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1.
Proc Natl Acad Sci U S A ; 120(27): e2302367120, 2023 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-37364107

RESUMO

Antimicrobial susceptibility testing plays a pivotal role in the discovery of new antibiotics. However, the development of simple, sensitive, and rapid assessment approaches remains challenging. Herein, we report an activated alkyne-based cascade signal amplification strategy for ultrafast and high-throughput antibiotic screening. First of all, a novel water-soluble aggregation-induced emission (AIE) luminogen is synthesized, which contains an activated alkyne group to enable fluorescence turn-on and metal-free click bioconjugation under physiological conditions. Taking advantage of the in-house established method for bacterial lysis, a number of clickable biological substances (i.e., bacterial solutes and debris) are released from the bacterial bodies, which remarkably increases the quantity of analytes. By means of the activated alkyne-mediated turn-on click bioconjugation, the system fluorescence signal is significantly amplified due to the increased labeling sites as well as the AIE effect. Such a cascade signal amplification strategy efficiently improves the detection sensitivity and thus enables ultrafast antimicrobial susceptibility assessment. By integration with a microplate reader, this approach is further applied to high-throughput antibiotic screening.


Assuntos
Alcinos , Antibacterianos , Antibacterianos/farmacologia , Fluorescência , Química Click/métodos , Azidas
2.
Anal Bioanal Chem ; 416(13): 3139-3148, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38632131

RESUMO

The rapid discrimination of bacteria is currently an emerging trend in the fields of food safety, medical detection, and environmental observation. Traditional methods often require lengthy culturing processes, specialized analytical equipment, and bacterial recognition receptors. In response to this need, we have developed a paper-based fluorescence sensor array platform for identifying different bacteria. The sensor array is based on three unique carbon quantum dots (CQDs) as sensing units, each modified with a different antibiotic (polymyxin B, ampicillin, and gentamicin). These antibiotic-modified CQDs can aggregate on the bacterial surface, triggering aggregation-induced fluorescence quenching. The sensor array exhibits varying fluorescent responses to different bacterial species. To achieve low-cost and portable detection, CQDs were formulated into fluorescent ink and used with an inkjet printer to manufacture paper-based sensor arrays. A smartphone was used to collect the responses generated by the bacteria and platform. Diverse machine learning algorithms were utilized to discriminate bacterial types. Our findings showcase the platform's remarkable capability to differentiate among five bacterial strains, within a detection range spanning from 1.0 × 103 CFU/mL to 1.0 × 107 CFU/mL. Its practicality is further validated through the accurate identification of blind bacterial samples. With its cost-effectiveness, ease of fabrication, and high degree of integration, this platform holds significant promise for on-site detection of diverse bacteria.


Assuntos
Bactérias , Carbono , Aprendizado de Máquina , Papel , Pontos Quânticos , Pontos Quânticos/química , Carbono/química , Bactérias/isolamento & purificação , Fluorescência , Espectrometria de Fluorescência/métodos , Técnicas Biossensoriais/métodos , Técnicas Biossensoriais/instrumentação , Antibacterianos/análise , Antibacterianos/farmacologia , Algoritmos
3.
Int J Mol Sci ; 24(16)2023 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-37628846

RESUMO

Trans-10-hydroxy-2-decenoic acid (10-HDA) is a unique fatty acid found in royal jelly that possesses potential health benefits such as anti-inflammatory. However, further research is needed to fully understand its mechanisms of action and therapeutic potential for inflammation-associated diseases. In this present study, liquid chromatography-tandem mass spectrometry (LC-MS/MS) and RNA-seq analyses were conducted to comprehensively analyze the in vitro anti-inflammatory effects of 10-HDA on lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Our results demonstrated that 128 differentially expressed metabolites and 1721 differentially expressed genes were identified in the 10-HDA-treated groups compared to the LPS groups. Metabolites were significantly enriched in amino acid metabolism pathways, including methionine metabolism, glycine and serine metabolism, and tryptophan metabolism. The differentially expressed genes enrichment analysis indicated that antigen processing and presentation, NOD-like receptor signaling pathway, and arginine biosynthesis were enriched with the administration of 10-had. The correlation analysis revealed that glycerophospholipid metabolism and s-adenosylmethionine-dependent methylation processes might be involved in the response to the 10-HDA treatment. Overall, the findings from this study showed that 10-HDA might involve the modulation of certain signaling pathways involved in the inflammatory response, but further research is needed to determine the safety and efficacy as a therapeutic agent.


Assuntos
Lipopolissacarídeos , Transcriptoma , Animais , Camundongos , Lipopolissacarídeos/farmacologia , Cromatografia Líquida , Células RAW 264.7 , Espectrometria de Massas em Tandem
4.
Anal Chem ; 94(7): 3303-3312, 2022 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-35133812

RESUMO

The maintenance of an intact membrane structure is of great importance for bacteria to execute various biological functions. However, chemical probes for monitoring the dynamic changes of bacterial membranes are barely reported. Herein, we, for the first time, report a novel polarity-sensitive probe for reflecting the packing degree of bacterial membrane lipids. Specifically, we synthesize a membrane-targeting fluorescent probe (TICT-lipid) that possesses both twist intramolecular charge transfer and aggregation-induced emission properties. TICT-lipid exhibits sensitive responses to the minute difference in the packing degree of membrane lipids, facilitating rapid differentiation of Gram-negative and Gram-positive bacteria. Interestingly, in the presence of membrane-disrupting antibiotics, the localization of TICT-lipid shifts from the outer membrane to the cell membrane by outputting blue-shifted and enhanced emission, making the mechanism of action of antibiotics clearly visible. TICT-lipid is a polarity-sensitive fluorescent probe, holding great promise in the study of membrane-related bacterial processes and antibiotic screening.


Assuntos
Corantes Fluorescentes , Lipídeos de Membrana , Bactérias/metabolismo , Membrana Celular/química , Corantes Fluorescentes/química , Lipídeos de Membrana/análise , Membranas/metabolismo
5.
Environ Res ; 212(Pt D): 113488, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35597292

RESUMO

BACKGROUND: Lung is one of the primary target organs of benzene, toluene, ethylbenzene, xylene, and styrene (BTEXS). Small airways dysfunction (SAD) might be a sensitive indicator of early chronic respiratory disease. Here, we explored the relationships between exposure to BTEXS and small airways function, and identified the priority control pollutants in BTEXS mixtures. METHODS: 635 petrochemical workers were recruited. Standard spirometry testing was conducted by physicians. The cumulative exposure dose (CED) of BTEXS for each worker was estimated. The peak expiratory flow (PEF), forced expiratory flow between 25 and 75% of forced vital capacity (FEF25∼75%), and the expiratory flow rate found at 25%, 50%, and 75% of the remaining exhaled vital capacity (MEF25%, MEF50%, and MEF75%) were measured. SAD was also evaluated based on measured parameters. The associations between exposure to BTEXS individuals or mixtures and small airways function were evaluated using generalized linear regression models (GLMs) and quantile g-computation models (qgcomp). Meanwhile, the weights of each homolog in the association were estimated. RESULTS: The median CED of BTEXS are 9.624, 19.306, 24.479, 28.210, and 46.781 mg/m3·years, respectively. A unit increase in ln-transformed styrene CED was associated with a decrease in FEF25∼75% and MEF50% based on GLMs. One quartile increased in BTEXS mixtures (ln-transformed) was significantly associated with a 0.325-standard deviation (SD) [95% confidence interval (CI): -0.464, -0.185] decline in FEF25∼75%, a 0.529-SD (95%CI: -0.691, -0.366) decline in MEF25%, a 0.176-SD (95%CI: -0.335, -0.017) decline in MEF75%, and increase in the risk of abnormal of SAD [risk ratios (95%CI): 1.520 (95%CI: 1.143, 2.020)]. Benzene and styrene were the major chemicals in BTEXS for predicting the overall risk of SAD. CONCLUSION: Our novel findings demonstrate the significant association between exposure to BTEXS mixture and small airways function decline and the potential roles of key homologs (benzene and styrene) in SAD.


Assuntos
Benzeno , Xilenos , Benzeno/toxicidade , Derivados de Benzeno/toxicidade , Estudos Transversais , Humanos , Estireno/toxicidade , Tolueno/toxicidade , Xilenos/toxicidade
6.
Pestic Biochem Physiol ; 180: 104994, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34955187

RESUMO

Honey bees are important and highly efficient pollinators of agricultural crops and have been negatively affected by insecticides in recent years. Circular RNA (circRNA) plays an important role in the regulation of multiple biological and pathological processes; however, its role in the honey bee brain after exposure to dinotefuran is not well understood. Here, the expression profiles and potential modulation networks of circRNAs in the brains of workers (Apis mellifera) were comprehensively investigated using RNA sequencing and bioinformatics. In total, 33, 144, and 211 differentially expressed (DE) circRNAs were identified on the 1st, 5th and 10th days after exposure to dinotefuran, respectively. Enrichment analyses revealed that the host genes of DE circRNAs were enriched in the Hippo signaling pathway-fly, Wnt signaling pathway, and neuroactive ligand-receptor interaction. circ_0002266, circ_0005080, circ_0010239 and circ_0005415 were found to have translational potential due to the presence of an internal ribosome entry site (IRES). An integrated analysis of the DE circRNA-miRNA-mRNA networks suggest that circ_0008898 and circ_0001829 may participate in the immune response to dinotefuran exposure by acting as miRNA sponges. Our results provide invaluable basic data on A. mellifera brain circRNA patterns and a molecular basis for further study of the biological function of circRNAs in the development and immune response of honey bees.


Assuntos
Abelhas , Guanidinas/toxicidade , Neonicotinoides , Nitrocompostos/toxicidade , RNA Circular , Animais , Abelhas/efeitos dos fármacos , Abelhas/genética , Encéfalo/efeitos dos fármacos , Redes Reguladoras de Genes , Via de Sinalização Hippo , Neonicotinoides/toxicidade , Via de Sinalização Wnt
7.
BMC Genomics ; 22(1): 502, 2021 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-34217210

RESUMO

BACKGROUND: Dinotefuran (CAS No. 165252-70-0), a neonicotinoid insecticide, has been used to protect various crops against invertebrate pests and has been associated with numerous negative sublethal effects on honey bees. Long noncoding RNAs (lncRNAs) play important roles in mediating various biological and pathological processes, involving transcriptional and gene regulation. The effects of dinotefuran on lncRNA expression and lncRNA function in the honey bee brain are still obscure. RESULTS: Through RNA sequencing, a comprehensive analysis of lncRNAs and mRNAs was performed following exposure to 0.01 mg/L dinotefuran for 1, 5, and 10 d. In total, 312 lncRNAs and 1341 mRNAs, 347 lncRNAs and 1458 mRNAs, and 345 lncRNAs and 1155 mRNAs were found to be differentially expressed (DE) on days 1, 5 and 10, respectively. Gene set enrichment analysis (GSEA) indicated that the dinotefuran-treated group showed enrichment in carbohydrate and protein metabolism and immune-inflammatory responses such as glycine, serine and threonine metabolism, pentose and glucuronate interconversion, and Hippo and transforming growth factor-ß (TGF-ß) signaling pathways. Moreover, the DE lncRNA TCONS_00086519 was shown by fluorescence in situ hybridization (FISH) to be distributed mainly in the cytoplasm, suggesting that it may serve as a competing endogenous RNA and a regulatory factor in the immune response to dinotefuran. CONCLUSION: This study characterized the expression profile of lncRNAs upon exposure to neonicotinoid insecticides in young adult honey bees and provided a framework for further study of the role of lncRNAs in honey bee growth and the immune response.


Assuntos
RNA Longo não Codificante , Animais , Abelhas , Encéfalo , Guanidinas , Hibridização in Situ Fluorescente , Neonicotinoides , Nitrocompostos
8.
Angew Chem Int Ed Engl ; 60(35): 19222-19231, 2021 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-33991002

RESUMO

We reported an efficient multicomponent polyannulation for in situ generation of heteroaromatic hyperbranched polyelectrolytes by using readily accessible internal diynes and low-cost, commercially available arylnitriles, NaSbF6 , and H2 O/AcOH. The polymers were obtained in excellent yields (up to 99 %) with extraordinary high molecular weights (Mw up to 1.011×106 ) and low polydispersity indices. The resulting polymers showed good processibility and high quantum yields with tunable emission in the solid state, making them ideal materials for highly ordered fluorescent photopatterning. These hyperbranched polyelectrolytes also possessed strong ability to generate reactive oxygen species, which allowed their applications in efficient bacterial killing and customizable photodynamic patterning of living organisms in a simple and cost-effective way.


Assuntos
Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Compostos Heterocíclicos/farmacologia , Hidrocarbonetos Aromáticos/farmacologia , Polieletrólitos/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Bactérias/metabolismo , Compostos Heterocíclicos/química , Hidrocarbonetos Aromáticos/química , Estrutura Molecular , Peso Molecular , Polieletrólitos/síntese química , Polieletrólitos/química , Espécies Reativas de Oxigênio/metabolismo
9.
Med Sci Monit ; 25: 637-642, 2019 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-30666992

RESUMO

BACKGROUND Worldwide, stroke results in healthcare costs and economic costs, particularly in patients aged <45 years. This study aimed to evaluate the factors influencing the economic burden of ischemic stroke in younger patients in China based on the Trial of Org 10172 in Acute Stroke Treatment (TOAST) etiological classification. MATERIAL AND METHODS Retrospective review of the medical records of 961 patients aged between 18-45 years, diagnosed with acute ischemic stroke, was performed to identify healthcare costs for one year. Stroke severity was assessed using the modified Rankin Scale (mRS) score and the National Institutes of Health Stroke Scale (NIHSS) score. Stroke was categorized according to the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification as being due to large artery atherosclerosis (LAA), cardioembolism (CE), small artery occlusion (SAO), other determined causes (OC), and undetermined etiology (UND). RESULTS Total direct medical costs at one-year follow-up were US$10,954.14, including inpatient cost of US$5,958.44, and outpatient cost of US$3,397.60. Inpatient and total costs at one year were significantly increased in the CE subtype (P<0.001), and were significantly less in the UND subtype (P<0.001). Multivariable logistic regression analysis showed that mRS score, TOAST category, NIHSS score, and the presence of atrial fibrillation were the significant factors influencing cost at one-year follow-up and total cost in younger patients with ischemic stroke. Overall, patient costs in China were less than those in high-income countries. CONCLUSIONS In the younger patient population in China, etiological factors influenced the economic burden of ischemic stroke.


Assuntos
Isquemia Encefálica/economia , Isquemia Encefálica/etiologia , Acidente Vascular Cerebral/economia , Acidente Vascular Cerebral/etiologia , Adolescente , Adulto , Isquemia Encefálica/complicações , China , Efeitos Psicossociais da Doença , Feminino , Humanos , Masculino , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Adulto Jovem
10.
ACS Appl Bio Mater ; 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38408887

RESUMO

Bacterial patterning has emerged as a pivotal biofabrication technique in the biomedical field. In the past 2 decades, a diverse array of bacterial patterning approaches have been developed to enable the precise manipulation of the spatial distribution of bacterial patterns for various applications. Despite the significance of these advancements, there is a deficiency of review articles providing an overview of bacterial patterning technologies. In this mini-review, we systematically summarize the progress of bacterial patterning over the past 2 decades. This review commences with an elucidation of the definition and fundamental principles of bacterial patterning. Subsequently, we introduce the established bacterial patterning strategies, accompanied by discussions about the advantages and limitations of each approach. Furthermore, we showcase the biomedical applications of these strategies, highlighting their efficacy in spatial control of biofilms, biosensing, and biointervention. Finally, this mini-review is concluded with a summary and an outlook on future challenges and opportunities. It is anticipated that this mini-review can serve as a concise guide for those who are interested in this exciting and rapidly evolving research area.

11.
Biomater Sci ; 12(11): 2914-2929, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38639605

RESUMO

Photothermal therapy (PTT) has emerged as a promising approach for treating bacterial infections. However, achieving a high photothermal conversion efficiency (PCE) of photothermal agents (PTAs) remains a challenge. Such a problem is usually compensated by the use of a high-intensity laser, which inevitably causes tissue damage. Here, we present a universal strategy to enhance PCE by regulating the molecular aggregation states of PTAs within thermoresponsive nanogels. We demonstrate the effectiveness of this approach using aggregation-induced emission (AIE) and aggregation-caused quenching (ACQ) PTAs, showing significant enhancements in PCE without the need for intricate molecular modifications. Notably, the highest PCEs reach up to 80.9% and 64.4% for AIE-NG and ACQ-NG, respectively, which are nearly 2-fold of their self-aggregate counterparts. Moreover, we elucidate the mechanism underlying PCE enhancement, highlighting the role of strong intermolecular π-π interactions facilitated by nanogel-induced volume contraction. Furthermore, we validate the safety and efficacy of this strategy in in vitro and in vivo models of bacterial infections at safe laser power densities, demonstrating its potential for clinical translation. Our findings offer a straightforward, universal, and versatile method to improve PTT outcomes while minimizing cytotoxicity, paving the way for enhanced treatment of bacterial infections with safe PTT protocols.


Assuntos
Terapia Fototérmica , Animais , Camundongos , Humanos , Infecções Bacterianas/terapia , Nanogéis/química
12.
J Clin Endocrinol Metab ; 109(1): 293-302, 2023 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-37497620

RESUMO

CONTEXT: Burosumab is approved for the treatment of X-linked hypophosphatemia (XLH). OBJECTIVE: To assess the efficacy and safety of burosumab in XLH patients, we conducted a systematic review and meta-analysis. METHODS: We searched PubMed, the Cochrane Library, Embase, ClinicalTrials.gov, and Web of Science for studies on the use of burosumab in patients with XLH. Meta-analysis of randomized controlled trials (RCTs) and single-arm trials (SATs) was done to explore burosumab treatment on the efficacy and safety of XLH. RESULTS: Of the 8 eligible articles, 5 were from RCTs and 3 were from SATs. Compared with the control group in RCTs, serum phosphorus level was significantly increased in the burosumab group (0.52 mg/dL, 95% CI 0.24-0.80 mg/dL). A meta-analysis of the burosumab arms in all trials revealed significant increase in serum phosphorus levels (0.78 mg/dL, 95% CI 0.61-0.96 mg/dL), TmP/GFR (0.86 mg/dL, 95% CI 0.60-1.12 mg/dL), and 1,25-dihydroxyvitamin D level (13.23 pg/mL, 95% CI 4.82-21.64 pg/mL) as well. Changes in secondary events also validated the effects of burosumab treatment. Compared with the control group, in RCTs, the safety profile of burosumab is not much different from the control group. Data of the single-arm combined group demonstrated the incidence of any treatment emergency adverse event (TEAE) and the related TEAE rate were high, but the severity of most adverse events is mild to moderate, and the rate of serious TEAE is low. CONCLUSION: This study suggests that burosumab can be an option for patients with XLH and did not significantly increase the incidence of adverse events.


Assuntos
Raquitismo Hipofosfatêmico Familiar , Hipofosfatemia , Humanos , Anticorpos Monoclonais/efeitos adversos , Fatores de Crescimento de Fibroblastos , Fósforo , Hipofosfatemia/induzido quimicamente
13.
Adv Sci (Weinh) ; 10(11): e2206865, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36775864

RESUMO

Photothermal therapy (PTT) has emerged as an attractive technique for the treatment of bacterial infections. However, the uncontrolled heat generation in conventional PTT inevitably causes thermal damages to healthy tissues and/or organs. It is thus essential to develop a smart and universal strategy to regulate the photothermal equilibrium temperature to a preset safe threshold. Herein, a thermoresponsive hydrogel-enabled thermostatic PTT system for enhanced healing of bacteria-infected wounds is reported. In this system, the near-infrared (NIR)-triggered heat generation by photothermal nanomaterials is spontaneously transferred to a thermoresponsive hydrogel with a lower critical solution temperature (LCST), leading to its rapid phase transition by forming considerable light-scattering centers to block NIR penetration. Such a dynamic and reversible process automatically regulates the photothermal equilibrium temperature to the phase-transition point of the LCST-type hydrogel. In contrast to temperature-uncontrolled conventional PTT with severe thermal damages, the thermoresponsive hydrogel-enabled thermostatic PTT provides effective protection on healthy tissues and/or organs, which remarkably accelerates wound healing by efficient bacterial eradication. This study establishes a smart, simple and universal PTT platform, holding great promise in the safe and efficient treatment of bacterial skin infections.


Assuntos
Hidrogéis , Terapia Fototérmica , Fototerapia , Bactérias , Cicatrização
14.
Sci Total Environ ; 868: 161637, 2023 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-36649770

RESUMO

The widespread use of fungicides for plant protection has increased the potential for pollinator exposure. This study therefore aimed at assessing the acute and chronic effects of fungicides on pollinators. For this purpose, the acute oral toxicity of the common fungicides azoxystrobin, pyraclostrobin, and boscalid to Eastern honeybee Apis cerana cerena was first evaluated, and the chronic effects on multiple aspects were investigated after exposure to a one-tenth medium lethal dose (LD50) for 10 days. This study revealed that the LD50 values of azoxystrobin, pyraclostrobin and boscalid for adult Eastern honeybees were 12.7 µg/bee, 36.6 µg/bee, and >119 µg/bee, respectively. Midgut epithelial cells revealed that fungicide exposure caused increased intercellular spaces and varying degrees of vacuolization. Exposure to these three fungicides and their binary mixtures significantly affected glycerophospholipid, alanine, aspartate, and glutamate metabolism in Eastern honeybee midguts. Additionally, the relative composition of Lactobacillus, the dominant functional genus in Eastern honeybee guts decreased and microbial balance was disrupted. All fungicides and their mixtures induced strong transcriptional upregulation of genes associated with the immune response and encoding enzymes related to oxidative phosphorylation and metabolism, including abaecin, apidaecin, hymenotaecin, cyp4c3, cyp6a2 and hbg3. Our study provides important insight for understanding the effects of commonly used fungicides on nontarget pollinator and contributes to a more comprehensive assessment of fungicide effects on ecological and environmental safety.


Assuntos
Fungicidas Industriais , Himenópteros , Abelhas , Animais , Fungicidas Industriais/toxicidade
15.
Oxid Med Cell Longev ; 2022: 4472751, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35464771

RESUMO

Background: Recent experimental studies have shown that vegetable oil supplementation ameliorates high-fat diet- (HFD-) induced hyperlipidemia and oxidative stress in mice via modulating hepatic lipid metabolism and the composition of the gut microbiota. The aim of this study was to investigate the efficacy of the Torreya grandis kernel oil (TKO) rich in unpolysaturated fatty acid against hyperlipidemia and gain a deep insight into its potential mechanisms. Methods: Normal mice were randomly divided into three groups: ND (normal diet), LO (normal diet supplement with 4% TKO), and HO (normal diet supplement with 8% TKO). Hyperlipidemia mice were randomly divided into two groups: HFN (normal diet) and HFO (normal diet supplement with 8% TKO). Blood biochemistry and histomorphology were observed; liver RNA-seq, metabolomics, and gut 16S rRNA were analyzed. Results: Continuous supplementation of TKO in normal mice significantly ameliorated serum total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and free fatty acid (FFA) accumulation, decreased blood glucose and malondialdehyde (MDA), and enhanced superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) levels. According to GO and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, most differentially expressed genes (DEGs) were significantly enriched in the biosynthesis of unsaturated fatty acid pathways, and significantly changed metabolites (SCMs) might be involved in the metabolism of lipids. High-dose TKO improved gut alpha diversity and beta diversity showing that the microbial community compositions of the five groups were different. Conclusion: Supplementation of TKO functions in the prevention of hyperlipidemia via regulating hepatic lipid metabolism and enhancing microbiota richness in normal mice. Our study is the first to reveal the mechanism of TKO regulating blood lipid levels by using multiomics and promote further studies on TKO for their biological activity.


Assuntos
Microbioma Gastrointestinal , Hiperlipidemias , Taxaceae , Animais , HDL-Colesterol , Dieta Hiperlipídica/efeitos adversos , Hiperlipidemias/metabolismo , Metabolismo dos Lipídeos , Fígado/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , RNA Ribossômico 16S/metabolismo , Taxaceae/metabolismo
16.
Chem Sci ; 13(14): 4139-4149, 2022 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-35440990

RESUMO

Photodynamic therapy (PDT) has attracted much attention in disease treatments. However, the exploration of a novel method for the construction of outstanding photosensitizers (PSs) with stimuli-responsiveness remains challenging. In this study, we, for the first time, report a novel and effective strategy to boost reactive oxygen species (ROS) generation by bridging donor-acceptor (D-A) type PSs with the azo group. In contrast to the counterpart without azo-bridging, the azo-bridged PSs exhibit remarkably enhanced ROS generation via both type-I and type-II photochemical reactions. Theoretical calculations suggest that azo-bridging leads to a prominent reduction in ΔE ST, thereby enabling enhanced ROS generation via efficient intersystem crossing (ISC). The resulting azo-bridged PS (denoted as Azo-TPA-Th(+)) exhibits a particularly strong bactericidal effect against clinically relevant drug-resistant bacteria, with the killing efficiency up to 99.999999% upon white light irradiation. Since azo-bridging generates an azobenzene structure, Azo-TPA-Th(+) can undergo trans-to-cis isomerization upon UV irradiation to form emissive aggregates by shutting down the ISC channel. By virtue of the fluorescence turn-on property of unbound Azo-TPA-Th(+), we propose a straightforward method to directly discern the effective photodynamic bactericidal dose without performing the tedious plate-counting assay. This study opens a brand-new avenue for the design of advanced PSs with both strong ROS generation and stimuli-responsiveness, holding great potential in high-quality PDT with rapid prediction of the therapeutic outcome.

17.
Chem Commun (Camb) ; 58(50): 7058-7061, 2022 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-35648071

RESUMO

A receptor-targeting AIE photosensitizer (CE-TPA) is synthesized by conjugating cephalothin with a cationic D-A type AIE photosensitizer for selective killing of Gram-positive bacteria over Gram-negative bacteria and normal mammalian cells. By virtue of the strong photosensitization capability, CE-TPA exhibits efficient killing against Gram-positive methicillin-resistant Staphylococcus aureus. More importantly, the photodynamic bactericidal outcome can be conveniently reflected in a real-time fashion by the polarity-sensitive property of CE-TPA.


Assuntos
Staphylococcus aureus Resistente à Meticilina , Fotoquimioterapia , Animais , Bactérias Gram-Negativas , Bactérias Gram-Positivas , Mamíferos , Fármacos Fotossensibilizantes/farmacologia
18.
Adv Mater ; 34(44): e2205653, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36082584

RESUMO

Photothermal therapy (PTT) has attracted extensive attention in disease treatments. However, conventional photothermal systems do not possess a temperature-control mechanism, which poses a serious risk to healthy tissues and/or organs due to inevitable thermal damage. Herein, a smart photothermal nanosystem with an intrinsic temperature-control mechanism for thermostatic treatment of bacterial infections is reported. The smart photothermal nanosystem is constructed by loading a thermochromic material into a hollow-structured silica nanocarrier, in which the thermochromic material is composed of naturally occurring phase-change materials (PCMs), a proton-responsive spirolactone, and a proton source. The resulting nanosystem shows strong near-infrared (NIR) absorption and efficient photothermal conversion in solid PCMs but becomes NIR-transparent when PCMs are melted upon NIR irradiation. Such an attractive feature can precisely regulate the photothermal equilibrium temperature to the melting point of PCMs, regardless of the variation in external experimental parameters. In contrast to conventional PTT with severe thermal damage, the reported smart photothermal nanosystem provides an internal protection mechanism on healthy tissues and/or organs, which remarkably accelerates the recovery of bacteria-infected wounds. The smart photothermal nanosystem is a versatile PTT platform, holding great promise in the safe and efficient treatment of bacterial infections and multimodality synergistic therapy.


Assuntos
Infecções Bacterianas , Nanopartículas , Neoplasias , Humanos , Temperatura , Prótons , Neoplasias/terapia , Dióxido de Silício , Fototerapia/métodos , Infecções Bacterianas/terapia
19.
Environ Pollut ; 310: 119894, 2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-35932901

RESUMO

Inhalation is the most frequent route and the lung is the primary damaged organ for human exposure to benzene, toluene, ethylbenzene, xylene, and styrene (BTEXS). However, there is limited information on the risk and dose-effect of the BTEXS mixture on pulmonary function, particularly the overall effect. We conducted a cross-sectional study in a petrochemical plant in southern China. Spirometry and cumulative exposure dose (CED) of BTEXS were used to measure lung function and exposure levels for 635 workers in 2020, respectively. Forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) were tested and interpreted as percentages to predicted values [FVC or FEV1% predicted], and FEV1 to FVC ratio [FEV1/FVC (%)]. We found the reduction in FVC% predicted and the risk of lung ventilation dysfunction (LVD) and its two subtypes (mixed and restrictive ventilation dysfunction, MVD, and MVD) were significantly associated with BTEXS individuals. In addition, pulmonary function damage associated with BTEXS was modified by the smoking status and age. Generalized weighted quantile sum (gWQS) regressions were used to estimate the overall dose-effect on lung function damage induced by the BTEXS mixture. Our results show wqs, an index of weighted quartiles for BTEXS, was potentially associated with the reduction in FVC and FEV1% predicted with the coefficients [95% confidence intervals (CI)] between -1.136 (-2.202, -0.070) and -1.230 (-2.265, -0.195). Odds ratios (ORs) and 95% CIs for the wqs index of LVD, MVD, and RVD were 1.362 (1.129, 1.594), 1.323 (1.084, 1.562), and 1.394 (1.096, 1.692), respectively. Furthermore, xylene, benzene, and toluene in the BTEXS mixture potentially contribute to the development of lung function impairment. Our novel findings demonstrated the dose-response relationships between pulmonary function impairment and the BTEXS mixture and disclosed the potential key pollutants in the BTEXS mixture.


Assuntos
Benzeno , Xilenos , Derivados de Benzeno , Estudos Transversais , Humanos , Pulmão , Medição de Risco , Estireno , Tolueno
20.
Polymers (Basel) ; 11(5)2019 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-31083573

RESUMO

To improve the hemocompatibility of the biodegradable medical poly(ether-ester-urethane) (PEEU), containing uniform-size aliphatic hard segments that was prepared in our lab, a copolymer containing phosphorylcholine (PC) groups was blended with the PEEU. The PC-copolymer of poly(MPC-co-EHMA) (PMEH) was first obtained by copolymerization of 2-methacryloyloxyethyl phosphorylcholine (MPC) and 2-ethylhexyl methacrylate (EHMA), and then dissolved in mixed solvent of ethanol/chloroform to obtain a homogeneous solution. The composite films (PMPU) with varying PMEH content were prepared by solvent evaporation method. The physicochemical properties of the composite films with varying PMEH content were researched. The PMPU films exhibited higher thermal stability than that of the pure PEEU film. With the PMEH content increasing from 5 to 20 wt%, the PMPU films also possessed satisfied tensile properties with ultimate stress of 22.9-15.8 MPa and strain at break of 925-820%. The surface and bulk hydrophilicity of the films were improved after incorporation of PMEH. In vitro degradation studies indicated that the degradation rate increased with PMEH content, and it took 12-24 days for composite films to become fragments. The protein adsorption and platelet-rich plasma contact tests were adapted to evaluate the surface hemocompatibility of the composite films. It was found that the amount of adsorbed protein and adherent platelet on the surface decreased significantly, and almost no activated platelets were observed when PMEH content was above 5 wt%, which manifested good surface hemocompatibility. Due to the biodegradability, acceptable tensile properties and good surface hemocompatibility, the composites can be expected to be applied in blood-contacting implant materials.

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