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1.
Chemosphere ; : 143423, 2024 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-39341393

RESUMO

The accurate quantification of volatile organic compound (VOC) emission rates from porous media to the air is a challenging problem, as measurements are affected by the chemical and physical characteristics of the porous media, and the operating parameters of the sampling device itself. The main objective of this study is to investigate how flux chamber (the most commonly used sampling device) configurations influence emission rate measurement from three selected porous media. Various parameters were studied, including sweep air flow rate, presence of a mixing fan, headspace volume and thickness of media. Controlled experiments focused on the behaviour of two VOCs commonly found in area sources: acetic acid and 1-butanol. Sweep gas flow rate emerged as the most influential factor, inducing turbulence and dilution over porous media surfaces and impacting emission rate measurements more significantly than headspace volume and fan installation. Variations in porous media properties also affected mass transfer, with emissions from coco coir showing higher mass transfer as its porosity and particle size facilitated gas transportation. While behaviour of acetic acid emission through the media supported the diffusion theory, emission of 1-butanol was affected by a combination of factors, highlighting the role of both diffusive and advective transport mechanisms. Understanding how flux chamber setups and porous media properties influence emission rates is crucial for accurately interpreting data. This knowledge also guides the design of studies, especially when investigating complex sources like biosolids and organic-amended soil.

2.
J Exp Clin Cancer Res ; 43(1): 223, 2024 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-39128990

RESUMO

BACKGROUND: CRISPR-Cas13a is renowned for its precise and potent RNA editing capabilities in cancer therapy. While various material systems have demonstrated efficacy in supporting CRISPR-Cas13a to execute cellular functions in vitro efficiently and specifically, the development of CRISPR-Cas13a-based therapeutic agents for intravesical instillation in bladder cancer (BCa) remains unexplored. METHODS: In this study, we introduce a CRISPR-Cas13a nanoplatform, which effectively inhibits PDL1 expression following intravesical instillation. This system utilizes a fusion protein CAST, created through the genetic fusion of CRISPR-Cas13 and the transmembrane peptide TAT. CAST acts as a potent transmembrane RNA editor and is assembled with the transepithelial delivery carrier fluorinated chitosan (FCS). Upon intravesical administration into the bladder, the CAST-crRNAa/FCS nanoparticles (NPs) exhibit remarkable transepithelial capabilities, significantly suppressing PDL1 expression in tumor tissues.To augment immune activation within the tumor microenvironment, we integrated a fenbendazole (FBZ) intravesical system (FBZ@BSA/FCS NPs). This system is formulated through BSA encapsulation followed by FCS coating, positioning FBZ as a powerful chemo-immunological agent. RESULTS: In an orthotropic BCa model, the FBZ@BSA/FCS NPs demonstrated pronounced tumor cell apoptosis, synergistically reduced PDL1 expression, and restructured the immune microenvironment. This culminated in an enhanced synergistic intravesical instillation approach for BCa. Consequently, our study unveils a novel RNA editor nanoagent formulation and proposes a potential synergistic therapeutic strategy. This approach significantly bolsters therapeutic efficacy, holding promise for the clinical translation of CRISPR-Cas13-based cancer perfusion treatments.


Assuntos
Sistemas CRISPR-Cas , Neoplasias da Bexiga Urinária , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/terapia , Humanos , Animais , Administração Intravesical , Camundongos , Linhagem Celular Tumoral , Feminino
3.
Adv Mater ; 36(39): e2407750, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39115352

RESUMO

Thin endometrium (TE) is closely associated with infertility in reproductive medicine. Estrogen therapy gains unsatisfactory outcomes. In this study, an artificial mucus based on dopamine (L-DOPA)-modified hyaluronic acid combining phytoestrogen cajaninstilbene acid and rat urinary exosomes (CUEHD) is constructed for TE treatment using a rat TE model. In the rat TE model, the dominant elastic behavior and adhesive properties of CUEHD guarantee adequate retention, rendering superior synergistic treatment efficacy and favorable biosafety characteristics. CUEHD treatment significantly increases endometrial thickness and promotes receptivity and fertility. Mechanistically, estrogen homeostasis, inflammation inhibition, and endometrial regeneration are achieved through the crosstalk between ER-NLRP3-IL1ß and Wnt-ß catenin-TGFß-smad signaling pathways. Moreover, the therapeutic potential of exosomes from human urine and adipose tissue-derived stem cells (ADSCs) and rat ADSCs are also demonstrated, indicating extensive use of the artificial mucus system. Thus, this study illustrates a platform combining phytoestrogen and exosomes with promising implications for TE treatment.


Assuntos
Dopamina , Endométrio , Exossomos , Ácido Hialurônico , Muco , Fitoestrógenos , Animais , Ácido Hialurônico/química , Feminino , Exossomos/metabolismo , Exossomos/química , Endométrio/metabolismo , Endométrio/efeitos dos fármacos , Endométrio/citologia , Ratos , Humanos , Muco/metabolismo , Dopamina/urina , Dopamina/metabolismo , Fitoestrógenos/química , Fitoestrógenos/farmacologia , Ratos Sprague-Dawley
4.
Science ; 385(6705): 204-209, 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38991078

RESUMO

Relaxor ferroelectric (RFE) films are promising energy-storage candidates for miniaturizing high-power electronic systems, which is credited to their high energy density (Ue) and efficiency. However, advancing their Ue beyond 200 joules per cubic centimeter is challenging, limiting their potential for next-generation energy-storage devices. We implemented a partitioning polar-slush strategy in RFEs to push the boundary of Ue. Guided by phase-field simulations, we designed and fabricated high-performance Bi(Mg0.5Ti0.5)O3-SrTiO3-based RFE films with isolated slush-like polar clusters, which were realized through suppression of the nonpolar cubic matrix and introduction of highly insulating networks. The simultaneous enhancement of the reversible polarization and breakdown strength leads to a Ue of 202 joules per cubic centimeter with a high efficiency of ~79%. The proposed strategy provides a design freedom for next-generation high-performance dielectrics.

5.
Foodborne Pathog Dis ; 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-39042484

RESUMO

To investigate the epidemiology of Shiga toxin-producing Escherichia coli (STEC) in dairy cattle, 975 samples (185 feces, 34 silage, 36 cattle drinking water, 360 raw milk, and 360 teat skin swabs) were collected from two dairy farms in Baoji and Yangling, Shaanxi Province, China, and were screened for STEC. Whole-genome sequencing was used to analyze the genomic characteristics and potential transmission of STEC isolates. A total of 32 samples were contaminated with STEC, including 4.0% (19/479) in Farm A and 2.6% (13/496) in Farm B. Compared with adult cows (4.5%), nonadult cows had a higher rate (21.3%) of STEC colonization. A total of 14 serotypes and 11 multilocus sequence typing were identified in 32 STEC isolates, among which O55:H12 (25.0%) and ST101 (31.3%) were the most predominant, respectively. Six stx subtypes/combinations were identified, including stx1a (53.1%), stx2g (15.6%), stx2d, stx2a+stx2d, stx1a+stx2a (6.3%, for each), and stx2a (3.1%). Of 32 STEC isolates, 159 virulence genes and 27 antibiotic resistance genes were detected. Overall, STEC isolates showed low levels of resistance to the 16 antibiotics tested (0-40.6%), with most common resistance to ampicillin (40.6%). The phylogenetic analysis confirmed that STEC in the gut of cattle can be transmitted through feces. The results of this study help to improve our understanding of the epidemiological aspects of STEC in dairy cattle and provide early warning and control of the prevalence and spread of the bacterium.

6.
J Nanobiotechnology ; 22(1): 432, 2024 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-39034393

RESUMO

Rheumatoid arthritis (RA) involves chronic joint inflammation. Combining acupuncture and medication for RA treatment faces challenges like spatiotemporal variability, limited drug loading in acupuncture needles, and premature or untargeted drug release. Here, we designed a new type of tubular acupuncture needles, with an etched hollow honeycomb-like structure to enable the high loading of therapeutics, integrating the traditional acupuncture and drug repository into an all-in-one therapeutic platform. In these proof-of-concept experiments, we fabricated injectable hollow honeycomb electroacupuncture needles (HC-EA) loaded with melittin hydrogel (MLT-Gel), enabling the combination treatment of acupuncture stimulation and melittin therapy in a spatiotemporally synchronous manner. Since the RA microenvironment is mildly acidic, the acid-responsive chitosan (CS)/sodium beta-glycerophosphate (ß-GP)/ hyaluronic acid (HA) composited hydrogel (CS/GP/HA) was utilized to perform acupuncture stimulation and achieve the targeted release of injected therapeutics into the specific lesion site. Testing our therapeutic platform involved a mouse model of RA and bioinformatics analysis. MLT-Gel@HC-EA treatment restored Th17/Treg-mediated immunity balance, reduced inflammatory factor release (TNF-α, IL-6, IL-1ß), and alleviated inflammation at the lesion site. This novel combination of modified acupuncture needle and medication, specifically melittin hydrogel, holds promise as a therapeutic strategy for RA treatment.


Assuntos
Terapia por Acupuntura , Artrite Reumatoide , Hidrogéis , Meliteno , Agulhas , Animais , Meliteno/farmacologia , Meliteno/química , Camundongos , Artrite Reumatoide/terapia , Artrite Reumatoide/tratamento farmacológico , Hidrogéis/química , Terapia por Acupuntura/métodos , Quitosana/química , Ácido Hialurônico/química , Masculino , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL
7.
ACS Appl Mater Interfaces ; 16(31): 41185-41193, 2024 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-39069883

RESUMO

The enhancement of piezoelectricity without compromising the Curie temperature of a piezoelectric is challenging due to phenomenological incompatibility. In the present work, the phase diagram of (0.68-x)BiFeO3-xBiScO3-0.32PbTiO3, with varied addition of BiScO3 (x = 0, 0.05, 0.10, 0.15, and 0.20), was constructed through systematic studies of the dielectric, ferroelectric, and piezoelectric properties. A rhombohedral-tetragonal phase boundary was observed near x = 0.10 BiScO3 addition, of which the piezoelectricity was found to be seven times larger than that without BiScO3 (∼208 pm/V vs ∼38 pm/V). Most importantly, a high Curie temperature of 430 °C is successfully inherited from binary 0.68BiFeO3-0.32PbTiO3. This is explained by optimized Bi compensation, which is observed critical regulating Curie temperature in BFO-based binary and ternary systems. These results open up a paradigm for collaboratively optimizing the Curie temperature and piezoelectric response for a number of ferroelectrics and provide a promising BiFeO3-BiScO3-PbTiO3 film with integrated prominent performance for potential applications at elevated temperatures.

8.
Nanomedicine ; 58: 102743, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38484918

RESUMO

Cancer-associated fibroblasts (CAFs) play a crucial role in creating an immunosuppressive environment and remodeling the extracellular matrix within tumors, leading to chemotherapy resistance and limited immune cell infiltration. To address these challenges, integrating CAFs deactivation into immunogenic chemotherapy may represent a promising approach to the reversal of immune-excluded tumor. We developed a tumor-targeted nanomedicine called the glutathione-responsive nanocomplex (GNC). The GNC co-loaded dasatinib, a CAF inhibitor, and paclitaxel, a chemotherapeutic agent, to deactivate CAFs and enhance the effects of immunogenic chemotherapy. Due to the modification with hyaluronic acid, the GNC preferentially accumulated in the tumor periphery and responsively released cargos, mitigating the tumor stroma as well as overcoming chemoresistance. Moreover, GNC treatment exhibited remarkable immunostimulatory efficacy, including CD8+ T cell expansion and PD-L1 downregulation, facilitating immune checkpoint blockade therapy. In summary, the integration of CAF deactivation and immunogenic chemotherapy using the GNC nanoplatform holds promise for rebuilding immune-excluded tumors.


Assuntos
Fibroblastos Associados a Câncer , Paclitaxel , Fibroblastos Associados a Câncer/efeitos dos fármacos , Fibroblastos Associados a Câncer/imunologia , Fibroblastos Associados a Câncer/patologia , Fibroblastos Associados a Câncer/metabolismo , Animais , Humanos , Camundongos , Paclitaxel/farmacologia , Paclitaxel/uso terapêutico , Dasatinibe/farmacologia , Dasatinibe/uso terapêutico , Neoplasias/imunologia , Neoplasias/tratamento farmacológico , Neoplasias/terapia , Neoplasias/patologia , Linhagem Celular Tumoral , Nanopartículas/química , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/imunologia , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Feminino , Glutationa/metabolismo
9.
J Control Release ; 368: 533-547, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38462043

RESUMO

Inflammation-related diseases impose a significant global health burden, necessitating urgent exploration of novel treatment modalities for improved clinical outcomes. We begin by discussing the limitations of conventional approaches and underscore the pivotal involvement of immune cells in the inflammatory process. Amidst the rapid growth of immunology, the therapeutic potential of immune cell-derived extracellular vesicles (EVs) has garnered substantial attention due to their capacity to modulate inflammatory response. We provide an in-depth examination of immune cell-derived EVs, delineating their promising roles across diverse disease conditions in both preclinical and clinical settings. Additionally, to direct the development of the next-generation drug delivery systems, we comprehensively investigate the engineered EVs on their advanced isolation methods, cargo loading techniques, and innovative engineering strategies. This review ends with a focus on the prevailing challenges and considerations regarding the clinical translation of EVs in future, emphasizing the need of standardized characterization and scalable production processes. Ultimately, immune cell-derived EVs represent a cutting-edge therapeutic approach and delivery platform, holding immense promise in precision medicine.


Assuntos
Vesículas Extracelulares , Medicina de Precisão , Sistemas de Liberação de Medicamentos
10.
Sci Total Environ ; 924: 171657, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38490413

RESUMO

Global occurrences of foodborne disease outbreaks have been documented, involving fresh agricultural produce contaminated by various pathogens. This contamination can occur at any point in the supply chain. However, studies on the prevalence of total coliforms, Salmonella and microbial diversity in vegetable and associated environments are limited. This study aimed to assess 1) the number of total coliforms (n = 299) and diversity of microbial communities (n = 52); 2) the prevalence, antibiotic susceptibility, genomic characteristics, and potential transmission relationships of Salmonella in soil-irrigation water-vegetable system (n = 506). Overall, 84.28 % samples were positive to total coliforms, with most frequently detected in soil (100 %), followed by irrigation water (79.26 %) and vegetables (62.00 %). A seasonal trend in coliform prevalence was observed, with significantly higher levels in summer (P < 0.05). Detection rates of Salmonella in soil, vegetable and irrigation water were 2.21 %, 4.74 % and 9.40 %. Fourteen serotypes and sequence types (STs) were respectively annotated in 56 Salmonella isolates, ST13 S. Agona (30.36 %, 17/56), ST469 S. Rissen (25.00 %, 14/56), and ST36 S. Typhimurium (12.50 %, 7/56) were dominant serotypes and STs. Thirty-one (55.36 %) isolates were multi-drug resistant, and the resistance was most frequently found to ampicillin (55.36 %, 31/56), followed by to sulfamethoxazole (51.79 %, 29/56) and tetracycline (50.00 %, 28/56). The genomic characteristics and antibiotic resistance patterns of Salmonella isolates from soil, vegetables, and irrigation water within a coherent geographical locale exhibited remarkable similarities, indicating Salmonella may be transmitted among these environments or have a common source of contamination. Microbial alpha diversity indices in soil were significantly higher (P < 0.05) than that in vegetable and irrigation water. The microbial phylum in irrigation water covered that in the vegetable, demonstrating a significant overlap in the microbial communities between the vegetables and the irrigation water.


Assuntos
Solo , Verduras , Irrigação Agrícola , Salmonella , Antibacterianos , Água , Testes de Sensibilidade Microbiana
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