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1.
Spectrochim Acta A Mol Biomol Spectrosc ; 324: 125013, 2025 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-39186875

RESUMEN

As a reactive sulfur species, sulfur dioxide (SO2) and its derivatives play crucial role in various physiological processes, which can maintain redox homeostasis at normal levels and lead to the occurrence of many diseases at abnormal levels. So, the development of a suitable fluorescent probe is a crucial step in advancing our understanding of the role of SO2 derivatives in living organisms. Herein, we developed a near-infrared fluorescent probe (SP) based on the ICT mechanism to monitor SO2 derivatives in living organisms in a ratiometric manner. The probe SP exhibited excellent selectivity, good sensitivity, fast response rate (within 50 s), and low detection limit (1.79 µM). In addition, the cell experiment results suggested that the SP has been successfully employed for the real-time monitoring of endogenous and exogenous SO2 derivatives with negligible cytotoxicity. Moreover, SP was effective in detecting SO2 derivatives in mice.


Asunto(s)
Colorantes Fluorescentes , Dióxido de Azufre , Colorantes Fluorescentes/química , Colorantes Fluorescentes/síntesis química , Dióxido de Azufre/análisis , Animales , Ratones , Humanos , Límite de Detección , Espectrometría de Fluorescencia , Imagen Óptica , Células HeLa
2.
J Environ Sci (China) ; 147: 230-243, 2025 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-39003043

RESUMEN

Enhancing soil organic matter characteristics, ameliorating physical structure, mitigating heavy metal toxicity, and hastening mineral weathering processes are crucial approaches to accomplish the transition of tailings substrate to a soil-like substrate. The incorporation of biomass co-pyrolysis and plant colonization has been established to be a significant factor in soil substrate formation and soil pollutant remediation. Despite this, there is presently an absence of research efforts aimed at synergistically utilizing these two technologies to expedite the process of mining tailings soil substrate formation. The current study aimed to investigate the underlying mechanism of geochemical changes and rapid mineral weathering during the process of transforming tailings substrate into a soil-like substrate, under the combined effects of biomass co-smoldering pyrolysis and plant colonization. The findings of this study suggest that the incorporation of smoldering pyrolysis and plant colonization induces a high-temperature effect and biological effects, which enhance the physical and chemical properties of tailings, while simultaneously accelerating the rate of mineral weathering. Notable improvements include the amelioration of extreme pH levels, nutrient enrichment, the formation of aggregates, and an increase in enzyme activity, all of which collectively demonstrate the successful attainment of tailings substrate reconstruction. Evidence of the accelerated weathering was verified by phase and surface morphology analysis using X-ray diffraction and scanning electron microscopy. Discovered corrosion and fragmentation on the surface of minerals. The weathering resulted in corrosion and fragmentation of the surface of the treated mineral. This study confirms that co-smoldering pyrolysis of biomass, combined with plant colonization, can effectively promote the transformation of tailings into soil-like substrates. This method has can effectively address the key challenges that have previously hindered sustainable development of the mining industry and provides a novel approach for ecological restoration of tailings deposits.


Asunto(s)
Biomasa , Minería , Contaminantes del Suelo , Suelo , Suelo/química , Pirólisis , Plantas , Biodegradación Ambiental
3.
Opt Lett ; 49(19): 5471-5474, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-39352984

RESUMEN

Metasurfaces provide an unprecedented platform for precise and subwavelength-scale modulation of optical phases, leading to innovative advancements in wavefront shaping and holography devices. This study presents a single-layer umbrella-like metasurface capable of multichannel holography, encoded with both polarization and wavelength. By leveraging a unique chiral-assisted strategy, we achieve simultaneous decoupling of wavelength and spin states through single-parameter modulation. This approach circumvents the complex structure designs and multi-parameter adjustments typically required in previous methods. Numerical simulations confirm the effectiveness of this metasurface, demonstrating wavelength- and spin-decoupled phase modulation at 1550 and 980 nm. Furthermore, we successfully demonstrate a four-channel hologram operable in both transmission and reflection modes, showcasing the potential applications of this metasurface in compact functional integration, information encryption, and 3D displays. This work paves the way for the development of multifunctional optical devices with enhanced integration and performance.

4.
Cell Commun Signal ; 22(1): 475, 2024 Oct 04.
Artículo en Inglés | MEDLINE | ID: mdl-39367496

RESUMEN

Peroxisomes are dynamic organelles involved in various cellular processes, including lipid metabolism, redox homeostasis, and intracellular metabolite transfer. Accumulating evidence suggests that peroxisomal homeostasis plays a crucial role in human health and disease, particularly in metabolic disorders and ferroptosis. The abundance and function of peroxisomes are regulated by a complex interplay between biogenesis and degradation pathways, involving peroxins, membrane proteins, and pexophagy. Peroxisome-dependent lipid metabolism, especially the synthesis of ether-linked phospholipids, has been implicated in modulating cellular susceptibility to ferroptosis, a newly discovered form of iron-dependent cell death. This review discusses the current understanding of peroxisome homeostasis, its roles in redox regulation and lipid metabolism, and its implications in human diseases. We also summarize the main mechanisms of ferroptosis and highlight recent discoveries on how peroxisome-dependent metabolism and signaling influence ferroptosis sensitivity. A better understanding of the interplay between peroxisomal homeostasis and ferroptosis may provide new insights into disease pathogenesis and reveal novel therapeutic strategies for peroxisome-related metabolic disorders and ferroptosis-associated diseases.


Asunto(s)
Ferroptosis , Homeostasis , Enfermedades Metabólicas , Peroxisomas , Peroxisomas/metabolismo , Humanos , Enfermedades Metabólicas/metabolismo , Enfermedades Metabólicas/patología , Animales , Metabolismo de los Lípidos
5.
Biochem Biophys Res Commun ; 734: 150739, 2024 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-39357338

RESUMEN

The rising prevalence of obesity is a global health concern. Supplementation with (S)-ß-aminoisobutyric acid (L-BAIBA) has shown potential in preventing obesity and related metabolic disorders induced by high-fat diets. However, developing effective and low-toxicity BAIBA derivatives remains a challenging yet promising field. In this study, we introduce Oct-B, a novel BAIBA ester compound, which exhibits 80-fold greater efficacy than L-BAIBA in alleviating obesity in high-fat diet-fed mice. Our results demonstrate that Oct-B significantly reduces serum TG, TC, LDL-C, and the activities of ALT and AST, and also reduces TG and TC in liver, surpassing the effects of L-BAIBA. Histological analysis shows that Oct-B significantly decreases lipid accumulation in liver tissues, normalizes mast cells in white adipose tissue, and upregulates the expression of UCP1 protein in white adipose tissue. The qRT-PCR results indicated Oct-B alleviates obesity by downregulating lipogenic genes (PPARγ, ACC1, FAS), upregulating lipolysis related genes (PPARα, HSL) and thermogenic gene UCP1. Additionally, quantitative mass spectrometry reveals a marked increase in L-BAIBA levels in white fat, brown fat, serum, and muscle following Oct-B administration. These findings suggest that Oct-B is an efficient L-BAIBA substitute, offering a promising therapeutic approach for preventing and treating high-fat diet-induced obesity.

6.
J Mol Cell Biol ; 2024 Sep 23.
Artículo en Inglés | MEDLINE | ID: mdl-39313323

RESUMEN

Telomeres are repetitive DNA sequences and associated protein complexes located at the end of chromatin. As a result of the DNA replication ending issue, telomeric DNA shortens during each cell cycle. The shelterin protein complex caps telomeric ends and forms a high-order protein-DNA structure to protect telomeric DNA. The stability of telomeres is critical for cellular function and is related to the progression of many human diseases. Telomeric repeat-containing RNA (TERRA) is a noncoding RNA transcribed from telomeric DNA regions. TERRA plays an essential role in regulating and maintaining the stability of telomeres. Heterogeneous nuclear ribonucleoproteins (hnRNPs) are RNA-binding proteins associated with complex and diverse biological processes. HnRNPA1 can recognize both TERRA and telomeric DNA. Previous research reported that hnRNPA1, TERRA, and POT1, a component of the shelterin complex, worked coordinately and displaced replication protein A from telomeric ssDNA after DNA replication, promoting telomere capping to preserve genomic integrity. However, the detailed molecular mechanism has remained unclear for over twenty years. Our study revealed the molecular structure through which the hnRNPA1 UP1 domain interacts with TERRA. Through structural analysis, we identified critical residues on the interacting surface between UP1 and TERRA. Furthermore, we proved that nucleic acids significantly increase the phase separation ability of hnRNPA1 and disrupting the UP1-TERRA interaction extraordinarily affects hnRNPA1 droplet formation both in vitro and in vivo. Taken together, these data revealed the molecular mechanism of the droplet formation of hnRNPA1 and TERRA and the possible function of the droplets for maintaining genomic stability.

7.
Artículo en Inglés | MEDLINE | ID: mdl-39269015

RESUMEN

OBJECTIVES: The relationship between sleep and memory has been well documented. However, it remains unclear whether a mind-body exercise, i.e., Tai Chi exercise, can improve memory performance in older adults by improving their subjective and objective sleep. METHOD: A randomized controlled trial was conducted with participants (M = 67.36, 56-79 years) randomly assigned to Tai Chi and control groups. The primary outcomes were sleep, both subjectively reported and objectively assessed by actigraphy, and memory performance, as well as the mediating role of sleep in memory improvement with Tai Chi practice. RESULTS: Tai Chi exercise led to improvements in subjective sleep, as indicated by ISI (p < 0.001, Cohen's d = 0.62) and daytime dysfunction of the PSQI (p = 0.02, Cohen's d = 0.80), and in actigraphy-assessed sleep onset latency (p < 0.01, Cohen's d = 0.61), as well as improved memory performance on digit span forward (p < 0.001, Cohen's d = 1.20) and visual spatial memory tasks (p < 0.01, Cohen's d = 0.83) compared to the control group. Importantly, Tai Chi practice improved digit span forward memory performance through parallel mediation of both subjective sleep (i.e., daytime dysfunction of the PSQI) and objective sleep (i.e., sleep onset latency; b = 0.29, p < 0.01). DISCUSSION: Our findings uncovered the potential benefits of Tai Chi exercise in relation to both subjective and objective sleep in older adults, in turn, how sleep changes played a role in the link between Tai Chi exercise and memory changes in older adults.

8.
Biochim Biophys Acta Mol Basis Dis ; 1871(1): 167498, 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-39243827

RESUMEN

BACKGROUND: Acute myeloid leukemia (AML) is an immunosuppressive hematologic malignancy with a poor prognosis. An immunosuppressive microenvironment blunts AML therapy. However, the prognostic and therapeutic roles of the factors that mediate immunosuppression in AML remain elusive. METHODS: S100 calcium-binding protein A4 (S100A4) was identified as an immunosuppression-mediating factor by analyzing The Cancer Genome Atlas AML project (TCGA-LAML) transcriptome data and data from AML-bearing mice and AML patients. The S100A4-mediated signaling pathway in myeloid-derived suppressor cells (MDSCs) was evaluated. RESULTS: Elevated S100A4 expression was positively associated with worse survival of AML patients, MDSCs, macrophages and immune checkpoints. S100A4 silencing downregulated the expression levels of MDSC-associated CD14, CCR2 and CCL2, reduced MDSC expansion and impaired MDSC-mediated inhibition of T cell activation and proliferation. S100A4-based prognostic signature (SPS) was an independent risk factor for AML patients. The high-risk group based on SPS was not only associated with adverse survival, MDSCs and macrophages and immune checkpoints but also insensitive to 25 chemotherapy drugs. It was also found that CCAAT enhancer binding protein beta (CEBPB) mediated S100A4 transcription. CEBPB silencing downregulated the expression levels of MDSC-associated CD14, CCR2 and CCL2. Mechanistically, S100A4 activated GP130/JAK2/STAT3 signaling in MDSCs by interacting with the cytokine-binding domain of GP130. Moreover, S100A4 mediated MDSC expansion through JAK2/STAT3 signaling. CONCLUSION: This study uncovers the critical role of S100A4 in MDSC accumulation, and S100A4-based prognostic signature may guide chemotherapy sensitivity in patients with AML.

9.
J Affect Disord ; 368: 151-159, 2024 Sep 14.
Artículo en Inglés | MEDLINE | ID: mdl-39278472

RESUMEN

BACKGROUND: Vascular endothelial growth factor (VEGF) is a candidate mediator of blood-brain barrier (BBB) disruption in depression. However, previous studies have mainly focused on peripheral blood VEGF levels, and the results are heterogeneous. Here we use astrocyte-derived extracellular vesicles (ADEVs) isolated from plasma to explore the in vivo changes of VEGF levels in patients with major depressive disorder (MDD). METHODS: Thirty-five unmedicated patients with MDD and 35 healthy controls (HCs) were enrolled, and plasma ADEVs were isolated from each participant. VEGF levels in ADEVs and glial fibrillary acidic protein (GFAP) in plasma were measured. Additionally, Alix and CD81, two established extracellular vesicle markers, were quantified in ADEVs. RESULTS: At baseline, MDD patients exhibited significantly increased levels of VEGF in ADEVs and GFAP in plasma. Following four weeks of selective serotonin reuptake inhibitor treatment, these target protein levels did not significantly change. ROC curve analysis revealed an AUC of 0.711 for VEGF in ADEVs. In exploratory analysis, VEGF levels in ADEVs were positively correlated with Alix and CD81. LIMITATIONS: Multiple factors regulate BBB permeability. This study focused solely on VEGF and the sample size for longitudinal analysis was relatively small. CONCLUSION: Our study is the first to confirm increased ADEV-derived VEGF levels in patients with MDD, thereby providing preliminary evidence supporting the hypothesis that the BBB is disrupted in depression.

10.
Nat Commun ; 15(1): 8242, 2024 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-39300075

RESUMEN

Fueled by the rapid advancement of nanofabrication, metasurface has provided unprecedented opportunities for 3D holography. Large depth 3D meta-holography not only greatly increases information storage capacity, but also enables distinguishing of the relative spatial relationship of 3D objects, which has important applications in fields like optical information storage and medical diagnosis. Although the methods based on Fresnel diffraction theory can reconstruct the real depth information of 3D objects, the maximum depth is only 2 mm. Here, we develop a 3D meta-holography based on angular spectrum diffraction theory to break through the depth limit. By developing the angular spectrum diffraction theory into meta-holography, the metasurface structure with independent polarization control is used to create a polarization multiplexing 3D meta-hologram. The fabricated amorphous silicon metasurface increases the depth range by 47.5 times and realizes 0.95 dm depth reconstruction for polarization independent and different color 3D meta-hologram in visible. Such polarization controlled large-depth color meta-holography is expected to open avenue for data storage, display, information security and virtual reality.

11.
Eur J Radiol ; 180: 111712, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39222565

RESUMEN

BACKGROUND: Brain metastases (BMs) represents a severe neurological complication stemming from cancers originating from various sources. It is a highly challenging clinical task to accurately distinguish the pathological subtypes of brain metastatic tumors from lung cancer (LC).The utility of 2.5-dimensional (2.5D) deep learning (DL) in distinguishing pathological subtypes of LC with BMs is yet to be determined. METHODS: A total of 250 patients were included in this retrospective study, divided in a 7:3 ratio into training set (N=175) and testing set (N=75). We devised a method to assemble a series of two-dimensional (2D) images by extracting adjacent slices from a central slice in both superior-inferior and anterior-posterior directions to form a 2.5D dataset. Multi-Instance learning (MIL) is a weakly supervised learning method that organizes training instances into "bags" and provides labels for entire bags, with the purpose of learning a classifier based on the labeled positive and negative bags to predict the corresponding class for an unknown bag. Therefore, we employed MIL to construct a comprehensive 2.5D feature set. Then we used the single-slice as input for constructing the 2D model. DL features were extracted from these slices using the pre-trained ResNet101. All feature sets were inputted into the support vector machine (SVM) for evaluation. The diagnostic performance of the classification models were evaluated using five-fold cross-validation, with accuracy and area under the curve (AUC) metrics calculated for analysis. RESULTS: The optimal performance was obtained using the 2.5D DL model, which achieved the micro-AUC of 0.868 (95% confidence interval [CI], 0.817-0.919) and accuracy of 0.836 in the test cohort. The 2D model achieved the micro-AUC of 0.836 (95 % CI, 0.778-0.894) and accuracy of 0.827 in the test cohort. CONCLUSIONS: The proposed 2.5D DL model is feasible and effective in identifying pathological subtypes of BMs from lung cancer.


Asunto(s)
Neoplasias Encefálicas , Aprendizaje Profundo , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/patología , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/secundario , Femenino , Masculino , Estudios Retrospectivos , Persona de Mediana Edad , Anciano , Diagnóstico Diferencial , Imagen por Resonancia Magnética/métodos , Adulto , Interpretación de Imagen Asistida por Computador/métodos , Sensibilidad y Especificidad
12.
Nat Commun ; 15(1): 7782, 2024 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-39237571

RESUMEN

Floquet engineering is a promising tool to manipulate quantum systems coherently. A well-known example is the optical Stark effect, which has been used for optical trapping of atoms and breaking time-reversal symmetry in solids. However, as a coherent nonlinear optical effect, Floquet engineering typically requires high field intensities obtained in ultrafast pulses, severely limiting its use. Here, we demonstrate using cavity engineering of the vacuum modes to achieve orders-of-magnitude enhancement of the effective Floquet field, enabling Floquet effects at an extremely low fluence of 450 photons/µm2. At higher fluences, the cavity-enhanced Floquet effects lead to 50 meV spin and valley splitting of WSe2 excitons, corresponding to an enormous time-reversal breaking, non-Maxwellian magnetic field of over 200 T. Utilizing such an optically controlled effective magnetic field, we demonstrate an ultrafast, picojoule chirality XOR gate. These results suggest that cavity-enhanced Floquet engineering may enable the creation of steady-state or quasi-equilibrium Floquet bands, strongly non-perturbative modifications of materials beyond the reach of other means, and application of Floquet engineering to a wide range of materials and applications.

13.
Environ Res ; 262(Pt 2): 119917, 2024 Sep 07.
Artículo en Inglés | MEDLINE | ID: mdl-39251178

RESUMEN

Vacuum collected toilet wastewater (VCTW) contains high and fluctuating contents of organics and nitrogen, which exerts technological challenges to biological treatment processes. A partial nitrification-denitrification and anammox (PND-AMX) process was developed in sequencing batch reactor (SBR) and moving bed biofilm reactor (MBBR) to achieve effective nitrogen removal in VCTW at low ambient temperature. Stable PND was achieved, and nitrogen removal efficiency in SBR could be manipulated by adjusting influent COD/N ratios. As temperature ≥18 °C, 91.0% nitrogen was removed in PND-AMX process. In spite of the decreased anammox activity at 13-18 °C, more than 90% nitrogen removal could be obtained by adjusting SBR influent COD/N to 2.43 ± 0.32 with methanol. In MBBR reactor, Candidatus Kuenenia was the dominant anammox bacteria and contributed to more than 90% nitrogen removal capacity. Co-existing anammox and denitrifying bacteria synergistically contributed to the removal of ammonium, nitrite, nitrate, and COD in MBBR.

14.
Eur J Pharmacol ; 983: 177002, 2024 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-39293571

RESUMEN

Gastric cancer (GC) is a common malignant disease that has a fifth highest incidence and fourth highest mortality worldwide. The Warburg effect is a common phenomenon observed in tumors, which suggests that tumor cells would enhance glucose uptake by overexpressing multiple glucose transporters. Sodium glucose transporter 2 (SGLT2) is one of glucose transporters which highly expressed in several cancers, but its role in gastric cancer is still unclear. Our research found that there was a high expression level of SGLT2 in gastric cancer tissues. We found that Dapagliflozin (a SGLT2 inhibitor) could suppress gastric cancer cell proliferation and migration in vitro and tumor growth in vivo. In present study, we revealed how dapagliflozin would suppress gastric cancer progression in a novel mechanism. We proved that dapagliflozin decreased the expression level of OTU deubiquitinase 5 (OTUD5), which further increased the ubiquitination and degradation of YAP1. Overexpression of OTUD5 in gastric cancer cells partly reversed the anti-tumor effect of dapagliflozin. Our findings revealed a novel mechanism by which dapagliflozin has an antitumor effect on gastric cancer and proposed a beneficial strategy for the application of dapagliflozin in gastric cancer patients.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales , Compuestos de Bencidrilo , Proliferación Celular , Glucósidos , Neoplasias Gástricas , Factores de Transcripción , Ubiquitinación , Proteínas Señalizadoras YAP , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/patología , Neoplasias Gástricas/metabolismo , Glucósidos/farmacología , Glucósidos/uso terapéutico , Humanos , Ubiquitinación/efectos de los fármacos , Proteínas Señalizadoras YAP/metabolismo , Compuestos de Bencidrilo/farmacología , Compuestos de Bencidrilo/uso terapéutico , Proliferación Celular/efectos de los fármacos , Línea Celular Tumoral , Animales , Factores de Transcripción/metabolismo , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Ratones , Transportador 2 de Sodio-Glucosa/metabolismo , Inhibidores del Cotransportador de Sodio-Glucosa 2/farmacología , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Ratones Desnudos , Masculino , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Movimiento Celular/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Ensayos Antitumor por Modelo de Xenoinjerto , Proteasas Ubiquitina-Específicas/metabolismo
15.
Environ Sci Technol ; 58(37): 16386-16398, 2024 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-39236260

RESUMEN

Plastic additive-related chemicals, particularly in polyvinyl chloride (PVC) plastics, have become a key issue in plastic pollution. Although addressing plastic pollution through the life-cycle approach is crucial, the environmental impacts of typical plastic additive-related chemicals in PVC plastics during the cradle-to-gate stage remain unexplored. Consequently, managing the life-cycle environmental impacts of these additives remains challenging. Herein, the environmental impacts of 23 typical plastic additive-related chemicals and six PVC plastic products were evaluated throughout the cradle-to-gate life-cycle stage using a life cycle assessment-material flow analysis (LCA-MFA) coupled model. The results indicate that plastic additives significantly contribute to the environmental impacts of PVC plastic products across various end point indicators, ranging from 8.7 to 40.6%. Additionally, scenario analysis (SA) reveals that conventional strategies for addressing plastic pollution may not be highly effective in mitigating the environmental impacts associated with plastic additives. Specifically, compared to primary polymers, these additives exhibit 4 to 13% lower mitigation potential under the same policy scenarios. However, technical adjustment strategies targeting additives show a mitigation potential of 12 to 39%, suggesting that guiding the plastic additive industry toward green transformation is a key strategy for reducing environmental impacts.


Asunto(s)
Plásticos , Cloruro de Polivinilo , Cloruro de Polivinilo/química , Ambiente , Contaminación Ambiental
16.
Sci Rep ; 14(1): 22150, 2024 09 27.
Artículo en Inglés | MEDLINE | ID: mdl-39333668

RESUMEN

The plasminogen activator inhibitor-1 (PAI-1)→mature brain-derived neurotrophic factor (mBDNF) pathway plays a pivotal role in the conversion of probrain-BDNF (ProBDNF) to mBDNF, but its clinical relevance in patients with alcohol use disorder (AUD) remains unknown. Enzyme-linked immunosorbent assays were used to examine the relevant protein levels of components of the PAI-1→mBDNF pathway in plasma samples from three groups of subjects, and statistical analysis was performed using analysis of variance (ANOVA) and one-way repeated-measures ANOVA. Our findings revealed significant alterations induced by alcohol. (1) AUD was associated with significant decreases in tissue plasminogen activator (tPA), mBDNF, and tropomyosin receptor kinase B (TrkB); significant increases in PAI-1, ProBDNF, and P75 neurotrophin receptor (P75NTR); and inhibited conversion of ProBDNF to mBDNF. (2) Following abstinence, the levels of tPA, mBDNF, and TrkB in the AUD group significantly increased, whereas the levels of PAI-1, ProBDNF, and P75NTR significantly decreased, promoting the conversion of ProBDNF to mBDNF. These clinical outcomes collectively suggest that AUD inhibits the conversion of ProBDNF to mBDNF and that abstinence reverses this process. The PAI-1→mBDNF cleavage pathway is hypothesized to be associated with AUD and abstinence treatment.


Asunto(s)
Alcoholismo , Factor Neurotrófico Derivado del Encéfalo , Inhibidor 1 de Activador Plasminogénico , Activador de Tejido Plasminógeno , Factor Neurotrófico Derivado del Encéfalo/sangre , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Humanos , Alcoholismo/metabolismo , Alcoholismo/sangre , Inhibidor 1 de Activador Plasminogénico/metabolismo , Inhibidor 1 de Activador Plasminogénico/sangre , Masculino , Adulto , Activador de Tejido Plasminógeno/metabolismo , Activador de Tejido Plasminógeno/sangre , Femenino , Transducción de Señal , Receptores de Factor de Crecimiento Nervioso/metabolismo , Persona de Mediana Edad , Receptor trkB/metabolismo , Abstinencia de Alcohol , Precursores de Proteínas/metabolismo , Glicoproteínas de Membrana , Proteínas del Tejido Nervioso
17.
Gene ; 933: 148955, 2024 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-39303819

RESUMEN

BACKGROUND: Hepatocellular Carcinoma (HCC) is the most common digestive system malignancy, with unclear pathogenesis and low survival rates. AP1M2 is associated with tumor progression, but its role and molecular mechanisms in HCC remain poorly understood and require further investigation. METHODS: We utilized the Gene Expression Omnibus (GEO) and Expression Analysis Interactive Hub (XENA) databases to assess AP1M2 mRNA expression levels in HCC patients. Additionally, we employed the Cancer Genome Atlas (TCGA) database to identify pathways associated with both AP1M2 and HCC development. To evaluate the effect of AP1M2 on HCC cell proliferation and migration, we employed various techniques including EdU, CCK-8, Colony formation assay, and Transwell assays. Furthermore, Western blot analysis was conducted to examine the signaling pathways influenced by AP1M2. RESULTS: AP1M2 expression was significantly increased at the mRNA level in HCC tissues(P<0.001). Importantly, overall survival (OS) analysis confirmed the association between higher AP1M2 expression and a poorer prognosis in HCC patients compared to those with lower AP1M2 expression (P<0.019).Multivariate Cox regression analysis showed that AP1M2 was an independent prognostic factor and a valid predictor for HCC patients. Furthermore, GSEA results indicated differential enrichment of lipid, metal metabolism, and coagulation processes in HCC samples demonstrating a high AP1M2 expression phenotype. In vitro experiments supported these findings by demonstrating that AP1M2 promotes HCC cell proliferation and migration, while activating the JNK/ERK pathway. CONCLUSION: Our findings indicate that AP1M2 expression may serve as a potential molecular marker indicating a poor prognosis for HCC patients. Furthermore, we have demonstrated that AP1M2 significantly influences HCC cell proliferation and migration, with the JNK/ERK signaling pathway playing a key role in AP1M2-mediated regulation in the context of HCC.

18.
Int J Nanomedicine ; 19: 8971-8985, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39246428

RESUMEN

Purpose: To investigate the neuroplasticity hypothesis of depression by measuring brain-derived neurotrophic factor (BDNF) levels in plasma astrocyte-derived extracellular vesicles (ADEVs) and to evaluate their potential as biomarkers for depression compared with plasma BDNF levels. Patients and Methods: Thirty-five patients with major depressive disorder (MDD) and 35 matched healthy controls (HCs) were enrolled. Plasma ADEVs were isolated using a combination of ultracentrifugation and immunoaffinity capture. Isolated ADEVs were validated using transmission electron microscopy, nanoparticle tracking analysis, and Western blotting. BDNF levels were quantified in both ADEVs and plasma. ALG-2-interacting protein X (Alix) and cluster of differentiation 81 (CD81) levels, two established extracellular vesicle markers, were measured in ADEVs. Results: After false discovery rate correction, patients with MDD exhibited higher CD81 levels (P FDR = 0.040) and lower BDNF levels (P FDR = 0.043) in ADEVs than HCs at baseline. BDNF levels in ADEVs normalized to CD81 (P FDR = 0.002) and Alix (P FDR = 0.040) remained consistent with this finding. Following four weeks of selective serotonin reuptake inhibitor treatment (n=10), CD81 levels in ADEVs decreased (P FDR = 0.046), while BDNF levels normalized to CD81 increased (P FDR = 0.022). BDNF levels in ADEVs were more stable than in plasma. Exploratory analysis revealed no correlation between BDNF levels in ADEVs and plasma (ρ=0.117, P = 0.334). Conclusion: This study provides human in vivo evidence supporting the neuroplasticity hypothesis of depression by demonstrating altered BDNF levels in ADEVs. ADEVs may be more suitable for developing biomarkers of depression than plasma-derived biomarkers.


Asunto(s)
Astrocitos , Biomarcadores , Factor Neurotrófico Derivado del Encéfalo , Trastorno Depresivo Mayor , Vesículas Extracelulares , Plasticidad Neuronal , Humanos , Factor Neurotrófico Derivado del Encéfalo/sangre , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/química , Masculino , Femenino , Plasticidad Neuronal/fisiología , Adulto , Persona de Mediana Edad , Trastorno Depresivo Mayor/sangre , Trastorno Depresivo Mayor/metabolismo , Biomarcadores/sangre , Astrocitos/metabolismo , Tetraspanina 28/metabolismo , Inhibidores Selectivos de la Recaptación de Serotonina/farmacología , Estudios de Casos y Controles , Proteínas de Unión al Calcio , Proteínas de Ciclo Celular , Complejos de Clasificación Endosomal Requeridos para el Transporte
19.
J Phys Chem Lett ; 15(36): 9239-9246, 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39226390

RESUMEN

It is important to attain red hot exciton materials applicable in highly efficient organic light-emitting diodes with low-efficiency roll-off, but their development is restricted by the energy gap law. Herein, the sulfur atom was replaced by a heavier selenium atom based on benzothiadiazole to obtain a new benzoselenadiazole acceptor with a heavy atom effect and stronger electron-withdrawing ability. Two novel red hot exciton materials named BSe-DtBuTPA and BSe-2PhCz-d24 were designed and synthesized based on the benzoselenadiazole unit. Benefiting from the heavy-atom effect of selenium and the small ΔES1T2, both emitters exhibited ultrafast high-lying reverse intersystem crossing rate constants (7.00 × 107 and 1.17 × 107 s-1). The devices based on BSe-DtBuTPA and BSe-2PhCz-d24 demonstrated maximum external quantum efficiencies of 4.81 and 7.15% with emission peaks at 653 and 596 nm, respectively. The device based on deep-red BSe-DtBuTPA exhibited negligible efficiency roll-off of 18.5% at 10000 cd/m2.

20.
Biomed Pharmacother ; 180: 117438, 2024 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-39298908

RESUMEN

Cancer poses a substantial global health challenge, necessitating the widespread use of chemotherapy and radiotherapy. Despite these efforts, issues like resistance development and severe side effects remain. As such, the search for more effective alternatives is critical. Andrographolide, a naturally occurring compound, has recently gained attention for its extensive biological activities. This review explores the role of andrographolide in cancer therapy, especially focusing on the molecular mechanisms that drive its anti-tumor properties. It also examines innovative methods to enhance andrographolide's bioavailability, thus boosting its effectiveness against cancer. Notably, andrographolide has potential for use in combination with various clinical drugs, and both preclinical and clinical studies provide strong evidence supporting its broader anticancer applications. Additionally, this paper proposes future research directions for andrographolide's anti-cancer effects and discusses the challenges in its clinical usage along with current research efforts to address these issues. In summary, this review underscores andrographolide's potential roles and contributes to the development of improved cancer treatment strategies.

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