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AIMS/HYPOTHESIS: The relationship between metabolic dysfunction-associated steatotic liver disease (MASLD) and type 2 diabetes mellitus, insulin resistance and the metabolic syndrome is well established. While zinc finger BED-type containing 3 (ZBED3) has been linked to type 2 diabetes mellitus and the metabolic syndrome, its role in MASLD remains unclear. In this study, we aimed to investigate the function of ZBED3 in the context of MASLD. METHODS: Expression levels of ZBED3 were assessed in individuals with MASLD, as well as in cellular and animal models of MASLD. In vitro and in vivo analyses were conducted using a cellular model of MASLD induced by NEFA and an animal model of MASLD induced by a high-fat diet (HFD), respectively, to investigate the role of ZBED3 in MASLD. ZBED3 expression was increased by lentiviral infection or tail-vein injection of adeno-associated virus. RNA-seq and bioinformatics analysis were employed to examine the pathways through which ZBED3 modulates lipid accumulation. Findings from these next-generation transcriptome sequencing studies indicated that ZBED3 controls SREBP1c (also known as SREBF1; a gene involved in fatty acid de novo synthesis); thus, co-immunoprecipitation and LC-MS/MS were utilised to investigate the molecular mechanisms by which ZBED3 regulates the sterol regulatory element binding protein 1c (SREBP1c). RESULTS: In this study, we found that ZBED3 was significantly upregulated in the liver of individuals with MASLD and in MASLD animal models. ZBED3 overexpression promoted NEFA-induced triglyceride accumulation in hepatocytes in vitro. Furthermore, the hepatocyte-specific overexpression of Zbed3 promoted hepatic steatosis. Conversely, the hepatocyte-specific knockout of Zbed3 resulted in resistance of HFD-induced hepatic steatosis. Mechanistically, ZBED3 interacts directly with polypyrimidine tract-binding protein 1 (PTBP1) and affects its binding to the SREBP1c mRNA precursor to regulate SREBP1c mRNA stability and alternative splicing. CONCLUSIONS/INTERPRETATION: This study indicates that ZBED3 promotes hepatic steatosis and serves as a critical regulator of the progression of MASLD. DATA AVAILABILITY: RNA-seq data have been deposited in the NCBI Gene Expression Omnibus ( www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE231875 ). MS proteomics data have been deposited to the ProteomeXchange Consortium via the iProX partner repository ( https://proteomecentral.proteomexchange.org/cgi/GetDataset?ID=PXD041743 ).
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Multiplex assay has emerged as a robust and versatile method for the simultaneous detection of multiple analytes in a single test. However, challenges in terms of poor accuracy and complexity remained. In this work, we developed a multiplex aptamer-based fluorescence assay using magnetism-encoded nanoparticles for the simultaneous detection of multiple pathogenic bacteria. The encapsulation of different amounts of Fe3O4 nanoparticles in zeolitic imidazolate framework-90 (ZIF-90) leads to the formation of Fe3O4@ZIF-90 (FZ) composites with distinct magnetism strengths. By functionalizing a specific aptamer on the surface of the FZ composites, target bacteria can be specifically and precisely separated from a mixed sample in a sequential manner. This property allows for the simultaneous quantitative analysis of multiple target bacteria by using a single-color fluorescence label, thereby resulting in minimal spectral crosstalk interference and improved accuracy. The successful determination of multiple bacteria in contaminated milk samples demonstrates the applicability of this multiplex assay in complex biological matrices. Compared to conventional multiplex fluorescence assays, this approach offers distinct advantages of simplicity, efficiency, and implementation. We believe that this study can provide valuable insights into the development of the multiplex assay while introducing a new method for the simultaneous detection of multiple bacteria.
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Aptámeros de Nucleótidos , Estructuras Metalorgánicas , Nanopartículas , Límite de Detección , BacteriasRESUMEN
OBJECTIVE: Growing research indicates that daily stress is associated with poorer same-day cognitive performance, for example, memory and attention. However, it is unclear whether this relationship holds across diverse ages and engagement in physical activity (PA), or whether these factors might buffer the relationship between daily stress and subjective cognitive function. METHODS: Ecological momentary assessment data were collected from adults aged 25-88 across British Columbia, Canada. For 14 days, participants (N = 204) wore a tri-axial physical activity monitor, reported stressor occurrence in mobile surveys 4 times per day, and rated their subjective attention and memory at the end of each day. RESULTS: Multilevel models evaluated daily stressor occurrence as a predictor of subjective attention and memory, with same-day PA engagement and age as moderators. Subjective attention and memory were lower on days when a stressor had occurred, compared to stressor-free days. Neither PA nor age moderated the within-person associations of daily stressors with subjective cognition. CONCLUSION: The lack of stress-buffering effects for same-day PA and age raises questions about the contexts in which PA promotes cognitive functioning and about age-related processes underlying stress and cognition. Future work could examine the mechanisms that might explain the link between daily stress and cognition function, as well as the associations of different intensity and forms of physical activity on stress across age groups.
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OBJECTIVE: Abundant research has linked nightly sleep as an antecedent of daily psychosocial experiences; however, less is known about sleep's influence on daily expectations of these experiences. Therefore, this research examined the day-to-day associations of sleep quality, duration, and efficiency with next-day expectations for stress(ors) and positive experiences, as well as whether these expectations were related to end-of-day reports of physical symptoms. METHODS: In Study 1, U.S. adults ( n = 354; ages 19 to 74) completed twice-daily diaries for 10 weekdays about sleep, expectations for encountering daily stressors and positive events, and physical symptoms. In Study 2, adults in Canada ( n = 246; ages 25 to 87) wore a sleep watch for 14 consecutive days and completed mobile surveys 5×/day about sleep, stressfulness and pleasantness expectations, and physical symptoms. RESULTS: Multilevel models indicated that self-reported sleep quality and duration, but not efficiency, were associated with lower next-day expectations for stressors (Study 1) and stressfulness (Study 2). Self-reported sleep quality (Study 1) and all sleep indices (Study 2) predicted greater next-day expectations for positive events and pleasantness, respectively. For actigraphy-assessed sleep (Study 2), only longer-than-usual actigraphic sleep duration was associated with lower stressfulness expectations, whereas both sleep duration and efficiency were positively linked with daily pleasantness expectations. Only pleasantness expectations (Study 2)-but not daily stressfulness and event expectations (Study 1)-predicted end-of-day physical symptoms. CONCLUSION: Findings suggest the importance of sleep on expectations of next-day stress and positive experiences, of which may have implications for daily physical health.
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Calidad del Sueño , Estrés Psicológico , Humanos , Masculino , Adulto , Femenino , Persona de Mediana Edad , Anciano , Adulto Joven , Anciano de 80 o más Años , Estados Unidos , Canadá , Actigrafía , Sueño/fisiologíaRESUMEN
Phthalates (PEs), such as di(2-ethylhexyl) phthalate (DEHP), dibutyl phthalate (DBP) and butyl benzyl phthalate (BBP) could cause reproductive and developmental toxicities, while human beings are increasingly exposed to them at low-doses. Phytochemical quercetin (Que) is a flavonoid that has estrogenic effect, anti-inflammatory and anti-oxidant effects. This study was conducted to assess the alleviative effect of Que. on male reproductive toxicity induced by the mixture of three commonly used PEs (MPEs) at low-dose in rats, and explore the underlying mechanism. Male rats were treated with MPEs (16 mg/kg/day) and/or Que. (50 mg/kg/d) for 91 days. The results showed that MPEs exposure caused male reproductive injuries, such as decreased serum sex hormones levels, abnormal testicular pathological structure, increased abnormal sperm rate and changed expressions of PIWIL1 and PIWIL2. Furthermore, MPEs also changed the expression of steroidogenic proteins in steroid hormone metabolism, including StAR, CYP11A1, CYP17A1, 17ß-HSD, CYP19A1. However, the alterations of these parameters were reversed by Que. MPEs caused male reproductive injuries in rats; Que. inhibited MPEs' male reproductive toxicity, which might relate to the improvement of testosterone biosynthesis.
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Dietilhexil Ftalato , Ácidos Ftálicos , Humanos , Ratas , Masculino , Animales , Quercetina/farmacología , Testosterona , Ratas Sprague-Dawley , Semen/metabolismo , Ácidos Ftálicos/toxicidad , Ácidos Ftálicos/metabolismo , Testículo , Dietilhexil Ftalato/toxicidad , Proteínas Argonautas/metabolismo , Proteínas Argonautas/farmacologíaRESUMEN
AIMS: There is limited research on the relationship between food insecurity and mortality among individuals with diabetes. This study aims to investigate the impact of food insecurity on all-cause and cause-specific mortality in adults with diabetes. RESEARCH DESIGN AND METHODS: This study included 5749 adults with diabetes from the National Health and Nutrition Examination Survey cycles 2003-2018 and followed up until 31 December 2019. Food insecurity was measured by the Food Security Survey Module. Cox proportional hazard models were employed to estimate hazard ratios (HRs) and 95% confidence intervals for both all-cause mortality and cause-specific mortality. RESULTS: The weighted prevalence of full food security, marginal food security, low food security, and very low food security was 70.8%, 11.0%, 10.4%, and 7.8%, respectively. Food insecurity demonstrated a significant correlation with diminished diet quality and reduced consumption of healthy foods. Over the course of 42,272.0 person-years of follow-up, we documented 1091 deaths, of which 370 were attributed to cardiovascular disease and 180 to cancer. After adjusting for multiple variables, food insecurity scores were significantly and linearly associated with increased all-cause mortality. Comparing to full food security, participants experiencing very low food security had a multivariate-adjusted HR of 1.48 (1.12, 1.95) for all-cause mortality (ptrend = 0.010). CONCLUSIONS: Food insecurity was associated with increased all-cause mortality and compromised diet quality, especially in individuals experiencing very low food security. Future strategies may necessitate the monitoring of and interventions for food insecurity among individuals with diabetes.
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Diabetes Mellitus , Abastecimiento de Alimentos , Adulto , Humanos , Encuestas Nutricionales , Estudios Retrospectivos , Diabetes Mellitus/epidemiología , Inseguridad AlimentariaRESUMEN
RLR helicases RIG-I and MDA5, which are known as pattern recognition receptors to sense cytoplasmic viral RNAs and trigger antiviral immune responses, are DExD/H-box helicases. In teleost, whether and how non-RLR helicases regulate RLR helicases to affect viral infection remains unclear. Here, we report that the non-RLR helicase DHX40 from grass carp (namely gcDHX40) is a negative regulator of grass carp reovirus (GCRV) infection and RLR-mediated type I IFN production. GcDHX40 was a cytoplasmic protein. Ectopic expression of gcDHX40 facilitated GCRV replication and suppressed type I IFN production induced by GCRV infection and by those genes involved the RLR antiviral signaling pathway. Mechanistically, gcDHX40 promoted the generation of viral inclusion bodies (VIBs) by interacting with the NS38 protein of GCRV. Additionally, gcDHX40 interacted with RLR helicase, and impaired the formation of RLR-MAVS functional complexes. Taken together, our results indicate that gcDHX40 is a novel important proviral host factor involving in promoting the generation of GCRV VIBs and inhibiting the production of RLR-mediated type I IFNs.
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Carpas , ARN Helicasas DEAD-box , Enfermedades de los Peces , Proteínas de Peces , Inmunidad Innata , Infecciones por Reoviridae , Reoviridae , Proteínas no Estructurales Virales , Animales , Proteínas no Estructurales Virales/genética , Proteínas no Estructurales Virales/inmunología , Proteínas no Estructurales Virales/metabolismo , Enfermedades de los Peces/inmunología , Enfermedades de los Peces/virología , Proteínas de Peces/genética , Proteínas de Peces/inmunología , Carpas/inmunología , Carpas/genética , Infecciones por Reoviridae/veterinaria , Infecciones por Reoviridae/inmunología , Reoviridae/fisiología , ARN Helicasas DEAD-box/genética , ARN Helicasas DEAD-box/inmunología , ARN Helicasas DEAD-box/metabolismo , Inmunidad Innata/genética , ARN Helicasas/genética , ARN Helicasas/metabolismo , ARN Helicasas/inmunología , Regulación de la Expresión Génica/inmunologíaRESUMEN
Graphitic carbon nitride (g-C3N4 or GCN) shows promise in photocatalytic water splitting, despite facing the challenge of rapid electron-hole recombination. In this study, we investigated the influence of boron/oxygen codoping on the photocatalytic performance of GCN systems for hydrogen generation. First-principles calculations and nonadiabatic molecular dynamics (NAMD) simulations were employed to reveal that the recombination time of photogenerated carriers could be increased by 16% to 64% in the codoped systems compared to the pristine GCN. The time-dependent density functional theory (TDDFT) scheme was utilized to select energy windows and initiate dynamics in cluster models of B/O co-doped heptazine with water molecules. Notably, we observed efficient direct photodissociation of hydrogen atoms from water molecules within 60 fs and proton hops within the hydrogen-bonded network within 80 fs in the co-doped system, diverging from the previously proposed mechanism for pristine heptazine in NAMD simulations. This discovery underscores the significant role of faster proton-coupled electron transfer (PCET) reactions and rapid radiationless relaxation in achieving high photocatalytic efficiency in water splitting. Our work enhances the understanding of the internal mechanism of highly efficient photocatalysts for water splitting and provides a new design strategy for doped GCN.
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Over the past few decades, molecular machines have been extensively studied, since they are composed of single molecules for functional materials capable of responding to external stimuli, enabling motion at scales ranging from the microscopic to the macroscopic level within molecular aggregates. This advancement holds the potential to efficiently transform external resources into mechanical movement, achieved through precise control of conformational changes in stimuli-responsive materials. However, the underlying mechanism that links microscopic and macroscopic motions remains unclear, demanding computational development associated with simulating the construction of molecular machines from single molecules. This bottleneck has impeded the design of more efficient functional materials. Advancements in theoretical simulations have successfully been developed in various computational models to unveil the operational mechanisms of stimulus-responsive molecular machines, which could help us reduce the costs in experimental trial-and-error procedures. It opens doors to the computer-aided design of innovative functional materials. In this perspective, we have reviewed theoretical approaches employed in simulating dynamic processes involving conformational changes in molecular machines, spanning different scales and environmental conditions. In addition, we have highlighted current challenges and anticipated future trends in the collective control of aggregates within molecular machines. Our goal is to provide a comprehensive overview of recent theoretical advancements in the field of molecular machines, offering valuable insights for the design of novel smart materials.
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Understanding how the electronic state of transition metal atoms can influence molecular adsorption on a substrate is of great importance for many applications. Choosing NH3 as a model molecule, its adsorption behavior on defected SnS2 monolayers is investigated. The number of valence electrons n is controlled by decorating the monolayer with different transition metal atoms, ranging from Sc to Zn. Density-Functional Theory based calculations show that the adsorption energy of NH3 molecules oscillates with n and shows a clear odd-even pattern. There is also a mirror symmetry of the adsorption energies for large and low electron numbers. This unique behavior is mainly governed by the oxidation state of the TM ions. We trace back the observed trends of the adsorption energy to the orbital symmetries and ligand effects which affect the interaction between the 3σ orbitals (NH3) and the 3d orbitals of the transition metals. This result unravels the role which the spin state of TM ions plays in different crystal fields for the adsorption behavior of molecules. This new understanding of the role of the electronic structure on molecular adsorption can be useful for the design of high efficiency nanodevices in areas such as sensing and photocatalysis.
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Two-dimensional material-supported single metal atom catalysts have been extensively studied and proved effective in electrocatalytic reactions in recent years. In this work, we systematically investigate the OER catalytic properties of single metal atoms supported by the NiN2 monolayer. Several typical transition metals with high single atom catalytic activity, such as Fe, Co, Ru, Rh, Pd, Ir, and Pt, were selected as catalytic active sites. The energy calculations show that transition metal atoms (Fe, Co, Ru, Rh, Pd, Ir, and Pt) are easily embedded in the NiN2 monolayer with Ni vacancies due to the negative binding energy. The calculated OER overpotentials of Fe, Co, Ru, Rh, Pd, Ir and Pt embedded NiN2 monolayers are 0.92 V, 0.47 V, 1.13 V, 0.66 V, 1.25 V, 0.28 V, and 0.94 V, respectively. Compared to the 0.57 V OER overpotential of typical OER noble metal catalysts IrO2, Co@NiN2 and Ir@NiN2 exhibit high OER catalytic activity due to lower overpotential, especially for Ir@NiN2. The high catalytic activity of the Ir embedded NiN2 monolayer can be explained well by the d-band center model. It is found that the adsorption strength of the embedded TM atoms with intermediates follows a linear relationship with their d-band centers. Besides, the overpotential of the Ir embedded NiN2 monolayer can be further reduced to 0.24 V under -2% biaxial strain. Such findings are expected to be employed in more two-dimensional material-supported single metal atom catalyzed reactions.
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Fusarium proliferatum is the main pathogen that causes Panax notoginseng root rot. The shortcomings of strong volatility and poor water solubility of Illicium verum essential oil (EO) limit its utilization. In this study, we prepared traditional emulsion (BDT) and nanoemulsion (Bneo) of I. verum EO by ultrasonic method with Tween-80 and absolute ethanol as solvents. The chemical components of EO, BDT, and Bneo were identified by gas chromatography-mass spectrometry (GC-MS) and the antifungal activity and mechanism were compared. The results show that Bneo has good stability and its particle size is 34.86 nm. The contents of (-) -anethole and estragole in Bneo were significantly higher than those in BDT. The antifungal activity against F. proliferatum was 5.8-fold higher than BDT. In the presence of I. verum EO, the occurrence of P. notoginseng root rot was significantly reduced. By combining transcriptome and metabolomics analysis, I. verum EO was found to be involved in the mutual transformation of pentose and glucuronic acid, galactose metabolism, streptomycin biosynthesis, carbon metabolism, and other metabolic pathways of F. proliferatum, and it interfered with the normal growth of F. proliferatum to exert antifungal effects. This study provide a theoretical basis for expanding the practical application of Bneo.
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Antifúngicos , Emulsiones , Fusarium , Illicium , Metabolómica , Aceites Volátiles , Aceites Volátiles/farmacología , Aceites Volátiles/química , Fusarium/efectos de los fármacos , Fusarium/genética , Fusarium/metabolismo , Illicium/química , Antifúngicos/farmacología , Antifúngicos/metabolismo , Antifúngicos/química , Emulsiones/química , Transcriptoma , Cromatografía de Gases y Espectrometría de Masas , Enfermedades de las Plantas/microbiología , Enfermedades de las Plantas/prevención & control , Perfilación de la Expresión GénicaRESUMEN
PURPOSE: To assess the predictive value of an ultrasound-based radiomics-clinical nomogram for grading residual cancer burden (RCB) in breast cancer patients. METHODS: This retrospective study of breast cancer patients who underwent neoadjuvant therapy (NAC) and ultrasound scanning between November 2020 and July 2023. First, a radiomics model was established based on ultrasound images. Subsequently, multivariate LR (logistic regression) analysis incorporating both radiomic scores and clinical factors was performed to construct a nomogram. Finally, Receiver operating characteristics (ROC) curve analysis and decision curve analysis (DCA) were employed to evaluate and validate the diagnostic accuracy and effectiveness of the nomogram. RESULTS: A total of 1122 patients were included in this study. Among them, 427 patients exhibited a favorable response to NAC chemotherapy, while 695 patients demonstrated a poor response to NAC therapy. The radiomics model achieved an AUC value of 0.84 in the training cohort and 0.83 in the validation cohort. The ultrasound-based radiomics-clinical nomogram achieved an AUC value of 0.90 in the training cohort and 0.91 in the validation cohort. CONCLUSIONS: Ultrasound-based radiomics-clinical nomogram can accurately predict the effectiveness of NAC therapy by predicting RCB grading in breast cancer patients.
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Neoplasias de la Mama , Clasificación del Tumor , Neoplasia Residual , Nomogramas , Ultrasonografía Mamaria , Humanos , Femenino , Neoplasias de la Mama/diagnóstico por imagen , Estudios Retrospectivos , Persona de Mediana Edad , Ultrasonografía Mamaria/métodos , Adulto , Neoplasia Residual/diagnóstico por imagen , Valor Predictivo de las Pruebas , Anciano , Terapia Neoadyuvante , Mama/diagnóstico por imagen , Carga Tumoral , RadiómicaRESUMEN
BACKGROUND: Lower eyelid suspension, a common therapeutic procedure for facial paralysis-induced eyelid retraction, faces challenges due to high recurrence in patients lacking facial muscle function and impedes wider adoption. This research aims to explore the potential effects of restoring orbicularis oculi muscle tension through facial nerve reanimation prior to lower eyelid suspension and to define the indications for lower eyelid suspension. METHODS: The study encompassed 32 individuals with complete facial paralysis, segmented into group A (reanimation group) and group B (non-reanimation group), based on whether the orbicularis oculi muscle's tension was restored through facial nerve reconstruction prior to lower eyelid suspension. Subjective assessments of eyelid closure (the inter-eyelid gap upon gentle closure) and objective methods measures of scleral show (the distance from the pupil's center to the lower eyelid margin, MRD2) were used to provide a comprehensive analysis of long-term effectiveness. RESULTS: The group A exhibited significantly greater long-term improvement in lagophthalmos and lower eyelid ectropion. The alterations in MRD2 measured 2.66 ± 0.27 mm in the group A versus 2.08 ± 0.53 mm in the group B, denoting a statistically significant variance (p < 0.001). Moreover, while the ratio of MRD2 preoperative 6 months postoperative revealed no significant difference between groups, a significant difference emerged in 12 months postoperative (group A: 1.02 ± 0.21; group B: 1.18 ± 0.24; p < 0.05), with the values in group A closer to 1, indicative of enhanced symmetry. CONCLUSIONS: Restoring the tension in the orbicularis oculi muscle through facial nerve reconstruction prior to palmaris longus tendon sling could effectively sustain long-term outcomes of lower eyelid retraction correction and reduce the recurrence rate. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
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Retinal ischemia plays a vital role in vision-threatening retinal ischemic disorders, such as diabetic retinopathy, age-related macular degeneration, glaucoma, etc. The aim of this study was to investigate the effects of S-allyl L-cysteine (SAC) and its associated therapeutic mechanism. Oxidative stress was induced by administration of 500 µM H2O2 for 24 h; SAC demonstrated a dose-dependent neuroprotective effect with significant cell viability effects at 100 µM, and it concurrently downregulated angiogenesis factor PKM2 and inflammatory biomarker MCP-1. In a Wistar rat model of high intraocular pressure (HIOP)-induced retinal ischemia and reperfusion (I/R), post-administration of 100 µM SAC counteracted the ischemic-associated reduction of ERG b-wave amplitude and fluorogold-labeled RGC reduction. This study supports that SAC could protect against retinal ischemia through its anti-oxidative, anti-angiogenic, anti-inflammatory, and neuroprotective properties.
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Glaucoma , Fármacos Neuroprotectores , Daño por Reperfusión , Enfermedades de la Retina , Ratas , Animales , Ratas Wistar , Cisteína/farmacología , Cisteína/uso terapéutico , Peróxido de Hidrógeno/uso terapéutico , Daño por Reperfusión/tratamiento farmacológico , Enfermedades de la Retina/tratamiento farmacológico , Isquemia/tratamiento farmacológico , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Antiinflamatorios/uso terapéutico , Glaucoma/tratamiento farmacológicoRESUMEN
This study deciphered the ameliorating effect and molecular mechanism of the total glucosides of White Paeony Capsules(TGP) in the treatment of mice model with acute lung injury(ALI) via NOD-like receptor thermal protein domain associated protein 3(NLRP3) signaling pathway of the inflammasome. The study established an inflammasome activation model of primed bone marrow-derived macrophages(BMDMs), and its molecular mechanism was investigated by Western blot(WB), immunofluorescence staining, enzyme-linked immunosorbent assay(ELISA), and flow cytometry. C57BL/6J mice were randomly divided into a blank control group, a TGP group, a model group(LPS group), LPS+low-and high-dose TGP groups, LPS+MCC950 group, and LPS+MCC950+TGP group, with eight mice per group. The ALI model was induced in mice. Finally, bronchoalveolar lavage fluid(BALF) and lung tissue were collected. Lung index and lung weight wet-to-dry ratio were determined for each group of mice. The pathological changes in lung tissue were observed through hematoxylin-eosin(HE) staining. The number of neutrophils in the BALF of each group was detected using flow cytometry. The levels of interleukin(IL)-1ß, IL-6, and tumor necrosis factor(TNF)-α in the BALF were determined by ELISA. The expressions of IL-1ß, IL-18, IL-6, and TNF-α in the lung tissue were determined by real-time quantitative PCR(RT-qPCR). This study demonstrated that TGP dramatically blocked the activation of the NLRP3 inflammasome by inhibiting the production of upstream mitochondrial reactive oxygen species(mtROS) and the subsequent oligomerization of apoptosis-associated specks(ASC). Additionally, in the ALI mice model, compared with the blank control group, the model group showed alveolar structure rupture, thic-kening of alveolar septa, and dramatically increased lung index, lung weight wet-to-dry ratio in lung tissue, neutrophil count, and inflammatory factor levels. Compared with the model group, the pathological morphology of lung tissue was significantly ameliorated in the TGP and MCC950 groups, and the lung index and lung weight wet-to-dry ratio were significantly reduced. Neutrophil counts were reduced, and levels of inflammatory factors were significantly downregulated. Notably, compared with the MCC950 group, there was no significant difference in effect in the MCC950+TGP group. Collectively, the study reveals that TGP may ameliorate ALI in mice by inhibiting the activation of NLRP3 inflammasome, providing a safe and effective drug candidate for the prevention or treatment of ALI/ARDS.
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Lesión Pulmonar Aguda , Medicamentos Herbarios Chinos , Glucósidos , Inflamasomas , Ratones Endogámicos C57BL , Proteína con Dominio Pirina 3 de la Familia NLR , Paeonia , Animales , Lesión Pulmonar Aguda/tratamiento farmacológico , Lesión Pulmonar Aguda/metabolismo , Lesión Pulmonar Aguda/inmunología , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Glucósidos/farmacología , Glucósidos/química , Ratones , Inflamasomas/metabolismo , Inflamasomas/efectos de los fármacos , Masculino , Paeonia/química , Medicamentos Herbarios Chinos/administración & dosificación , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/química , Cápsulas , Pulmón/efectos de los fármacos , Pulmón/inmunología , Pulmón/metabolismo , Humanos , Interleucina-1beta/genética , Interleucina-1beta/inmunología , Interleucina-1beta/metabolismoRESUMEN
Patient navigation is an effective intervention measure to promote the integration of medical systems and services. By providing individualized, coordinated, and continuous care, patient navigation offers a way to address the problem of fragmented services across institutions and levels of care in the whole-process management of lung cancer, providing assistance to patients with complex healthcare needs. Herein, we reviewed the origin, the development, the models, and the application status of patient navigation in China and other countries. We also analyzed the considerations regarding introducing patient navigation in the whole-process management of lung cancer against the background of medical consortiums in China, discussing why patient navigation should be introduced, how to introduce patient navigation, as well as potential challenges and coping strategies. Patient navigation meets the current needs for equitable, accessible, systematic, continuous, and integrated prevention and treatment services for chronic diseases in the context of the Healthy China Strategy. It helps fill the gaps in the continuity and coordination of whole-process management of lung cancer patients in the context of medical consortiums. However, introducing patient navigation in medical consortiums involving multiple institutions and levels of care may face challenges, including incompatibility between the health information systems of different institutions, poor cross-institutional collaboration and communication, and limited resources. Further improvement is needed in medical informatization, coordination and communication mechanisms, and benefit distribution mechanisms within the medical consortiums. In this paper, we intend to provide insights and suggestions for developing patient navigation models that suit China's local characteristics and for promoting the implementation and development of whole-process management of lung cancer in the context of the medical consortium system.
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Neoplasias Pulmonares , Navegación de Pacientes , Humanos , Neoplasias Pulmonares/terapia , ChinaRESUMEN
BACKGROUND: This study aimed to explore and evaluate the development trends and differential changes in the prevalence of mental and behavioral disorders among the earthquake survivors in exposure groups (highly hard-hit areas) and control groups (general disaster areas) from 2015 to 2019, as well as to investigate the potential influencing factors. METHODS: Data was obtained from the Sichuan Health Information System and the Sichuan Health Yearbook, the prevalence of the exposure group and the control group were calculated, the difference between the two groups was evaluated using the prevalence rate ratio, and a fixed effect model was developed to investigate the potential influencing factors of the prevalence. RESULTS: The prevalence by gender and age in the exposure group was always greater than those in the control group (RR>1), although the disparity between the two proceeded to diminish with time. The urbanization rate (ß = 0.0448, P < 0.05) and disaster area levels (ß = 0.0104, P < 0.05) were risk factors for the prevalence of mental and behavioral disorders. LIMITATIONS: The study only collected data at the group level following the Wenchuan earthquake. Consequently, the findings are only applicable at the group level. Furthermore, diagnostic criteria for various types of mental and behavioral disorders diseases were not provided. CONCLUSIONS: The earthquake has a significant long-term impact on mental health. It is necessary to continuously monitor the mental health of Wenchuan earthquake survivors and take appropriate post-disaster intervention measures.
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Macrodatos , Desastres , Terremotos , Trastornos Mentales , Sobrevivientes , Humanos , China/epidemiología , Masculino , Femenino , Persona de Mediana Edad , Adulto , Trastornos Mentales/epidemiología , Desastres/estadística & datos numéricos , Sobrevivientes/psicología , Sobrevivientes/estadística & datos numéricos , Prevalencia , Adolescente , Anciano , Adulto Joven , Factores de Riesgo , Niño , UrbanizaciónRESUMEN
Precision drug delivery and multimodal synergistic therapy are crucial in treating diverse ailments, such as cancer, tissue damage, and degenerative diseases. Electrodes that emit electric pulses have proven effective in enhancing molecule release and permeability in drug delivery systems. Moreover, the physiological electrical microenvironment plays a vital role in regulating biological functions and triggering action potentials in neural and muscular tissues. Due to their unique noncentrosymmetric structures, many 2D materials exhibit outstanding piezoelectric performance, generating positive and negative charges under mechanical forces. This ability facilitates precise drug targeting and ensures high stimulus responsiveness, thereby controlling cellular destinies. Additionally, the abundant active sites within piezoelectric 2D materials facilitate efficient catalysis through piezochemical coupling, offering multimodal synergistic therapeutic strategies. However, the full potential of piezoelectric 2D nanomaterials in drug delivery system design remains underexplored due to research gaps. In this context, the current applications of piezoelectric 2D materials in disease management are summarized in this review, and the development of drug delivery systems influenced by these materials is forecast.