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1.
Spectrochim Acta A Mol Biomol Spectrosc ; 324: 124997, 2025 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-39173322

RESUMEN

Polylactic acid (PLA) straws hold eco-friendly potential; however, residual diisocyanates used to enhance the mechanical strength can generate carcinogenic primary aromatic amines (PAAs), posing health risks. Herein, we present a rapid, comprehensive strategy to detecting PAAs in 18 brands of food-grade PLA straws and assessing their migration into diverse food simulants. Surface-enhanced Raman spectroscopy was conducted to rapidly screen straws for PAAs. Subsequently, qualitative determination of migrating PAAs into various food simulants (4 % acetic acid, 10 % ethanol, 50 % ethanol) occurred at 70 °C for 2 h using liquid chromatography-mass spectrometry. Three PAAs including 4,4'-methylenedianiline, 2,4'-methylenedianiline, and 2,4-diaminotoluene were detected in all straws. Specifically, 2,4-diaminotoluene in 50 % ethanol exceeded specific migration limit of 2 µg/kg, raising safety concerns. Notably, PAAs migration to 10 % and 50 % ethanol surpassed that to 4 % acetic acid within a short 2-hour period. Moreover, PLA straws underwent varying degrees of shape changes before and after migration. Straws with poly(butylene succinate) resisted deformation compared to those without, indicating enhanced heat resistance, while poly(butyleneadipate-co-terephthalate) improved hydrolysis resistance. Importantly, swelling study unveiled swelling effect wasn't the primary factor contributing to the increased PAAs migration in ethanol food simulant, as there was no significant disparity in swelling degrees across different food simulants. FT-IR and DSC analysis revealed higher PAAs content in 50 % ethanol were due to highly concentrated polar ethanol disrupting hydrogen bonds and van der Waal forces holding PLA molecules together. Overall, minimizing contact between PLA straws and alcoholic foods is crucial to avoid potential safety risks posed by PAAs.


Asunto(s)
Aminas , Poliésteres , Espectrometría Raman , Poliésteres/química , Espectrometría Raman/métodos , Cromatografía Liquida/métodos , Aminas/análisis , Aminas/química , Espectrometría de Masas/métodos , Contaminación de Alimentos/análisis , Embalaje de Alimentos , Cromatografía Líquida con Espectrometría de Masas
2.
Neural Regen Res ; 20(7): 2038-2052, 2025 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38993139

RESUMEN

JOURNAL/nrgr/04.03/01300535-202507000-00026/figure1/v/2024-09-09T124005Z/r/image-tiff Parkinson's disease is primarily caused by the loss of dopaminergic neurons in the substantia nigra compacta. Ferroptosis, a novel form of regulated cell death characterized by iron accumulation and lipid peroxidation, plays a vital role in the death of dopaminergic neurons. However, the molecular mechanisms underlying ferroptosis in dopaminergic neurons have not yet been completely elucidated. NADPH oxidase 4 is related to oxidative stress, however, whether it regulates dopaminergic neuronal ferroptosis remains unknown. The aim of this study was to determine whether NADPH oxidase 4 is involved in dopaminergic neuronal ferroptosis, and if so, by what mechanism. We found that the transcriptional regulator activating transcription factor 3 increased NADPH oxidase 4 expression in dopaminergic neurons and astrocytes in an 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine-induced Parkinson's disease model. NADPH oxidase 4 inhibition improved the behavioral impairments observed in the Parkinson's disease model animals and reduced the death of dopaminergic neurons. Moreover, NADPH oxidase 4 inhibition reduced lipid peroxidation and iron accumulation in the substantia nigra of the Parkinson's disease model animals. Mechanistically, we found that NADPH oxidase 4 interacted with activated protein kinase C α to prevent ferroptosis of dopaminergic neurons. Furthermore, by lowering the astrocytic lipocalin-2 expression, NADPH oxidase 4 inhibition reduced 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine-induced neuroinflammation. These findings demonstrate that NADPH oxidase 4 promotes ferroptosis of dopaminergic neurons and neuroinflammation, which contribute to dopaminergic neuron death, suggesting that NADPH oxidase 4 is a possible therapeutic target for Parkinson's disease.

3.
Sci Rep ; 14(1): 21047, 2024 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-39251834

RESUMEN

Prediction of water-conducting fractured zone (WCFZ) of mine overburden is the premise for reducing or eliminating water inrush hazards in undersea mining. To obtain a more robust and precise prediction of WCFZ in undersea mining, a WCFZ prediction dataset with 122 cases of fractured zones was constructed. Five machine learning algorithms (linear regression, XGBRegressor, RandomForestRegressor, LineareSVR, and KNeighborsRegressor) were employed to develop five corresponding predictive models, taking multiple factors into account.The optimal parameters for each model are obtained through ten-fold cross-validation (10CV). The model's predictive performance was validated and assessed using two metrics, namely the coefficient of determination (R2) and mean squared error (MSE). A comparison was made with the regression performance of commonly used empirical formulas. The results indicate that the constructed model outperforms reliance solely on theoretical criteria, showing a high R2 value of up to 0.925 and a low MSE value of 3.61. The proposed model was validated in a recently established mining area on Sanshan Island, China. It shows low absolute and relative errors of 0.71 m and 2.01%, respectively, between the predicted value from the model and observation result from the field, demonstrating a high level of consistency with on-site conditions. This paves a path to leveraging machine learning algorithms for predicting the height of WCFZ.

4.
J Adv Res ; 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-39243941

RESUMEN

INTRODUCTION: Taurine is a naturally occurring sulfonic acid involved in various physiological and pathological processes, such as the regulation of calcium signaling, immune function, inflammatory response, and cellular aging. It has the potential to predict tumor malignant transformation and formation. Our previous work discovered the elevated taurine in lung cancer patients. However, the precise impact and mechanism of elevated serum taurine levels on lung cancer progression and the suitability of taurine or taurine-containing drinks for lung cancer patients remain unclear. OBJECTIVES: Our study aimed to systematically investigate the role of taurine in lung cancer, with the ultimate goal of contributing novel strategies for lung cancer treatment. METHODS: Lung cancer C57 and nude mice models, RNA sequencing, and stable transfection were applied to explored the effects and mechanisms of taurine on lung cancer. Tissues of 129 non-small cell lung cancer (NSCLC) patients derived from 2014 to 2017 for immunohistochemistry were collected in Taihe Hospital. RESULTS: Low doses of taurine, as well as taurine-infused beverages at equivalent doses, significantly enhanced lung tumor growth. Equally intriguing is that the promoting effect of taurine on lung cancer progression wanes as the dosage increases. The Nuclear factor erythroid 2-like 1 (Nfe2l1 or Nrf1)-reactive oxygen species (ROS)-PD-1 axis may be a potential mechanism for dual role of taurine in lung cancer progression. However, taurine's impacts on lung cancer progression and the anti-tumor function of Nfe2l1 were mainly determined by the immune competence. Taurine inhitited lung tumor growth probably by inhibiting NF-κB-mediated inflammatory responses in nude mice rather than by affecting Nfe2l1 function. As patients age increased, Nfe2l1 gene and protein gradually returned to the levels observed in healthy individuals, but lost its anti-lung cancer effects. CONCLUSIONS: Taurine emerges as a potential biomarker for lung cancer progression, predicting poor prognosis and unsuitability for specific patients. Lung cancer patients, especially young patients, should be conscious of potential effects of taurine-containing drinks. Conversely, taurine or its drinks may be more suitable for older or immune-deficient patients.

5.
Zhongguo Dang Dai Er Ke Za Zhi ; 26(9): 926-932, 2024.
Artículo en Chino | MEDLINE | ID: mdl-39267507

RESUMEN

OBJECTIVES: To explore the clinical value of the renal phosphorus threshold (ratio of tubular maximum reabsorption of phosphate to glomerular filtration rate, TmP/GFR) in the diagnosis and treatment of children with X-linked hypophosphatemic rickets (XLH). METHODS: A retrospective study was conducted, including 83 children diagnosed with XLH at Children's Hospital of Nanjing Medical University from January 2010 to January 2023. Initial diagnosis and follow-up data were collected to investigate the correlation of TmP/GFR with the severity of rickets, calcium and phosphorus metabolism indicators, and the dosage of phosphate treatment. Children were divided into two groups based on the occurrence of renal calcification: the renal calcification group (n=47) and the non-renal calcification group (n=36). Clinical data between the two groups were compared. Multivariate logistic regression analysis was used to identify factors influencing renal calcification in XLH children. The predictive value of TmP/GFR for renal calcification in XLH children was evaluated using receiver operating characteristic (ROC) curves. RESULTS: In the 83 XLH children, the initial TmP/GFR was (0.78±0.21) mmol/L, with significant individual variation (range: 0.28-1.24 mmol/L). TmP/GFR showed no significant correlation with the severity of rickets (P>0.05). Parathyroid hormone was negatively correlated with TmP/GFR (rs=-0.020, P=0.008), while blood phosphorus (rs=0.384, P<0.001), blood calcium (rs=0.251, P<0.001), and 25-hydroxyvitamin D (rs=0.179, P<0.001) were positively correlated with TmP/GFR. No significant correlation was found between TmP/GFR and alkaline phosphatase (rs=-0.002, P=0.960) or phosphate treatment dosage (rs=0.012, P=0.800). Blood calcium and TmP/GFR levels were significantly lower in the renal calcification group than in the non-renal calcification group (P<0.05), while parathyroid hormone and urine calcium levels were significantly higher in the renal calcification group (P<0.05). Multivariate logistic regression analysis indicated that TmP/GFR and urine calcium levels were closely associated with renal calcification in XLH children (P<0.05). ROC curve analysis revealed that the areas under the curve for TmP/GFR, urine calcium, and their combined detection predicting renal calcification in XLH children were 0.696, 0.679, and 0.761, respectively. CONCLUSIONS: TmP/GFR may serve as an important diagnostic indicator for pediatric XLH; however, it does not reflect the severity or activity of rickets and cannot be used to judge the efficacy of traditional treatment. Urine calcium and TmP/GFR are valuable predictors for renal calcification in XLH children.


Asunto(s)
Raquitismo Hipofosfatémico Familiar , Tasa de Filtración Glomerular , Fósforo , Humanos , Fósforo/sangre , Masculino , Femenino , Raquitismo Hipofosfatémico Familiar/diagnóstico , Preescolar , Niño , Estudios Retrospectivos , Lactante , Riñón/fisiopatología , Adolescente , Calcio/sangre , Calcio/orina
6.
Int J Mol Sci ; 25(17)2024 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-39273683

RESUMEN

Macrophages, pivotal components of the immune system, orchestrate host defense mechanisms in humans and mammals. Their polarization into classically activated macrophages (CAMs or M1) and alternatively activated macrophages (AAMs or M2) dictates distinct functional roles in immunity and tissue homeostasis. While the negative regulatory role of CD32b within the FC gamma receptor (FCγR) family is recognized across various immune cell types, its influence on macrophage polarization remains elusive. This study aimed to elucidate the regulatory role of CD32b in macrophage polarization and discern the differential expression markers between the M1 and M2 phenotypes following CD32b siRNA transfection. The results revealed a decrease in the CD32b levels in lipopolysaccharide (LPS)-treated M1 and an increase in interleukin-4 (IL-4)-treated M2 macrophages, as observed in macrophage Raw264.7 cells. Furthermore, CD32b siRNA transfection significantly downregulated the M2 markers (IL-10, VEGF, Arg-1, and STAT6), while upregulating the M1 markers (IL-6, NF-κB, NOS2, and STAT1) in the Raw264.7 cells. Similar findings were recapitulated in macrophage-rich adherent cells isolated from mouse spleens. Additionally, the cytopathological analysis of pleural effusions and ascitic fluids from patients with cancer revealed a positive correlation between advanced tumor stages, metastasis, and elevated CD32b levels. In conclusion, this study highlights the regulatory influence of CD32b in suppressing M1 expression and promoting M2 polarization. Moreover, heightened M2 activation and CD32b levels appear to correlate with tumor progression. A targeted CD32b blockade may serve as a novel therapeutic strategy to inhibit M2 macrophage polarization and is promising for anti-tumor intervention.


Asunto(s)
Activación de Macrófagos , Macrófagos , Receptores de IgG , Animales , Ratones , Humanos , Macrófagos/metabolismo , Macrófagos/inmunología , Receptores de IgG/metabolismo , Células RAW 264.7 , Neoplasias/metabolismo , Neoplasias/patología , Neoplasias/inmunología , Progresión de la Enfermedad , Lipopolisacáridos/farmacología , Interleucina-4/metabolismo , Femenino , Masculino
7.
Curr Protoc ; 4(9): e70013, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39269316

RESUMEN

The study of human intestinal physiology and host-microbe interactions is crucial for understanding gastrointestinal health and disease. Traditional two-dimensional cell culture models lack the complexity of the native intestinal environment, limiting their utility in studying intestinal biology. Here, we present a detailed protocol for the set up and utilization of a three-dimensional (3D) in vitro bioreactor system for human intestinal studies and bacterial co-culture. This article outlines the design and assembly of the bioreactor system, scaffold fabrication, bacterial culture techniques, analysis methods, and troubleshooting tips. By providing step-by-step instructions, the goal is to enable other laboratories to utilize physiologically relevant tissue models of the human intestine, incorporating key features, such as nutrient flow, multiple human cell types, 3D architecture, and microbial communities. The incorporation of commensal bacteria into the bioreactor system allows for the investigation of complex host-microbe interactions, providing insight into gastrointestinal health and pathology. This article serves as a comprehensive resource for scientists seeking to advance their understanding of intestinal biology toward the development of novel therapeutic strategies for gastrointestinal disorders. © 2024 Wiley Periodicals LLC. Basic Protocol 1: Scaffold design Basic Protocol 2: Intestinal cell culture: Caco2 cells Basic Protocol 3: Intestinal cell culture: organoids Basic Protocol 4: Bioreactor design and set up Basic Protocol 5: Bacteria in 3D bioreactor set up Basic Protocol 6: Bacteria and drug dosing.


Asunto(s)
Reactores Biológicos , Técnicas de Cocultivo , Intestinos , Humanos , Reactores Biológicos/microbiología , Técnicas de Cocultivo/métodos , Técnicas de Cocultivo/instrumentación , Intestinos/microbiología , Intestinos/citología , Células CACO-2 , Microbioma Gastrointestinal , Técnicas de Cultivo Tridimensional de Células/métodos , Técnicas de Cultivo Tridimensional de Células/instrumentación
8.
Ultrasonics ; 144: 107450, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-39222597

RESUMEN

Medical Speed-of-sound (SoS) imaging, which can characterize medical tissue properties better by quantifying their different SoS, is an effective imaging method compared with conventional B-mode ultrasound imaging. As a commonly used diagnostic instrument, a hand-held array probe features convenient and quick inspection. However, artifacts will occur in the single-angle SoS imaging, resulting in indistinguishable tissue boundaries. In order to build a high-quality SoS image, a number of raw data are needed, which will bring difficulties to data storage and processing. Compressed sensing (CS) theory offers theoretical support to the feasibility that a sparse signal can be rebuilt with random but less sampling data. In this study, we proposed an SoS reconstruction method based on CS theory to process signals obtained from a hand-held linear array probe with a passive reflector positioned on the opposite side. The SoS reconstruction method consists of three parts. Firstly, a sparse transform basis is selected appropriately for a sparse representation of the original signal. Then, considering the mathematical principles of SoS imaging, the ray-length matrix is used as a sparse measurement matrix to observe the original signal, which represents the length of the acoustic propagation path. Finally, the orthogonal matching pursuit algorithm is introduced for image reconstruction. The experimental result of the phantom proves that SoS imaging can clearly distinguish tissues that show similar echogenicity in B-mode ultrasound imaging. The simulation and experimental results show that our proposed method holds promising potential for reconstructing precision SoS images with fewer signal samplings, transmission, and storage.


Asunto(s)
Algoritmos , Fantasmas de Imagen , Ultrasonografía , Ultrasonografía/métodos , Procesamiento de Imagen Asistido por Computador/métodos , Procesamiento de Señales Asistido por Computador , Humanos
9.
New Phytol ; 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39267260

RESUMEN

Monolignol serves as the building blocks to constitute lignin, the second abundant polymer on Earth. Despite two decades of diligent efforts, complete identification of all metabolites in the currently proposed monolignol biosynthesis pathway has proven elusive. This limitation also hampers their potential application. One of the primary obstacles is the challenge of assembling a collection of all molecules, because many are commercially unavailable or prohibitively costly. In this study, we established systematic pipelines to synthesize all 24 molecules through the conversions between functional groups on a core structure followed by the application to other core structures. We successfully identified all of them in Populus trichocarpa and Eucalyptus grandis, two representative species respectively from malpighiales and myrtales in angiosperms. Knowledge about monolignol metabolite chemosynthesis and identification will form the foundation for future studies.

10.
Oncogene ; 2024 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-39285230

RESUMEN

The RNA helicase DDX21 is vital for ribosome biogenesis and is upregulated in CRC, but the mechanism by which DDX21 is dysregulated and by which DDX21 promotes tumorigenesis in CRC remains poorly understood. Here, we showed that DDX21 is a direct transcriptional target gene of ß-catenin and mediates the protumorigenic function of ß-catenin in CRC. DDX21 expression is correlated with the expression and activity of ß-catenin, and high DDX21 expression is associated with a poor prognosis in CRC patients. Loss of DDX21 leads to cytoplasmic translocation and decreased transcriptional activity of YAP and suppresses the proliferation and migration of CRC cells, which can be partially rescued by YAP reactivation. Importantly, by using translation elongation inhibitors and DNA intercalators, we showed that ribosomal stress upregulates DDX21 expression and induces the downregulation of LATS and the activation of YAP, probably through the ZAKα-MKK4/7-JNK axis. Overall, our study revealed the transcriptional activation mechanism of DDX21 in CRC and the activation of YAP in the ribosomal stress response, indicating the potential of combination therapy involving the induction of ribosomal stress and YAP inhibition.

11.
Am J Prev Cardiol ; 19: 100726, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39286651

RESUMEN

Background and aims: Different lipoprotein(a) [Lp(a)] assays may affect risk stratification of individuals and thus clinical decision-making. We aimed to investigate how transitioning between Lp(a) assays at a large central laboratory affected the proportion of individuals with Lp(a) result above clinical thresholds. Methods: We studied nationwide clinical laboratory data including 185,493 unique individuals (47.7 % women) aged 18-50 years with 272,463 Lp(a) measurements using Roche (2000-2009) and Siemens Lp(a) assay (2009-2019). Results: While the majority of individuals (66-75 %) had low levels of Lp(a) (<30 mg/dL) independent of the assay used, the Roche assay detected 20 % more individuals with Lp(a) >50 mg/dL, 40 % more individuals with Lp(a) >100 mg/dL and 80 % more individuals with Lp(a) > 180 mg/dL than the currently used Siemens assay, likely due to calibration differences. Conclusion: Transitioning from one Lp(a) immunoassay to another had significant impact on Lp(a) results, particularly in individuals approaching clinically relevant Lp(a) thresholds.

12.
J Inflamm Res ; 17: 6345-6362, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39291081

RESUMEN

Background: Ulcerative colitis (UC) is a debilitating intestinal disorder that imposes a significant burden on those affected. Fatty acid metabolism plays a pivotal role in regulating immune cell function and maintaining internal homeostasis. This study investigates the biological and clinical significance of fatty acid metabolism within the context of UC. Methods: Gene expression profiles from patients with UC and healthy controls were retrieved, enabling the identification of differentially expressed genes (DEGs) specific to UC. These DEGs were then intersected with genes related to fatty acid metabolism, resulting in the identification of differentially expressed fatty acid metabolism-related genes (FAM-DEGs). Machine learning was employed to pinpoint key feature genes from the FAM-DEGs, which were subsequently used to construct a predictive UC model and to uncover molecular subtypes associated with fatty acid metabolism in UC. An animal model of UC was established using 3% dextran sulfate sodium (DSS) administration. Western blot analysis confirmed the expression levels of genes in intestinal tissues. Results: The machine learning analysis identified three pivotal genes-ACAT1, ACOX2, and HADHB-culminating in a highly predictive nomogram. Consensus cluster analysis further categorized 637 UC samples into two distinct subgroups. The molecular subtypes related to fatty acid metabolism in UC exhibited significant differences in gene expression, biological activities, and enrichment pathways. Immune infiltration analysis highlighted elevated expression of two genes (excluding HADHB) in subtype 1, which corresponded with a marked increase in immune cell infiltration within this subtype. Western blot analysis demonstrated that ACAT1, ACOX2, and HADHB expression levels in the DSS group were significantly reduced, paralleling those observed in the normal group. Conclusion: This study highlights the critical role of specific fatty acid metabolism-related genes in UC, emphasizing their potential as targets for therapeutic intervention and shedding light on the underlying mechanisms of UC progression.

13.
Emerg Microbes Infect ; 13(1): 2400546, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-39221898

RESUMEN

The vast majority of data obtained from sequence analysis of influenza A viruses (IAVs) have revealed that nonstructural 1 (NS1) proteins from H1N1 swine, H3N8 equine, H3N2 avian and the correspondent subtypes from dogs have a conserved four C-terminal amino acid motif when independent cross-species transmission occurs between these species. To test the influence of the C-terminal amino acid motifs of NS1 protein on the replication and virulence of IAVs, we systematically generated 7 recombinants, which carried naturally truncated NS1 proteins, and their last four C-terminal residues were replaced with PEQK and SEQK (for H1N1), EPEV and KPEI (for H3N8) and ESEV and ESEI (for H3N2) IAVs. Another recombinant was generated by removing the C-terminal residues by reverse genetics. Remarkably, the ESEI and KPEI motifs circulating in canines largely contributed efficient replication in cultured cells and these had enhanced virulence. In contrast, the avian ESEV motif was only responsible for high pathogenicity in mice. We examined the effects of these motifs upon interferon (IFN) induction. The 7 mutant viruses replicated in vitro in an IFN-independent manner, and the canine SEQK motif was able to induced higher levels of IFN-ß in human cell lines. These findings shed further new light on the role of the four C-terminal residues in replication and virulence of IAVs and suggest that these motifs can modulate viral replication in a species-specific manner.


Asunto(s)
Secuencias de Aminoácidos , Subtipo H1N1 del Virus de la Influenza A , Infecciones por Orthomyxoviridae , Proteínas no Estructurales Virales , Replicación Viral , Proteínas no Estructurales Virales/genética , Proteínas no Estructurales Virales/metabolismo , Proteínas no Estructurales Virales/química , Animales , Perros , Virulencia , Ratones , Subtipo H1N1 del Virus de la Influenza A/genética , Subtipo H1N1 del Virus de la Influenza A/patogenicidad , Subtipo H1N1 del Virus de la Influenza A/fisiología , Infecciones por Orthomyxoviridae/virología , Humanos , Células de Riñón Canino Madin Darby , Ratones Endogámicos BALB C , Enfermedades de los Perros/virología , Subtipo H3N2 del Virus de la Influenza A/genética , Subtipo H3N2 del Virus de la Influenza A/patogenicidad , Subtipo H3N2 del Virus de la Influenza A/fisiología , Subtipo H3N8 del Virus de la Influenza A/genética , Subtipo H3N8 del Virus de la Influenza A/patogenicidad , Femenino
14.
Brain Res Bull ; 217: 111077, 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39265741

RESUMEN

Neuropathic pain results from damage to nerves or the brain, and is characterized by symptoms such as allodynia, spontaneous pain, and hyperalgesia. The causes of this type of pain are intricate, which can make it difficult to treat. Sodium aescinate (SA), a natural extract from horse chestnut tree seeds, has been shown to act as a neuroprotector by inhibiting microglia activation. This study aims to explore the therapeutic potential of SA for neuropathic pain and the molecular mechanisms regulated by SA treatment. Through in vivo animal models and experiments, we found that SA treatment significantly reduced mechanical allodynia and heat hyperalgesia in neuropathic pain models. Additionally, SA inhibited O-GlcNAc-transferase (OGT)-induced O-GlcNAcylation (O-GlcNAc) modification in neuropathic pain mice. OGT overexpression could impede the therapeutic effects of SA on neuropathic pain. Further investigation revealed that Toll-like receptor 3 (TLR3), stabilized by OGT-induced O-GlcNAc modification, could activate the Mitogen activated protein kinase (MAPK) signaling pathway. Further in vivo experiments demonstrated that TLR3-mediated p38 mitogen-activated protein kinase (p38MAPK) activation is involved in SA-mediated relief of neuropathic pain. In conclusion, this study uncovers a novel molecular pathway deactivated by SA treatment in neuropathic pain.

15.
Int J Mol Sci ; 25(17)2024 Sep 07.
Artículo en Inglés | MEDLINE | ID: mdl-39273634

RESUMEN

Host cell proteins (HCPs) are one of the process-related impurities that need to be well characterized and controlled throughout biomanufacturing processes to assure the quality, safety, and efficacy of monoclonal antibodies (mAbs) and other protein-based biopharmaceuticals. Although ELISA remains the gold standard method for quantification of total HCPs, it lacks the specificity and coverage to identify and quantify individual HCPs. As a complementary method to ELISA, the LC-MS/MS method has emerged as a powerful tool to identify and profile individual HCPs during the downstream purification process. In this study, we developed a sensitive, robust, and reproducible analytical flow ultra-high-pressure LC (UHPLC)-high-resolution accurate mass (HRAM) data-dependent MS/MS method for HCP identification and monitoring using an Orbitrap Ascend BioPharma Tribrid mass spectrometer. As a case study, the developed method was applied to an in-house trastuzumab product to assess HCP clearance efficiency of the newly introduced POROS™ Caprylate Mixed-Mode Cation Exchange Chromatography resin (POROS Caprylate mixed-mode resin) by monitoring individual HCP changes between the trastuzumab sample collected from the Protein A pool (purified by Protein A chromatography) and polish pool (purified by Protein A first and then further purified by POROS Caprylate mixed-mode resin). The new method successfully identified the total number of individual HCPs in both samples and quantified the abundance changes in the remaining HCPs in the polish purification sample.


Asunto(s)
Anticuerpos Monoclonales , Cricetulus , Espectrometría de Masas en Tándem , Espectrometría de Masas en Tándem/métodos , Cromatografía Líquida de Alta Presión/métodos , Anticuerpos Monoclonales/aislamiento & purificación , Anticuerpos Monoclonales/química , Células CHO , Animales , Trastuzumab/química , Trastuzumab/análisis , Humanos
16.
Plants (Basel) ; 13(17)2024 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-39273921

RESUMEN

Invasive alien plants (IAPs) pose a significant threat to island biodiversity and severely impact ecosystems. Understanding the species-area relationship and environmental determinants of growth forms for IAP species on subtropical islands is crucial for establishing an IAP's early warning mechanism, enhancing island ecological management, and protecting the ecosystems of Fujian and other subtropical islands. The study identified significant species-area relationships for IAPs and different life-form plants (trees, shrubs, and herbs), with slopes of 0.27, 0.16, 0.15, and 0.24, respectively. The small island effect does not apply to all species. Isolation has little effect on species richness, and the IAPs on Fujian islands do not conform to the isolation effect in island biogeography. Landscape factors are the main determinants of IAPs and different life-form species richness, with area, shape index, and perimeter-area ratio being the three primary landscape factors. These environmental factors are closely related to habitat heterogeneity. Besides landscape factors, different life forms respond differently to environmental factors. Climate drives the species richness distribution of shrubs and herbs, while trees are mainly influenced by human activities. Overall, landscape, human disturbance, and climate jointly drive the distribution of IAPs, with landscape factors being the most significant.

17.
Nutrients ; 16(17)2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39275199

RESUMEN

This study aimed to investigate the associations between carbohydrate intake and gout risk, along with interactions between genetic susceptibility and carbohydrates, and the mediating roles of biomarkers. We included 187,387 participants who were free of gout at baseline and completed at least one dietary assessment in the UK Biobank. Cox proportional hazard models were used to estimate the associations between carbohydrate intake and gout risk. Over a median follow-up of 11.69 years, 2548 incident cases of gout were recorded. Total carbohydrate intake was associated with a reduced gout risk (Q4 vs. Q1: HR 0.67, 95% CI 0.60-0.74), as were total sugars (0.89, 0.80-0.99), non-free sugars (0.70, 0.63-0.78), total starch (0.70, 0.63-0.78), refined grain starch (0.85, 0.76-0.95), wholegrain starch (0.73, 0.65-0.82), and fiber (0.72, 0.64-0.80), whereas free sugars (1.15, 1.04-1.28) were associated with an increased risk. Significant additive interactions were found between total carbohydrates and genetic risk, as well as between total starch and genetic risk. Serum urate was identified as a significant mediator in all associations between carbohydrate intake (total, different types, and sources) and gout risk. In conclusion, total carbohydrate and different types and sources of carbohydrate (excluding free sugars) intake were associated with a reduced risk of gout.


Asunto(s)
Carbohidratos de la Dieta , Predisposición Genética a la Enfermedad , Gota , Humanos , Gota/genética , Gota/epidemiología , Carbohidratos de la Dieta/administración & dosificación , Carbohidratos de la Dieta/efectos adversos , Reino Unido/epidemiología , Masculino , Estudios Prospectivos , Femenino , Persona de Mediana Edad , Factores de Riesgo , Adulto , Ácido Úrico/sangre , Modelos de Riesgos Proporcionales , Anciano , Dieta/efectos adversos , Biomarcadores/sangre
18.
Chemosphere ; : 143336, 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39277039

RESUMEN

Photoelectrochemical (PEC) detection technology is key for fighting pollution, leveraging the photoelectric conversion of the photoelectrode material. A specialized photoelectrode was developed to detect Hg2+ ions with exceptional sensitivity, utilizing an anodic PEC sensor composed of Er3NbO7/P@g-C3N4/SnS2 ternary nanocomposite. Rare earth metal niobates (RENs) were chosen due to their underexplored potential, whose performance was enhanced through bandgap engineering and surface modification, facilitated by P@g-C3N4 as an immobilization matrix and SnS2, belonging to the I-IV semiconductors category fostering hybrid heterojunction formation for boasting optical properties and suitable redox potentials. Introducing Hg2+ into the system, a specific amalgamation reaction occurs between reduced Hg and Sn. This reaction obstructs electron transfer to the FTO electrode surface, leading to the recombination of charges. The proposed PEC sensor exhibited remarkable analytical performance for Hg2+ detection, high sensitivity, a detection limit of 0.019 pM, excellent selectivity, and a detectable concentration range of 0.002 to 0.15 nM. Additionally, it demonstrated good recovery and low relative standard deviation when analyzing Hg2+ in water samples, highlighting the potential application of the heterostructure in detecting heavy metal ions via PEC technology.

19.
Pestic Biochem Physiol ; 204: 106062, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39277376

RESUMEN

MicroRNAs (miRNAs) represent a class of short, non-coding RNAs that are widely acknowledged as crucial participants in virus-host interactions. MiR-184, a highly conserved and abundant miRNA in insects, has yet to be extensively studied for its involvement in baculovirus infection. In this study, we investigated how miR-184 affects the infection and replication of Autographa californica multiple nucleopolyhedrovirus (AcMNPV). The results indicated that after AcMNPV infection, there was an initial increase in the expression of miR-184 within 24 h, followed by a subsequent decrease. MiR-184 can inhibit AcMNPV's DNA replication and budded virus production by directly targeting four viral genes, namely ie1, ac66, p49, and lef9. Moreover, suppressing miR-184 expression enhanced the insecticidal efficacy of AcMNPV against Spodoptera exigua larvae and markedly elevated the host ATPase gene expressions. These findings showed that miR-184 had a substantial impact on the interactions between baculoviruses and insects, presenting a prospective candidate for developing highly effective miRNA-based biopesticides.


Asunto(s)
MicroARNs , Nucleopoliedrovirus , Spodoptera , Replicación Viral , Nucleopoliedrovirus/genética , Nucleopoliedrovirus/fisiología , MicroARNs/genética , MicroARNs/metabolismo , Animales , Spodoptera/virología , Spodoptera/genética , Células Sf9 , Larva/virología , Larva/genética
20.
Langmuir ; 40(37): 19799-19803, 2024 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-39224945

RESUMEN

Electrical double layer (EDL) plays a crucial role in colloidal chemistry, which can be modified by changing the pH and ionic strength of a solution. Even though EDL is well-recognized, there are limited studies exploring interactions between two-dimensional (2D) and zero-dimensional nanoparticles. Herein, we demonstrate a simple pH-based approach to control the EDL of boron nitride nanosheets (BNNSs) and gold nanoparticles (AuNPs) that plays a crucial role in their interaction, displaying a one-way gate effect. We observed that as the EDL decreases, AuNPs can come into closer interaction with BNNSs, and this also resulted in a deceleration of the aggregation process of AuNPs when functionalized with l-cysteine. This work provides a fundamental understanding of how modulation of the EDL of 2D nanomaterials can be achieved through functionalizing strategies.

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