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Ion channels, which are key to physiological regulation and drug discovery, control ion flux across membranes, and their dysregulation leads to various diseases. Ca2+ monitoring is crucial for cellular signaling when performing Ca-based assays in ion channel research; these assays are widely utilized in both academic and pharmaceutical contexts for drug screening and pharmacological profiling. However, existing detection methods are limited by slow detection speeds, low throughput, complex processes, and low analyte viability. In this study, we developed a label-free optical biosensing method using a conical Au/polydimethylsiloxane platform tailored to detect Ca2+ influx in A549-originated nanovesicles facilitated by the transient receptor potential ankyrin 1 (TRPA1) channel. Nanovesicles expressing cellular signaling components mimic TRPA1 signal transduction in cell membranes and improve analyte viability. The conical Au/polydimethylsiloxane sensor converted Ca2+ influx events induced by specific agonist exposure into noticeable changes in relative transmittance under visible light. The optical transmittance change accompanying Ca2+ influx resulted in an enhanced sensing response, high accuracy and reliability, and rapid detection (â¼5 s) without immobilization or ligand treatments. In the underlying sensing mechanism, morphological variations in nanovesicles, which depend on Ca2+ influx, induce a considerable light scattering change at an interface between the nanovesicle and Au, revealed by optical simulation. This study provides a foundation for developing biosensors based on light-matter interactions. These sensors are simple and cost-effective with superior performance and diverse functionality.
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Técnicas Biossensoriais , Cálcio , Dimetilpolisiloxanos , Ouro , Ouro/química , Dimetilpolisiloxanos/química , Humanos , Técnicas Biossensoriais/instrumentação , Cálcio/metabolismo , Células A549 , Canal de Cátion TRPA1/metabolismoRESUMO
Prefiltration before chromatographic analysis is critical in the monitoring of environmental micropollutants (MPs). However, in an aqueous matrix, such monitoring often leads to out-of-specification results owing to the loss of MPs on syringe filters. Therefore, this study investigated the loss of seventy MPs on eight different syringe filters by employing Random Forest, a machine learning algorithm. The results indicate that the loss of MPs during filtration is filter specific, with glass microfiber and polytetrafluoroethylene filters being the most effective (<20%) compared with nylon (>90%) and others (regenerated-cellulose, polyethersulfone, polyvinylidene difluoride, cellulose acetate, and polypropylene). The Random Forest classifier showed outstanding performance (accuracy range 0.81-0.95) for determining whether the loss of MPs on filters exceeded 20%. Important factors in this classification were analyzed using the SHapley Additive exPlanation value and Kruskal-Wallis test. The results show that the physicochemical properties (LogKow/LogD, pKa, functional groups, and charges) of MPs are more important than the operational parameters (sample volume, filter pore size, diameter, and flow rate) in determining the loss of most MPs on syringe filters. However, other important factors such as the implications of the roles of pH for nylon and pre-rinsing for PTFE syringe filters should not be ignored. Overall, this study provides a systematic framework for understanding the behavior of various MP classes and their potential losses on syringe filters.
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Filtração , Aprendizado de Máquina , Seringas , Poluentes Químicos da Água , Filtração/instrumentação , Filtração/métodos , Poluentes Químicos da Água/análise , Monitoramento Ambiental/métodos , AlgoritmosRESUMO
Extracellular vesicles (EVs) are emerging as crucial materials for precision theragnostic applications. However, current separation methods are time-consuming, costly, and not scalable and deliver limited yields or purity. Here, we present EV precipitation by ionic strength modulation (ExoPRISM), a simple, low-cost, user-friendly, and readily adaptable approach for separating EVs in high yields without compromising their biological functions. Adding an electrolyte solution to blood plasma in small increments generates the sequential precipitation of proteins and EVs, allowing for fractional separation of EVs using low-speed centrifugation. The coprecipitated electrolytes are easily washed away, and the entire EV separation and washing process takes less than an hour. This approach successfully separates EVs from a broad range of volumes and types of biological fluids, including culture medium, urine, plasma, and serum, showing promise as a robust tool for next-generation liquid biopsies and regenerative medicine.
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Accurate identification of protein-protein interaction (PPI) sites remains a computational challenge. We propose Spatom, a novel framework for PPI site prediction. This framework first defines a weighted digraph for a protein structure to precisely characterize the spatial contacts of residues, then performs a weighted digraph convolution to aggregate both spatial local and global information and finally adds an improved graph attention layer to drive the predicted sites to form more continuous region(s). Spatom was tested on a diverse set of challenging protein-protein complexes and demonstrated the best performance among all the compared methods. Furthermore, when tested on multiple popular proteins in a case study, Spatom clearly identifies the interaction interfaces and captures the majority of hotspots. Spatom is expected to contribute to the understanding of protein interactions and drug designs targeting protein binding.
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Redes Neurais de Computação , Mapeamento de Interação de Proteínas , Mapeamento de Interação de Proteínas/métodos , Ligação Proteica , Proteínas/metabolismoRESUMO
Here, we describe the use of TriNet to predict peptides with anticancer and antimicrobial properties by a tri-fusion neural network. We detail the use of TriNet for both the offline Python script version and the online service, thereby demonstrating its convenience for users. In addition, we provide a detailed explanation of the training process of TriNet to enhance the understanding of researchers seeking to leverage deep learning techniques for peptide classification. For complete details on the use and execution of this protocol, please refer to Zhou et al.1.
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Anti-Infecciosos , Anti-Infecciosos/farmacologia , Anti-Infecciosos/uso terapêutico , Redes Neurais de Computação , PeptídeosRESUMO
We synthesized low-cost cathodes for use in the electrochemical NO3- reduction reaction (NO3RR) via the simple reconstruction of AISI 420 stainless steel (SS). Thermochemical treatment of the SS in oxalic acid generated iron oxalate (FeC2O4) microrods (BL-SS), with further anodization affording Cr-doped Fe2O3 (R-SS) or FeC2O4 (G-SS). G-SS displayed supreme N2 selectivity during galvanostatic electrolysis at circumneutral pH. Electroanalysis and descriptor/scavenger analysis indicated that Fe sites were the primary active sites of NO3- adsorption, with C2O42- as the H-binding sites. The C2O42- ligands and Cr dopants altered the electronic structures of the Fe sites. A parametric study of the current density, pH, [NO3-]0, and [Cl-]0 indicated an Eley-Rideal N2 generation mechanism, with NO2- as an intermediate. Cl- elevated the N2 selectivity but reduced the NO3RR efficiency. To demonstrate the practical applicability of G-SS with a proposed regeneration strategy, its durability was examined in synthetic and real wastewater matrices. Compared with that in synthetic wastewater, G-SS displayed more stable performance in real wastewater owing to the natural buffering capacity at the cathode, which reduced the corrosion rate. Cr-doped FeC2O4 is viable for use in the low-cost, efficient electrochemical treatment of wastewater containing NO3-.
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Owing to the surge in plastic waste generated during the COVID-19 pandemic, concerns regarding microplastic pollution in aqueous environments are increasing. Since microplastics (MPs) are broken down into submicron (< 1 µm) and nanoscale plastics, their real-time morphological detection in water is necessary. However, the decrease in the scattering cross-section of MPs in aqueous media precludes morphological detection by bright-field microscopy. To address this problem, we propose and demonstrate a differential interference contrast (DIC) system that incorporates a magnification-enhancing system to detect MPs in aqueous samples. To detect MPs in both the stationary and mobile phases, a microfluidic chip was designed, taking into consideration the imaging depth of focus and flow resistance. MPs of various sizes flowing in deionized, tap, and pond water at varying speeds were observed under Static and Flow conditions. Successful real-time morphological detection and quantification of polystyrene beads down to 200 nm at a constant flow rate in water were achieved. Thus, the proposed novel method can significantly reduce analysis time and improve the size-detection limit. The proposed DIC microscopy system can be coupled with Raman or infrared spectroscopy in future studies for chemical composition analysis. ENVIRONMENTAL IMPLICATION: Microplastics (MPs), particularly submicron plastics < 1-µm, can pose a risk to human health and aquatic ecosystems. Existing methods for detecting MPs in the aqueous phase have several limitations, including the use of expensive instruments and prolonged and labor-intensive procedures. Our results clearly demonstrated that a new low-cost flow-channeled differential interference contrast microscopy enables the real-time morphological detection and quantification of MPs down to 200 nm under flowing conditions without sample labeling. Consequently, our proposed rapid method for accurate quantitative measurements can serve as a valuable reference for detecting submicron plastics in water samples.
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COVID-19 , Poluentes Químicos da Água , Humanos , Plásticos/análise , Microplásticos , Ecossistema , Microscopia , Pandemias , Poluentes Químicos da Água/análise , Monitoramento Ambiental , Água/análiseRESUMO
The accurate identification of anticancer peptides (ACPs) and antimicrobial peptides (AMPs) remains a computational challenge. We propose a tri-fusion neural network termed TriNet for the accurate prediction of both ACPs and AMPs. The framework first defines three kinds of features to capture the peptide information contained in serial fingerprints, sequence evolutions, and physicochemical properties, which are then fed into three parallel modules: a convolutional neural network module enhanced by channel attention, a bidirectional long short-term memory module, and an encoder module for training and final classification. To achieve a better training effect, TriNet is trained via a training approach using iterative interactions between the samples in the training and validation datasets. TriNet is tested on multiple challenging ACP and AMP datasets and exhibits significant improvements over various state-of-the-art methods. The web server and source code of TriNet are respectively available at http://liulab.top/TriNet/server and https://github.com/wanyunzh/TriNet.
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We propose a lightguide-type super multi-view near-eye display that uses a digital micromirror device and a LED array. The proposed method presents three-dimensional images with a natural monocular depth cue using a compact combiner optics which consists of a thin lightguide and holographic optical elements (HOEs). Feasibility of the proposed method is verified by optical experiments which demonstrate monocular three-dimensional image presentation over a wide depth range. We also analyze the degradation of the image quality stemming from the spectral spread of the HOEs and show its reduction by a pre-compensation exploiting an adaptive moment estimation (Adam) optimizer.
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Holografia , Dispositivos Ópticos , Holografia/métodos , Imageamento Tridimensional , Visão Ocular , Óptica e FotônicaRESUMO
BACKGROUND: Cancer is widely regarded as a complex disease primarily driven by genetic mutations. A critical concern and significant obstacle lies in discerning driver genes amid an extensive array of passenger genes. FINDINGS: We present a new method termed DriverMP for effectively prioritizing altered genes on a cancer-type level by considering mutated gene pairs. It is designed to first apply nonsilent somatic mutation data, proteinâprotein interaction network data, and differential gene expression data to prioritize mutated gene pairs, and then individual mutated genes are prioritized based on prioritized mutated gene pairs. Application of this method in 10 cancer datasets from The Cancer Genome Atlas demonstrated its great improvements over all the compared state-of-the-art methods in identifying known driver genes. Then, a comprehensive analysis demonstrated the reliability of the novel driver genes that are strongly supported by clinical experiments, disease enrichment, or biological pathway analysis. CONCLUSIONS: The new method, DriverMP, which is able to identify driver genes by effectively integrating the advantages of multiple kinds of cancer data, is available at https://github.com/LiuYangyangSDU/DriverMP. In addition, we have developed a novel driver gene database for 10 cancer types and an online service that can be freely accessed without registration for users. The DriverMP method, the database of novel drivers, and the user-friendly online server are expected to contribute to new diagnostic and therapeutic opportunities for cancers.
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OBJECTIVES: This study investigated whether long-term benzodiazepine use is associated with increased 90-day mortality among patients with sepsis. METHODS: A retrospective population-based cohort study based on health records obtained from the National Health Insurance Service database in South Korea was conducted. All adult patients (≥18 years) admitted to the hospital with a primary diagnosis of sepsis or septic shock during 2010-2018 were included in the study. Sepsis and septic shock were diagnosed based on the International Classification of Diseases (10th revision: A40, A41 and R65.2). Benzodiazepine users were defined as individuals who were prescribed regular benzodiazepine continuously for over 6 months before admission. RESULTS: A total of 251 837 patients with sepsis were included in this study, 16 686 of which (6.6%) were benzodiazepine users, and 235 151 (93.4%) were non-users. After propensity score (PS) matching, 33 370 patients (16 685 in both groups) were ultimately included. Moreover, following PS matching, the 90-day mortality among benzodiazepine users and non-users was 60.9% (10 167) and 41.4% (6916), respectively. Cox regression analysis further revealed the hazard ratio (HR) for 90-day mortality in benzodiazepine users to be 1.75, compared with non-users [95% confidence interval (CI): 1.70-1.81; P < .001]. Sensitivity analyses showed that, compared with non-users, HRs for 90-day mortality in benzodiazepine users without and with other psychiatric illnesses were 1.43 (95% CI: 1.38-1.49; P < .001) and 1.89 (95% CI: 1.84-1.94; P < .001), respectively. CONCLUSION: Long-term benzodiazepine use is associated with increased 90-day mortality among adult patients with sepsis compared with non-users. This association was more evident in benzodiazepine users with other psychiatric diseases, such as depression or anxiety disorder.
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Benzodiazepinas , Sepse , Adulto , Benzodiazepinas/efeitos adversos , Estudos de Coortes , Humanos , República da Coreia/epidemiologia , Estudos Retrospectivos , Sepse/tratamento farmacológicoRESUMO
OBJECTIVE: Systemic absorption of irrigation fluid can lead to a disturbed coagulation cascade. We compared the changes in hemostatic properties on using nonelectrolyte solution in monopolar hysteroscopic surgery (HS) with that on using isotonic saline in bipolar HS via rotational thromboelastometry (ROTEM) analysis. METHODS: A total of 54 patients were randomized into 2 groups: 1 group underwent monopolar HS using a mixture of 2.7% sorbitol and 0.54% mannitol (the HSMP group), whereas the other group underwent bipolar HS using 0.9% isotonic saline (the HSBP group). The effects of these 2 methods on coagulation were assessed via pre and postoperative laboratory tests, including estimation of the international normalized ratio of prothrombin time and activated partial thromboplastin time and ROTEM analysis. In addition, the hemoglobin, hematocrit, and electrolyte levels and the platelet count were analyzed. RESULTS: Patient characteristics, volume of irrigation fluid absorbed, and type of procedure were comparable between the 2 groups. There were no significant differences in the pre and postoperative values of ROTEM parameters between the 2 groups. Most postoperative ROTEM parameters, as compared with preoperative values, changed in both groups; clot formation time was prolonged, and the α-angle and maximum clot firmness were decreased. All ROTEM parameters were maintained within the normal range. Hematological parameters, including hemoglobin and hematocrit levels and platelet count, were significantly decreased postoperatively in both groups compared to the preoperative values. No pre and postoperative hematological and hemostatic parameters were significantly different between the 2 groups. CONCLUSION: Irrigation fluid absorbed in healthy women during HS caused hypocoagulable changes in the blood, irrespective of the irrigant type, and no significant differences between HS using monopolar and bipolar electrodes were demonstrated.
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Hemostasia , Histeroscopia/métodos , Soluções , Tromboelastografia , Adulto , Coagulação Sanguínea , Feminino , Humanos , Masculino , Manitol , Pessoa de Meia-Idade , Gravidez , Solução Salina , Sorbitol , Irrigação Terapêutica/instrumentaçãoRESUMO
BACKGROUND: The Y-splitting procedure has been used both to treat up-shoots and down-shoots in Duane syndrome, and as a substitute for posterior fixation suture. The Y-split is often performed in conjunction with a hang-back recession when a large amount of recession or an adjustable suture is necessary. Herein, we evaluated the stability of Y-splitting hang-back recession in the rectus muscle. METHODS: Under general anesthesia, a 5-mm hang-back recession of the superior rectus muscle (SR) with Y-splitting was performed in ten eyes from ten rabbits (hang-back group). A conventional recession was performed in the SR of the fellow eye (control group). Six weeks after the procedure, the distance between the original insertion and the recessed SR (recession amount) and the width between the nasal and temporal halves of the SR were measured. These values were compared to the measurements taken at the time of surgery. RESULTS: The hang-back group had a significantly larger forward displacement than the control group (P < 0.001 for both the nasal and temporal halves). The width change between the nasal and temporal halves was also significantly larger in the hang-back group (4.94 ± 1.32 mm) than in the control group (1.14 ± 0.60 mm, P < 0.001). Additionally, the Y-configuration appeared to be more collapsed in the hang-back group than in the control group. CONCLUSION: Y-splitting of the rectus muscle may be unstable when it is combined with a hang-back recession. Surgeons should consider this possibility when performing Y-splitting procedures.
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Músculos Oculomotores/cirurgia , Procedimentos Cirúrgicos Oftalmológicos , Técnicas de Sutura , Animais , Síndrome da Retração Ocular/cirurgia , Poliglactina 910 , Coelhos , Esclera/cirurgia , Estrabismo/cirurgia , SuturasRESUMO
OBJECTIVES: Area probability sampling was used to conduct a women's health survey in Boston, MA. Sexual minority women (SMW) and heterosexual adult women were compared on a variety of health-related measures. METHODS: SMW-rich census tracts were identified and mapped onto zip code boundaries. Eligible respondents were women 18 and older who lived within the defined area, who were able to complete a personal interview or self-administered questionnaire in English. Differences in significant health-related outcomes by sexual orientation were examined. RESULTS: SMW and heterosexual women differed on access to health care and utilization of screening tests. There were no significant differences in smoking rates, eating less calories or fat, and intentions to follow mammography recommendations. CONCLUSIONS: In certain respects, study results are congruent with previous non-probability surveys, while in others the results are different. It is likely that real differences exist in some health-related variables by sexual orientation category.