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Advanced portable healthcare devices with high efficiencies, small pressure drops, and high-temperature resistance are urgently desired in harsh environments with high temperatures, high humidities, and high levels of atmospheric pollution. Triboelectric nanogenerators (TENGs), which serve as energy converters in a revolutionary self-powered sensor device, present a sustainable solution for meeting these requirements. In this work, we developed a porous negative triboelectric material by synthesizing ZIF-8 on the surface of a cellulose/graphene oxide aerogel, grafting it with trimethoxy(1H,1H,2H,2H-heptadecafluorodecyl)silane, and adding a negative corona treatment, and it was combined with a positive triboelectric material to create a cellulose nanofiber-based TENG self-powered filter. The devices achieved a balance between a small pressure drop (53 Pa) and high filtration efficiency (98.97%, 99.65%, and 99.93% for PM0.3, PM0.5, and PM1, respectively), demonstrating robust filtration properties at high temperatures and high humidities. Our work provides a new approach for developing self-powered wearable healthcare devices with excellent air filtration properties.
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Nonapomictic citrus tetraploids are desirable in citrus breeding for the production of triploid, seedless varieties, and polyploid rootstocks. However, only a few lines have been reported, and they were all generated using chemical methods. A 2x + 4 × cytochimera of the nonapomictic citrus variety 'Orah' mandarin, which developed from a bud mutant, was found due to its morphology differing from that of diploid plants and characterised via ploidy analysis combining flow cytometry and chromosome observation. The chimaera was stable, and there were 1.86-1.90 times as tetraploid cells as diploid cells. Anatomical structure observation revealed that the 'Orah' chimaera may be a periclinal chimaera with diploid cells in the L1 layer and tetraploid cells in the L2 and L3 layers. The chimaera showed some typical traits of polyploid plants, including thicker shoots, wider and thicker leaves, larger flowers and fruits, and fewer but larger seeds in fruits than in diploid plants. Almost all the seeds of the chimaera were monoembryonic. Most of the self-pollinated progenies of the chimaera were identified as tetraploids, and some triploid, pentaploid, and hexaploid plants were found. As a female, the chimaera produced allotriploids when crossed with Australian finger lime. In addition, 6 plants developed from polyembryonic seeds of the chimaera were identified as sexual tetraploid progenies with low-level recombinant genomes. Therefore, the 'Orah' 2x + 4 × chimaera can be used as a female parent to produce hybrid triploid and tetraploid citrus plants with high efficiency. Identification of the chimaera demonstrated that tetraploid citrus plants, especially nonapomictic varieties, can be generated from shoot bud mutants. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-024-01456-x.
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Microalgae are considered to be natural producers of bioactive pigments, with the production of pigments from microalgae being a sustainable and economical strategy that promises to alleviate growing demand. Chlorophyll, as the main pigment of photosynthesis, has been widely studied, but its medicinal applications as an antioxidant, antibacterial, and antitumor reagent are still poorly understood. Chlorophyll is the most important pigment in plants and algae, which not only provides food for organisms throughout the biosphere, but also plays an important role in a variety of human and man-made applications. The biological activity of chlorophyll is closely related to its chemical structure; its specific structure offers the possibility for its medicinal applications. This paper reviews the structural and functional roles of microalgal chlorophylls, commonly used extraction methods, and recent advances in medicine, to provide a theoretical basis for the standardization and commercial production and application of chlorophylls.
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Microalgas , Humanos , Clorofila/química , Fotosíntesis , Antioxidantes/farmacología , Antioxidantes/química , PlantasRESUMEN
A fluorescence biosensor for determination of aflatoxin B1 (AFB1) based on polydiacetylene (PDA) liposomes and exonuclease III (EXO III)-assisted recycling amplification was developed. The AFB1 aptamer partially hybridizes with complementary DNA (cDNA), which is released upon recognition of AFB1 by the aptamer. Subsequently, the cDNA hybridizes with hairpin H to form double-stranded DNA that undergoes digestion by EXO III, resulting in the cyclic release of cDNA and generation of capture DNA for further reaction. The capture DNA then hybridizes with probe modified on PDA liposomes, leading to aggregation of liposomes and subsequent fluorescence production. This strategy exhibited a limit of detection of 0.18 ng/mL within the linear range 1-100 ng/mL with a determination coefficient > 0.99. The recovery ranged from 92.81 to 106.45%, with relative standard deviations (RSD) between 1.73 and 4.26%, for corn, brown rice, peanut butter, and wheat samples. The stability, accuracy, and specificity of the method demonstrated the applicability for real sample analysis.
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Aflatoxina B1 , Técnicas Biosensibles , Exodesoxirribonucleasas , Límite de Detección , Liposomas , Polímero Poliacetilénico , Polímero Poliacetilénico/química , Liposomas/química , Exodesoxirribonucleasas/química , Exodesoxirribonucleasas/metabolismo , Técnicas Biosensibles/métodos , Aflatoxina B1/análisis , Aptámeros de Nucleótidos/química , Técnicas de Amplificación de Ácido Nucleico/métodos , Poliinos/química , Espectrometría de Fluorescencia/métodos , Zea mays/química , Triticum/química , Oryza/química , Polímeros/química , Contaminación de Alimentos/análisisRESUMEN
The accurate estimation of the optical properties of turbid media by using a spatially resolved (SR) technique remains a challenging task due to measurement errors in the acquired spatially resolved diffuse reflectance (SRDR) and challenges in inversion model implementation. In this study, what we believe to be a novel data-driven model based on a long short-term memory network and attention mechanism (LSTM-attention network) combined with SRDR is proposed for the accurate estimation of the optical properties of turbid media. The proposed LSTM-attention network divides the SRDR profile into multiple consecutive and partially overlaps sub-intervals by using the sliding window technique, and uses the divided sub-intervals as the input of the LSTM modules. It then introduces an attention mechanism to evaluate the output of each module automatically and form a score coefficient, finally obtaining an accurate estimation of the optical properties. The proposed LSTM-attention network is trained with Monte Carlo (MC) simulation data to overcome the difficulty in preparing training (reference) samples with known optical properties. Experimental results of the MC simulation data showed that the mean relative error (MRE) with 5.59% for the absorption coefficient [with the mean absolute error (MAE) of 0.04â cm-1, coefficient of determination (R2) of 0.9982, and root mean square error (RMSE) of 0.058â cm-1] and 1.18% for the reduced scattering coefficient (with an MAE of 0.208â cm-1, R2 of 0.9996, and RMSE of 0.237â cm-1), which were significantly better than those of the three comparative models. The SRDR profiles of 36 liquid phantoms, collected using a hyperspectral imaging system that covered a wavelength range of 530-900â nm, were used to test the performance of the proposed model further. The results showed that the LSTM-attention model achieved the best performance (with the MRE of 14.89%, MAE of 0.022â cm-1, R2 of 0.9603, and RMSE of 0.026â cm-1 for the absorption coefficient; and the MRE of 9.76%, MAE of 0.732â cm-1, R2 of 0.9701, and RMSE of 1.470â cm-1for the reduced scattering coefficient). Therefore, SRDR combined with the LSTM-attention model provides an effective method for improving the estimation accuracy of the optical properties of turbid media.
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Both anti-glomerular basement membrane (GBM) disease and the anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) are common causes of pulmonary-renal syndrome. Organizing pneumonia (OP), a special pattern of interstitial lung disease, is extremely rare either in AAV or anti-GBM disease. We report an old woman presented with OP on a background of co-presentation with both ANCA and anti-GBM antibodies.
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Enfermedad por Anticuerpos Antimembrana Basal Glomerular , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos , Glomerulonefritis , Neumonía Organizada , Neumonía , Femenino , Humanos , Anticuerpos Anticitoplasma de Neutrófilos , Autoanticuerpos , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/complicacionesRESUMEN
BACKGROUND: Chronic kidney disease (CKD) leads to end-stage renal failure and cardiovascular events. An attribute to these progressions is abnormalities in inflammation, which can be evaluated using the neutrophil-to-lymphocyte ratio (NLR). We aimed to investigate the association of NLR with the progression of end stage of renal disease (ESRD), cardiovascular disease (CVD) and all-cause mortality in Chinese patients with stages 1-4 CKD. METHODS: Patients with stages 1-4 CKD (18-74 years of age) were recruited at 39 centers in 28 cities across 22 provinces in China since 2011. A total of 938 patients with complete NLR and other relevant clinical variables were included in the current analysis. Cox regression analysis was used to estimate the association between NLR and the outcomes including ESRD, CVD events or all-cause mortality. RESULTS: Baseline NLR was related to age, hypertension, serum triglycerides, total serum cholesterol, CVD history, urine albumin to creatinine ratio (ACR), chronic kidney disease-mineral and bone disorder (CKD-MBD), hyperlipidemia rate, diabetes, and estimated glomerular filtration rate (eGFR). The study duration was 4.55 years (IQR 3.52-5.28). Cox regression analysis revealed an association of NLR and the risk of ESRD only in patients with stage 4 CKD. We did not observe any significant associations between abnormal NLR and the risk of either CVD or all-cause mortality in CKD patients in general and CKD patients grouped according to the disease stages in particular. CONCLUSION: Our results suggest that NLR is associated with the risk of ESRD in Chinese patients with stage 4 CKD. NLR can be used in risk assessment for ESRD among patients with advanced CKD; this application is appealing considering NLR being a routine test. Trial registration ClinicalTrials.gov Identifier NCT03041987. Registered January 1, 2012. (retrospectively registered) ( https://www.clinicaltrials.gov/ct2/show/NCT03041987?term=Chinese+Cohort+Study+of+Chronic+Kidney+Disease+%28C-STRIDE%29&rank=1 ).
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Pueblo Asiatico , Fallo Renal Crónico/sangre , Fallo Renal Crónico/etiología , Linfocitos/patología , Neutrófilos/patología , Insuficiencia Renal Crónica/sangre , Insuficiencia Renal Crónica/complicaciones , Enfermedades Cardiovasculares/complicaciones , Enfermedades Cardiovasculares/mortalidad , Estudios de Cohortes , Femenino , Humanos , Incidencia , Estimación de Kaplan-Meier , Fallo Renal Crónico/mortalidad , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Insuficiencia Renal Crónica/mortalidadRESUMEN
Aggregated metastatic cancer cells, referred to as circulating tumor cell (CTC) clusters, are present in the blood of cancer patients and contribute to cancer metastasis. However, the origin of CTC clusters, especially intravascular aggregates, remains unknown. Here, we employ suspension culture methods to mimic CTC cluster formation in the circulation of breast cancer patients. CTC clusters generated using these methods exhibited an increased metastatic potential that was defined by the overexpression of heparanase (HPSE). Heparanase induced FAK- and ICAM-1-dependent cell adhesion, which promoted intravascular cell aggregation. Moreover, knockdown of heparanase or inhibition of its activity with JG6, a heparanase inhibitor, was sufficient to block the formation of cell clusters and suppress breast cancer metastasis. Our data reveal that heparanase-mediated cell adhesion is critical for metastasis mediated by intravascular CTC clusters. We also suggest that targeting the function of heparanase in cancer cell dissemination might limit metastatic progression.
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Neoplasias de la Mama/fisiopatología , Agregación Celular/fisiología , Glucuronidasa/fisiología , Metástasis de la Neoplasia/fisiopatología , Células Neoplásicas Circulantes/metabolismo , Animales , Adhesión Celular/fisiología , Línea Celular Tumoral , Femenino , Quinasa 1 de Adhesión Focal/metabolismo , Glucuronidasa/genética , Humanos , Molécula 1 de Adhesión Intercelular/metabolismo , Ratones Endogámicos BALB C , Paxillin/metabolismo , Regulación hacia Arriba , Familia-src Quinasas/metabolismoRESUMEN
Wu-tou Decoction (WTD) is a classic herbal formula in traditional Chinese medicine for the treatment of joint diseases, neuropathic pain (NP) and inflammatory pain. In this study we investigated whether WTD produced analgesic action in a mouse spinal nerve ligation (SNL) model and elucidated the underlying molecular mechanisms. Mice were subjected to SNL and orally treated with WTD (3.15, 6.30 or 12.60 g·kg-1·d-1) for 21 d. SNL induced mechanical hyperalgesia and heat hyperalgesia characterized by rapid and persistent pain hypersensitivity. In addition, the expression levels of IL-1ß, TNF-α, CCL2 and CXCL1 in the spinal cord dorsal horn were dramatically increased on the 10th d post-surgery. Oral administration of WTD dose-dependently suppressed both mechanical and heat hyperalgesia as well as the expression levels of inflammatory cytokines in the spinal cord dorsal horn on the 21st d post-surgery. Then whole-genome microarray analyses were conducted to detect the gene expression profiles of spinal cord dorsal horn in SNL mice with or without WTD treatment. After construction of the WTD-SNL-network and topological analysis, a list of candidate target genes of WTD acting on SNL-induced NP was identified and found to be functionally enriched in several glial cell activation-related pathways and neuroinflammatory pathways. Our data have clarified the gene expression patterns in the mouse spinal cord under the NP condition. We also demonstrate the analgesic action of WTD through suppression of glial cell activation and neuroinflammation, which suggest the potential of WTD as a promising candidate for the treatment of NP.
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Analgésicos/farmacología , Medicamentos Herbarios Chinos/farmacología , Perfilación de la Expresión Génica/métodos , Medicina Tradicional China/métodos , Neuralgia/tratamiento farmacológico , Análisis de Secuencia por Matrices de Oligonucleótidos , Asta Dorsal de la Médula Espinal/efectos de los fármacos , Biología de Sistemas/métodos , Administración Oral , Analgésicos/administración & dosificación , Animales , Conducta Animal/efectos de los fármacos , Citocinas/genética , Citocinas/metabolismo , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Medicamentos Herbarios Chinos/administración & dosificación , Regulación de la Expresión Génica , Redes Reguladoras de Genes/efectos de los fármacos , Masculino , Ratones Endogámicos ICR , Neuralgia/genética , Neuralgia/metabolismo , Neuralgia/fisiopatología , Umbral del Dolor/efectos de los fármacos , Células del Asta Posterior/efectos de los fármacos , Células del Asta Posterior/metabolismo , Transducción de Señal/efectos de los fármacos , Asta Dorsal de la Médula Espinal/metabolismo , Asta Dorsal de la Médula Espinal/fisiopatología , Factores de Tiempo , TranscriptomaRESUMEN
Malformations of cortical development (MCD) are critical brain development disorders associated with varied abnormalities in both anatomic structures and neural functioning. It is also a very common etiology to the epilepsy, in which the alteration on excitability of cortical neurons is hypothesized as one of important causes to the epileptic seizures. Due to the key role in regulating neuron firing properties, the plasticity of axon initial segment (AIS) was investigated in present study to further determine the relation between MCD and epilepsy. Our results showed a prolonged decrease in the length of AIS occurred in MCD animal models. Besides, the AIS was also found greatly shortened in MCD models during the acute, but not chronic phase of status epileptics compared with intact controls. Our findings of identification of AIS plasticity in MCD animal models and its hypersensitivity to status epilepsy are significant in furthering our understanding of the pathophysiological mechanisms involved in this disorder.
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Segmento Inicial del Axón/efectos de los fármacos , Hipersensibilidad/etiología , Malformaciones del Desarrollo Cortical/complicaciones , Neuronas/efectos de los fármacos , Estado Epiléptico/complicaciones , Animales , Modelos Animales de Enfermedad , Femenino , Plasticidad Neuronal/efectos de los fármacos , Plasticidad Neuronal/fisiología , Neuronas/fisiología , Pilocarpina/farmacología , Ratas Sprague-Dawley , Estado Epiléptico/inducido químicamenteRESUMEN
BACKGROUND: Processed Chuanwu (PCW), the mother root of Aconitum carmichaelii Debeauxv, has been widely used as a classic Traditional Chinese Medicine for pain relieve for over two millennia clinically. However, its action on chronic inflammatory pain has not been clarified. Here, we investigated the antinociceptive effect of PCW in complete freund's adjuvant (CFA)-induced mice and its possible mechanisms associated with opioid system and TRPV1 ion channel. METHODS: Male ICR mice were intraplantarly injected with CFA. PCW (0.34, 0.68 and 1.35 g/kg) was orally given to mice once a day for 7 days. Von frey hairs and planter test were assessed to evaluate the antinociceptive effect of PCW. To investigate the participation of dynorphin/opioid system in PCW antinociception, subtype-specific opioid receptor antagonists or anti-dynorphin A antiserum were used. To eliminate other central mechanisms that contribute to PCW antinociception, hot plate (50 °C) test were performed. Further, involvements of TRPV1 in PCW antinociception were evaluated in CFA-induced TRPV1(-/-) and TRPV1(+/+) C57BL/6 male mice, and in capsaicin-induced nociception ICR naive mice pretreated with nor-BNI. Meanwhile, calcium imaging was performed in HEK293T-TRPV1 cells. Finally, rotarod, open-field tests and body temperature measurement were carried out to assess side effects of PCW. RESULTS: PCW dose-dependently attenuated mechanical and heat hypersensitivities with no tolerance, which could be partially attenuated by coadministration of k-opioid receptor antagonist nor-binaltorphimine (nor-BNI) or anti-dynorphin A (1-13) antiserum. And PCW antinociception was totally erased by pretreatment with nor-BNI in the hot plate test. In addition, PCW antinociception was decreased in TRPV1(-/-) mice compared to TRPV1(+/+) group. And PCW still manifested inhibitory effects in capsaicin-induced nociception with nor-BNI pretreatment. PCW significantly inhibited capsaicin-induced calcium influx in HEK293T-TRPV1 cells. Finally, no detectable side effects were found in naive mice treated with PCW. CONCLUSIONS: This study shows PCW's potent antinociceptive effect in inflammatory conditions without obvious side effects. This effect may result from the activation of κ-opioid receptor via dynorpin release and the inhibition of TRPV1. These findings indicate that PCW might be a potential agent for the management of chronic inflammatory pain.
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Aconitum/química , Analgésicos/química , Dinorfinas/metabolismo , Extractos Vegetales/química , Receptores Opioides kappa/metabolismo , Canales Catiónicos TRPV/metabolismo , Administración Oral , Analgésicos Opioides/química , Animales , Temperatura Corporal , Calibración , Supervivencia Celular , Cromatografía Líquida de Alta Presión , Dinorfinas/antagonistas & inhibidores , Dinorfinas/química , Adyuvante de Freund/química , Células HEK293 , Humanos , Inflamación/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos ICR , Raíces de Plantas/químicaRESUMEN
O-GlcNAcylation is a post-translational modification that regulates a broad range of nuclear and cytoplasmic proteins and is emerging as a key regulator of various biological processes. Previous studies have shown that increased levels of global O-GlcNAcylation and O-GlcNAc transferase (OGT) are linked to the incidence of metastasis in breast cancer patients, but the molecular basis behind this is not fully known. In this study, we have determined that the actin-binding protein cofilin is O-GlcNAcylated by OGT and mainly, if not completely, mediates OGT modulation of cell mobility. O-GlcNAcylation at Ser-108 of cofilin is required for its proper localization in invadopodia at the leading edge of breast cancer cells during three-dimensional cell invasion. Loss of O-GlcNAcylation of cofilin leads to destabilization of invadopodia and impairs cell invasion, although the actin-severing activity or lamellipodial localization is not affected. Our study provides insights into the mechanism of post-translational modification in fine-tuning the regulation of cofilin activity and suggests its important implications in cancer metastasis.
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Acetilglucosamina/metabolismo , Factores Despolimerizantes de la Actina/metabolismo , Neoplasias de la Mama/metabolismo , Factores Despolimerizantes de la Actina/genética , Animales , Neoplasias de la Mama/patología , Línea Celular Tumoral , Movimiento Celular , Femenino , Glicosilación , Humanos , Mutación , N-Acetilglucosaminiltransferasas/metabolismo , Invasividad Neoplásica , Seudópodos/metabolismo , Seudópodos/patología , RatasRESUMEN
BACKGROUND: Steroid-induced osteonecrosis of the femoral head (steroid-induced ONFH) presents great challenges due to the various effects of steroids on multi-system pathways involved into osteoblast differentiation, osteoblast and osteoclast apoptosis, lipid metabolism, calcium metabolism and coagulation. As one of the most frequently used herbs in Traditional Chinese Medicine formulas that are prescribed for the regulation of bone and mineral metabolism, the therapeutic effects of Achyranthes bidentata on steroid-induced ONFH remain unclear. Thus, the aim of the current study was to verify whether Achyranthes bidentata extract (ABE) can be used to prevent steroid-induced ONFH and to investigate its underlying pharmacological mechanisms. METHODS: Steroid-induced ONFH rat models were established to evaluate the effects of ABE treatment on osteonecrotic changes and repair processes. Microfocal computed tomography (Micro-CT) was performed to assess the effects of ABE treatment on bone mass, microstructure, and vascularization. Then, the effects of ABE treatment on osteoclast differentiation and bone formation were also evaluated in vivo and in vitro. In addition, receptor activator of nuclear factor kappa B (RANK), RANK ligand (RANKL), and osteoprotegerin (OPG) expression in sera, femoral heads and bone marrow-derived mesenchymal stem cells (BMSCs) were detected at both protein and mRNA levels. RESULTS: The ratio of empty lacuna, adipose tissue area, and adipocyte perimeter in the bone marrow were markedly lower in the ABE treatment groups than in the model group. Micro-CT evaluation indicated that ABE treatment could improve the microstructure of the trabecular bone, increase bone mineral density and promote vascularization in steroid-induced ONFH rats. Moreover, ABE treatment inhibited osteoclast differentiation and activated bone formation markers. Interestingly, OPG downregulation, RANK and RANKL upregulation, and an increased ratio of RANKL to OPG in sera and necrotic femoral head could be reversed by ABE treatment, which also effectively inhibited RANKL-induced osteoclast differentiation and regulated RANKL and OPG expression of in vitro. CONCLUSION: ABE may prevent steroid-induced ONFH and alleviate steroid-induced bone deterioration by regulating the RANKL/RANK/OPG signaling pathway.
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Achyranthes/química , Cabeza Femoral/efectos de los fármacos , Osteonecrosis/prevención & control , Extractos Vegetales/farmacología , Prednisolona/efectos adversos , Transducción de Señal , Animales , Secuencia de Bases , Densidad Ósea , Desarrollo Óseo/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Cartilla de ADN , Cabeza Femoral/metabolismo , Cabeza Femoral/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Osteoclastos/citología , Osteoclastos/efectos de los fármacos , Osteonecrosis/metabolismo , Osteoprotegerina/metabolismo , Ligando RANK/metabolismo , Ratas , Ratas Wistar , Reacción en Cadena en Tiempo Real de la Polimerasa , Receptor Activador del Factor Nuclear kappa-BRESUMEN
BACKGROUND: The role of ferroptosis in lupus nephritis (LN) is unclear. This study aimed to explore the effects of ferroptosis-related genes in LN through bioinformatics prediction and experimental validation. METHODS: Sample data were collected from the GEO dataset and divided into glomeruli and tubulointerstitium. We collected 382 ferroptosis-related genes. The intersection of ferroptosis-related genes with glomeruli and tubulointerstitium data, respectively, was performed. Machine learning methods (including unsupervised cluster typing and random forests) were operated to identify ferroptosis subtyping and ferroptosis important genes in LN. Immune infiltration and functional analysis were performed. The expression of ferroptosis important gene ATF3 was validated in vivo and in vitro. RESULTS: 6 ferroptosis important genes common to glomeruli and tubulointerstitium were screened, including ATF3, CD44, CYBB, JUN, NCF2, and NNMT. ATF3 decreased in the LN group compared to the Control. Silencing ATF3 mitigated LPS/erastin-induced ferroptosis. Functional analysis showed that ATF3 was markedly enriched in the interferon-gamma-mediated signaling pathway, ECM-receptor interaction, and cell adhesion. In glomeruli, T cells regulatory (Tregs) infiltration decreased and Macrophages M1 levels increased with elevated ATF3 expression. Levels of immune cell infiltration were altered in different ferroptosis subtypes of LN glomeruli and tubulointerstitium. CONCLUSIONS: Ferroptosis-related ATF3 levels decreased in LN. Inhibition of ATF3 might alleviate LN development by affecting the macrophage M1 and Treg cell infiltration. These implied that ATF3 might be a potential target for developing LN therapeutic strategies.
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Objective To confirm that Hantaan virus (HTNV) can infect BEAS-2B human normal lung epithelial cells and examine the host immune response and metabolic changes induced by HTNV infection by transcriptomic analysis. Methods Western blotting, quantitative real-time PCR and immunofluorescence assay were used to assess the viral load in BEAS-2B cells, and RNA sequencing was employed for transcriptomic analysis. Results Following the infection of BEAS-2B cells with HTNV, there was an increase in the expression of HTNV nucleocapsid protein (NP) and small segment (S) over time. A transcriptomic analysis of these infected cells at 48-hour mark identified 328 genes that were differentially expressed. GO and KEGG enrichment analysis revealed that these differences were primarily associated with interferon response and innate immune pattern recognition receptor pathways. Protein-protein interaction network analysis identified several genes related to innate immune responses, including four genes encoding disintegrin and metalloproteinase with thrombospondin motifs. Metabolic pathway analysis showed three genes related to terpenoid backbone biosynthesis, two genes related to glycolysis/gluconeogenesis and two genes related to steroid hormone biosynthesis. Subcellular localization analysis indicated that many of the differentially expressed genes were located in mitochondria. Conclusion HTNV is capable of effectively infecting BEAS-2B cells, making them a suitable in vitro model for studying HTNV infection in human lung epithelial. By utilizing bioinformatics methods to screen for differentially expressed genes and metabolic pathways associated with HTNV infection, researchers can establish a theoretical foundation for investigating the molecular mechanisms underling HTNV infection.
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Células Epiteliales , Virus Hantaan , Inmunidad Innata , Pulmón , Humanos , Células Epiteliales/virología , Células Epiteliales/inmunología , Células Epiteliales/metabolismo , Virus Hantaan/fisiología , Virus Hantaan/inmunología , Pulmón/virología , Pulmón/inmunología , Pulmón/metabolismo , Línea Celular , Perfilación de la Expresión Génica/métodos , Mapas de Interacción de ProteínasRESUMEN
It is not clear whether different radiation methods have different effects on enamel. The purpose of this study was to compare the effects of single and fractionated radiation on enamel and caries susceptibility and to provide an experimental basis for further study of radiationrelated caries. Thirty-six caries-free human third molars were collected and randomly divided into three groups (n = 12). Group1 (control group) was not exposed to radiation. Group 2 received single radiation with a cumulative dose of 70 Gy. Group 3 underwent fractionated radiation, receiving 2 Gy/day for 5 days followed by a 2-day rest period, for a total of 7 weeks with a cumulative dose of 70 Gy. Changes in microhardness, roughness, surface morphology, bacterial adhesion and ability of acid resistance of each group were tested. Scanning electron microscope revealed that the enamel surface in both radiation groups exhibited unevenness and cracks. Compared with the control group, microhardness and acid resistance of enamel decreased, while roughness and bacterial adhesion increased in both the single radiation and fractionated radiation groups. Compared with the single radiation group, the enamel surface microhardness and acid resistance decreased in the fractionated radiation group, while roughness and bacterial adhesion increased. Both single radiation and fractionated radiation resulting in changes in the physical and biological properties of enamel, with these changes being more pronounced in the fractionated radiation group. Therefore, fractionated radiation is recommended as a more suitable method for constructing a radiationrelated caries model in vitro.
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Adhesión Bacteriana , Caries Dental , Esmalte Dental , Propiedades de Superficie , Humanos , Esmalte Dental/efectos de la radiación , Esmalte Dental/microbiología , Caries Dental/microbiología , Caries Dental/patología , Adhesión Bacteriana/efectos de la radiación , Propiedades de Superficie/efectos de la radiación , Microscopía Electrónica de Rastreo , Susceptibilidad a Caries Dentarias , DurezaRESUMEN
Colorectal cancer (CRC) is a prevalent and aggressive malignancy with high mortality rates and significant risks to human well-being. Population-wide screening for tumor suppressor genes and oncogenes shows promise for reducing the incidence and fatality of CRC. Recent studies have suggested that NLRX1, an innate immunity suppressor, may play a role in regulating chronic inflammation and tumorigenesis. However, further investigation is needed to understand the specific role of NLRX1 in CRC. To evaluate the impact of NLRX1 on migration, invasion, and metastasis, two human colon cancer cell lines were studied in vitro. Additionally, a knockout mouse tumor-bearing model was used to validate the inhibitory effect of NLRX1 on tumor emergence and progression. The Seahorse XF96 technology was employed to assess mitochondrial function and glycolysis in colorectal cancer cells overexpressing NLRX1. Moreover, public databases were consulted to analyze gene and protein expression levels of NLRX1. Finally, the results were validated using a series of CRC patient samples. Our findings demonstrate that downregulation of NLRX1 enhances proliferation, colony formation, and tumor-forming capacity in HCT116 and LoVo cells. Conversely, overexpression of NLRX1 negatively impacts basal respiration and mitochondrial ATP-linked respiration in both cell lines, resulting in a notable decrease in maximal respiration during the standard mitochondrial stress test. Furthermore, analysis of data from the TCGA database reveals a significant reduction in NLRX1 expression in colon and rectal cancer tissues compared to normal tissues. This result was validated using clinical samples, where immunohistochemistry staining and western blotting demonstrated a notable reduction in NLRX1 protein levels in CRC compared to adjacent normal tissues. The decreased expression of NLRX1 may serve as a significant prognostic indicator and diagnostic biomarker for CRC patients.
Asunto(s)
Neoplasias Colorrectales , Progresión de la Enfermedad , Mitocondrias , Proteínas Mitocondriales , Humanos , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/genética , Animales , Mitocondrias/metabolismo , Mitocondrias/patología , Ratones , Proteínas Mitocondriales/metabolismo , Proteínas Mitocondriales/genética , Línea Celular Tumoral , Ratones Noqueados , Proliferación Celular , Células HCT116 , Movimiento CelularRESUMEN
Hantaan virus (HTNV) is a major public health concern due to its ability to cause hemorrhagic fever with renal syndrome (HFRS) in Eurasia. Symptoms of HFRS include fever, hemorrhage, immune dysfunction and renal impairment, and severe cases can be fatal. T cell-mediated adaptive immune responses play a pivotal role in countering HTNV infection. However, our understanding of HTNV and T cell interactions in the disease progression is limited. In this study, we found that human CD4+ T cells can be directly infected with HTNV, thereby facilitating viral replication and production. Additionally, T-cell immunoglobulin and mucin 1 (TIM-1) participated in the process of HTNV infection of Jurkat T cells, and further observed that HTNV enters Jurkat T cells via the clathrin-dependent endocytosis pathway. These findings not only affirm the susceptibility of human CD4+ T lymphocytes to HTNV but also shed light on the viral tropism. Our research elucidates a mode of the interaction between the virus infection process and the immune system. Critically, this study provides new insights into the pathogenesis of HTNV and the implications for antiviral research.