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1.
Biosens Bioelectron ; 267: 116798, 2024 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-39312836

RESUMEN

Hydrogen sulfide (H2S) has emerged as a crucial signaling molecule in plant stress responses, playing a significant role in regulating various physiological and biochemical processes. In this study, we report an aggregation-induced emission (AIE)-based ratiometric fluorescent probe TPN-H2S for the highly selective detection of H2S in plant tissues. The probe exhibited excellent sensitivity and selectivity towards H2S over other analytes, enabling real-time monitoring of H2S dynamics in living cell. Furthermore, the AIE-based ratiometric probe TPN-H2S allowed for accurate quantification of H2S levels, providing valuable insights into the spatiotemporal distribution of Cys metabolism produces H2S. Importantly, the physiological pathways and signaling mechanisms of H2S production of was investigated in plant tissues under Cr and nano-plastics stress. Utilizing a high-throughput screening approach, we identified exogenous substances such as calcium chloride (CaCl2) and abscisic acid (ABA) that could induce higher level of H2S production during the stress response in plants. Overall, those findings demonstrate the potential of the AIE-based ratiometric fluorescent probe TPN-H2S as a powerful tool for unraveling the role of H2S in plant stress responses and pave the way for further exploration of H2S-mediated signaling pathways in plants.

2.
Materials (Basel) ; 17(18)2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39336200

RESUMEN

Freshwater resources are scarce in coastal areas, and using seawater as mixing water can alleviate the scarcity of freshwater resources. However, the presence of chloride ions in seawater affects the generation of hydration products and the durability of concrete structures. In order to investigate the effect of hydrated calcium silicate (C-S-H) gel and calcium hydroxide (CH) generation in seawater-mixed cement pastes under 50 °C curing, their microscopic morphology was investigated using differential scanning calorimetry analysis, X-ray diffraction (XRD), and scanning electron microscopy (SEM). The relationship between the amount of C-S-H gel and CH production and the amount of chloride ion dosing, fly ash dosing, and the age of curing were investigated. The degree of influence between hydration products and influencing factors was analyzed using the grey correlation analysis. It was shown that 50 °C curing promoted the hydration reaction and generated more hydration products compared with ASTM standard. The content of C-S-H gel and CH increased with chloride dosage. The content of C-S-H gel increased by 13.5% under 50 °C curing compared with the control group at a chloride dosage of 1.3%. Fly ash is rich in active SiO2 and AI2O3, and other components, which can react with Ca(OH)2 generated by cement hydration and then generate C-S-H gel. With the increase of fly ash, the content of C-S-H gel also increases, but the CH content decreases. When 25% of fly ash was doped under 50 °C curing, the C-S-H gel content increased by 5.02% compared to the control group. The CH content decreased by 31.8% compared to the control group. With the growth of the maintenance age, the hydration reaction continues, the generation of C-S-H gel and CH will continue to increase, and their microstructures will become denser. C-S-H gel and CH content increased the most by raising the curing temperature at 7 days of curing, increasing by 10.11% and 22.62%, respectively. C-S-H gel and CH content had the highest gray relation with fly ash dosing. Chloride dosage and age of maintenance had the highest correlation with CH content at room temperature maintenance of 0.788 and 0.753, respectively.

3.
J Am Chem Soc ; 146(38): 26081-26094, 2024 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-39283331

RESUMEN

The heteroanionic materials (HAMs) have attracted more and more attention because they can better balance the functional properties of materials. However, their rational structural design is still a great challenge. Here, by using the antiperovskite Ba3S[GeS4] as a template and calculating the tolerance factor (t) as a reference, eight heteroanionic oxychalcogenides with balanced properties were finally synthesized by a partially group-substitution method. Among them, Ba3[CO3][MQ4] (M = Ge, Sn; Q = S, Se) are centrosymmetric (CS) crystals and realize optimization of band gaps and birefringence. For Ae3[TO3][SnOQ3] (Ae = Sr, Ba; T = Si, Ge; Q = S, Se), thanks to the novel [TO4SnQ3] polyanionic groups for the regulation to the antiperovskite structures and the contributions to the nonlinear optical (NLO) properties, they achieve the structural transition from CS to noncentrosymmetry and accomplish an excellent balance among the critical performance parameters as the potential candidates for the infrared NLO materials, including phase-matchable behavior, wide band gaps (Eg = 3.26-3.95 eV), high laser damage threshold (LDT = 3.2-4.4 × AgGaS2), suitable birefringence (Δn = 0.065-0.098@2090 nm) and sufficiently strong second-harmonic generation responses (about 0.6-0.9 × AgGaS2). Moreover, benefiting from crystallization in the polar space groups, they exhibit ferroelectricity and piezoelectricity at room temperature. As far as we know, this is the first reported fully inorganic antiperovskite ferroelectric. These demonstrate that our strategy is desirable and can provide some unique insights into the development of HAMs or antiperovskite materials with specific functions or structures.

4.
Materials (Basel) ; 17(16)2024 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-39203127

RESUMEN

Mixing cement with seawater will cause the hydration process of cement to be different from that of ordinary cement, which will significantly affect cement's mechanical properties and durability. This article investigates the effects of chloride ion concentration, curing temperature, and nano-metakaolin content on the evolution process of Friedel's salts and ettringite (AFt) crystals in cement pastes. The study was conducted using X-ray diffraction (XRD), thermal analysis (TG), scanning electron microscopy (SEM), and mercury-intrusion porosimetry (MIP). The results show that chlorine salt can increase the production of Friedel's salt and ettringite, and the delayed AFt production increases by up to 27.95% after the addition of chlorine salt, which has an adverse effect on cement-based materials. Increasing the curing temperature and increasing the nano-metakaolin dosage increased the generation of Friedel's salt and decreased the delayed AFt generation, which resulted in a decrease in the length and diameter of the AFt crystals. After 28 days of high-temperature curing and the addition of nano-metakaolin, Friedel's salt production increased by 13.40% and 14.34%, respectively, and ettringite production decreased by 9.68% and 7.93%, respectively. Increasing the curing temperature and adding nano-metakaolin can reduce the adverse effect of delayed ettringite increases due to chloride ion binding.

5.
Int J Biol Macromol ; 278(Pt 3): 134860, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39163956

RESUMEN

Exploring nutritional therapies that manipulate tryptophan metabolism to activate AhR signaling represents a promising approach for mitigating chronic colitis. Arabinoxylan is a bioactive constituent abundant in wheat bran. Here, we comprehensively investigated anti-colitis potentials of wheat bran arabinoxylan (WBAX), its synbiotic and postbiotic derived from WBAX and Limosilactobacillus reuteri WX-94 (i.e., a probiotic strain exhibiting tryptophan metabolic activity). WBAX fueled L. reuteri and promoted microbial conversion of tryptophan to AhR ligands during in vitro fermentation in the culture medium and in the fecal microbiota from type 2 diabetes. The WBAX postbiotic outperformed WBAX and its synbiotic in augmenting efficacy of tryptophan in restoring DSS-disturbed serum immune markers, colonic tight junction proteins and gene profiles involved in amino acid metabolism and FoxO signaling. The WBAX postbiotic remodeled gut microbiota and superiorly enhanced AhR ligands (i.e., indole metabolites and bile acids), alongside with elevation in colonic AhR and IL-22. Associations between genera and metabolites modified by the postbiotic and colitis in human were verified and strong binding capacities between metabolites and colitis-related targets were demonstrated by molecular docking. Our study advances the novel perspective of WBAX in manipulating tryptophan metabolism and anti-colitis potentials of WBAX postbiotic via promoting gut microbiota-dependent AhR signaling.


Asunto(s)
Colitis , Fibras de la Dieta , Microbioma Gastrointestinal , Limosilactobacillus reuteri , Simbióticos , Xilanos , Xilanos/farmacología , Xilanos/química , Xilanos/metabolismo , Limosilactobacillus reuteri/metabolismo , Colitis/metabolismo , Colitis/microbiología , Microbioma Gastrointestinal/efectos de los fármacos , Fibras de la Dieta/metabolismo , Humanos , Animales , Ratones , Receptores de Hidrocarburo de Aril/metabolismo , Triptófano/metabolismo , Simulación del Acoplamiento Molecular , Fermentación , Masculino , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/microbiología , Multiómica
6.
Environ Pollut ; 359: 124696, 2024 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-39122174

RESUMEN

Human hair is increasingly employed as a non-invasive biomonitoring matrix for exposure to organic contaminants (OCs). Decontamination procedures are generally needed to remove external contamination from hair prior to analysis of OCs. Despite various existing decontamination protocols, their impacts on internally incorporated (endogenous) OCs in hair remain poorly understood. This study aims to quantitatively assess the impact of decontamination procedures on endogenous OCs in hair, and investigate optimal decontamination processes and factors influencing the removal of endogenous OCs. In this study, guinea pig was exposed to 6 OCs (triphenyl phosphate (TPHP), tris(1,3-dichloro-2-propyl) phosphate (TDCPP), and tri-n-butyl phosphate (TNBP), bisphenol A (BPA), perfluorooctanoic acid (PFOA), and phenanthrene (PHE)), and 6 decontamination procedures with different solvents (methanol, n-hexane, acetone, ultrapure water, Triton X-100, and sodium dodecyl sulfate) were used to rinse exposed guinea pig hair. All OCs and three metabolites (diphenyl phosphate (DPHP), dibutyl phosphate (DBP), and bis(1,3-dichloro-2-propyl) phosphate (BDCPP)) were detected in the majority of washing solutions. The decontamination procedures apparently resulted in the release of endogenous OCs from hair. The percentages of residual OCs in hair exhibited a linear or exponential decrease with more washing cycles. Furthermore, the residuals of OCs in hair washed with organic and aqueous solvents showed negative correlations with molecular weight, polarizability, and their initial concentrations. Although these findings need to be validated with a broader range of OCs, the results obtained in this study provide compelling evidence that current hair decontamination procedures have significant impacts on the analysis of endogenous OCs in hair. Therefore, it is important to interpret quantitative data on hair OC concentrations with caution and to thoroughly consider each decontamination procedure during analysis.


Asunto(s)
Monitoreo Biológico , Descontaminación , Cabello , Descontaminación/métodos , Cabello/química , Cobayas , Animales , Fluorocarburos/metabolismo , Fluorocarburos/análisis , Contaminantes Orgánicos Persistentes/metabolismo , Compuestos de Bencidrilo , Fenoles/análisis , Caprilatos , Organofosfatos/metabolismo , Fenantrenos/metabolismo , Monitoreo del Ambiente/métodos
7.
Inflamm Res ; 73(10): 1765-1780, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39112648

RESUMEN

BACKGROUND: Acute Kidney Injury (AKI), a prevalent complication of Liver Transplantation (LT) that occurs during the perioperative period has been established to profoundly impact the prognosis of transplant recipients. This study aimed to investigate the mechanism of the hepatic IRI-induced AKI and to identify potential therapeutic targets for treating this condition and improving the prognosis of LT patients. METHODS: An integrated transcriptomics and proteomics approach was employed to investigate transcriptional and proteomic alterations in hepatic IRI-induced AKI and the hypoxia-reoxygenation (H/R) model using TCMK-1 cells and the hepatic IRI-induced AKI mouse model using male C57BL/6 J mice were employed to elucidate the underlying mechanisms. Hematoxylin-eosin staining, reverse transcription quantitative polymerase chain reaction, enzyme-linked immunosorbent assay and Western blot were used to assess the effect of Rosiglitazone (RGZ) on hepatic IRI-induced AKI in vitro and in vivo. RESULTS: According to the results, 322 genes and 128 proteins were differentially expressed between the sham and AKI groups. Furthermore, Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomics (KEGG) pathway analyses revealed significant enrichment in pathways related to amino acid and lipid metabolism. Additionally, the Protein-Protein Interaction (PPI) network analysis of the kidney tissues obtained from a hepatic IRI-induced AKI mouse model highlighted arachidonic acid metabolism as the most prominent pathway. Animal and cellular analyses further revealed that RGZ, a PPAR-γ agonist, could inhibit the expression of the PPAR-γ/NF-κB signaling pathway-associated proteins in in vitro and in vivo. CONCLUSIONS: These findings collectively suggest that RGZ ameliorates hepatic IRI-induced AKI via PPAR-γ/NF-κB signaling pathway modulation, highlighting PPAR-γ as a crucial therapeutic target for AKI prevention post-LT.


Asunto(s)
Lesión Renal Aguda , Ácido Araquidónico , Hígado , Ratones Endogámicos C57BL , FN-kappa B , PPAR gamma , Daño por Reperfusión , Rosiglitazona , Transducción de Señal , Animales , Lesión Renal Aguda/tratamiento farmacológico , Lesión Renal Aguda/metabolismo , Lesión Renal Aguda/etiología , Lesión Renal Aguda/prevención & control , Masculino , Rosiglitazona/farmacología , Rosiglitazona/uso terapéutico , PPAR gamma/metabolismo , FN-kappa B/metabolismo , Daño por Reperfusión/metabolismo , Daño por Reperfusión/tratamiento farmacológico , Hígado/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , Ácido Araquidónico/metabolismo , Transducción de Señal/efectos de los fármacos , Ratones , Línea Celular , Riñón/efectos de los fármacos , Riñón/patología , Riñón/metabolismo , Mapas de Interacción de Proteínas
8.
Exp Dermatol ; 33(7): e15133, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39045898

RESUMEN

The management of hypertrophic scars (HSs), characterized by excessive collagen production, involves various nonsurgical and surgical interventions. However, the absence of a well-defined molecular mechanism governing hypertrophic scarring has led to less-than-ideal results in clinical antifibrotic treatments. Therefore, our study focused on the role of decorin (DCN) and its regulatory role in the TGF-ß/Smad signalling pathway in the development of HSs. In our research, we observed a decrease in DCN expression within hypertrophic scar tissue and its derived cells (HSFc) compared to that in normal tissue. Then, the inhibitory effect of DCN on collagen synthesis was confirmed in Fc and HSFc via the detection of fibrosis markers such as COL-1 and COL-3 after the overexpression and knockdown of DCN. Moreover, functional assessments revealed that DCN suppresses the proliferation, migration and invasion of HSFc. We discovered that DCN significantly inhibits the TGF-ß1/Smad3 pathway by suppressing TGF-ß1 expression, as well as the formation and phosphorylation of Smad3. This finding suggested that DCN regulates the synthesis of collagen-based extracellular matrix and fibrosis through the TGF-ß1/Smad3 pathway.


Asunto(s)
Cicatriz Hipertrófica , Decorina , Proteína smad3 , Factor de Crecimiento Transformador beta , Decorina/genética , Decorina/metabolismo , Cicatriz Hipertrófica/metabolismo , Cicatriz Hipertrófica/patología , Factor de Crecimiento Transformador beta/metabolismo , Transducción de Señal , Técnicas de Silenciamiento del Gen , Humanos , Proteína smad3/metabolismo , Colágeno Tipo I/metabolismo , Colágeno Tipo III/metabolismo , Matriz Extracelular/metabolismo , Proliferación Celular , Movimiento Celular
9.
Food Chem ; 459: 140356, 2024 Nov 30.
Artículo en Inglés | MEDLINE | ID: mdl-38981384

RESUMEN

Puffiness, a physiological disorder commonly observed during the ripening and post-harvest processes of fruits in Citrus reticulata, significantly affects the quality and shelf-life of citrus fruits. The complex array of factors contributing to puffiness has obscured the current understanding of its mechanistic basis. This study examined the puffing index (PI) of 12 citrus varieties at full ripeness, focusing on the albedo layer as a crucial tissue, and investigated the correlation between cellular structural characteristics, key primary metabolites and PI. The findings revealed that the cell gap difference and the number of lipid droplets were closely linked to PI. Chlorogenic acid, Ferulic acid, D-Galacturonic acid, D-Glucuronic acid, (9Z,11E)-Octadecadienoic acid, and 9(10)-EpOME were identified as pivotal primary metabolites for rind puffing. Determination of lignin, protopectin, cellulose and lipoxygenase content further validated the relationship between cell wall, lipid metabolism and rind puffing. This study furnishes novel insights into the mechanisms underlying puffing disorder.


Asunto(s)
Citrus , Frutas , Metabolómica , Citrus/metabolismo , Citrus/química , Frutas/química , Frutas/metabolismo , Frutas/crecimiento & desarrollo , Pared Celular/metabolismo , Pared Celular/química , Metabolismo de los Lípidos
10.
J Hazard Mater ; 477: 135278, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-39047566

RESUMEN

Human hair has become a promising non-invasive matrix in assessing exposure to environmental organic pollutants (OPs). However, exogenous contaminants, which were absorbed into the hair via sweat, sebum, and air particles/dust, could contribute to OP levels in hair and interfere with the precise exposure assessment. So far, the microscopic mechanisms underlying the absorption of exogenous OPs into hair remain inadequately understood. This study focused on the in-situ investigation of the diffusion processes of exogenous OPs into the hair structure using secondary ion mass spectrometry (SIMS) and isotopic tracer techniques. Results showed that the relative signal intensities of deuterium-labeled tris(1,3-dichloro-2-propyl) phosphate (TDCPP), 1-hydroxypyrene (1-OH-Pry), and bisphenol A (BPA) in the hair cortex were notably elevated after a 6-hour exposure. Diffusion coefficients of contaminants were related to their molecular weight, and absorption volumes to their water solubility and molecular structures. Exposure duration and solvent influenced the rate of diffusion and absorption volumes. The distribution of deuterium-labeled molecules in exposed hair samples after washing with two different solvents (acetone or water) was similar to that before washing. Our findings revealed the diffusion of OPs in hair cross-sections, indicating exogenous contributions to contaminants that are biologically incorporated into the hair.


Asunto(s)
Contaminantes Ambientales , Cabello , Espectrometría de Masa de Ion Secundario , Humanos , Cabello/química , Contaminantes Ambientales/química , Contaminantes Ambientales/análisis , Compuestos de Bencidrilo/análisis , Compuestos de Bencidrilo/química , Fenoles/análisis , Fenoles/química , Femenino , Compuestos Orgánicos/análisis , Compuestos Orgánicos/química , Adulto , Monitoreo del Ambiente/métodos , Difusión
11.
Nat Commun ; 15(1): 5899, 2024 Jul 13.
Artículo en Inglés | MEDLINE | ID: mdl-39003324

RESUMEN

Challenges in direct catalytic oxidation of biomass-derived aldehyde and alcohol into acid with high activity and selectivity hinder the widespread biomass application. Herein, we demonstrate that a Pd/Ni(OH)2 catalyst with abundant Ni2+-O-Pd interfaces allows electrooxidation of 5-hydroxymethylfurfural to 2, 5-furandicarboxylic acid with a selectivity near 100 % and 2, 5-furandicarboxylic acid yield of 97.3% at 0.6 volts (versus a reversible hydrogen electrode) in 1 M KOH electrolyte under ambient conditions. The rate-determining step of the intermediate oxidation of 5-hydroxymethyl-2-furancarboxylic acid is promoted by the increased OH species and low C-H activation energy barrier at Ni2+-O-Pd interfaces. Further, the Ni2+-O-Pd interfaces prevent the agglomeration of Pd nanoparticles during the reaction, greatly improving the stability of the catalyst. In this work, Pd/Ni(OH)2 catalyst can achieve 100% 5-hydroxymethylfurfural conversion and >90% 2, 5-furandicarboxylic acid selectivity in a flow-cell and work stably over 200 h under a fixed cell voltage of 0.85 V.

12.
J Adv Res ; 2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-39029900

RESUMEN

INTRODUCTION: The intestine, frequently subjected to pelvic or abdominal radiotherapy, is particularly vulnerable to delayed effects of acute radiation exposure (DEARE) owing to its high radiation sensitivity. Radiation-induced intestinal senescence, a result of DEARE, profoundly affects the well-being and quality of life of radiotherapy patients. However, targeted pharmaceutical interventions for radiation-induced senescence are currently scarce. Our findings showcase that nicotinamide riboside(NR) effectively alleviates radiation-induced intestinal senescence, offering crucial implications for utilizing NR as a pharmacological agent to combat intestinal DEARE. OBJECTIVES: The aim of this study was to investigate the ability of NR to reduce radiation induced intestinal senescence and explore its related mechanisms. METHODS: Male C57BL/6J mice were randomly divided into CON, IR, and IR + NR groups. The mice in the IR and IR + NR groups were subjected to a 6.0 Gy γ-ray total body exposure. After 8 weeks, the mice in the IR + NR group received NR via gavage at a dose of 400 mg/kg/d for 21 days. Then the mice were used for sample collection. RESULTS: Our results demonstrate that NR can significantly mitigate radiation-induced intestinal senescence. Furthermore, our findings indicate that NR can mitigate oxidative damage, restore the normal function of intestinal stem cells, regulate the disruption of the intestinal symbiotic ecosystem and address metabolic abnormalities. In addition, the underlying mechanisms involve the activation of SIRT6, SIRT7 and the inhibition of the mTORC1 pathway by NR. CONCLUSION: In conclusion, our results reveal the substantial inhibitory effects of NR on radiation-induced intestinal senescence. These findings offer valuable insights into the potential therapeutic use of NR as a pharmacological agent for alleviating intestinal DEARE.

13.
J Agric Food Chem ; 72(29): 16221-16236, 2024 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-38996349

RESUMEN

A hundred million tons of young apples are thinned and discarded in the orchard per year, aiming to increase the yield and quality of apples. We fermented thinned young apples using a potential probiotic fungus, Eurotium cristatum, which notably disrupted the microstructure of raw samples, as characterized by the scanning electron microscope. Fermentation substantially altered the metabolite profiles of samples, which are predicted to alleviate colitis via regulating inflammatory response and response to lipopolysaccharide by using network pharmacology analysis. In vivo, oral gavage of water extracts of E. cristatum fermented young apples (E.YAP) effectively alleviated DSS-induced colitis, restored the histopathology damage, reduced the levels of inflammatory cytokines, and promoted colonic expressions of tight junction proteins. Moreover, E.YAP ameliorated gut dysbacteriosis by increasing abundances of Lactobacillus,Blautia, Muribaculaceae, and Prevotellaceae_UCG-001 while inhibiting Turicibacter, Alistipes, and Desulfovibrio. Importantly, E.YAP increased colonic bile acids, such as CA, TCA, DCA, TUDCA, and LCA, thereby alleviating colitis via PXR/NF-κB signaling. Furthermore, a synbiotic combination with Limosilactobacillus reuteri WX-94, a probiotic strain isolated from feces of healthy individuals with anti-inflammatory properties, augmented anticolitis capacities of E.YAP. Our findings demonstrate that E.YAP could be a novel, potent, food-based anti-inflammatory prebiotic for relieving inflammatory injuries.


Asunto(s)
Bacterias , Colitis , Eurotium , Fermentación , Malus , Ratones Endogámicos C57BL , Animales , Malus/química , Ratones , Colitis/microbiología , Colitis/metabolismo , Colitis/inducido químicamente , Humanos , Masculino , Eurotium/metabolismo , Eurotium/química , Bacterias/clasificación , Bacterias/genética , Bacterias/aislamiento & purificación , Bacterias/metabolismo , Microbioma Gastrointestinal/efectos de los fármacos , Probióticos/administración & dosificación , Probióticos/farmacología , Frutas/química , Frutas/microbiología , Colon/microbiología , Colon/metabolismo , Colon/inmunología
14.
Spectrochim Acta A Mol Biomol Spectrosc ; 321: 124672, 2024 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-38905899

RESUMEN

Nitroxyl (HNO), a reactive nitrogen species (RNS), is essential for plant growth. However, the action of HNO in plants has been difficult to understand due to the lack of highly sensitive and real-time in-situ monitoring tools. Herein, we presented a near-infrared fluorescent probe, DCI-HNO, based on dicyanoisophorone fluorophore, for real-time mapping HNO in plants. The introduction of a phosphine moiety as a specific HNO recognition unit can inhibit the intramolecular charge transfer (ICT) of probe DCI-HNO. However, in the presence of HNO, the ICT process occurred, leading to the emission at 665 nm. Probe DCI-HNO exhibited high sensitivity (97 nM), rapid response time (8 min), large Stokes shift (135 nm) for detection of HNO in plants. The novel developed probe has successfully imaged endogenous HNO produced during NO/H2S cross-talk in plant tissues. Additionally, the up-regulated in HNO levels during tobacco aging and in response to stress has been confirmed. Therefore, probe DCI-HNO has provided a reliable method for monitoring the NO/H2S cross-talk and revealing the role of HNO in plants.


Asunto(s)
Colorantes Fluorescentes , Óxidos de Nitrógeno , Colorantes Fluorescentes/química , Colorantes Fluorescentes/síntesis química , Óxidos de Nitrógeno/análisis , Óxidos de Nitrógeno/química , Nicotiana/química , Nicotiana/metabolismo , Espectrometría de Fluorescencia/métodos , Plantas/química , Plantas/metabolismo
15.
Sci Transl Med ; 16(752): eabq7074, 2024 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-38896602

RESUMEN

Epidermal growth factor receptor inhibitors (EGFRis) are used to treat many cancers, but their use is complicated by the development of a skin rash that may be severe, limiting their use and adversely affecting patient quality of life. Most studies of EGFRi-induced rash have focused on the fully developed stage of this skin disorder, and early pathological changes remain unclear. We analyzed high-throughput transcriptome sequencing of skin samples from rats exposed to the EGFRi afatinib and identified that keratinocyte activation is an early pathological alteration in EGFRi-induced rash. Mechanistically, the induction of S100 calcium-binding protein A9 (S100A9) occurred before skin barrier disruption and led to keratinocyte activation, resulting in expression of specific cytokines, chemokines, and surface molecules such as interleukin 6 (Il6) and C-C motif chemokine ligand 2 (CCL2) to recruit and activate monocytes through activation of the Janus kinase (JAK)-signal transducers and activators of transcription (STAT) pathway, further recruiting more immune cells. Topical JAK inhibition suppressed the recruitment of immune cells and ameliorated the severity of skin rash in afatinib-treated rats and mice with epidermal deletion of EGFR, while having no effect on EGFRi efficacy in tumor-bearing mice. In a pilot clinical trial (NCT05120362), 11 patients with EGFRi-induced rash were treated with delgocitinib ointment, resulting in improvement in rash severity by at least one grade in 10 of them according to the MASCC EGFR inhibitor skin toxicity tool (MESTT) criteria. These findings provide a better understanding of the early pathophysiology of EGFRi-induced rash and suggest a strategy to manage this condition.


Asunto(s)
Receptores ErbB , Exantema , Inhibidores de las Cinasas Janus , Animales , Femenino , Humanos , Masculino , Ratones , Persona de Mediana Edad , Ratas , Administración Tópica , Afatinib/farmacología , Afatinib/uso terapéutico , Receptores ErbB/antagonistas & inhibidores , Receptores ErbB/metabolismo , Exantema/inducido químicamente , Exantema/patología , Inhibidores de las Cinasas Janus/farmacología , Inhibidores de las Cinasas Janus/uso terapéutico , Quinasas Janus/metabolismo , Quinasas Janus/antagonistas & inhibidores , Queratinocitos/efectos de los fármacos , Queratinocitos/metabolismo , Queratinocitos/patología , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Estudios Prospectivos
16.
J Affect Disord ; 360: 336-344, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-38824965

RESUMEN

BACKGROUND: The absence of clinically-validated biomarkers or objective protocols hinders effective major depressive disorder (MDD) diagnosis. Compared to healthy control (HC), MDD exhibits anomalies in plasma protein levels and neuroimaging presentations. Despite extensive machine learning studies in psychiatric diagnosis, a reliable tool integrating multi-modality data is still lacking. METHODS: In this study, blood samples from 100 MDD and 100 HC were analyzed, along with MRI images from 46 MDD and 49 HC. Here, we devised a novel algorithm, integrating graph neural networks and attention modules, for MDD diagnosis based on inflammatory cytokines, neurotrophic factors, and Orexin A levels in the blood samples. Model performance was assessed via accuracy and F1 value in 3-fold cross-validation, comparing with 9 traditional algorithms. We then applied our algorithm to a dataset containing both the aforementioned protein quantifications and neuroimages, evaluating if integrating neuroimages into the model improves performance. RESULTS: Compared to HC, MDD showed significant alterations in plasma protein levels and gray matter volume revealed by MRI. Our new algorithm exhibited superior performance, achieving an F1 value and accuracy of 0.9436 and 94.08 %, respectively. Integration of neuroimaging data enhanced our novel algorithm's performance, resulting in an improved F1 value and accuracy, reaching 0.9543 and 95.06 %. LIMITATIONS: This single-center study with a small sample size requires future evaluations on a larger test set for improved reliability. CONCLUSIONS: In comparison to traditional machine learning models, our newly developed MDD diagnostic model exhibited superior performance and showed promising potential for inclusion in routine clinical diagnosis for MDD.


Asunto(s)
Biomarcadores , Trastorno Depresivo Mayor , Imagen por Resonancia Magnética , Redes Neurales de la Computación , Neuroimagen , Humanos , Trastorno Depresivo Mayor/sangre , Trastorno Depresivo Mayor/diagnóstico por imagen , Biomarcadores/sangre , Imagen por Resonancia Magnética/métodos , Adulto , Femenino , Masculino , Neuroimagen/métodos , Persona de Mediana Edad , Algoritmos , Orexinas/sangre , Sustancia Gris/diagnóstico por imagen , Sustancia Gris/patología , Citocinas/sangre , Aprendizaje Automático , Atención , Estudios de Casos y Controles
17.
Adv Mater ; 36(32): e2404688, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38815983

RESUMEN

Machine learning (ML) has taken drug discovery to new heights, where effective ML training requires vast quantities of high-quality experimental data as input. Non-absorbable oral drugs (NODs) have unique safety advantage for chronic diseases due to their zero systemic exposure, but their empirical discovery is still time-consuming and costly. Here, a synergistic ML method, integrating small data-driven multi-layer unsupervised learning, in silico quantum-mechanical computations, and minimal wet-lab experiments is devised to identify the finest NODs from massive inorganic materials to achieve multi-objective function (high selectivity, large capacity, and stability). Based on this method, a NH4-form nanoporous zeolite with merlinoite (MER) framework (NH4-MER) is discovered for the treatment of hyperkalemia. In three different animal models, NH4-MER shows a superior safety and efficacy profile in reducing blood K+ without Na+ release, which is an unmet clinical need in chronic kidney disease and Gordon's syndrome. This work provides a synergistic ML method to accelerate the discovery of NODs and other shape-selective materials.


Asunto(s)
Aprendizaje Automático , Animales , Administración Oral , Nanoporos , Zeolitas/química , Ratones , Descubrimiento de Drogas , Potasio/química
18.
Int J Med Inform ; 188: 105478, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38743994

RESUMEN

BACKGROUND: Health misinformation (HM) has emerged as a prominent social issue in recent years, driven by declining public trust, popularisation of digital media platforms and escalating public health crisis. Since the Covid-19 pandemic, HM has raised critical concerns due to its significant impacts on both individuals and society as a whole. A comprehensive understanding of HM and HM-related studies would be instrumental in identifying possible solutions to address HM and the associated challenges. METHODS: Following the PRISMA procedure, 11,739 papers published from January 2013 to December 2022 were retrieved from five electronic databases, and 813 papers matching the inclusion criteria were retained for further analysis. This article critically reviewed HM-related studies, detailing the factors facilitating HM creation and dissemination, negative impacts of HM, solutions to HM, and research methods employed in those studies. RESULTS: A growing number of studies have focused on HM since 2013. Results of this study highlight that trust plays a significant while latent role in the circuits of HM, facilitating the creation and dissemination of HM, exacerbating the negative impacts of HM and amplifying the difficulty in addressing HM. CONCLUSION: For health authorities and governmental institutions, it is essential to systematically build public trust in order to reduce the probability of individuals acceptation of HM and to improve the effectiveness of misinformation correction. Future studies should pay more attention to the role of trust in how to address HM.


Asunto(s)
COVID-19 , Comunicación , Humanos , COVID-19/epidemiología , Comunicación en Salud/normas , Difusión de la Información , Salud Pública , SARS-CoV-2 , Medios de Comunicación Sociales , Confianza , Desinformación
19.
Talanta ; 274: 126010, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38569372

RESUMEN

Intracellular glucose detection is crucial due to its pivotal role in metabolism and various physiological processes. Precise glucose monitoring holds significance in diabetes management, metabolic studies, and biotechnological applications. In this study, we developed an innovative and expedient cell-permeable nanoreactor for intracellular glucose based on surface-enhanced Raman scattering (SERS). The nanoreactor was designed with gold nanoparticles (AuNPs), which were engineered with glucose oxide (GOx) and a H2O2-responsive Raman reporter 2-mercaptohydroquinone (2-MHQ). The interaction between 2-MHQ and H2O2 generated by glucose and GOx could simultaneously induce the appearance in the peak at 985 cm-1. Our results showed excellent performance in detecting glucose within the concentration range from 0.1 µM to 10 mM, with a low detection limitation of 14.72 nM. In addition, the glucose distribution in single HeLa cells was evaluated by real time SERS mapping. By combining noble metal particles and natural oxidases, the nanoreactor possesses both Raman activity and enzymatic functionality, thus enables sensitive glucose detection and facilitates imaging at a single cell level, which offers an insightful monitoring of cellular processes.


Asunto(s)
Glucosa , Oro , Nanopartículas del Metal , Espectrometría Raman , Espectrometría Raman/métodos , Humanos , Células HeLa , Oro/química , Nanopartículas del Metal/química , Glucosa/análisis , Glucosa/metabolismo , Peróxido de Hidrógeno/análisis , Peróxido de Hidrógeno/química , Glucosa Oxidasa/química , Glucosa Oxidasa/metabolismo
20.
RSC Adv ; 14(16): 10953-10961, 2024 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-38577433

RESUMEN

Purine nucleoside ester is one of the derivatives of purine nucleoside, which has antiviral and anticancer activities. In this work, a continuous flow synthesis of purine nucleoside esters catalyzed by lipase TL IM from Thermomyces lanuginosus was successfully achieved. Various parameters including solvent, reaction temperature, reaction time/flow rate and substrate ratio were investigated. The best yields were obtained with a continuous flow microreactor for 35 min at 50 °C with the substrate ratio of 1 : 5 (nucleosides to vinyl esters) in the solvent of tert-amyl alcohol. 12 products were efficiently synthesized with yields of 78-93%. Here we reported for the first time the use of lipase TL IM from Thermomyces lanuginosus in the synthesis of purine nucleoside esters. The significant advantages of this methodology are a green solvent and mild conditions, a simple work-up procedure and the highly reusable biocatalyst. This research provides a new technique for rapid synthesis of anticancer and antiviral nucleoside drugs and is helpful for further screening of drug activity.

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