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1.
Carbohydr Polym ; 346: 122638, 2024 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-39245503

RESUMEN

Applying conductive hydrogels in electronic skin, health monitoring, and wearable devices has aroused great research interest. Yet, it remains a significant challenge to prepare conductive hydrogels simultaneously with superior mechanical, self-recovery, and conductivity performance. Herein, a dual ionically cross-linked double network (DN) hydrogel is fabricated based on K+ and Fe3+ ion cross-linked κ-carrageenan (κ-CG) and Fe3+ ion cross-linked poly(sodium acrylate-co-acrylamide) P(AANa-co-AM). Benefiting from the abundance of hydrogen bonds and metal coordination bonds, the conductive hydrogel has excellent mechanical properties (fracture strain up to 1420 %, fracture stress up to 2.30 MPa, and toughness up to 20.63 MJ/m3) and good self-recovery performance (the recovery rate of the toughness can reach 85 % after waiting for 1 h). Meanwhile, due to the introduction of dual metal ions of K+ and Fe3+, the ionic conductivity of conductive hydrogel is up to 1.42 S/m. Furthermore, the hydrogel strain sensor has good sensitivity with a gauge factor (GF) of 2.41 (0-100 %). It can be a wearable sensor that monitors different human motions, such as sit-ups. This work offers a new synergistic strategy for designing a hydrogel strain sensor with high mechanical, self-recovery, and conductive properties.

2.
Angew Chem Int Ed Engl ; : e202411044, 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-39235423

RESUMEN

The strategy of isomerization is known for its simple yet effective role in optimizing molecular configuration and enhancing the power conversion efficiency (PCE) of organic solar cells (OSCs). However, the impact of isomerization on the design of dimer acceptors has been rarely investigated, and the relationship between the chemical structure and optoelectronic property remains unclear. In this study, we designed and synthesized two dimer acceptor isomers named D-TPh and D-TN, which differ in the positional arrangement of their end capping groups. Compared to D-TN, D-TPh exhibited enhanced backbone planarity, elevated lowest unoccupied molecular orbital energy level, and more ordered molecular stacking. Consequently, the OSC device based on PM6:D-TPh achieved a PCE of 19.05%, higher than that (PCE = 18.42%) of the device based on PM6:D-TN. Large-area PM6:D-TPh devices (1 cm²) yielded a PCE of 18.0%. More importantly, the extrapolated T80 lifetime of the PM6:D-TPh device is over 2800 h with MPP tracking under continuous one-sun illumination. These results suggest that isomerization strategy is an effective way to optimize the molecular configuration of dimer acceptors for the fabrication of high-efficiency and stable OSCs.

3.
Circ Res ; 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39224974

RESUMEN

BACKGROUND: Chronic inflammation initiated by inflammatory monocytes underlies the pathogenesis of atherosclerosis. However, approaches that can effectively resolve chronic low-grade inflammation targeting monocytes are not readily available. The small chemical compound 4-phenylbutyric acid (4-PBA) exhibits broad anti-inflammatory effects in reducing atherosclerosis. Selective delivery of 4-PBA reprogrammed monocytes may hold novel potential in providing targeted and precision therapeutics for the treatment of atherosclerosis. METHODS: Systems analyses integrating single-cell RNA sequencing and complementary immunologic approaches characterized key resolving characteristics as well as defining markers of reprogrammed monocytes trained by 4-PBA. Molecular mechanisms responsible for monocyte reprogramming were assessed by integrated biochemical and genetic approaches. The intercellular propagation of homeostasis resolution was evaluated by coculture assays with donor monocytes trained by 4-PBA and recipient naive monocytes. The in vivo effects of monocyte resolution and atherosclerosis prevention by 4-PBA were assessed with the high-fat diet-fed ApoE-/- mouse model with IP 4-PBA administration. Furthermore, the selective efficacy of 4-PBA-trained monocytes was examined by IV transfusion of ex vivo trained monocytes by 4-PBA into recipient high-fat diet-fed ApoE-/- mice. RESULTS: In this study, we found that monocytes can be potently reprogrammed by 4-PBA into an immune-resolving state characterized by reduced adhesion and enhanced expression of anti-inflammatory mediator CD24. Mechanistically, 4-PBA reduced the expression of ICAM-1 (intercellular adhesion molecule 1) via reducing peroxisome stress and attenuating SYK (spleen tyrosine kinase)-mTOR (mammalian target of rapamycin) signaling. Concurrently, 4-PBA enhanced the expression of resolving mediator CD24 through promoting PPARγ (peroxisome proliferator-activated receptor γ) neddylation mediated by TOLLIP (toll-interacting protein). 4-PBA-trained monocytes can effectively propagate anti-inflammation activity to neighboring monocytes through CD24. Our data further demonstrated that 4-PBA-trained monocytes effectively reduce atherosclerosis pathogenesis when administered in vivo. CONCLUSIONS: Our study describes a robust and effective approach to generate resolving monocytes, characterizes novel mechanisms for targeted monocyte reprogramming, and offers a precision therapeutics for atherosclerosis based on delivering reprogrammed resolving monocytes.

4.
BMC Pediatr ; 24(1): 587, 2024 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-39285316

RESUMEN

BACKGROUND: Congenital cytomegalovirus (cCMV) infection can lead to a range of adverse outcomes. The majority of cCMV neonates with clinical symptoms are infected postnatally; however, established cases of intrauterine infection are uncommon, resulting in a paucity of reports on clinical findings and lymphocytes expression in CMV-infected neonates. CASE PRESENTATION: We followed a neonate with cCMV infection from the onset of hospitalization to several months of follow-up. This infant was intrauterine CMV-positive in the amniotic fluid of the mother at 21 weeks' gestation and received intravenous ganciclovir infusion and sequential oral valganciclovir after birth. The typical clinical signs manifested in the nervous system, liver, and peripheral blood and were documented during the hospitalizaion period and up to the follow-up visit. Flow cytometry was employed to examine the expression of T cells, their subsets, and the associated cytokines in peripheral blood samples at various time points. The flow data for the cCMV neonate were compared with those of the controls at each time point. Following treatment, clinical symptoms improved and the infant became CMV negative. However, developmental delays occurred later in life. The proportion of CD8+CD28- Tregs in the peripheral blood of the neonate with congenital CMV infection was higher than that in the controls at the three time points. The expression levels of perforin and granzyme B secreted by γδ T cells (Vδ1 and Vδ2 T cells), increased during the course of hospitalization until follow-up and were higher than those in the controls at the three time points. CONCLUSIONS: Despite the alleviation of clinical symptoms, developmental delay in later life remains inevitable in this intrauterine cCMV neonate. CD8+CD28- Tregs and Vδ1 and Vδ2 T cells secreting perforin and granzyme B may be involved in congenital CMV infection, although this hypothesis requires validation in a larger study. This report may contribute to our understanding of the effect of current treatment and the immune status of intrauterine cCMV-infected neonates.


Asunto(s)
Infecciones por Citomegalovirus , Linfocitos T Reguladores , Humanos , Infecciones por Citomegalovirus/inmunología , Infecciones por Citomegalovirus/diagnóstico , Infecciones por Citomegalovirus/tratamiento farmacológico , Recién Nacido , Femenino , Linfocitos T Reguladores/inmunología , Embarazo , Linfocitos T CD8-positivos/inmunología , Antígenos CD28 , Complicaciones Infecciosas del Embarazo , Perforina/metabolismo , Antivirales/uso terapéutico , Masculino , Ganciclovir/uso terapéutico , Granzimas/metabolismo
5.
Clin Toxicol (Phila) ; : 1-7, 2024 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-39222074

RESUMEN

BACKGROUND: Since 2016, diquat has replaced paraquat in China, resulting in increased diquat poisoning cases. However, understanding of diquat poisoning is still limited. This study aimed to investigate the relationship between initial diquat plasma concentration, severity index, and in-hospital mortality in acute diquat poisoning cases. METHODS: This retrospective cohort study, conducted from January 2016 to July 2023 in a tertiary care hospital, used univariate logistic regression to examine the link between the initial diquat plasma concentration, severity index, and in-hospital mortality in acute diquat poisoned patients. A receiver operating characteristic curve assessed the predictive value of these parameters for prognosis. RESULTS: Among the 87 participants, the median age was 32 years, 35 (40.2%) were female. The overall mortality rate was 37.9%. Logistic regression analysis revealed that the initial diquat plasma concentration and severity index were associated with increased in-hospital mortality. These factors also effectively predicted the prognosis of acute diquat poisoning, with an area under the receiver operating characteristic curve of 0.851 and an optimal diquat concentration threshold of 2.25 mg/L (sensitivity 90.9%, specificity 74.1%, P < 0.05) and an area under the receiver operating characteristic curve of 0.845 with an optimal cut-off value for the sevity index of 9.1 mg/L*min (sensitivity 97%, specificity 74.1%, P < 0.05). DISCUSSION: Our results are limited by the retrospective design of this study. However, if validated, these results could impact management strategies, especially in East Asia. Further research is needed due to potential confounding factors. CONCLUSIONS: The findings suggest that a higher initial plasma concentration and severity index in patients with acute diquat poisoning were correlated with higher in-hospital mortality. Prospective validation will confirm the predicative value of these findings.

6.
J Hazard Mater ; 478: 135542, 2024 Oct 05.
Artículo en Inglés | MEDLINE | ID: mdl-39154481

RESUMEN

Epidemiological studies have shown that coke oven emissions (COEs) affect the deterioration of asthma, but has not been proven by experimental results. In this study, we found for the first time that COEs exacerbate allergen house dust mite (HDM)-induced allergic asthma in the mouse model. The findings reveal that airway inflammation, airway remodeling and allergic reaction were aggravated in the COE + HDM combined exposure group compared with the individual exposure group. Mechanism studies indicated higher levels of iron and MDA in the COE + HDM combined exposure group, along with increased expression of Ptgs2 and reduced GPX4 expression. Iron chelator deferoxamine (DFO) effectively inhibited ferroptosis induced by COE synergistically with HDM in vitro. Further studies highlighted the role of ferritinophagy in the COE + HDM-induced ferroptosis. 3-methyladenine (3-MA) could inhibit ferroptosis in the COE + HDM exposure group. Interestingly, we injected DFO intraperitoneally into mice in the combined exposure group and found DFO could significantly inhibit the COE-exacerbated ferroptosis and allergic asthma. Our findings link ferroptosis with COE-exacerbated allergic asthma, implying that ferroptosis may have important therapeutic potential for asthma in patients with occupational exposure of COE.


Asunto(s)
Asma , Células Epiteliales , Ferroptosis , Ratones Endogámicos BALB C , Animales , Ferroptosis/efectos de los fármacos , Asma/inducido químicamente , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Pyroglyphidae/inmunología , Ratones , Deferoxamina/farmacología , Femenino , Contaminantes Atmosféricos/toxicidad , Hierro/metabolismo , Ciclooxigenasa 2/metabolismo
7.
ACS Appl Mater Interfaces ; 16(33): 43114-43133, 2024 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-39110026

RESUMEN

Solid-state electrolytes (SSEs), as the heart of all-solid-state batteries (ASSBs), are recognized as the next-generation energy storage solution, offering high safety, extended cycle life, and superior energy density. SSEs play a pivotal role in ion transport and electron separation. Nonetheless, interface compatibility and stability issues pose significant obstacles to further enhancing ASSB performance. Extensive research has demonstrated that interface control methods can effectively elevate ASSB performance. This review delves into the advancements and recent progress of SSEs in interfacial engineering over the past years. We discuss the detailed effects of various regulation strategies and directions on performance, encompassing enhancing Li+ mobility, reducing energy barriers, immobilizing anions, introducing interlayers, and constructing unique structures. This review offers fresh perspectives on the development of high-performance lithium-metal ASSBs.

8.
Artículo en Inglés | MEDLINE | ID: mdl-39099209

RESUMEN

Immunoprevention is an emerging consideration for solid tumors, including pancreatic ductal adenocarcinoma (PDAC). We and others have shown that Kras mutations in genetic models of spontaneous pancreatic intraepithelial neoplasia (PanIN), which is a precursor to PDAC, results in CD73 expression in the neoplastic epithelium and some populations of infiltrating immune cells, including macrophages and CD8 T cells. CD73 is an ecto-enzyme that converts extracellular adenosine monophosphate (AMP) to adenosine, a critical immune inhibitory molecule in PDAC. We hypothesized inhibition of CD73 would reduce the incidence of PanIN formation and alter the immune microenvironment. To test our hypothesis, we used the KrasG12D; PdxCre1 (KC) genetically engineered mouse (GEM) model and tested the utility of AB-680, a small molecule inhibitor targeting CD73, to inhibit PanIN progression. AB-680, or vehicle control, was administered using oral gavage delivery three days/week at 10mg/kg, beginning when the mice were two months old and lasting three months. We euthanized the mice at five months old. In the KC model, we quantified significantly less pancreatitis, early and advanced PanIN, and quantified a significant increase in M1 macrophages in AB-680-treated mice. Single Cell RNA sequencing (scRNA-seq) of pancreata of AB-680 treated mice revealed increased infiltration of CD4+ T cells, CD8+ T cells, and mature B cells. The scRNA-seq analysis showed that CD73 inhibition reduced M2 macrophages, acinar, and PanIN cell populations. CD73 inhibition enhanced immune surveillance and expanded unique clonotypes of TCR and BCR, indicating that inhibition of CD73 augments adaptive immunity early in the neoplastic microenvironment.

9.
Lung Cancer ; 195: 107933, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39191079

RESUMEN

OBJECTIVES: Non-small cell lung cancer (NSCLC) patients with exon 20 insertion mutations (ex20ins) of the epidermal growth factor receptor (EGFR) were resistant to monotherapy of immune checkpoint inhibitor (ICI). However, recent reports have shown that the combination of ICI and chemotherapy (ICI-combined regimen) exhibited certain efficacy for NSCLC with EGFR ex20ins. The mechanisms behind this phenomenon have not been thoroughly clarified. Hence, we conducted this study tofind correlations between the tumor immune microenvironment of EGFR ex20ins and the efficacy of ICI-combined regimen. METHODS: We performed single-cell transcriptome sequencing and multiplex immunofluorescence staining (mIF) to investigate the immune microenvironment of NSCLC patients with EGFR ex20ins, L858R, and EGFR wild-type. We analyzed 15 treatment-naïve NSCLC samples utilizing single-cell RNA sequencing (scRNA-seq). Another 30 cases of EGFR L858R and 4 cases of wild-type were recruited to compare the immune microenvironment with that of EGFR ex20ins (28 cases) by mIF. RESULTS: We observed that cell components, function and interactions varied between EGFR ex20ins, L858R, and wild-type NSCLC.We discovered similar T cell and CD8+ T cell distributions among groups but found noninferior or even better T cell activation in ex20ins patients. Infiltrating CD8+ FOXP3- T cells were significantly lower in the tumor region of EGFR ex20ins compared to wild-type. T cells from the ex20ins group had a greater tendency to promote cancer cell inflammation and epithelial-mesenchymal transition (EMT) compared to wild-type group. For macrophages, there were more M2-like macrophages in ex20ins patients. M1-like macrophages in ex20ins group produced fewer antitumor cytokines than in other groups. CONCLUSIONS: The immune microenvironment of EGFR ex20ins is more suppressive than that of L858R and wild-type, suggesting that ICI monotherapy may not be sufficient for these patients. ICI-combined regimen might be a treatment option for EGFR ex20ins due to tumor-promoting inflammation and noninferior T cell functions in the immune microenvironment.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Receptores ErbB , Exones , Inhibidores de Puntos de Control Inmunológico , Neoplasias Pulmonares , Microambiente Tumoral , Humanos , Microambiente Tumoral/inmunología , Microambiente Tumoral/genética , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/inmunología , Receptores ErbB/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/inmunología , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Exones/genética , Masculino , Femenino , Persona de Mediana Edad , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Mutagénesis Insercional , Pronóstico
10.
Sci Total Environ ; 951: 175702, 2024 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-39179040

RESUMEN

Costal eutrophication leads to increased sulfide levels in sediments, which has been identified as a major cause of the global decline in seagrass beds. The seagrass Thalassia hemprichii, a dominant tropical species in the Indo-Pacific, is facing a potential threat from sulfide, which can be easily reduced from sulfate in porewater under the influence of global climate change and eutrophication. However, its metabolic response and tolerance mechanisms to high sulfide remain unclear. Thus, the current study investigated the physiological responses and programmed metabolic networks of T. hemprichii through a three-week mesocosm experiment, integrating physiology, stable isotope, widely targeted metabolomics, transcriptomics, and microbial diversity assessments. High sulfide reduced the sediment microbial diversity, while increased sediment sulfate reduced bacterial abundance and δ34S. The exposure to sulfide enhanced root δ34S while decreased leaf δ34S in T. hemprichii. High sulfide was shown to inhibit photosynthesis via damaging PSII, which further reduced ATP production. In response, abundant up-regulated differentially expressed genes in energy metabolism, especially in oxidative phosphorylation, were activated to compensate high energy requirement. High sulfide also promoted autophagy by overexpressing the genes related to phagocytosis and phagolysosome. Meanwhile, metabolomic profiling revealed that the contents of many primary metabolites, such as carbohydrates and amino acids, were reduced in both leaves and roots, likely to provide more energy and synthesize stress-responsive secondary metabolites. Genes related to nitrate reduction and transportation were up-regulated to promote N uptake for sulfide detoxification. High sulfide levels specifically enhanced thiamine in roots, while increased jasmonic acid and flavonoid levels in leaves. The distinct differences in metabolism between roots and leaves might be related to sulfide levels and the growth-defense trade-off. Collectively, our work highlights the specific mechanisms underlying the response and tolerance of T. hemprichii to high sulfide, providing new insights into seagrass strategies for resisting sulfide.


Asunto(s)
Hydrocharitaceae , Redes y Vías Metabólicas , Metaboloma , Sulfuros , Transcriptoma , Hydrocharitaceae/metabolismo , Hydrocharitaceae/genética , Contaminantes Químicos del Agua , Eutrofización
11.
ACS Appl Mater Interfaces ; 16(36): 47486-47503, 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39186486

RESUMEN

This study investigates the impact of intrinsic strain and phase transitions on the thermodynamic stability and electronic properties of Cu1-xAxAlO2 solid solutions, which are key to their photocatalytic performance. It is demonstrated that Cu1-xAxAlO2 with A = Ag, Au, Pt can form continuous isostructural solid solutions due to relatively small compressive strain, while a substantial increase strain restricts Cu1-xPdxAlO2 to forming only limited solutions. For A = Li, Na, the formation of heterostructural solid solutions is facilitated by structural motif alterations, accommodating significant differences in ionic radii and A-O bond characteristics. Specifically, Cu1-xLixAlO2 exhibits a phase transition at x ≈ 0.333, whereas Cu1-xNaxAlO2 undergoes three distinct phase transitions. Electronic structure analysis indicates that in Cu1-xAxAlO2 (A = Ag, Au), d10-d10 closed-shell interactions dominate, enabling tunable band gaps with varying solubility. Nevertheless, increased intrinsic strain in metal sublattices, as seen in A = Pd and Pt, shifts antibonding states to the Fermi level, inducing a semiconductor-to-metal transition. Experimental evidence confirms that Ag+ ions modulate the band gaps and carrier dynamics in Cu1-xAgxAlO2, with Cu0.75Ag0.25AlO2 exhibiting heightened photoelectrochemical activity and a 38.5-fold enhancement in H2 production rate over CuAlO2. Additionally, the coordination environment changes between alkali metals and O, induced by phase transitions, effectively tune the band edge positions and carrier dynamics of Cu1-xAxAlO2 (A = Li, Na) heterostructural solid solutions. Therefore, 3R-Cu0.97Li0.03AlO2 with asymmetric nonlinear dumbbell O-Cu-O demonstrates the highest photocatalytic H2 production activity, 72.9 times greater than CuAlO2. In contrast, α-Cu1-xAxAlO2 with a smaller CuO6 octahedral splitting energy exhibits increased band gaps, resulting in diminished photocatalytic activity. This research underscores that strain-driven phase transition provides an additional control factor and new mechanism for regulating the photo(electro)catalytic activity of Cu1-xAxAlO2 solid solutions.

12.
Adv Sci (Weinh) ; : e2406370, 2024 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-39136133

RESUMEN

Immune dysfunction in early pregnancy including overactivation of cytotoxic CD16+ NK cells and proinflammatory M1 macrophages at the maternal-fetal interface interferes with trophoblast invasion, spiral artery remodeling, and decidualization, potentially leading to miscarriage. Immunosuppressants like glucocorticoids (GCs) are used to regulate the immune microenvironment in clinical treatment, but the lack of safe and efficient tissue-specific drug delivery systems, especially immune cell-specific vectors, limits their widespread clinical application. Here, a previously uncharacterized delivery system is reported, termed GC-Exo-CD16Ab, in which GCs are loaded into purified exosomes derived from human umbilical cord mesenchymal stem cells, and subsequently decorated with antibody CD16Ab. GC-Exo-CD16Ab is biocompatible and has remarkable delivery efficiency toward CD16+ decidual natural killer (NK) cells and CD16+ macrophages in mice. This innovative approach effectively suppresses the cytotoxicity of decidual NK cells, inhibits M1 macrophage polarization, and regulates the decidual microenvironment, thereby enhancing placental and fetal morphology, and ultimately mitigating miscarriage risk in the abortion-prone mice. The developed GC-Exo-CD16Ab provides a feasible platform for precise and tissue-specific therapeutic strategies for miscarriage and pregnancy-related diseases.

13.
Sci Adv ; 10(35): eado1432, 2024 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-39196923

RESUMEN

The histone acylation reader eleven-nineteen leukemia (ENL) plays a pivotal role in sustaining oncogenesis in acute leukemias, particularly in mixed-lineage leukemia-rearranged (MLL-r) leukemia. ENL relies on its reader domain to recognize histone lysine acylation promoting oncogenic gene expression and leukemia progression. Here, we report the development of MS41, a highly potent and selective von Hippel-Lindau-recruiting ENL degrader that effectively inhibits the growth of ENL-dependent leukemia cells. MS41-induced ENL degradation reduces the chromatin occupancy of ENL-associated transcription elongation machinery, resulting in the suppression of key oncogenic gene expression programs and the activation of differentiation genes. MS41 is well-tolerated in vivo and substantially suppresses leukemia progression in a xenograft mouse model of MLL-r leukemia. Notably, MS41 also induces the degradation of mutant ENL proteins identified in Wilms' tumors. Our findings emphasize the therapeutic potential of pharmacological ENL degradation for treating ENL-dependent cancers, making MS41 not only a valuable chemical probe but also potential anticancer therapeutic for further development.


Asunto(s)
Progresión de la Enfermedad , Leucemia , Humanos , Animales , Ratones , Línea Celular Tumoral , Leucemia/genética , Leucemia/patología , Leucemia/tratamiento farmacológico , Leucemia/metabolismo , Factores de Elongación Transcripcional/metabolismo , Factores de Elongación Transcripcional/genética , Ensayos Antitumor por Modelo de Xenoinjerto , Regulación Leucémica de la Expresión Génica/efectos de los fármacos , Proteolisis/efectos de los fármacos , Proteína Supresora de Tumores del Síndrome de Von Hippel-Lindau/genética , Proteína Supresora de Tumores del Síndrome de Von Hippel-Lindau/metabolismo , Proliferación Celular/efectos de los fármacos
14.
J Environ Qual ; 53(5): 604-617, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39104163

RESUMEN

High-precision evaluations of water environment quality are highly important for improving the accuracy of early warning systems of regional water pollution risk and improving the regional water environment. This paper employs the chimp optimization algorithm (ChOA) to enhance the traditional random forest model, resulting in the chimp optimization algorithm-random forest (ChOA-RF) water quality assessment model for evaluating the Jiansanjiang area in Heilongjiang Province, China. The results show that the overall water environment in Jiansanjiang has the following characteristics: "The water quality of farms in the northwest is poor, and the quality of groundwater is better than that of surface water." Total nitrogen (TN) and total phosphorus (TP) in surface water and ammonium nitrogen (NH3-N), ferrum (Fe), and manganese (Mn) in groundwater are the main pollutants. The TP and TN in surface water and the NH3-N in groundwater exceeded the relevant standards, likely due to the excessive application of chemical fertilizers, especially nitrogen fertilizers. Additionally, Fe and Mn are harmful native substances. According to these findings, targeted improvement strategies, such as reducing nitrogen fertilizer application, plugging well, and increasing the surface water utilization rate, are proposed. Moreover, the ChOA-RF model is compared with the traditional empirical value model and the particle swarm optimization-random forest (PSO-RF) model. The results show that the ChOA-RF model can effectively reduce the root mean square error and mean absolute percentage error and improve the coefficient of determination. The running time and convergence ability are also better than those of the PSO-RF model, which is a more accurate and efficient machine learning model. The model can be used not only for high-precision evaluation of regional water environment quality but also for other machine learning fields.


Asunto(s)
Algoritmos , Monitoreo del Ambiente , Monitoreo del Ambiente/métodos , China , Agua Subterránea/análisis , Agua Subterránea/química , Hidrología , Calidad del Agua , Nitrógeno/análisis , Fósforo/análisis , Modelos Teóricos , Contaminantes Químicos del Agua/análisis , Bosques Aleatorios
15.
Res Sq ; 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39149497

RESUMEN

Sporadic early-onset Alzheimer's disease (sEOAD) represents a significant but less-studied subtype of Alzheimer's disease (AD). Here, we generated a single-nucleus multiome atlas derived from the postmortem prefrontal cortex, entorhinal cortex, and hippocampus of nine individuals with or without sEOAD. Comprehensive analyses were conducted to delineate cell type-specific transcriptomic changes and linked candidate cis-regulatory elements (cCREs) across brain regions. We prioritized seven conservative transcription factors in glial cells in multiple brain regions, including RFX4 in astrocytes and IKZF1 in microglia, which are implicated in regulating sEOAD-associated genes. Moreover, we identified the top 25 altered intercellular signaling between glial cells and neurons, highlighting their regulatory potential on gene expression in receiver cells. We reported 38 cCREs linked to sEOAD-associated genes overlapped with late-onset AD risk loci, and sEOAD cCREs enriched in neuropsychiatric disorder risk loci. This atlas helps dissect transcriptional and chromatin dynamics in sEOAD, providing a key resource for AD research.

16.
J Adv Nurs ; 2024 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-39206870

RESUMEN

AIM: To investigate the levels of information literacy, evidence-based nursing competence and innovative behaviour in specialist nurses, determine the impact of information literacy and evidence-based nursing competence on the innovative behaviour of specialist nurses and to analyse the mediating role of evidence-based nursing competence between information literacy and innovative behaviour among specialist nurses. DESIGN: A multicenter cross-sectional design. METHODS: In March 2024, a survey was conducted on 313 specialist nurses in four tertiary Grade A comprehensive hospitals in China. Data collection involved the utilization of general demographic questionnaire, the Information Literacy Questionnaire, the Evidence-Based Nursing Competence Scale and the Nurse Innovation Behaviour Scale. The data were analysed using IBM SPSS26 and Amos28 software. RESULTS: Specialist nurses scored above average in information literacy, evidence-based nursing competence and innovative behaviour. Information literacy significantly positively correlated with innovative behaviour. Evidence-based nursing competence also positively affected innovative behaviour and partially mediated the relationship between information literacy and innovative behaviour. CONCLUSION: This research indicated that specialist nurses exhibited above-average levels of evidence-based nursing competence, information literacy and innovative behaviour. Both information literacy and evidence-based nursing competence positively impacted innovative behaviour, with evidence-based nursing competence playing a significant mediating role between information literacy and innovative behaviour. IMPACT: The findings suggest that nursing managers should focus on enhancing information literacy and evidence-based nursing competence in specialist nurses. Improving these abilities will support the implementation of innovative practices and advance the nursing field. REPORTING METHOD: The research findings were presented in strict accordance with the STROBE statement. PATIENT OR PUBLIC CONTRIBUTION: Not applicable. CONTRIBUTE TO THE WIDER GLOBAL CLINICAL COMMUNITY: It provides reference guidance and theoretical basis for global nursing managers to formulate targeted interventions, so as to effectively enhance the innovative behaviour of specialist nurses.

17.
Hum Vaccin Immunother ; 20(1): 2388347, 2024 Dec 31.
Artículo en Inglés | MEDLINE | ID: mdl-39140222

RESUMEN

Cervical cancer remains a significant health burden in China, characterized by high incidence and mortality rates, which are exacerbated by low Human Papillomavirus (HPV) vaccination coverage, leading to substantial loss of productivity, emotional suffering, and family strain. Understanding factors that influence HPV awareness and knowledge is crucial for developing effective educational strategies. This cross-sectional study, conducted from September to October 2022, involved 2,679 college students from various educational institutions in Jiangsu Province, China. Data were collected via an online questionnaire covering demographics, HPV knowledge, and vaccination behaviors. Statistical analyses, including Chi-square tests and multifactorial logistic regression, were used to identify factors influencing HPV knowledge. The study revealed that while over 90% of students correctly identified HPV's transmission and risks, significant knowledge gaps and misconceptions persist, particularly regarding HPV's association with HIV/AIDS and its treatment. Factors significantly associated with better HPV knowledge included age (22-24 years), female gender, being a medical major, being in a relationship, familiarity with HPV, and participation in sexual education programs. Despite a high willingness to receive the HPV vaccine (91.64%), actual vaccination rates remained low. These findings suggest that while Chinese college students were generally aware of HPV, targeted educational interventions are essential to address knowledge gaps and promote HPV vaccination effectively.


Asunto(s)
Conocimientos, Actitudes y Práctica en Salud , Infecciones por Papillomavirus , Vacunas contra Papillomavirus , Estudiantes , Humanos , Femenino , Estudios Transversales , Estudiantes/psicología , Infecciones por Papillomavirus/prevención & control , Infecciones por Papillomavirus/psicología , Masculino , China/epidemiología , Adulto Joven , Vacunas contra Papillomavirus/administración & dosificación , Universidades , Encuestas y Cuestionarios , Adulto , Vacunación/psicología , Vacunación/estadística & datos numéricos , Neoplasias del Cuello Uterino/prevención & control , Neoplasias del Cuello Uterino/virología , Adolescente , Aceptación de la Atención de Salud/estadística & datos numéricos , Aceptación de la Atención de Salud/psicología , Virus del Papiloma Humano
18.
Int Immunopharmacol ; 139: 112669, 2024 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-39029231

RESUMEN

BACKGROUND: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is very common worldwide, and alcohol consumption is a notable contributing factor. Researches have shown that gut microbiota can be influenced by alcohol consumption and is an important mediator in regulating Th17 cell immunity. However, it is still unclear the exact mechanism by which alcohol exacerbates the CP/CPPS and the role of gut microbiota in this process. METHOD: We first constructed the most-commonly used animal model for CP/CPPS, the experimental autoimmune prostatitis (EAP) model, through immunoassay. Based on this, mice were divided into EAP group and alcohol-consuming EAP group. By 16S rRNA sequencing and non-targeted metabolomics analysis, differential gut microbiota and their metabolites between the two groups were identified. Subsequently, metabolomics detection targeting cholesterols was carried out to identify the exact difference in cholesterol. Furthermore, multiple methods such as flow cytometry and immunohistochemistry were used to detect the differentiation status of Th17 cells and severity of prostatitis treated with 27-hydroxycholesterol (the differential cholesterol) and its upstream regulatory factor-sterol regulatory element-binding protein 2 (SREBP2). Lastly, fecal transplantation was conducted to preliminary study on whether alcohol intake exacerbates EAP in immune receptor mice. RESULTS: Alcohol intake increased the proportion of Th17 cells and levels of related inflammatory factors. It also led to an altered gut bacterial richness and increased gut permeability. Further metabolomic analysis showed that there were significant differences in a variety of metabolites between EAP and alcohol-fed EAP mice. Metabolic pathway enrichment analysis showed that the pathways related to cholesterol synthesis and metabolism were significantly enriched, which was subsequently confirmed by detecting the expression of metabolic enzymes. By targeting cholesterol synthesis, 27-hydroxycholesterol was significantly increased in alcohol-fed EAP mice. Subsequent mechanistic research showed that supplementation with 27-hydroxycholesterol could aggravate EAP and promote Th17 cell differentiation both in vivo and in vitro, which is regulated by SREBP2. In addition, we observed that fecal transplantation from mice with alcohol intake aggravated EAP in immunized recipient mice fed a normal diet. CONCLUSION: Our study is the first to show that alcohol intake promotes Th17 cell differentiation and exacerbates EAP through microbiota-derived cholesterol biosynthesis.


Asunto(s)
Consumo de Bebidas Alcohólicas , Enfermedades Autoinmunes , Diferenciación Celular , Colesterol , Modelos Animales de Enfermedad , Microbioma Gastrointestinal , Ratones Endogámicos C57BL , Prostatitis , Células Th17 , Animales , Masculino , Células Th17/inmunología , Prostatitis/inmunología , Prostatitis/microbiología , Prostatitis/metabolismo , Prostatitis/inducido químicamente , Microbioma Gastrointestinal/efectos de los fármacos , Microbioma Gastrointestinal/inmunología , Enfermedades Autoinmunes/inmunología , Enfermedades Autoinmunes/inducido químicamente , Ratones , Diferenciación Celular/efectos de los fármacos , Consumo de Bebidas Alcohólicas/efectos adversos , Colesterol/metabolismo , Proteína 2 de Unión a Elementos Reguladores de Esteroles/metabolismo , Proteína 2 de Unión a Elementos Reguladores de Esteroles/genética
19.
Adv Mater ; 36(35): e2403890, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39007481

RESUMEN

Dimer acceptors in organic solar cells (OSCs) offer distinct advantages, including a well-defined molecular structure and excellent batch-to-batch reproducibility. Their high glass transition temperature (Tg) aids in achieving an optimal kinetic morphology, thereby enhancing device stability. Currently, most of dimer acceptor materials are linked with conjugated units in order to obtain high power conversion efficiencies (PCEs). In this study, different from previous works on conjugation-linked dimer acceptors, a novel series of dimer acceptors are synthesized (named T1, T4, T6, and T12), each linked with different flexible alkyl linkers, and investigated their PCEs, device stability, and flexibility robustness. When blended with PM6, the T6-based device achieves a PCE of 17.09%, comparable to the fully conjugated T0-based device's PCE of 17.12%. The molecular dynamics simulations and density functional theory calculations suggested that flexible conjugation-broken linkers (FCBLs) promote intermolecular electronic couplings, thereby maintaining good electron mobilities of dimer acceptors. Notably, the T6-based device exhibits impressive long-term stability with a T80 lifetime of 1427 h, while in the T0-based device, T80 is only 350 h. The present work has thus established the relationship between the length of flexible alkyl linkers in such dimer acceptors and the performance and stability of OSCs, which is important to further designing new materials for the fabrication of efficient and stable OSCs.

20.
Immun Inflamm Dis ; 12(7): e1280, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38967362

RESUMEN

BACKGROUND: Adaptive immunity is an important disease mediator of pulmonary vascular remodeling during pulmonary hypertension (PH) development, especially T-cells lymphocytes. However, data for bibliometric analysis of T cell immunity in PH is currently vacant. This aimed to provide a comprehensive and visualized view of T-cells research in PH pathogenesis and to lay a solid foundation for further studies. METHODS: The data was acquired from the Web of Science Core Collection database. Web of Science analytic tool was used to analysis the publication years, authors, journals, countries, and organizations. CiteSpace 6.2.R3, VOSviewer 1.6.16, and Scimago Graphica 1.0.35.0 were applied to conduct a visualization bibliometric analysis about authors, countries, institutions, journals, references, and keywords. RESULTS: Nine hundred and eight publications from 1992 to 2022 were included in the analysis. The results showed that Humbert Marc was the most prolific author. American Journal of Physiology Lung Cellular and Molecular Physiology had the most related articles. The institution with the most articles was Udice French Research University. The United States was far ahead in the article output. Keywords analysis showed that "Pulmonary hypertension" was the most usually appeared keyword in the relevant literature, and included "T-cells", "Regulatory T cells", and "Activated T cell." "miRNA" of reference co-citation clustering analysis demonstrated the possible T-cell immunity activation mechanisms in PH. The most cited literature was published in the European Heart Journal by Galie N in 2016. The strongest citation burst of keyword is "gene expression" and terms such as "vascular remodeling," "growth," "proliferation," and "fibrosis" are among the list, indicating that T-cells interact with stromal vascular cells to induce pulmonary vascular remodeling. The strongest burst of cited reference is "Galie N, 2016." CONCLUSIONS: T-cell immunity is an important pathogenesis mechanism for PH development, which may have interaction with miRNAs and stromal vascular cells, but the possible T-cell immunity activation mechanisms in PH need to be investigated further.


Asunto(s)
Bibliometría , Hipertensión Pulmonar , Linfocitos T , Hipertensión Pulmonar/inmunología , Humanos , Linfocitos T/inmunología , Animales
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