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1.
Adv Mater ; : e2401445, 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-39233550

RESUMEN

RNA therapeutics have been successfully transitioned into clinical applications. Lipid nanoparticles (LNPs) are widely employed as nonviral delivery vehicles for RNA therapeutics in commercial vaccine and gene therapy products. However, the bottleneck in expanding the clinical applications of LNP-based RNA therapeutics lies in the tendency of these nanoparticles to preferentially accumulate in the liver. This challenge underscores the need to design LNPs capable of delivering RNA to organs beyond the liver. In this perspective, recent progress is discussed in developing strategies for designing LNPs to deliver RNA to extrahepatic organs. Organ-selective targeting capability is achieved by either altering the composition of the LNP formulation or chemically modifying the ionizable lipid component. Both approaches result in changes in the physicochemical properties of the LNPs, which subsequently alters the composition of the biomolecular corona that adsorbs onto its surface following administration. The biomolecular corona is a known mechanism that mediates organ-selective LNP delivery. Furthermore, this perspective aims to provide an outlook on shaping the next-generation LNP delivery platforms. Potential efforts include targeting specific cell types, improving the safety profile of LNPs, and developing strategies to overcome physiological barriers against organ-specific delivery.

2.
Proc Natl Acad Sci U S A ; 121(37): e2403421121, 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39226350

RESUMEN

Drug-resistant Tuberculosis (TB) is a global public health problem. Resistance to rifampicin, the most effective drug for TB treatment, is a major growing concern. The etiological agent, Mycobacterium tuberculosis (Mtb), has a cluster of ATP-binding cassette (ABC) transporters which are responsible for drug resistance through active export. Here, we describe studies characterizing Mtb Rv1217c-1218c as an ABC transporter that can mediate mycobacterial resistance to rifampicin and have determined the cryo-electron microscopy structures of Rv1217c-1218c. The structures show Rv1217c-1218c has a type V exporter fold. In the absence of ATP, Rv1217c-1218c forms a periplasmic gate by two juxtaposed-membrane helices from each transmembrane domain (TMD), while the nucleotide-binding domains (NBDs) form a partially closed dimer which is held together by four salt-bridges. Adenylyl-imidodiphosphate (AMPPNP) binding induces a structural change where the NBDs become further closed to each other, which downstream translates to a closed conformation for the TMDs. AMPPNP binding results in the collapse of the outer leaflet cavity and the opening of the periplasmic gate, which was proposed to play a role in substrate export. The rifampicin-bound structure shows a hydrophobic and periplasm-facing cavity is involved in rifampicin binding. Phospholipid molecules are observed in all determined structures and form an integral part of the Rv1217c-1218c transporter system. Our results provide a structural basis for a mycobacterial ABC exporter that mediates rifampicin resistance, which can lead to different insights into combating rifampicin resistance.


Asunto(s)
Transportadoras de Casetes de Unión a ATP , Proteínas Bacterianas , Microscopía por Crioelectrón , Farmacorresistencia Bacteriana , Mycobacterium tuberculosis , Rifampin , Rifampin/farmacología , Rifampin/metabolismo , Transportadoras de Casetes de Unión a ATP/metabolismo , Transportadoras de Casetes de Unión a ATP/química , Transportadoras de Casetes de Unión a ATP/ultraestructura , Transportadoras de Casetes de Unión a ATP/genética , Mycobacterium tuberculosis/metabolismo , Mycobacterium tuberculosis/efectos de los fármacos , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/química , Proteínas Bacterianas/ultraestructura , Proteínas Bacterianas/genética , Modelos Moleculares , Adenilil Imidodifosfato/metabolismo
3.
Research (Wash D C) ; 7: 0473, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39268501

RESUMEN

Lung ischemia-reperfusion injury (IRI) stands as the primary culprit behind primary graft dysfunction (PGD) after lung transplantation, yet viable therapeutic options are lacking. In the present study, we used a murine hilar clamp (1 h) and reperfusion (3 h) model to study IRI. The left lung tissues were harvested for metabolomics, transcriptomics, and single-cell RNA sequencing. Metabolomics of plasma from human lung transplantation recipients was also performed. Lung histology, pulmonary function, pulmonary edema, and survival analysis were measured in mice. Integrative analysis of metabolomics and transcriptomics revealed a marked up-regulation of arachidonate 12-lipoxygenase (ALOX12) and its metabolite 12-hydroxyeicosatetraenoic acid (12-HETE), which played a pivotal role in promoting ferroptosis and neutrophil extracellular trap (NET) formation during lung IRI. Additionally, single-cell RNA sequencing revealed that ferroptosis predominantly occurred in pulmonary endothelial cells. Importantly, Alox12-knockout (KO) mice exhibited a notable decrease in ferroptosis, NET formation, and tissue injury. To investigate the interplay between endothelial ferroptosis and NET formation, a hypoxia/reoxygenation (HR) cell model using 2 human endothelial cell lines was established. By incubating conditioned medium from HR cell model with neutrophils, we found that the liberation of high mobility group box 1 (HMGB1) from endothelial cells undergoing ferroptosis facilitated the formation of NETs by activating the TLR4/MYD88 pathway. Last, the administration of ML355, a targeted inhibitor of Alox12, mitigated lung IRI in both murine hilar clamp/reperfusion and rat left lung transplant models. Collectively, our study indicates ALOX12 as a promising therapeutic strategy for lung IRI.

4.
Lipids Health Dis ; 23(1): 294, 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39267042

RESUMEN

BACKGROUND AND AIM: Remnant cholesterol (RC) is substantially related to negative outcomes in cardiac patients. Patients with coexisting hypertension and heart failure (HF) often develop left ventricular hypertrophy (LVH) and have poor prognoses. This study investigated baseline RC levels and LV remodelling and patients' prognoses. METHODS AND RESULTS: Six hundred thirty consecutive individuals with hypertension and HF participated in this prospective trial from October 2018 to August 2020. Based on left ventricular mass index (LVMI), 560 those eligible were separated into LVH and non-LVH groups. Multiple linear regression and receiver operating characteristic (ROC) curves examined the RC and LV relationship. A Cox regression analysis was conducted to examine the predictive value of RC for clinical outcomes. The LVH group presented significantly elevated values of RC, triglyceride, and cholesterol and decreased high-density lipoprotein cholesterol (HDLC). The optimal cutoff value for RC to predict LV remodelling was 0.49. The subjects were observed for a median of 58 months, and 104 participants met the primary endpoint. The risk models involving the two Cox models were adjusted to incorporate confounding factors, which revealed that those with elevated baseline levels of RC were more susceptible to cardiovascular mortality, as shown by an increased hazard ratio. (HR: 1.91, 95% CI: 1.62-2.26 vs. HR: 1.75, 95% CI: 1.43-2.16, P < 0.001). CONCLUSIONS: RC is linked to LV remodelling in patients with hypertensive HF, with LVH having greater RC values. Moreover, patients with hypertensive HF who had a higher RC suffered from an increased risk of cardiovascular mortality. TRIAL REGISTRATION: NCT03727828, 21 Oct 2018.


Asunto(s)
Colesterol , Insuficiencia Cardíaca , Hipertensión , Hipertrofia Ventricular Izquierda , Triglicéridos , Humanos , Hipertrofia Ventricular Izquierda/sangre , Masculino , Femenino , Hipertensión/complicaciones , Hipertensión/sangre , Insuficiencia Cardíaca/sangre , Insuficiencia Cardíaca/mortalidad , Insuficiencia Cardíaca/complicaciones , Colesterol/sangre , Persona de Mediana Edad , Estudios Prospectivos , Anciano , Pronóstico , Triglicéridos/sangre , Remodelación Ventricular , Curva ROC , Modelos de Riesgos Proporcionales , HDL-Colesterol/sangre , Factores de Riesgo
5.
Bioresour Technol ; : 131480, 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39265751

RESUMEN

Acetobacterium woodii and Megasphaera hexanoica were co-cultured for caproic acid (CA) production from Lactic acid (LA) and CO2. Also, various concentrations (1 g/L, 3 g/L, 5 g/L, and 10 g/L) of Zero Valent Iron (ZVI) were introduced to study its impact on the co-culture system. In flask experiments, 10 g/L LA and 1.0 bar CO2 produced 0.6 g/L CA with some biomass growth. ZVI increased LA consumption and CA production. Indeed, 3 g/L ZVI boosted CA production by 186 % and biomass accumulation by 103 %, suggesting that ZVI controls the carbon flux. Subsequent automated bioreactor studies showed that 3 g/L ZVI produced 1.842 g/L CA at stable pH, compared to 0.969 g/L without ZVI (control). Further, metabolic activity showed that both bacteria could directly use H2, generated by ZVI (3 g/L), as electron donor. Higher ZVI concentrations (10 g/L) resulted in Fe2+ causing excessive oxidation pressure on M. hexanoica, with its carbon flux flowing preferentially towards biomass. Enzyme assays confirmed that A. woodii preferred 10 g/L ZVI while M. hexanoica preferred 3 g/L for optimal bioconversion.

6.
Environ Pollut ; 359: 124755, 2024 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-39151781

RESUMEN

This study aimed to investigate the spatial distribution of microplastics (MPs) and the features of the bacterial community in the Qiantang River urban river. Surface water samples from the Qiantang River were analyzed for this purpose. The results of the 16S high-throughput sequencing indicated that the microbial community diversity of MPs was significantly lower than in natural water but higher than in natural substrates. The biofilm of MPs was mainly composed of Enterobacteriaceae (28.00%), Bacillaceae (16.25%), and Phormidiaceae (6.75%). The biodiversity on MPs, natural water, and natural substrates varied significantly and was influenced by seasonal factors. In addition, the presence of MPs hindered the denitrification process in the aquatic environment and intensified N2O emission when the nitrate concentration was higher than normal. In particular, polyethylene terephthalate (PET) exhibited a 12% residue of NO3--N and a 4.2% accumulation of N2O after a duration of 48 h. Further findings on gene abundance and cell viability provided further confirmation that PET had a considerable impact on reducing the expression of nirS (by 0.34-fold) and nosZ (by 0.53-fold), hence impeding the generation of nicotinamide adenine dinucleotide (NADH) (by 0.79-fold). Notably, all MPs demonstrated higher the nirK gene abundances than the nirS gene, which could account for the significant accumulation of N2O. The results suggest that MPs can serve as a novel carrier substrate for microbial communities and as a potential promoter of N2O emission in aquatic environments.


Asunto(s)
Microplásticos , Ríos , Contaminantes Químicos del Agua , Ríos/química , Ríos/microbiología , Microplásticos/toxicidad , Contaminantes Químicos del Agua/análisis , Bacterias/genética , Bacterias/efectos de los fármacos , Monitoreo del Ambiente , Microbiota/efectos de los fármacos , Óxido Nitroso , China
7.
Phys Chem Chem Phys ; 26(34): 22593-22597, 2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39158020

RESUMEN

Chalcogen bonding (ChB) interactions have drawn intensive attention in the last few decades as interesting alternatives to hydrogen bonding. The applications of ChB were mostly centered on the solid state and have rarely been explored in solution. In this work, a novel strategy for forming ChB-based deep eutectic solvents (DESs) was exploited. We set forth the formation, physicochemical properties, and interaction sites in detail. This work not only provides a new idea to design DES systems but also to exploit the potential application of ChB complexes.

8.
NPJ Biofilms Microbiomes ; 10(1): 72, 2024 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-39191812

RESUMEN

Cophylogeny has been identified between gut bacteria and their animal host and is highly relevant to host health, but little research has extended to gut bacteriophages. Here we use bee model to investigate host specificity and cophylogeny in the "animal-gut bacteria-phage" tripartite system. Through metagenomic sequencing upon different bee species, the gut phageome revealed a more variable composition than the gut bacteriome. Nevertheless, the bacteriome and the phageome showed a significant association of their dissimilarity matrices, indicating a reciprocal interaction between the two kinds of communities. Most of the gut phages were host generalist at the viral cluster level but host specialist at the viral OTU level. While the dominant gut bacteria Gilliamella and Snodgrassella exhibited matched phylogeny with bee hosts, most of their phages showed a diminished level of cophylogeny. The evolutionary rates of the bee, the gut bacteria and the gut phages showed a remarkably increasing trend, including synonymous and non-synonymous substitution and gene content variation. For all of the three codiversified tripartite members, however, their genes under positive selection and genes involving gain/loss during evolution simultaneously enriched the functions into metabolism of nutrients, therefore highlighting the tripartite coevolution that results in an enhanced ecological fitness for the whole holobiont.


Asunto(s)
Bacterias , Bacteriófagos , Microbioma Gastrointestinal , Especificidad del Huésped , Filogenia , Animales , Bacteriófagos/genética , Bacteriófagos/fisiología , Abejas/virología , Abejas/microbiología , Bacterias/virología , Bacterias/genética , Bacterias/clasificación , Metagenómica/métodos , Metagenoma
9.
Nat Commun ; 15(1): 6756, 2024 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-39117613

RESUMEN

Renal dysfunction (RD) often characterizes the worse course of patients with advanced heart failure (AHF). Many prognosis assessments are hindered by researcher biases, redundant predictors, and lack of clinical applicability. In this study, we enroll 1736 AHF/RD patients, including data from Henan Province Clinical Research Center for Cardiovascular Diseases (which encompasses 11 hospital subcenters), and Beth Israel Deaconess Medical Center. We developed an AI hybrid modeling framework, assembling 12 learners with different feature selection paradigms to expand modeling schemes. The optimized strategy is identified from 132 potential schemes to establish an explainable survival assessment system: AIHFLevel. The conditional inference survival tree determines a probability threshold for prognostic stratification. The evaluation confirmed the system's robustness in discrimination, calibration, generalization, and clinical implications. AIHFLevel outperforms existing models, clinical features, and biomarkers. We also launch an open and user-friendly website www.hf-ai-survival.com , empowering healthcare professionals with enhanced tools for continuous risk monitoring and precise risk profiling.


Asunto(s)
Insuficiencia Cardíaca , Humanos , Insuficiencia Cardíaca/mortalidad , Insuficiencia Cardíaca/fisiopatología , Masculino , Femenino , Anciano , Pronóstico , Persona de Mediana Edad , Inteligencia Artificial , Medición de Riesgo/métodos , Análisis de Supervivencia , Insuficiencia Renal/mortalidad , Insuficiencia Renal/fisiopatología , Insuficiencia Renal/diagnóstico , Biomarcadores
10.
ACS Nano ; 18(33): 22596-22607, 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-39132820

RESUMEN

The isolation of viruses from complex biological samples is essential for creating sensitive bioassays that assess the efficacy and safety of viral therapeutics and vaccines, which have played a critical role during the COVID-19 pandemic. However, existing methods of viral isolation are time-consuming and labor-intensive due to the multiple processing steps required, resulting in low yields. Here, we introduce the rapid, efficient, and high-resolution acoustofluidic isolation of viruses from complex biological samples via Bessel beam excitation separation technology (BEST). BEST isolates viruses by utilizing the nondiffractive and self-healing properties of 2D, in-plane acoustic Bessel beams to continuously separate cell-free viruses from biofluids, with high throughput and high viral RNA yield. By tuning the acoustic parameters, the cutoff size of isolated viruses can be easily adjusted to perform dynamic, size-selective virus isolation while simultaneously trapping larger particles and separating smaller particles and contaminants from the sample, achieving high-precision isolation of the target virus. BEST was used to isolate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from human saliva samples and Moloney Murine Leukemia Virus from cell culture media, demonstrating its potential use in both practical diagnostic applications and fundamental virology research. With high separation resolution, high yield, and high purity, BEST is a powerful tool for rapidly and efficiently isolating viruses. It has the potential to play an important role in the development of next-generation viral diagnostics, therapeutics, and vaccines.


Asunto(s)
SARS-CoV-2 , Saliva , SARS-CoV-2/aislamiento & purificación , Humanos , Saliva/virología , COVID-19/virología , Acústica , Animales , ARN Viral/aislamiento & purificación , ARN Viral/genética
11.
Pharmacoepidemiol Drug Saf ; 33(8): e5880, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39135518

RESUMEN

BACKGROUND: Polypharmacy (PP) is common in elderly population and associated with some adverse clinical outcomes and increases healthcare burdens. We performed this systemic review and meta-analysis to estimate worldwide prevalence of PP and explore associated factors in the elderly. METHODS: The PubMed, Web of Science, Cochrane Library, and Ovid EMBASE databases were searched for studies published until May 30, 2022. We included observational studies representative of general patients aged ≥60 in which PP was defined as multiple drugs ≥5. Studies were excluded if only a particular group of the elderly population (e.g., with diabetes) were included. The primary outcome was the prevalence of PP. Random-effect models were employed to estimate the overall or variable-specific pooled estimates of PP. Secondary outcomes were hyperpolypharmacy (HPP, defined as multiple drugs ≥10) and PP prevalence based on different study years, genders, locations, populations, and so forth. RESULTS: We included 122 original observational studies with an overall population of 57 328 043 individuals in the meta-analysis. The overall prevalence of PP and HPP in the elderly population worldwide was 39.1% (95% confidence interval [CI], 35.5%-42.7%) and 13.3% (95% CI, 10.4%-16.5%), respectively. The prevalence of PP in Europe, Oceania, North America, Asia, and South America was 45.8% (95% CI, 41.5%-50.2%), 45.5% (95% CI, 26.7%-64.3%), 40.8% (95% CI, 29.8%-51.6%), 29.0% (95% CI, 20.0%-38.0%), and 28.4% (95% CI, 24.0%-32.8%), respectively (p < 0.01). Multivariate meta-regressions showed geographical regions of Europe or North America, age ≥70, and residence from nursing homes were independently associated with higher PP prevalence. CONCLUSIONS: Nearly 40% of the elderly population is exposed to PP. The prevalence of PP is significantly higher in elderly individuals aged 70 or older, in developed regions and in nursing homes. It is important to focus on avoiding inappropriate PP in this population to address the growing burden of PP.


Asunto(s)
Polifarmacia , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de Edad , Salud Global/estadística & datos numéricos , Estudios Observacionales como Asunto , Polifarmacia/estadística & datos numéricos , Prevalencia
12.
Cell Commun Signal ; 22(1): 402, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-39148040

RESUMEN

BACKGROUND: Helicobacter pylori (H. pylori) infection is critical in the development and occurrence of gastric cancer. H. pylori secretes gamma-glutamyl transferase (GGT), which affects energy metabolism and histone methylation in mesenchymal stem cells. However, its effect on human gastric epithelial cells remains unclear. This study aimed to investigate the effects of GGT on energy metabolism and histone methylation in gastric epithelial cells and determine its role in the development and progression of H. pylori-induced gastric cancer. METHODS: A GGT knockout H. pylori strain and mouse gastric cancer model were constructed, and alpha-ketoglutarate (α-KG) was added. The underlying mechanism was investigated using proteomics, immunohistochemistry, Western blotting, and other experimental assays. RESULTS: H. pylori can colonize the host's stomach and destroy the gastric epithelium. GGT secreted by H. pylori decreased the concentration of glutamine in the stomach and increased H3K9me3 and H3K27me3 expression, which promoted the proliferation and migration of gastric epithelial cells. Additionally, α-KG reversed this effect. GGT increased the tumorigenic ability of nude mice. GGT, secreted by H. pylori, promoted the expression of ribosomal protein L15 (RPL15), while GGT knockout and supplementation with α-KG and trimethylation inhibitors reduced RPL15 expression and Wnt signaling pathway expression. CONCLUSIONS: H. pylori secreted GGT decreased the expression of glutamine and α-KG in gastric epithelial cells, increased the expression of histones H3K9me3 and H3K27me3, and activated the Wnt signaling pathway through RPL15 expression, ultimately changing the biological characteristics of the gastric epithelium and promoting the occurrence of gastric cancer. Altered energy metabolism and histone hypermethylation are important factors involved in this process.


Asunto(s)
Metabolismo Energético , Células Epiteliales , Helicobacter pylori , Histonas , Neoplasias Gástricas , gamma-Glutamiltransferasa , Neoplasias Gástricas/microbiología , Neoplasias Gástricas/patología , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/genética , Animales , Histonas/metabolismo , Metilación , Células Epiteliales/metabolismo , Células Epiteliales/microbiología , Células Epiteliales/patología , gamma-Glutamiltransferasa/metabolismo , gamma-Glutamiltransferasa/genética , Ratones , Humanos , Ratones Desnudos , Mucosa Gástrica/metabolismo , Mucosa Gástrica/microbiología , Mucosa Gástrica/patología , Proliferación Celular , Infecciones por Helicobacter/metabolismo , Infecciones por Helicobacter/microbiología , Infecciones por Helicobacter/patología , Infecciones por Helicobacter/complicaciones , Ácidos Cetoglutáricos/metabolismo
13.
Chem Soc Rev ; 53(16): 8306-8378, 2024 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-39005165

RESUMEN

As natural living substances, microorganisms have emerged as useful resources in medicine for creating microbe-material hybrids ranging from nano to macro dimensions. The engineering of microbe-involved nanomedicine capitalizes on the distinctive physiological attributes of microbes, particularly their intrinsic "living" properties such as hypoxia tendency and oxygen production capabilities. Exploiting these remarkable characteristics in combination with other functional materials or molecules enables synergistic enhancements that hold tremendous promise for improved drug delivery, site-specific therapy, and enhanced monitoring of treatment outcomes, presenting substantial opportunities for amplifying the efficacy of disease treatments. This comprehensive review outlines the microorganisms and microbial derivatives used in biomedicine and their specific advantages for therapeutic application. In addition, we delineate the fundamental strategies and mechanisms employed for constructing microbe-material hybrids. The diverse biomedical applications of the constructed microbe-material hybrids, encompassing bioimaging, anti-tumor, anti-bacteria, anti-inflammation and other diseases therapy are exhaustively illustrated. We also discuss the current challenges and prospects associated with the clinical translation of microbe-material hybrid platforms. Therefore, the unique versatility and potential exhibited by microbe-material hybrids position them as promising candidates for the development of next-generation nanomedicine and biomaterials with unique theranostic properties and functionalities.


Asunto(s)
Bacterias , Humanos , Bacterias/efectos de los fármacos , Bacterias/metabolismo , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Animales , Neoplasias/tratamiento farmacológico , Antibacterianos/farmacología , Antibacterianos/química , Nanomedicina , Antineoplásicos/química , Antineoplásicos/farmacología , Sistemas de Liberación de Medicamentos
14.
Curr Opin Chem Biol ; 81: 102499, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38996568

RESUMEN

This review introduces the typical delivery process of messenger RNA (mRNA) nanomedicines and concludes that the delivery involves a at least four-step SCER cascade and that high efficiency at every step is critical to guarantee high overall therapeutic outcomes. This SCER cascade process includes selective organ-targeting delivery, cellular uptake, endosomal escape, and cytosolic mRNA release. Lipid nanoparticles (LNPs) have emerged as a state-of-the-art vehicle for in vivo mRNA delivery. The review emphasizes the importance of LNPs in achieving selective, efficient, and safe mRNA delivery. The discussion then extends to the technical and clinical considerations of LNPs, detailing the roles of individual components in the SCER cascade process, especially ionizable lipids and helper phospholipids. The review aims to provide an updated overview of LNP-based mRNA delivery, outlining recent innovations and addressing challenges while exploring future developments for clinical translation over the next decade.


Asunto(s)
Lípidos , Nanopartículas , ARN Mensajero , Humanos , Nanopartículas/química , ARN Mensajero/genética , ARN Mensajero/administración & dosificación , ARN Mensajero/metabolismo , Lípidos/química , Animales , Técnicas de Transferencia de Gen , Liposomas
15.
Artículo en Inglés | MEDLINE | ID: mdl-38973539

RESUMEN

BACKGROUND AND AIMS: Observational studies have shown bidirectional associations between psychological disorders (e.g. depression and anxiety) and functional gastrointestinal disorders. However, whether the relationships are causal is uncertain. Here, we used a bidirectional two-sample Mendelian randomization method to investigate the association between psychological disorders and functional gastrointestinal disorders (FGIDs). METHODS: We obtained genome-wide association study summary statistics for two common psychological disorders: depression (170 756 cases) and anxiety (31 977 cases), as well as for three common FGIDs: functional dyspepsia with 6666 cases, constipation with 26 919 cases, and irritable bowel syndrome (IBS) with 7053 cases. These summary statistics were retrieved from several publicly available genome-wide association study databases. The inverse variance weighted method was used as the main Mendelian randomization method. RESULTS: Inverse variance weighted Mendelian randomization analyses showed statistically significant associations between genetically predicted depression and risk of functional dyspepsia [odds ratio (OR): 1.40, 95% confidence interval (CI): 1.08-1.82], constipation (OR: 1.28, 95% CI: 1.13-1.44), and IBS (OR: 1.51, 95% CI: 1.37-1.67). Genetically predicted anxiety was associated with a higher risk of IBS (OR: 1.13, 95% CI: 1.10-1.17) instead of functional dyspepsia and constipation. In addition, genetically predicted IBS instead of functional dyspepsia and constipation was associated with a higher risk of depression (OR: 1.33, 95% CI: 1.12-1.57) and anxiety (OR: 2.05, 95% CI: 1.05-4.03). CONCLUSION: Depression is a causal risk factor for three common FGIDs. A bidirectional causal relationship between IBS and anxiety or depression was also identified.

16.
Langmuir ; 40(32): 16670-16689, 2024 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-38913990

RESUMEN

Waste polystyrene contributes considerably to environmental pollution due to its persistent nature, prompting a widespread consensus on the urgent need for viable recycling solutions. Owing to the aromatic groups structure of polystyrene, hyper-cross-linked polymers can be synthesized through the Friedel-Crafts cross-linking reaction using Lewis acids as catalysts. In addition, hyper-cross-linked polystyrene and its carbonaceous counterparts can be used in several important applications, which helps in their efficient recycling. This review systematically explores methods for preparing multifunctional hyper-cross-linked polymers from waste polystyrene and their applications in sustainable recycling. We have comprehensively outlined various synthetic approaches for these polymers and investigated their physical and chemical properties. These multifunctional polymers not only exhibit structural flexibility but also demonstrate diversity in performance, making them suitable for various applications. Through a systematic examination of synthetic methods, we showcase the cutting-edge positions of these materials in the field of hyper-cross-linked polymers. Additionally, we provide in-depth insights into the potential applications of these hyper-cross-linked polymers in intentional recycling, highlighting their important contributions to environmental protection and sustainable development. This research provides valuable references to the fields of sustainable materials science and waste management, encouraging further exploration of innovative approaches for the utilization of discarded polystyrene.

17.
Adv Mater ; 36(35): e2405682, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38877752

RESUMEN

Assembling ultrathin nanosheets into layered structure represents one promising way to fabricate high-performance nanocomposites. However, how to minimize the internal defects of the layered assemblies to fully exploit the intrinsic mechanical superiority of nanosheets remains challenging. Here, a dual-scale spatially confined strategy for the co-assembly of ultrathin nanosheets with different aspect ratios into a near-perfect layered structure is developed. Large-aspect-ratio (LAR) nanosheets are aligned due to the microscale confined space of a flat microfluidic channel, small-aspect-ratio (SAR) nanosheets are aligned due to the nanoscale confined space between adjacent LAR nanosheets. During this co-assembly process, SAR nanosheets can flatten LAR nanosheets, thus reducing wrinkles and pores of the assemblies. Benefiting from the precise alignment (orientation degree of 90.74%) of different-sized nanosheets, efficient stress transfer between nanosheets and interlayer matrix is achieved, resulting in layered nanocomposites with multiscale mechanical enhancement and superior fatigue durability (100 000 bending cycles). The proposed co-assembly strategy can be used to orderly integrate high-quality nanosheets with different sizes or diverse functions toward high-performance or multifunctional nanocomposites.

18.
Pest Manag Sci ; 2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-38940437

RESUMEN

BACKGROUND: Bacillus thuringiensis (Bt) is a Gram-positive bacterium that produces various insecticidal proteins used to control insect pests. Spodoptera frugiperda is a global insect pest which causes serious damage to crops, but bio-insecticides currently available to control this pest have limited activity and so new ones are always being sought. In this study we have tested the hypothesis that a biomarker for strain toxicity could be found that would greatly facilitate the identification of new potential products. RESULTS: Using genomic sequencing data we constructed a linkage network of insecticidal genes from 1957 Bt genomes and found that four gene families, namely cry1A, cry1I, cry2A and vip3A, showed strong linkage. For 95 strains isolated from soil samples we assayed them for toxicity towards S. frugiperda and for the presence of the above gene families. All of the strains that showed high toxicity also contained a member of the vip3A gene family. Two of them were more toxic than a commercially available strain and genomic sequencing identified a number of potentially novel toxin-encoding genes. CONCLUSIONS: The presence of a vip3A gene in the genome of a Bt strain proved to be a strong indicator of toxicity towards S. frugiperda validating this biomarker approach as a strategy for future discovery programs. © 2024 Society of Chemical Industry.

19.
Front Public Health ; 12: 1357715, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38903571

RESUMEN

Introduction: To enhance the precision of evaluating the impact of urban environments on resident health, this study introduces a novel fuzzy intelligent computing model designed to address health risk concerns using multi-media environmental monitoring data. Methods: Three cities were selected for the study: Beijing (B City), Kunming (K City), and Wuxi (W City), representing high, low, and moderate pollution levels, respectively. The study employs a Fuzzy Inference System (FIS) as the chosen fuzzy intelligent computing model, synthesizing multi-media environmental monitoring data for the purpose of urban health risk assessment. Results: (1) The model reliably estimates health risks across diverse cities and environmental conditions. (2) There is a positive correlation between PM2.5 concentrations and health risks, though the impact of noise levels varies by city. In cities B, K, and W, the respective correlation coefficients are 0.65, 0.55, and 0.7. (3) The Root Mean Square Error (RMSE) values for cities B, K, and W, are 0.0132, 0.0125, and 0.0118, respectively, indicating that the model has high accuracy. The R2 values for the three cities are 0.8963, 0.9127, and 0.9254, respectively, demonstrating the model's high explanatory power. The residual values for the three cities are 0.0087, 0.0075, and 0.0069, respectively, indicating small residuals and demonstrating robustness and adaptability. (4) The model's p-values for the Indoor Air Quality Index (IAQI), Thermal Comfort Index (TCI), and Noise Pollution Index (NPI) all satisfy p < 0.05 for the three cities, affirming the model's credibility in estimating health risks under varied urban environments. Discussion: These results showcase the model's ability to adapt to diverse geographical conditions and aid in the accurate assessment of existing risks in urban settings. This study significantly advances environmental health risk assessment by integrating multidimensional data, enhancing the formulation of comprehensive environmental protection and health management strategies, and providing scientific support for sustainable urban planning.


Asunto(s)
Ciudades , Monitoreo del Ambiente , Lógica Difusa , Humanos , Medición de Riesgo/métodos , Monitoreo del Ambiente/métodos , China , Material Particulado/análisis , Contaminación del Aire/análisis , Modelos Teóricos
20.
Clin Interv Aging ; 19: 1029-1039, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38863479

RESUMEN

Background: The respiratory rehabilitation technique is a crucial component of early cardiac recovery in geriatric patients with acute myocardial infarction (AMI). This study primarily investigated the effectiveness of a novel respiratory rehabilitation technique, metronomic breathing (MB), on geriatric patients after percutaneous coronary intervention for AMI and compliance with home-based rehabilitation compared to traditional respiratory rehabilitation. Methods: From June 2022 to March 2023, 75 acute myocardial infarction (AMI) patients admitted to the Shanghai Tenth People's Hospital Cardiovascular Department were consecutively enrolled. Ultimately, 46 patients completed the follow-up in this study-26 in the MB group and 20 in the control group-who underwent the novel MB technique and conventional abdominal breathing training. The primary endpoint of the study was left ventricular function measured by noninvasive hemodynamics three months after discharge. The secondary endpoints were compliance and quality of life after three months of home rehabilitation. Results: After the intervention, several cardiac functional parameters (SV, SVI, CO, CI, LCW, and LCWI), myocardial contractility parameters (VI), and systemic vascular resistance parameters (SVR and SVRI) were significantly greater in the MB group than in the preintervention group (P < 0.05). Furthermore, post-treatment, the MB group exhibited greater SV, SVI, CO, CI, and VI; lower SVR, SVRI, and SBP; and a lower readmission rate three months later than did the control group. The SF-36 scores after three months of MB intervention, PE, BP, GH, VT, SF, RE, and MH, were all significantly greater than those before treatment (P < 0.05). Moreover, the MB group displayed greater compliance with home-based cardiac rehabilitation (P < 0.05). Conclusion: Compared to conventional respiratory rehabilitation training methods, short-term metronomic respiratory therapy is more effective for reducing systemic vascular resistance, enhancing left ventricular ejection function, enhancing quality of life, and increasing home-based rehabilitation compliance in geriatric patients following AMI with PCI.


Asunto(s)
Infarto del Miocardio , Intervención Coronaria Percutánea , Calidad de Vida , Humanos , Masculino , Femenino , Proyectos Piloto , Anciano , Infarto del Miocardio/rehabilitación , Función Ventricular Izquierda , Ejercicios Respiratorios/métodos , Persona de Mediana Edad , China , Rehabilitación Cardiaca/métodos , Resultado del Tratamiento , Anciano de 80 o más Años , Hemodinámica , Cooperación del Paciente
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