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Sulfur in nature consists of two abundant stable isotopes, with two more neutrons in the heavy one (34S) than in the light one (32S). The two isotopes show similar physicochemical properties and are usually considered an integral system for chemical research in various fields. In this work, a model study based on a Li-S battery was performed to reveal the variation between the electrochemical properties of the two S isotopes. Provided with the same octatomic ring structure, the cyclo-34S8 molecules form stronger S-S bonds than cyclo-32S8 and are more prone to react with Li. The soluble Li polysulfides generated by the Li-34S conversion reaction show a stronger cation-solvent interaction yet a weaker cation-anion interaction than the 32S-based counterparts, which facilitates quick solvation of polysulfides yet hinders their migration from the cathode to the anode. Consequently, the Li-34S cell shows improved cathode reaction kinetics at the solid-liquid interface and inhibited shuttle of polysulfides through the electrolyte so that it demonstrates better cycling performance than the Li-32S cell. Based on the varied shuttle kinetics of the isotopic-S-based polysulfides, an electrochemical separation method for 34S/32S isotope is proposed, which enables a notably higher separation factor than the conventional separation methods via chemical exchange or distillation and brings opportunities to low-cost manufacture, utilization, and research of heavy chalcogen isotopes.
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Photodynamic therapy (PDT) is long-standing suffered from elevated tumor interstitial fluid pressure (TIFP) and prevalent hypoxic microenvironment within the solid malignancies. Herein, sound-activated flexocatalysis is developed to overcome the dilemma of PDT through both enhancing tumor penetration of photosensitizers by reducing TIFP and establishing an oxygen-rich microenvironment. In detail, a Schottky junction is constructed by flexocatalyst MoSe2 nanoflowers and Pt. Subsequently, the Schottky junction is loaded with the photosensitizer indocyanine green (ICG) and encapsulated within tumor cytomembrane to constitute a bionic-flexocatalytic nanomedicine (MPI@M). After targeting the tumor, MPI@M orchestrates flexocatalytic water splitting in tumor interstitial fluid under acoustic stimulation to lower TIFP, which boosted the tumor penetration of ICG. Concurrently, the oxygen released from the flexocatalytic water splitting overcomes the limitation of hypoxia against PDT. Furthermore, superfluous singlet oxygen generated by PDT can induce mitochondrial dysfunction for further tumor cell apoptosis. After 60 min of flexocatalysis, both the 30% decrease of TIFP and the relieved tumor hypoxia are observed, significantly promoting the therapeutic effect of PDT. Consequently, MoSe2/Pt junction nanoflowers, with the excellent flexocatalytic performance, hold significant potential for future applications in biocatalytic cancer therapies.
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Graphite has been serving as the key anode material of rechargeable Li-ion batteries, yet is difficultly charged within a quarter hour while maintaining stable electrochemistry. In addition to a defective edge structure that prevents fast Li-ion entry, the high-rate performance of graphite could be hampered by co-intercalation and parasitic reduction of solvent molecules at anode/electrolyte interface. Conventional surface modification by pitch-derived carbon barely isolates the solvent and electrons, and usually lead to inadequate rate capability to meet practical fast-charge requirements. Here we show that, by applying a MoOx-MoNx layer onto graphite surface, the interface allows fast Li-ion diffusion yet blocks solvent access and electron leakage. By regulating interfacial mass and charge transfer, the modified graphite anode delivers a reversible capacity of 340.3â mAh g-1 after 4000â cycles at 6â C, showing promises in building 10-min-rechargeable batteries with a long operation life.
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This study was designed to evaluate the gastroprotective activity of cirsilineol in hydrochloric acid (HCl)/ethanol-induced gastric ulcer model. Cirsilineol was administered at the doses of 20 and 40 mg/kg in HCl/ethanol-induced rats. The gastroprotective ability was verified by determining the ulcer score, total acidity, hemoglobin, inflammatory cytokines, lipid peroxides, and enzymatic antioxidants superoxide dismutase (SOD) and catalase (CAT) in gastric tissue and serum biochemical analysis. The results showed a favorable increase in the hemoglobin level, antioxidant enzymes (SOD and CAT), restored electrochemical balance (carbon dioxide & anion gap) while a noticeable decrease in ulcer index, total acidity, lipid peroxides, inflammatory cytokines (interleukin-1 beta [IL-1ß], IL-6, and tumor necrosis factor alpha) in rats treated with the cirsilineol. The serum biochemical analysis on liver markers (alkaline phosphatases, alanine aminotransferase, and aspartate aminotransferase), kidney markers (urea, creatinine, albumin, globulin, total protein), and lipid profile (triglyceride, high-density lipoprotein, total cholesterol) were attenuated by cirsilineol treatment in rats. Histopathology showed enhanced gastric protection and preserved the integrity of gastric mucosa upon cirsilineol administration. These results ultimately suggest that cirsilineol has gastroprotective effects that prevent the development of gastric ulcer.
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The epigenetic modification of DNA N4-methylcytosine (4mC) is vital for controlling DNA replication and expression. It is crucial to pinpoint 4mC's location to comprehend its role in physiological and pathological processes. However, accurate 4mC detection is difficult to achieve due to technical constraints. In this paper, we propose a deep learning-based approach 4mCPred-GSIMP for predicting 4mC sites in the mouse genome. The approach encodes DNA sequences using four feature encoding methods and combines multi-scale convolution and improved selective kernel convolution to adaptively extract and fuse features from different scales, thereby improving feature representation and optimization effect. In addition, we also use convolutional residual connections, global response normalization and pointwise convolution techniques to optimize the model. On the independent test dataset, 4mCPred-GSIMP shows high sensitivity, specificity, accuracy, Matthews correlation coefficient and area under the curve, which are 0.7812, 0.9312, 0.8562, 0.7207 and 0.9233, respectively. Various experiments demonstrate that 4mCPred-GSIMP outperforms existing prediction tools.
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ADN , Genoma , Animales , Ratones , Epigénesis GenéticaRESUMEN
In order to ensure the stability of flow rate and valve pressure difference during gas-water-coal mixture lifting, a multivariable non-singular terminal composite sliding mode (MNTCSM) controller based on accurate feedback linearization is proposed. The multi-input multi-output nonlinear system with time delay and coupling is transformed into a multi-input multi-output uncoupled linear system by using an improved Smith predictor and accurate feedback linearization. At the same time, the MNTCSM controller is designed to make the flow and pressure tracking errors of the decoupling system converge to zero in a finite time. Finally, simulations and experiments are designed for different control methods to verify the feasibility and effectiveness of the proposed scheme.
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PURPOSE: To investigate the prevalence of opioid use disorder (OUD) and medication treatment for OUD (MOUD) receipt in rural primary care settings and identify characteristics associated with MOUD among patients with OUD. METHODS: Secondary analyses based on electronic health records of all adult patients who visited 1 of the 6 rural primary care clinic sites from October 2019 to January 2021. Mixed effects logistic regression was conducted to assess MOUD receipt (Y/N) in relation to patient characteristics (eg, demographics, other substance use disorders [SUDs], mental health disorders, and chronic pain) and the number of MOUD prescribers per clinic. FINDINGS: The prevalence of OUD varied from 0.7% to 8.2% (Mean [SD] = 3.3% [95% CI: 0.4, 6.1]) among 36,762 primary care patients across 6 clinic sites. Among 1,164 patients with OUD, on average 50.1% received MOUD (95% CI: 28.0, 72.3). Patients in clinics with more than 3 MOUD prescribers had more than 3 times the odds of receiving MOUD (OR = 3.42; 95% CI, 1.22-9.62) as those in clinics with fewer than 3 prescribers. MOUD was positively associated with younger age (18-30 [OR = 6.97; 95% CI, 3.37-14.42], 31-64 [OR = 5.03; 95% CI, 2.64-9.57], relative to those 65 and older), having other co-occurring SUDs (OR = 3.77; 95% CI, 2.57-5.52), being male (OR = 1.50; 95% CI, 1.12-2.01), and negatively associated with having chronic pain disorders (OR = 0.69; 95% CI, 0.50-0.94). CONCLUSIONS: The prevalence of OUD and MOUD are high but vary considerably across rural primary care clinics; primary care MOUD prescribers play a key role on MOUD access in rural settings.
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Dolor Crónico , Trastornos Relacionados con Opioides , Adulto , Humanos , Masculino , Femenino , Dolor Crónico/tratamiento farmacológico , Dolor Crónico/epidemiología , Trastornos Relacionados con Opioides/tratamiento farmacológico , Trastornos Relacionados con Opioides/epidemiología , Instituciones de Atención Ambulatoria , Registros Electrónicos de Salud , Atención Primaria de SaludRESUMEN
The healing process of critical-sized bone defects urges for a suitable biomineralization environment. However, the unsatisfying repair outcome usually results from a disturbed intricate milieu and the lack of in situ mineralization resources. In this work, we have developed a composite hydrogel that mimics the natural bone healing processes and serves as a seedbed for bone regeneration. The oxidized silk fibroin and fibrin are incorporated as rigid geogrids, and amorphous calcium phosphate (ACP) and platelet-rich plasma serve as the fertilizers and loam, respectively. Encouragingly, the seedbed hydrogel demonstrates excellent mechanical and biomineralization properties as a stable scaffold and promotes vascularized bone regeneration in vivo. Additionally, the seedbed serves a succinate-like function via the PI3K-Akt signaling pathway and subsequently orchestrates the mitochondrial calcium uptake, further converting the exogenous ACP into endogenous ACP. Additionally, the seedbed hydrogel realizes the succession of calcium resources and promotes the evolution of the biotemplate from fibrin to collagen. Therefore, our work has established a novel silk-based hydrogel that functions as an in-situ biomineralization seedbed, providing a new insight for critical-sized bone defect regeneration.
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BACKGROUND: Co-occurring substance use disorders (SUDs) among individuals with opioid use disorder (OUD) are associated with additional impairment, overdose, and death. This study examined characteristics of patients who have OUD with and without co-occurring SUDs in rural primary care clinics. METHODS: Secondary analysis used electronic health record (EHR) data from six rural primary care clinics, including demographics, diagnoses, encounters, and prescriptions of medication for OUD (MOUD), as well as EHR data from an external telemedicine vendor that provided MOUD to some clinic patients. The study population included all adult patients who had a visit to the participating clinics from October 2019 to January 2021. RESULTS: We identified 1164 patients with OUD; 72.6 % had OUD only, 11.5 % had OUD and stimulant use disorder (OUD + StUD), and 15.9 % had OUD and other non-stimulant substance use disorder (OUD + Other). The OUD + StUD group had the highest rates of hepatitis C virus (25.4 % for OUD + StUD, 17.8 % for OUD + Other, and 7.5 % for OUD Only; p < 0.001) and the highest rates of mental health disorders (78.4 %, 69.7 %, and 59.9 %, respectively; p < 0.001). Compared to the OUD Only group, patients in the OUD + StUD and OUD + Other groups were more likely to receive telehealth services provided by clinic staff, in-clinic behavioral health services, and in-clinic MOUD. The OUD + StUD group had the highest proportion of referrals to the external telemedicine vendor. CONCLUSIONS: More than 27 % of patients with OUD in rural primary care clinics had other co-occurring SUDs, and these patients received more healthcare services than those with OUD only. Future studies should examine variations in outcomes associated with these other services among patients with OUD and co-occurring SUDs.
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Sobredosis de Droga , Trastornos Relacionados con Opioides , Adulto , Humanos , Instituciones de Atención Ambulatoria , Hepacivirus , Trastornos Relacionados con Opioides/epidemiología , Atención Primaria de SaludRESUMEN
OBJECTIVES: Factors associated with treatment retention on medications for opioid use disorder (MOUD) in rural settings are poorly understood. This study examines associations between social determinants of health (SDoH) and MOUD retention among patients with opioid use disorder (OUD) in rural primary care settings. METHODS: We analyzed patient electronic health records from 6 rural clinics. Participants (N = 575) were adult patients with OUD and had any prescription for MOUD from October 2019 to April 2020. MOUD retention was measured by MOUD days and continuity defined as continuous 180 MOUD days with no more than a 7-day gap. Mixed-effect regressions assessed associations between the outcomes and SDoH (Medicaid insurance, social deprivation index [SDI], driving time from home to the clinic), telehealth use, and other covariates. RESULTS: Mean patient MOUD days were 127 days (SD = 50.7 days). Living in more disadvantaged areas (based on SDI) (adjusted relative risk [aRR]: 0.98; 95% confidence interval [CI], 0.98-0.99) and having more than an hour (compared with an hour or less) driving time from home to clinic (aRR: 0.95; 95% CI, 0.93-0.97) were associated with fewer MOUD days. Using telehealth was associated with more MOUD days (aRR: 1.23; 95% CI, 1.21-1.26). In this cohort, 21.7% of the participants were retained on MOUD for at least 180 days. SDoH and use of telehealth were not associated with having continuity of MOUD. CONCLUSIONS: Addressing SDoH (eg, SDI) and providing telehealth (eg, improvements in public transportation, internet access) may improve MOUD days in rural settings.
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Tratamiento de Sustitución de Opiáceos , Trastornos Relacionados con Opioides , Atención Primaria de Salud , Población Rural , Determinantes Sociales de la Salud , Humanos , Masculino , Femenino , Trastornos Relacionados con Opioides/tratamiento farmacológico , Adulto , Persona de Mediana Edad , Población Rural/estadística & datos numéricos , Tratamiento de Sustitución de Opiáceos/estadística & datos numéricos , Telemedicina/estadística & datos numéricos , Estados Unidos , Continuidad de la Atención al Paciente/estadística & datos numéricos , Servicios de Salud Rural/estadística & datos numéricosRESUMEN
INTRODUCTION: Opioid and alcohol use disorders are increasingly being addressed in primary care, yet how medications to treat these disorders are prescribed in rural regions is unknown. METHODS: We determined prevalence, types, and duration of medication prescription for opioid and/or alcohol use disorder among adult patients in rural primary clinics. The sample included 1874 adult patients who visited one of six rural primary care sites in the Northeastern and Northwestern United States at least once from October 2019 to January 2021 and had a diagnosis code for opioid use disorder (OUD), alcohol use disorder (AUD), or co-occurring opioid and alcohol use disorder (OUD + AUD) during that time. RESULTS: Patients with OUD + AUD were more likely to be prescribed medication for at least one of these disorders (85.3 %) than patients with OUD only (63.7 %) or AUD only (10.3 %). Further, the OUD + AUD group had the highest number of days on medication (M = 264.7), followed by OUD only (M = 220.5), then the AUD only group (M = 62.5). Only 8.8 % of patients with OUD + AUD were prescribed naltrexone or medication for OUD + AUD to treat both substance use disorders. CONCLUSIONS: Medications for treating AUD as well as OUD are available, but few patients with OUD + AUD and even fewer with AUD received pharmacological treatment for AUD. The current work highlights the need for rural clinicians to consider medications for AUD as an important treatment method for patients with AUD only or OUD + AUD.
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Alcoholismo , Trastornos Relacionados con Opioides , Atención Primaria de Salud , Población Rural , Humanos , Trastornos Relacionados con Opioides/tratamiento farmacológico , Trastornos Relacionados con Opioides/epidemiología , Masculino , Femenino , Alcoholismo/tratamiento farmacológico , Alcoholismo/epidemiología , Adulto , Persona de Mediana Edad , Naltrexona/uso terapéutico , Estados Unidos/epidemiología , Prevalencia , Tratamiento de Sustitución de OpiáceosRESUMEN
BACKGROUND: Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS), acting as one common sepsis-associated organ injury, induces uncontrolled and self-amplifies pulmonary inflammation. Given the lack of clinically effective approaches, the mortality rate of it still remains high. Suramin(SUR), as an antiparasitic drug initially, was found to ameliorate sepsis associated ALI in our previous work. However, the underlying mechanism of its protective effects has not been clarified. Pyroptosis, categorized as an inflammatory form of programmed cell death, could aggravate lung inflammatory responses via inducing alveolar macrophages (AM) pyroptosis. METHODS: MH-S AM cell line was stimulated with or without lipopolysaccharide (LPS) or suramin, and the differential expression genes (DEGs) were excavated using RNA sequencing (RNA-seq). To identify the regulatory roles of these genes, pyroptosis-related genes (PRGs), GO/KEGG and GSEA analysis were conducted. We also performed WB, qRTPCR and ELISA to validate the RNA-seq results and further expound the protective effect of suramin. RESULTS: 624 DEGs were identified between control (CON) and lipopolysaccharide (LPS) groups, and enrichment analysis of these genes revealed significantly enriched pathways that related to immune system and signal transduction. Meanwhile, 500 DEGs were identified in LPS/SUR+LPS group. In addition to the pathways mentioned above, IL-17 pathway and C-type lectin receptor signaling pathway were also enriched. All 6 pathways were connected with pyroptosis. Concurrently, the "DESeq2" R package was used to identify differentially expressed PRGs. Nod1, Nod2, interleukin (IL)-1b, IL-6, tumor necrosis factor (TNF), NLRP3 were upregulated under LPS stimulation. Then, in SUR+LPS group, Nod2, IL-6, IL-1b, NLRP3 were downregulated. The validation results of WB, qRT-PCR, and ELISA showed: the protein and mRNA expression levels of NLRP3, caspase-1, GSDMD and the concentrations of IL-1b, IL-18 were decreased when treated with suramin and LPS. CONCLUSION: Suramin could inhibit NLRP3/caspase-1/GSDMD canonical pyroptosis pathway in LPS-induced MH-S alveolar macrophages.
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Macrófagos Alveolares , Sepsis , Humanos , Macrófagos Alveolares/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Caspasa 1/genética , Caspasa 1/metabolismo , Lipopolisacáridos/farmacología , Suramina/farmacología , Interleucina-6/genética , RNA-Seq , Inflamasomas/metabolismo , Proteínas de Unión a Fosfato/genética , Proteínas de Unión a Fosfato/farmacología , Proteínas Citotóxicas Formadoras de Poros/genética , Proteínas Citotóxicas Formadoras de Poros/metabolismo , Proteínas Citotóxicas Formadoras de Poros/farmacologíaRESUMEN
The practical efficacy of nanomedicines for treating solid tumors is frequently low, predominantly due to the elevated interstitial pressure within such tumors that obstructs the penetration of nanomedicines. This increased interstitial pressure originates from both liquid and solid stresses related to an undeveloped vascular network and excessive fibroblast proliferation. To specifically resolve the penetration issues of nanomedicines for tumor treatment, this study introduces a holistic "dual-faceted" approach. A treatment platform predicated on the WS2/Pt Schottky heterojunction was adopted, and flexocatalysis technology was used to disintegrate tumor interstitial fluids, thus producing oxygen and reactive oxygen species and effectively mitigating the interstitial fluid pressure. The chemotherapeutic agent curcumin was incorporated to further suppress the activity of cancer-associated fibroblasts, minimize collagen deposition in the extracellular matrix, and alleviate solid stress. Nanomedicines achieve homologous targeting by enveloping the tumor cell membrane. It was found that this multidimensional strategy not only alleviated the high-pressure milieu of the tumor interstitiumâwhich enhanced the efficiency of nanomedicine deliveryâbut also triggered tumor cell apoptosis via the generated reactive oxygen species and modulated the tumor microenvironment. This, in turn, amplified immune responses, substantially optimizing the therapeutic impacts of nanomedicines.
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The widespread use of surfactants raise challenges to biological wastewater treatment. Anaerobic ammonium oxidation (anammox) process has the potential to treat wastewater containing anionic surfactants, but the response of anammox consortia at the molecular level under long-term exposure is unclear. Using high-throughput sequencing and gene quantification, combined with molecular docking, the effect of sodium dodecyl sulfonate (SDS) on anammox consortia were investigated. Levels of reactive oxygen species (ROS) might be lower than the threshold of oxidative damage, while the increase of lactate dehydrogenase (LDH) represented the cell membrane damage. Decreased abundance of functional genes (hdh, hzsA and nirS) indicated the decrease of the anammox bacterial abundance. Trace amounts of N-acyl homoserine lactone (AHL, C6-HSL, C8-HSL and C12-HSL) contained in influent could induce endogenous quorum sensing (QS), which could regulate the correlation between functional bacteria to optimize the microbial community and strengthen the resistance of anammox consortia to SDS. In addition, the proliferation of disinfectant resistance genes might increase the environmental pathogenicity of sewage discharge. This work highlights the potential response mechanism of anammox consortium to surfactants and provides a universal microbial-friendly bioenhancement strategy based on QS.
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Percepción de Quorum , Tensoactivos , Eliminación de Residuos Líquidos , Tensoactivos/metabolismo , Eliminación de Residuos Líquidos/métodos , Aguas Residuales/microbiología , Oxidación-Reducción , Anaerobiosis , Compuestos de Amonio/metabolismo , Simulación del Acoplamiento Molecular , Consorcios Microbianos/fisiologíaRESUMEN
In tumor therapy, copper (Cu)-based nanozymes with peroxidase-like activity play a crucial role in converting hydrogen peroxide into hydroxyl radicals (OH). This process induces immunogenic cell death, which in turn activates the body's immune response, enhancing the efficacy of tumor immunotherapy. Nonetheless, the efficiency of this reaction is curtailed due to the oxidation of Cu(I) to Cu(II), leading to the self-depletion of the nanozyme's activity and an insufficient yield of OH for effective immunotherapeutic activation. To surmount this challenge, our research introduces a photocharging self-doped semiconductor nanozyme, copper sulfide (Cu9S8). The photocharging effect enables the nanozyme to convert internal Cu(II) back to Cu(I) through charge transfer induced by near-infrared (NIR)-II photothermal energy, thereby effectively maintaining the enzyme-like activity of the nanozyme. Additionally, Cu9S8 is enhanced with a calcium sulfide (CaS) coating. This coating reacts in the acidic microenvironment of tumors to generate hydrogen sulfide (H2S) gas, which in turn suppresses the catalase activity inherent in tumor cells, ensuring a plentiful supply of H2O2 for the nanozyme's operation. This dual strategy of amplifying enzyme-like activity and substrate availability culminates in the generation of ample OH within tumor cells, leading to significant immunogenic cell death and thereby realizing potent immunotherapy.
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INTRODUCTION: Rural primary care clinics can expand their medication treatment for opioid use disorder (MOUD) capacity by coordinating care with external telemedicine (TM) vendors specializing in addiction medicine. This study used mixed methods to identify factors that influence patient referrals from rural primary care clinics to TM vendors for MOUD. METHODS: Between July/August 2020 and January/February 2021, 582 patients with OUD were identified across six primary care sites; that included 68 referred to an external TM vendor to receive MOUD. Mixed effects logistic regression identified individual and site-level factors associated with being referred to the TM vendor. Clinic providers and staff participated in in-depth interviews and focus groups to discuss their considerations for referring patients to the TM vendor. RESULTS: Patient referrals were positively associated with local household broadband coverage (OR = 2.55, p < 0.001) and negatively associated with local population density (OR = 0.01, p = 0.003) and the number of buprenorphine prescribers in the county (OR = 0.85, p < 0.001). Clinic personnel expressed appreciation for psychiatric expertise and the flexibility to access MOUD brought by the TM vendor. Perceived concerns about TM referral included a lack of trust with external providers, uncertainty about TM service quality, workflow delays, and patients' technological and insurance challenges. CONCLUSION: This study revealed several clinic-level factors that may potentially influence patient referral to TM vendor services for MOUD. To facilitate the referral process and utilization of TM vendors, efforts should be made to foster open communication and trust between clinic providers and TM vendors, streamline workflows, and improve Internet access for patients.
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Background: Pseudouridine (Ψ) is one of the most abundant RNA modifications found in a variety of RNA types, and it plays a significant role in many biological processes. The key to studying the various biochemical functions and mechanisms of Ψ is to identify the Ψ sites. However, identifying Ψ sites using experimental methods is time-consuming and expensive. Therefore, it is necessary to develop computational methods that can accurately predict Ψ sites based on RNA sequence information. Methods: In this study, we proposed a new model called PseU-ST to identify Ψ sites in Homo sapiens (H. sapiens), Saccharomyces cerevisiae (S. cerevisiae), and Mus musculus (M. musculus). We selected the best six encoding schemes and four machine learning algorithms based on a comprehensive test of almost all of the RNA sequence encoding schemes available in the iLearnPlus software package, and selected the optimal features for each encoding scheme using chi-square and incremental feature selection algorithms. Then, we selected the optimal feature combination and the best base-classifier combination for each species through an extensive performance comparison and employed a stacking strategy to build the predictive model. Results: The results demonstrated that PseU-ST achieved better prediction performance compared with other existing models. The PseU-ST accuracy scores were 93.64%, 87.74%, and 89.64% on H_990, S_628, and M_944, respectively, representing increments of 13.94%, 6.05%, and 0.26%, respectively, higher than the best existing methods on the same benchmark training datasets. Conclusion: The data indicate that PseU-ST is a very competitive prediction model for identifying RNA Ψ sites in H. sapiens, M. musculus, and S. cerevisiae. In addition, we found that the Position-specific trinucleotide propensity based on single strand (PSTNPss) and Position-specific of three nucleotides (PS3) features play an important role in Ψ site identification. The source code for PseU-ST and the data are obtainable in our GitHub repository (https://github.com/jluzhangxinrubio/PseU-ST).
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A typical colorimetric sandwich-type sensor relies on dual antibodies/aptamers to specifically visualize the targets. The requirement of dual antibodies/aptamers and low signal intensity inevitably increases the design difficulty and compromises the sensing sensitivity. In this work, a novel sandwich-type aptasensor was developed using single aptamer-functionalized magnetic nanoparticles as a specific recognition unit to target cancer cells and a bimetallic metal-organic frameworks (MOFs)-based nanozymes as a colorimetric signal amplification unit. The well-defined crystalline structure of UIO-66 MOFs enabled the introduction of Fe/Zr bimetal nodes, which possessed integrated properties of the peroxidase-like nanozyme activity and direct coordinately binding to the cell surface. Such a novel construction strategy of sandwich-type aptasensors achieved simple, sensitive, and specific detection of the target cancer cells, which will inspire the development of biosensors.
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Aptámeros de Nucleótidos , Técnicas Biosensibles , Nanopartículas del Metal , Estructuras Metalorgánicas , Nanopartículas , Neoplasias , Estructuras Metalorgánicas/química , Colorimetría , Aptámeros de Nucleótidos/química , Nanopartículas del Metal/química , Límite de Detección , Neoplasias/diagnósticoRESUMEN
Metal-organic frameworks (MOFs) have been widely used as nanozymes with a great development prospect due to their unique advantages. It is known that the current Fe-based or Cu-based MOF, etc., exhibits the catalytic activity of nanozymes through the Fenton catalytic reaction. And the conversion efficiency of the Fe3+/Fe2+ or Cu2+/Cu+ cycle is key to the catalytic activity. Therefore, we proposed a novel co-catalytic method to promote the reaction rate of the rate-limiting step of Cu2+/Cu+ conversion in the Fenton reaction of Cu2+/H2O2 to enhance the catalytic activity of the nanozymes. As a proof of concept, the MoCu-2MI nanozyme with high catalytic activity was successfully synthesized using Mo-doped Cu-2MI (2-methylimidazole). By using 3,3',5,5'-tetramethylbenzidine (TMB) as the chromogenic substrate, MoCu-2MI exhibited higher peroxidase-like activity than pure Cu-2MI. Then, it was confirmed that the newly introduced Mo played a crucial co-catalytic role by characterizing the possible catalytic mechanism. Specifically, Mo acted as a co-catalyst to accelerate the electron transfer in the system, and then promote the Cu2+/Cu+ cycle in the Cu-Fenton reaction, which was conducive to accelerating the production of a large number of reactive oxygen species (ROS) from H2O2, and finally improve the activity. Ultimately, a biosensor platform combined with MoCu-2MI and cholesterol oxidase realized the one-step colorimetric detection of cholesterol in the range of 2-140 µM with the detection limit as low as 1.2 µM. This study provides a new strategy for regulating the activity of MOF nanozymes.