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1.
Small ; : e2400927, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38726949

RESUMO

Due to the presence of spatial barriers, persistent bacteria, and excessive inflammation in bacteria biofilm-infected wounds, current nanoplatforms cannot effectively address these issues simultaneously during the therapeutic process. Herein, a novel biomimetic photothermal nanoplatform integrating silver and polydopamine nanoparticles (Ag/PDAs) that can damage biofilms, kill bacterial persisters, and reduce inflammation for wound treatment is presented. These findings reveal that Ag/PDAs exhibit a broad-spectrum antimicrobial activity through direct damage to the bacterial membrane structure. Additionally, Ag/PDAs demonstrate a potent photothermal conversion efficiency. When combined with near-infrared (NIR) irradiation, Ag/PDAs effectively disrupt the spatial structure of biofilms and synergistically eradicate the resident bacteria. Furthermore, Ag/PDAs show remarkable anti-inflammatory properties in counteracting bacterium-induced macrophage polarization. The in vivo results confirm that the topical application of Ag/PDAs significantly suppress Staphylococcus aureus biofilm-infected wounds in murine models, concurrently facilitating wound healing. This research provides a promising avenue for the eradication of bacterial biofilms and the treatment of biofilm-infected wounds.

2.
ACS Nano ; 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38803167

RESUMO

The Pseudomonas aeruginosa biofilm in recalcitrant chronic lung infections not only develops high antimicrobial tolerance but also induces an aberrant host inflammatory response. The metabolic condition plays a vital role in both the antimicrobial susceptibility of bacteria and the inflammatory response of immune cells, thereby offering a potential therapeutic target. Herein, we described a metabolic modulation strategy by using ultrasound-responsive liposomal nanoparticles containing a sonosensitizer and a hypoxia-activated prodrug against biofilm-associated chronic lung infections. Under ultrasound stimulation, the sonosensitizer generates antibacterial reactive oxygen species by oxygen consumption. Subsequently, the oxygen consumption-mediated hypoxia not only induces the anaerobic metabolism of bacteria for antibiotic activation but also triggers the glycolysis pathway of immune cells for inflammatory activation. Such metabolic modulation strategy demonstrated efficient therapeutic efficacy for P. aeruginosa biofilm-induced chronic lung infections in mice models and provides a promising way for combating biofilm-associated chronic infections.

3.
Artigo em Inglês | MEDLINE | ID: mdl-38593051

RESUMO

In clinical settings, saliva has been established as a straightforward, noninvasive medium for diagnosing periodontitis. However, the precise diagnosis is often hampered by the absence of a specialized analyzer capable of detecting low concentrations of biomarkers typically found in saliva. In this study, we present a noninvasive, on-site screen-printed biomicrochip specifically engineered for the precise and sensitive quantification of lactate concentrations in saliva, a critical biomarker in the diagnosis of periodontitis. The microchip is constructed using a nanostructured ink formulation that includes MnFe@N-doped carbon nanotubes (MnFe@N-CNTs). These MnFe@N-CNTs exhibit a high degree of graphitization and low electrical resistance, significantly augmenting the electrocatalytic efficiency of the enzymatic reaction of lactate. This results in doubled sensitivity and a detection limit that surpasses those of the current advanced salivary assay methods. Remarkably, within just 30 s, the biomicrochip can quantitatively and precisely measure lactate concentrations in the saliva of 10 patients, which provides valuable insights into the severity of their periodontitis. This biosensor holds excellent potential for large-scale production and could broaden the scope of biomarker recognition, paving the way for the analysis of a wider range of oral diseases.

4.
Nano Lett ; 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38606881

RESUMO

Photocatalysis offers a direct, yet robust, approach to eradicate pathogenic bacteria. However, the practical implementation of photocatalytic disinfection faces a significant challenge due to low-efficiency photogenerated carrier separation and transfer. Here, we present an effective approach to improve photocatalytic disinfection performance by exploiting the pyro-phototronic effect through a synergistic combination of pyroelectric properties and photocatalytic processes. A set of comprehensive studies reveals that the temperature fluctuation-induced pyroelectric field promotes photoexcited carrier separation and transfer and thus facilitates the generation of reactive oxygen species and ultimately enhances photocatalytic disinfection performance. It is worth highlighting that the constructed film demonstrated an exceptional antibacterial efficiency exceeding 95% against pathogenic bacteria under temperature fluctuations and light irradiation. Moreover, the versatile modulation role of the pyro-phototronic effect in boosting photocatalytic disinfection was corroborated. This work paves the way for improving photocatalytic disinfection efficiency by harnessing the synergistic potential of various inherent material properties.

5.
Comput Biol Med ; 174: 108415, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38599070

RESUMO

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder that requires objective and accurate identification methods for effective early intervention. Previous population-based methods via functional connectivity (FC) analysis ignore the differences between positive and negative FCs, which provide the potential information complementarity. And they also require additional information to construct a pre-defined graph. Meanwhile, two challenging demand attentions are the imbalance of performance caused by the class distribution and the inherent heterogeneity of multi-site data. In this paper, we propose a novel dynamic graph Transformer network based on dual-view connectivity for ASD Identification. It is based on the Autoencoders, which regard the input feature as individual feature and without any inductive bias. First, a dual-view feature extractor is designed to extract individual and complementary information from positive and negative connectivity. Then Graph Transformer network is innovated with a hot plugging K-Nearest Neighbor (KNN) algorithm module which constructs a dynamic population graph without any additional information. Additionally, we introduce the PolyLoss function and the Vrex method to address the class imbalance and improve the model's generalizability. The evaluation experiment on 1102 subjects from the ABIDE I dataset demonstrates our method can achieve superior performance over several state-of-the-art methods and satisfying generalizability for ASD identification.


Assuntos
Algoritmos , Transtorno do Espectro Autista , Transtorno do Espectro Autista/fisiopatologia , Transtorno do Espectro Autista/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética/métodos , Criança , Masculino , Encéfalo/fisiopatologia , Encéfalo/diagnóstico por imagem , Redes Neurais de Computação , Feminino
6.
Adv Healthc Mater ; : e2304355, 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38387159

RESUMO

Amyloid beta-protein (AßAß) is a main hallmark of Alzheimer's disease (AD), and a low amount of Aß protein accumulation appears to be a potential marker for AD. Here, an electrochemical DNA biosensor based on polyamide/polyaniline carbon nanotubes (PA/PANI-CNTs) is developed with the aim of diagnosing AD early using a simple, low-cost, and accessible method to rapidly detect Aß42 in human blood. Electrospun PA nanofibers served as the skeleton for the successive in situ deposition of PANI and CNTs, which contribute both high conductivity and abundant binding sites for the Aß42 aptamers. After the aptamers are immobilized, this aptasensor exhibits precise and specific detection of Aß42 in human blood within only 4 min with an extremely fast response rate, lower detection limit, and excellent linear detection range. These findings make a significant contribution to advancing the development of serum-based detection techniques for Aß42, thereby paving the way for improved diagnostic capabilities in the field of AD.

7.
J Prosthodont ; 33(3): 266-272, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36951153

RESUMO

PURPOSE: To investigate the distribution of marginal excess cement in vented and non-vented crowns and evaluate the effect of clinical cleaning procedures on the reduction of excess cement. MATERIALS AND METHODS: Forty models with implant analogs in the position of the right maxillary first molar were divided into four groups (n = 10/group, vented/non-vented crowns with or without cleaning procedures). The abutment finish lines were placed 1 mm below the artificial gingiva buccally, mesially, and distally and at the gingival level palatally. A standardized amount (20 mg) of resin cement was applied in a thin layer to the intaglio surface of zirconia vented and non-vented crowns. The excess cement was removed by a dental explorer in groups with cleaning procedures. The distribution (area and depth) of the marginal excess cement was measured at each quadrant (buccal, mesial, palatal, and distal) for all study samples. The data were analyzed using descriptive and analytical statistics (ɑ = 0.05). RESULTS: The area and depth values of the excess cement in each quadrant in the vented group were significantly smaller than that in the non-vented group, both with and without cleaning (p < 0.001). Cleaning procedures significantly reduced the area of excess cement in both vented and non-vented groups (all, p < 0.001 except for p < 0.05 at the buccal aspect of the vented group). The depth of excess cement in the vented group was significantly decreased with cleaning in the buccal quadrant compared with that without cleaning (p < 0.01). However, the depth of excess cement of the non-vented group was significantly increased with cleaning in all quadrants compared with that without cleaning (all, p < 0.001 except for p < 0.05 at the distal aspect). CONCLUSIONS: Crown venting significantly reduced the area and depth of the marginal excess cement in vitro. Cleaning procedure with a dental explorer significantly reduced the area of marginal excess cement in vitro; however, the excess cement can be pushed deeper in the non-vented group.


Assuntos
Cimentação , Implantes Dentários , Zircônio , Cimentação/métodos , Cimentos Dentários , Cimentos de Ionômeros de Vidro , Coroas , Prótese Dentária Fixada por Implante , Dente Suporte
8.
J Colloid Interface Sci ; 657: 611-618, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38071810

RESUMO

Nanozymes hold great prospects for bacteria-infected wound management, yet the spatial control of their catalytic activity in infected area and normal tissues remains mired by the heterogeneity of tissue microenvironment. Here, we develop a novel two-dimensional ternary chalcogenide nanodots (Cu2MoS4, CMS NDs) with renal clearable ability and controlled catalytic activity for bacteria-infected wound treatment. The two-dimensional CMS NDs (∼4 nm) are prepared by a simple microwave-assisted chemical synthetic route. Our results show that CMS NDs not only have peroxidase-like activity in a pH-dependent manner (pH < 5.5). Based on the generation of hydroxyl radical (OH) by adding H2O2, CMS NDs show > 2 log bacterial inactivation for both Gram-positive methicillin-resistant Staphylococcus aureus (MRSA) and Gram-negative Escherichia coli (E. coli) under the acidic condition. Moreover, CMS NDs show good biocompatibility and can be excreted by the kidney in mice. In vivo results display that CMS NDs show good therapeutic effect against bacteria infected wound in the presence of H2O2, but no damage for normal tissues. Taken together, this work provides a renal clearable two-dimensional nanozyme with spatially controlled catalytic activity for the treatment of wounds and bacterial infections on the skin surface.


Assuntos
Infecções Bacterianas , Staphylococcus aureus Resistente à Meticilina , Camundongos , Animais , Antibacterianos/farmacologia , Antibacterianos/química , Escherichia coli , Peróxido de Hidrogênio/química
9.
Adv Sci (Weinh) ; 11(10): e2307048, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38109089

RESUMO

Host immune systems serving as crucial defense lines are vital resisting mechanisms against biofilm-associated implant infections. Nevertheless, biofilms hinder the penetration of anti-bacterial species, inhibit phagocytosis of immune cells, and frustrate host inflammatory responses, ultimately resulting in the weakness of the host immune system for biofilm elimination. Herein, a cell-like construct is developed through encapsulation of erythrocyte membrane fragments on the surface of Fe3 O4 nanoparticle-fabricated microbubbles and then loaded with hydroxyurea (EMB-Hu). Under ultrasound (US) stimulation, EMB-Hu undergoes a stable oscillation manner to act in an "exocytosis" mechanism for disrupting biofilm, releasing agents, and enhancing penetration of catalytically generated anti-bacterial species within biofilms. Additionally, the US-stimulated "exocytosis" by EMB-Hu can activate pro-inflammatory macrophage polarization and enhance macrophage phagocytosis for clearance of disrupted biofilms. Collectively, this work has exhibited cell-like microbubbles with US-stimulated "exocytosis" mechanisms to overcome the biofilm barrier and signal macrophages for inflammatory activation, finally achieving favorable therapeutic effects against implant infections caused by methicillin-resistant Staphylococcus aureus (MRSA) biofilms.


Assuntos
Staphylococcus aureus Resistente à Meticilina , Humanos , Microbolhas , Antibacterianos/farmacologia , Fagocitose , Macrófagos , Biofilmes , Complicações Pós-Operatórias
10.
Oncogenesis ; 12(1): 54, 2023 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-37957153

RESUMO

The mechanistic target of rapamycin complex 1 (mTORC1) signaling pathway is frequently reported to be hyperactivated in hepatocellular carcinoma (HCC) and contributes to HCC recurrence. However, the underlying regulatory mechanisms of mTORC1 signaling in HCC are not fully understood. In the present study, we found that the expression of kinesin family member 18B (KIF18B) was positively correlated with mTORC1 signaling in HCC, and the upregulation of KIF18B and p-mTOR was associated with a poor prognosis and HCC recurrence. Utilizing in vitro and in vivo assays, we showed that KIF18B promoted HCC cell proliferation and migration through activating mTORC1 signaling. Mechanistically, we identified Actin gamma 1 (γ-Actin) as a binding partner of KIF18B. KIF18B and γ-Actin synergistically modulated lysosome positioning, promoted mTORC1 translocation to lysosome membrane, and prohibited p70 S6K from entering lysosomes for degradation, which finally led to the enhancement of mTORC1 signaling transduction. Moreover, we found that KIF18B was a direct target of Forkhead box M1, which explains the potential mechanism of KIF18B overexpression in HCC. Our study highlights the potential of KIF18B as a therapeutic target for the treatment of HCC.

11.
World J Clin Cases ; 11(27): 6579-6586, 2023 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-37900244

RESUMO

BACKGROUND: Toripalimab and anlotinib have shown good response in esophageal cancer, with high objective response rate and progression free survival. Thus, they have been approved as second-line or above-line therapy for advanced or unresectable esophageal carcinoma. Combination of these two drugs may have synergistic effects, but evidence of which is lacking. CASE SUMMARY: Here, we report on a 73-year-old male, newly diagnosed with advanced esophageal squamous cell carcinoma (ESCC), who received a combination of toripalimab and anlotinib. Complete response was achieved after treatment for 3 mo and remission was maintained up to 14 mo. CONCLUSION: The combination therapy of toripalimab and anlotinib is a promising treatment for unresectable ESCC and related clinical trials are warranted.

12.
Bioinformatics ; 39(10)2023 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-37851379

RESUMO

MOTIVATION: Gene regulatory networks (GRNs) are a way of describing the interaction between genes, which contribute to revealing the different biological mechanisms in the cell. Reconstructing GRNs based on gene expression data has been a central computational problem in systems biology. However, due to the high dimensionality and non-linearity of large-scale GRNs, accurately and efficiently inferring GRNs is still a challenging task. RESULTS: In this article, we propose a new approach, iLSGRN, to reconstruct large-scale GRNs from steady-state and time-series gene expression data based on non-linear ordinary differential equations. Firstly, the regulatory gene recognition algorithm calculates the Maximal Information Coefficient between genes and excludes redundant regulatory relationships to achieve dimensionality reduction. Then, the feature fusion algorithm constructs a model leveraging the feature importance derived from XGBoost (eXtreme Gradient Boosting) and RF (Random Forest) models, which can effectively train the non-linear ordinary differential equations model of GRNs and improve the accuracy and stability of the inference algorithm. The extensive experiments on different scale datasets show that our method makes sensible improvement compared with the state-of-the-art methods. Furthermore, we perform cross-validation experiments on the real gene datasets to validate the robustness and effectiveness of the proposed method. AVAILABILITY AND IMPLEMENTATION: The proposed method is written in the Python language, and is available at: https://github.com/lab319/iLSGRN.


Assuntos
Algoritmos , Redes Reguladoras de Genes , Biologia de Sistemas , Algoritmo Florestas Aleatórias , Fatores de Tempo , Biologia Computacional/métodos
13.
Int J Nanomedicine ; 18: 4601-4616, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37600119

RESUMO

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.


Assuntos
Colite , Sequestradores de Radicais Livres , Indóis , Nanotubos , Polímeros , Espécies Reativas de Oxigênio , Indóis/química , Indóis/farmacologia , Indóis/uso terapêutico , Polímeros/química , Polímeros/farmacologia , Polímeros/uso terapêutico , Colite/tratamento farmacológico , Colite/patologia , Inflamação/tratamento farmacológico , Inflamação/patologia , Sequestradores de Radicais Livres/química , Sequestradores de Radicais Livres/farmacologia , Sequestradores de Radicais Livres/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo , Polaridade Celular , Cério , Animais , Camundongos , Células RAW 264.7 , Masculino , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças
14.
Small ; 19(52): e2304127, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37649207

RESUMO

Antibacterial theranostic nanoplatforms, which integrate diagnostic and therapeutic properties, exhibit gigantic application prospects in precision medicine. However, traditional theranostic nanoplatforms usually present an always-on signal output, which leads to poor specificity or selectivity in the treatment of bacterial infections. To address this challenge, stimuli-actuated turn-on nanoplatforms are developed for simultaneous activation of diagnostic signals (e.g., fluorescent, photoacoustic, magnetic signals) and initiation of antibacterial treatment. Specifically, by combining the infection microenvironment-responsive activation of visual signals and antibacterial activity, these theranostic nanoplatforms exert both higher accurate diagnosis rates and more effective treatment effects. In this review, the imaging and treatment strategies that are commonly used in the clinic are first briefly introduced. Next, the recent progress of stimuli-actuated turn-on theranostic nanoplatforms for treating bacterial infectious diseases is summarized in detail. Finally, current bottlenecks and future opportunities of antibacterial theranostic nanoplatforms are also outlined and discussed.


Assuntos
Neoplasias , Medicina de Precisão , Humanos , Nanomedicina Teranóstica/métodos , Diagnóstico por Imagem , Neoplasias/tratamento farmacológico , Microambiente Tumoral
15.
ACS Appl Mater Interfaces ; 15(34): 40369-40377, 2023 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-37594304

RESUMO

The chlorine evolution reaction (CER) is a key reaction in electrochemical oxidation (EO) of water treatment. Conventional anodes based on platinum group metals can be prohibitively expensive, which hinders further application of EO systems. Crystalline cobalt antimonate (CoSbxOy) was recently identified as a promising alternative to conventional anodes due to its high catalytic activity and stability in acidic media. However, its catalytic sites and reaction mechanism have not yet been elucidated. This study sheds light on the catalytically active sites in crystalline CoSbxOy anodes by using scanning electrochemical microscopy to compare the CER catalytic activities of a series of anode samples with different bulk Sb/Co ratios (from 1.43 to 2.80). The results showed that Sb sites served as more active catalytic sites than the Co sites. The varied Sb/Co ratios were also linked with slightly different electronic states of each element, leading to different CER selectivities in 30 mM chloride solutions under 10 mA cm-2 current density. The high activity of Sb sites toward the CER highlighted the significance of the electronic polarization that changed the oxidation states of Co and Sb.

16.
J Nanobiotechnology ; 21(1): 236, 2023 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-37482608

RESUMO

Therapeutic tumor vaccines have attracted considerable attention in the past decade; they can induce tumor regression, eradicate minimal residual disease, establish lasting immune memory and avoid non-specific and adverse side effects. However, the challenge in the field of therapeutic tumor vaccines is ensuring the delivery of immune components to the lymph nodes (LNs) to activate immune cells. The clinical response rate of traditional therapeutic tumor vaccines falls short of expectations due to inadequate lymph node delivery. With the rapid development of nanotechnology, a large number of nanoplatform-based LN-targeting nanovaccines have been exploited for optimizing tumor immunotherapies. In addition, some nanovaccines possess non-invasive visualization performance, which is benefit for understanding the kinetics of nanovaccine exposure in LNs. Herein, we present the parameters of nanoplatforms, such as size, surface modification, shape, and deformability, which affect the LN-targeting functions of nanovaccines. The recent advances in nanoplatforms with different components promoting LN-targeting are also summarized. Furthermore, emerging LNs-targeting nanoplatform-mediated imaging strategies to both improve targeting performance and enhance the quality of LN imaging are discussed. Finally, we summarize the prospects and challenges of nanoplatform-based LN-targeting and /or imaging strategies, which optimize the clinical efficacy of nanovaccines in tumor immunotherapies.


Assuntos
Vacinas Anticâncer , Neoplasias , Humanos , Linfonodos , Neoplasias/terapia , Imunoterapia , Nanotecnologia
17.
Biomater Res ; 27(1): 73, 2023 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-37481650

RESUMO

The advent of drug-resistant pathogens results in the occurrence of stubborn bacterial infections that cannot be treated with traditional antibiotics. Antibacterial immunotherapy by reviving or activating the body's immune system to eliminate pathogenic bacteria has confirmed promising therapeutic strategies in controlling bacterial infections. Subsequent studies found that antimicrobial immunotherapy has its own benefits and limitations, such as avoiding recurrence of infection and autoimmunity-induced side effects. Current studies indicate that the various antibacterial therapeutic strategies inducing immune regulation can achieve superior therapeutic efficacy compared with monotherapy alone. Therefore, summarizing the recent advances in nanomedicine with immunomodulatory functions for combating bacterial infections is necessary. Herein, we briefly introduce the crisis caused by drug-resistant bacteria and the opportunity for antibacterial immunotherapy. Then, immune-involved multimodal antibacterial therapy for the treatment of infectious diseases was systematically summarized. Finally, the prospects and challenges of immune-involved combinational therapy are discussed.

18.
Exp Ther Med ; 26(1): 342, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37383376

RESUMO

With time, the number of samples in clinical laboratories from therapeutic drug monitoring has increased. Existing analytical methods for blood cyclosporin A (CSA) monitoring, such as high-performance liquid chromatography (HPLC) and immunoassays, have limitations including cross-reactivity, time consumption, and the complicated procedures involved. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) has long been considered the reference standard owing to its high accuracy, specificity, and sensitivity. However, large numbers of blood samples, multi-step preparation procedures, and longer analytical times (2.5-20 min) are required as a consequence of the different technical strategies, to ensure good analytical performance and routine quality assurance. A stable, reliable, and high throughput detection method will save personnel time and reduce laboratory costs. Therefore, a high throughput and simple LC-MS/MS method was developed and validated for the detection of whole-blood CSA with CSA-d12 as the internal standard in the present study. Whole blood samples were prepared through a modified one-step protein precipitation method. A C18 column (50x2.1 mm, 2.7 µm) with a mobile phase flow rate of 0.5 ml/min was used for chromatographic separation with a total running time of 4.3 min to avoid the matrix effect. To protect the mass spectrometer, only part of the sample after LC separation was allowed to enter the mass spectrum, using two HPLC systems coupled to one mass spectrometry. In this way, throughput was improved with detection of two samples possible within 4.3 min using a shorter analytical time for each sample of 2.15 min. This modified LC-MS/MS method showed excellent analytical performance and demonstrated less matrix effect and a wide linear range. The design of multi-LC systems coupled with one mass spectrometry may play a notable role in the improvement of daily detection throughput, speeding up LC-MS/MS, and allowing it to be an integral part of continuous diagnostics in the near future.

19.
Adv Healthc Mater ; 12(26): e2300985, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37186891

RESUMO

The application of medical implants has greatly improved the survival rate and life quality of patients. Nevertheless, in recent years, there are increasing cases of implant dysfunction or failure because of bacterial infections. Despite significant improvements in biomedicine, there are still serious challenges in the treatment of implant-related infections. With the formation of bacterial biofilms and the development of bacterial resistance, these limitations lead to a low efficacy of conventional antibiotics. To address these challenges, it is urgent to exploit innovative treatment strategies for implant-related infections. Based on these ideas, environment-responsive therapeutic platforms with high selectivity, low drug resistance, and minor dose-limiting toxicity have attracted widespread attention. By using exogenous/endogenous stimuli, the antibacterial activity of therapeutics can be activated on demand and exhibit remarkable therapeutic effects. Exogenous stimuli include photo, magnetism, microwave, and ultrasound. Endogenous stimuli mainly include the pathological characteristics of bacterial infections such as acidic pH, anomalous temperature, and abnormal enzymatic activities. In this review, the recent progress of environment-responsive therapeutic platforms with spatiotemporally controlled drug release/activation is systematically summarized. Afterward, the limitations and opportunities of these emerging platforms are highlighted. Finally, it is hoped that this review will offer novel ideas and techniques to combat implant-related infections.


Assuntos
Infecções Bacterianas , Biofilmes , Humanos , Sistemas de Liberação de Medicamentos , Infecções Bacterianas/tratamento farmacológico , Bactérias , Próteses e Implantes , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico
20.
Environ Res ; 231(Pt 1): 116047, 2023 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-37149031

RESUMO

In recent years, biological sulfur (bio-S) was employed in sulfur autotrophic denitrification (SAD) in which autotrophic Thiobacillus denitrificans and heterotrophic Stenotrophomonas maltophilia played a key role. The growth pattern of T.denitrificans and S.maltophilia exhibited a linear relationship between OD600 and CFU when OD600 < 0.06 and <0.1, respectively. When S.maltophilia has applied alone, the NorBC and NosZ were undetected, and denitrification was incomplete. The DsrA of S.maltophilia could produce sulfide as an alternative electron donor for T.denitrificans. Even though T.denitrificans had complete denitrification genes, its efficiency was low when used alone. The interaction of T.denitrificans and S.maltophilia reduced nitrite accumulation, leading to complete denitrification. A sufficient quantity of S.maltophilia may trigger the autotrophic denitrification activity of T.denitrificans. When the colony-forming units (CFU) ratio of S.maltophilia to T.denitrificans was reached at 2:1, the highest denitrification performance was achieved at 2.56 and 12.59 times higher than applied alone. This research provides a good understanding of the optimal microbial matching for the future application of bio-S.


Assuntos
Desnitrificação , Elétrons , Enxofre , Processos Autotróficos , Sulfetos , Reatores Biológicos , Nitrogênio
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