multiple interactions. Additionally, this column was also used for the quantitative detection of uridine and inosine from cordyceps.
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This study aimed to evaluate the effect of circumferential pulmonary vein isolation (CPVI) on autonomic nervous function and prognosis in patients with paroxysmal atrial fibrillation (AF) with or without sinus bradycardia.A total of 66 patients with paroxysmal AF accompanied by sinus bradycardia and who underwent CPVI were recruited as the sinus bradycardia group. A total of 91 patients with paroxysmal AF but without sinus bradycardia and who underwent catheter ablation were selected as the control group. After surgical contraindications were eliminated, CPVI was performed by three-dimensional mapping system. 24-hour dynamic electrocardiogram was used to observe the changes of heart rate before and 2 days after surgery.A total of 45 (68%) and 51 (56%) patients in the sinus bradycardia and control groups, respectively, maintained sinus rhythm. There was an increase in heart rate after CPVI in both groups. The standard deviation of normal-to-normal (NN) intervals (SDNN), standard deviation of the average NN intervals (SDANN), low frequency (LF), and LF/high frequency (HF) in the sinus bradycardia and control groups decreased after CPVI (P < 0.01). Moreover, SDANN was higher in patients with sinus bradycardia treated by successful ablation than in those with recurrence (P < 0.01), while SDNN, a standard statistical measure of heart rate variability (rMSSD), LF, and HF were significantly lower in patients with sinus bradycardia (P < 0.05).CPVI was able to produce a significant reduction effect on vagal nerve and sympathetic activity regardless of whether patients with paroxysmal AF had sinus bradycardia. Moreover, CPVI exerted a certain influence on the success rate of AF catheter ablation.
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Coxsackievirus A21 (CVA21) is a naturally occurring RNA virus that, in preclinical studies and clinical trials, has demonstrated promising potential in treating a range of malignancies. Other oncolytic viruses, such as adenovirus, vesicular stomatitis virus, herpesvirus, and vaccinia virus, all can be engineered to carry one or more transgenes for various purposes, including immune modulation, virus attenuation, and induction of apoptosis of tumor cells. However, it remained unknown whether CVA21 can express therapeutic or immunomodulatory payloads due to its small size and high mutation rate. Using reverse genetics techniques, we demonstrated that a transgene encoding a truncated green fluorescent protein (GFP) of up to 141 amino acids (aa) can be successfully carried in the 5' end of the coding region. Furthermore, a chimeric virus carrying an eel fluorescent protein, UnaG (139 aa), was also made and shown to be stable, and it maintained efficient tumor cell-killing activity. Similar to other oncolytic viruses, the likelihood of delivering CVA21 by the intravenous route is low due to issues like blood absorption, neutralizing antibodies, and liver clearance. To address this problem, we designed the CVA21 cDNA under the control of a weak RNA polymerase II promoter, and subsequently, a stable cell pool in 293T cells was made by integrating the resulting CVA21 cDNA into the cell genome. We showed that the cells are viable and able to persistently generate rCVA21 de novo. The carrier cell approach described here may pave the way to designing new cell therapy strategies by arming with oncolytic viruses. IMPORTANCE As a naturally occurring virus, coxsackievirus A21 is a promising oncolytic virotherapy modality. In this study, we first used reverse genetics to determine whether A21 can stably carry transgenes and found that it could express up to 141 amino acids of foreign GFP. The chimeric virus carrying another fluorescent eel protein UnaG (139 amino acids) gene also appeared to be stable over at least 7 passages. Our results provided guidance on how to select and engineer therapeutic payloads for future A21 anticancer research. Second, the challenges of delivering oncolytic viruses by the intravenous route hamper the broader use of oncolytic viruses in the clinic. Here, we used A21 to show that cells could be engineered to stably carry and persistently release the virus by harboring the viral cDNA in the genome. The approach we presented here may pave a new way for oncolytic virus administration using cells as carriers.
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Enterovirus Humano A , Virus Oncolíticos , Aminoácidos/genética , Línea Celular Tumoral , ADN Complementario , Enterovirus Humano A/genética , Viroterapia Oncolítica/métodos , Virus Oncolíticos/genética , TransgenesRESUMEN
OBJECTIVE: Currently, only a few studies have been conducted on the mental status recovery in elderly aortic stenosis (AS) patients after treatment. How transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR) differentially impinge on the mental status of elderly AS patients is completely unknown. The present prospective study aims to investigate this question by comparing the post-treatment levels of depression and anxiety, quality of life and frailty. METHODS: A total of 120 elderly patients (age above 70) with symptomatic AS were included, where 78 of them were treated with TAVR and 42 of them were treated with SAVR. Levels of depression and anxiety, quality of life and frailty were assessed by the Chinese version of Hospital Anxiety and Depression Scale (HADS), World Health Organization Quality of Life Instrument-Older Adults Module (WHOQOL-OLD) and clinical frailty scale, respectively. Scores were recorded and compared at admission, 1 month, 4 months and 8 months after treatment. RESULTS: Before treatment, both patient groups had similar baseline characteristics and all mental parameters. During the follow-up period, patients in the TAVR group demonstrated significant improvement in all assessed mental parameters to certain extent compared to the SAVR group. Specifically, frailty was significantly improved in the TAVR-treated patients at all three follow-up time points. Levels of depression and anxiety were significantly improved 8 months after treatment, although the remaining patient number is limited. Quality of life was only significantly improved 1 month after treatment. CONCLUSION: TAVR may provide a better mental recovery outcome in elderly AS patients.
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Estenosis de la Válvula Aórtica , Fragilidad , Implantación de Prótesis de Válvulas Cardíacas , Reemplazo de la Válvula Aórtica Transcatéter , Anciano , Ansiedad , Válvula Aórtica/cirugía , Estenosis de la Válvula Aórtica/etiología , Estenosis de la Válvula Aórtica/cirugía , Depresión , Humanos , Estudios Prospectivos , Calidad de Vida , Factores de Riesgo , Reemplazo de la Válvula Aórtica Transcatéter/efectos adversos , Resultado del TratamientoRESUMEN
The industrial application of hydrate technology is greatly hindered by its slow generation rate, low gas storage rate, harsh generation conditions, and poor environmental friendliness of traditional additives. In this paper, the kinetic and thermodynamic promotion effects of graphene oxide (GO) and recovered graphene oxide (Re-GO) on methane hydrate in different systems were studied by the constant volume methods. The promotion mechanism was analyzed from the micro perspectives of molecular physical properties, interfacial reaction, and nucleation sites. It is found that GO has an excellent kinetic and thermodynamic promotion effect on CH4 hydrate generation. After the recovery process, the thermodynamic effect of Re-GO is basically unchanged, and the kinetic promotion effect is slightly reduced. Furthermore, it is verified that the GO material itself does not have a memory effect in hydrate formation. The results show that GO is an excellent accelerator of CH4 hydrate formation with high recovery value, which provides essential data and an experimental basis for the research and application of graphene oxide and hydrate technology in energy storage and cold storage.
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Background: Left bundle branch area pacing (LBBAP) is a recently proposed method for conduction system pacing. We performed a meta-analysis of controlled studies to compare the clinical outcome in patients who received LBBAP vs. biventricular pacing (BVP) for cardiac resynchronization therapy (CRT). Methods: PubMed, Embase, and Cochrane's Library databases were searched for relevant controlled studies. A random-effect model incorporating the potential heterogeneity was used to synthesize the results. Results: Four non-randomized controlled studies including 249 patients with heart failure (HF) for CRT were included, and the patients were followed for 6-12 months. Compared with BVP, LBBAP was associated with significantly shortened QRS duration [mean difference (MD): -29.18 ms, 95% confidence interval (CI): -33.55-24.80, I 2 = 0%, P < 0.001], improved left ventricular ejection fraction (MD: 6.93%, 95% CI: 4.69-9.17, I 2 = 0%, P < 0.001), reduced left ventricular end-diastolic dimension (MD: -2.96 mm, 95% CI: -5.48 to -0.44, I 2 = 0%, P = 0.02), and improved New York Heart Association class (MD: -0.54, 95% CI: -0.84 to -0.24, I 2 = 65%, P < 0.001). Moreover, patients who received LBBAP were more likely to achieve echocardiographic [odds ratio (OR): 5.04, 95% CI: 2.17-11.69, I 2 = 0%, P < 0.001] and clinical (OR: 7.33, 95% CI: 1.62-33.16, I 2 = 0%, P = 0.01) CRT responses. Conclusion: Current evidence from non-randomized studies suggests that LBBAP appears to be a promising method for CRT, which is associated with more remarkable improvements of symptoms and cardiac function in HF patients with indication for CRT.
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The bacterial flagellum is a complex, self-assembling macromolecular machine that powers bacterial motility. It plays diverse roles in bacterial virulence, including aiding in colonization and dissemination during infection. The flagellum consists of a filamentous structure protruding from the cell, and of the basal body, a large assembly that spans the cell envelope. The basal body is comprised of over 20 different proteins forming several concentric ring structures, termed the M- S- L- P- and C-rings, respectively. In particular, the MS rings are formed by a single protein FliF, which consists of two trans-membrane helices anchoring it to the inner membrane and surrounding a large periplasmic domain. Assembly of the MS ring, through oligomerization of FliF, is one of the first steps of basal body assembly. Previous computational analysis had shown that the periplasmic region of FliF consists of three structurally similar domains, termed Ring-Building Motif (RBM)1, RBM2, and RBM3. The structure of the MS-ring has been reported recently, and unexpectedly shown that these three domains adopt different symmetries, with RBM3 having a 34-mer stoichiometry, while RBM2 adopts two distinct positions in the complex, including a 23-mer ring. This observation raises some important question on the assembly of the MS ring, and the formation of this symmetry mismatch within a single protein. In this study, we analyze the oligomerization of the individual RBM domains in isolation, in the Salmonella enterica serovar Typhimurium FliF ortholog. We demonstrate that the periplasmic domain of FliF assembles into the MS ring, in the absence of the trans-membrane helices. We also report that the RBM2 and RBM3 domains oligomerize into ring structures, but not RBM1. Intriguingly, we observe that a construct encompassing RBM1 and RBM2 is monomeric, suggesting that RBM1 interacts with RBM2, and inhibits its oligomerization. However, this inhibition is lifted by the addition of RBM3. Collectively, this data suggest a mechanism for the controlled assembly of the MS ring.
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The propagation of premix methane/air flames in long half-open ducts with different inclination angles θ between the sidewall and the horizon was numerically investigated using the laminar model. The numerical result was compared with the experimental and theoretical ones to validate the numerical model. The results show that the numerical results are in good agreement with them. The investigation provides the basic understanding of the effects on changing the shape of the ducts to promote the premixed flame combustion. For methane/air, the position where the flame front begins to concave is pushed back with the increase in angle θ. The so-called "tulip" flame even disappeared, if the angle θ is bigger than one certain value. Moreover, the flame propagation speed and pressure are enhanced as the angle θ increases. In addition, the numerical simulation indicates that the burning gas creates an eddy near the tip of the flame, altering the flow field and causing the tulip flame to appear. However, with the angle θ increased, the flame propagation is restrained by the change in sidewalls, resulting in the different flow patterns to suppress the formation of tulip flames and promote flame combustion.
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BACKGROUND: The dynamic time warping (DTW) has recently been introduced to analyze neural signals such as EEG and fMRI where phase variability plays an important role in the data. NEW METHOD: In this study, we propose to adopt a more powerful method, referred to as the Fisher-Rao Registration (FRR), to study the phase variability. COMPARISON WITH EXISTING METHODS: We systematically compare FRR with DTW in three aspects: (1) basic framework, (2) mathematical properties, and (3) computational efficiency. RESULTS: We show that FRR has superior performance in all these aspects and the advantages are well illustrated with simulation examples. CONCLUSIONS: We then apply the FRR method to two real experimental recordings - one fMRI and one EEG data set. It is found the FRR method properly removes the phase variability in each set. Finally, we use the FRR framework to examine brain networks in these two data sets and the result demonstrates the effectiveness of the new method.
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Encéfalo , Electroencefalografía , Algoritmos , Encéfalo/diagnóstico por imagen , Simulación por Computador , TiempoRESUMEN
Elucidating the structure-activity relationships between biomolecules and hydroxyapatite (HAP) is essential to understand bone mineralization mechanisms, develop HAP-based implants, and design drug delivery vectors. Here, four peptides identified by phage display were selected as model HAP-binding peptides (HBPs) to examine the effects of primary amino acid sequence, phosphorylation of serine, presence of charged amino acid residues, and net charge of the peptide on (1) HAP-binding affinity, (2) secondary conformation, and (3) HAP nucleation and crystal growth. Binding affinities were determined by obtaining adsorption isotherms by mass depletion, and the conformations of the peptides in solution and bound states were observed by circular dichroism. Results showed that the magnitude of the net charge primarily controlled binding affinity, with little dependence on the other HBP features. The binding affinity and conformation results were in good agreement with our previous molecular dynamics simulation results, thus providing an excellent benchmark for the simulations. Transmission electron microscopy was used to explore the effect of these HBPs on calcium phosphate (Ca-PO4) nucleation and growth. Results indicated that HBPs may inhibit nucleation of Ca-PO4 nanoparticles and their phase transition to crystalline HAP, as well as control crystal growth rates in specific crystallographic directions, thus changing the classical needle-like morphology of inorganically grown HAP crystals to a biomimetic plate-like morphology.
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Durapatita , Péptidos , Adsorción , Secuencia de Aminoácidos , Relación Estructura-ActividadRESUMEN
The design of improved materials for orthopedic implants and bone tissue engineering scaffolds relies on materials mimicking the properties of bone. Calcium phosphate (Ca-PO4)-mineralized collagen fibrils arranged in a characteristic hierarchical structure constitute the building blocks of mineralized vertebrate tissues and control their biomechanical and biochemical properties. Large, flexible, acidic noncollagenous proteins (ANCPs) have been shown to influence collagen mineralization but little is known about mineralization mechanisms with the aid of small proteins. Osteocalcin (OCN) is a small, highly structured biomolecule known as a multifunctional hormone in its undercarboxylated form. Here, we examined the potential mechanism of collagen intrafibrillar mineralization in vitro mediated by OCN as a model protein. Rapid and random extrafibrillar mineralization of flakey Ca-PO4 particles was observed by transmission electron microscopy mainly on the outer surfaces of collagen fibrils of a preformed collagen scaffold in the absence of the protein. In contrast, the protein stabilized hydrated, spherical nanoclusters of Ca-PO4 on the outer surface of the fibrils, thereby retarding extrafibrillar mineralization. The nanoclusters then infiltrated the fibrils resulting in intrafibrillar mineralization with HAP crystals aligned with the fibrils. This mechanism is similar to that observed for unstructured ANCPs. Results of fibrillogenesis and immunogold labeling studies showed that OCN was associated primarily with the fibrils, consistent with ex vivo studies on mineralizing turkey tendon. The present findings contribute to expanding our understanding of collagen intrafibrillar mineralization and provide insight into design synthetic macromolecular matrices for orthopedic implants and bone regeneration.
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Biomimética , Colágeno , Matriz Extracelular , Ingeniería de Tejidos , Andamios del TejidoRESUMEN
Cancer remains a leading cause of death worldwide with more than 10 million new cases every year. Tumor-targeted nanomedicines have shown substantial improvements of the therapeutic index of anticancer agents, addressing the deficiencies of conventional chemotherapy, and have had a tremendous growth over past several decades. Due to the pathophysiological characteristics that almost all tumor tissues have lower pH in comparison to normal healthy tissues, among various tumor-targeted nanomaterials, pH-responsive polymeric materials have been one of the most prevalent approaches for cancer diagnosis and treatment. In this review, we summarized the types of pH-responsive polymers, describing their chemical structures and pH-response mechanisms; we illustrated the structure-property relationships of pH-responsive polymers and introduced the approaches to regulating their pH-responsive behaviors; we also highlighted the most representative applications of pH-responsive polymers in cancer imaging and therapy. This review article aims to provide general guidelines for the rational design of more effective pH-responsive nanomaterials for cancer diagnosis and treatment.
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Nanomedicina/métodos , Neoplasias/diagnóstico , Neoplasias/tratamiento farmacológico , Polímeros/química , Humanos , Concentración de Iones de HidrógenoRESUMEN
A number of machine learning-based predictors have been developed for identifying immunogenic T-cell epitopes based on major histocompatibility complex (MHC) class I and II binding affinities. Rationally selecting the most appropriate tool has been complicated by the evolving training data and machine learning methods. Despite the recent advances made in generating high-quality MHC-eluted, naturally processed ligandome, the reliability of new predictors on these epitopes has yet to be evaluated. This study reports the latest benchmarking on an extensive set of MHC-binding predictors by using newly available, untested data of both synthetic and naturally processed epitopes. 32 human leukocyte antigen (HLA) class I and 24 HLA class II alleles are included in the blind test set. Artificial neural network (ANN)-based approaches demonstrated better performance than regression-based machine learning and structural modeling. Among the 18 predictors benchmarked, ANN-based mhcflurry and nn_align perform the best for MHC class I 9-mer and class II 15-mer predictions, respectively, on binding/non-binding classification (Area Under Curves = 0.911). NetMHCpan4 also demonstrated comparable predictive power. Our customization of mhcflurry to a pan-HLA predictor has achieved similar accuracy to NetMHCpan. The overall accuracy of these methods are comparable between 9-mer and 10-mer testing data. However, the top methods deliver low correlations between the predicted versus the experimental affinities for strong MHC binders. When used on naturally processed MHC-ligands, tools that have been trained on elution data (NetMHCpan4 and MixMHCpred) shows better accuracy than pure binding affinity predictor. The variability of false prediction rate is considerable among HLA types and datasets. Finally, structure-based predictor of Rosetta FlexPepDock is less optimal compared to the machine learning approaches. With our benchmarking of MHC-binding and MHC-elution predictors using a comprehensive metrics, a unbiased view for establishing best practice of T-cell epitope predictions is presented, facilitating future development of methods in immunogenomics.