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1.
J Immunol ; 212(7): 1244-1253, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38334457

RESUMO

A variety of commercial platforms are available for the simultaneous detection of multiple cytokines and associated proteins, often employing Ab pairs to capture and detect target proteins. In this study, we comprehensively evaluated the performance of three distinct platforms: the fluorescent bead-based Luminex assay, the proximity extension-based Olink assay, and a novel proximity ligation assay platform known as Alamar NULISAseq. These assessments were conducted on human serum samples from the National Institutes of Health IMPACC study, with a focus on three essential performance metrics: detectability, correlation, and differential expression. Our results reveal several key findings. First, the Alamar platform demonstrated the highest overall detectability, followed by Olink and then Luminex. Second, the correlation of protein measurements between the Alamar and Olink platforms tended to be stronger than the correlation of either of these platforms with Luminex. Third, we observed that detectability differences across the platforms often translated to differences in differential expression findings, although high detectability did not guarantee the ability to identify meaningful biological differences. Our study provides valuable insights into the comparative performance of these assays, enhancing our understanding of their strengths and limitations when assessing complex biological samples, as exemplified by the sera from this COVID-19 cohort.


Assuntos
COVID-19 , Humanos , COVID-19/diagnóstico , Imunoensaio/métodos , Citocinas/metabolismo , Soro/metabolismo
2.
Am J Pathol ; 194(7): 1388-1404, 2024 07.
Artigo em Inglês | MEDLINE | ID: mdl-38670529

RESUMO

Intrahepatic cholangiocarcinoma (ICC) is a highly malignant neoplasm prone to metastasis. Whether cancer-associated fibroblasts (CAFs) affect the metastasis of ICC is unclear. Herein, ICC patient-derived CAF lines and related cancerous cell lines were established and the effects of CAFs on the tumor progressive properties of the ICC cancerous cells were analyzed. CAFs could be classified into cancer-restraining or cancer-promoting categories based on distinct tumorigenic effects. The RNA-sequencing analyses of ICC cancerous cell lines identified polycomb group ring finger 4 (PCGF4; alias BMI1) as a potential metastasis regulator. The changes of PCGF4 levels in ICC cells mirrored the restraining or promoting effects of CAFs on ICC migration. Immunohistochemical analyses on the ICC tissue microarrays indicated that PCGF4 was negatively correlated with overall survival of ICC. The promoting effects of PCGF4 on cell migration, drug resistance activity, and stemness properties were confirmed. Mechanistically, cancer-restraining CAFs triggered the proteasome-dependent degradation of PCGF4, whereas cancer-promoting CAFs enhanced the stability of PCGF4 via activating the IL-6/phosphorylated STAT3 pathway. In summary, the current data identified the role of CAFs in ICC metastasis and revealed a new mechanism of the CAFs on ICC progression in which PCGF4 acted as the key effector by both categories of CAFs. These findings shed light on developing comprehensive therapeutic strategies for ICC.


Assuntos
Neoplasias dos Ductos Biliares , Fibroblastos Associados a Câncer , Colangiocarcinoma , Metástase Neoplásica , Complexo Repressor Polycomb 1 , Animais , Humanos , Masculino , Camundongos , Neoplasias dos Ductos Biliares/patologia , Neoplasias dos Ductos Biliares/metabolismo , Neoplasias dos Ductos Biliares/genética , Fibroblastos Associados a Câncer/metabolismo , Fibroblastos Associados a Câncer/patologia , Linhagem Celular Tumoral , Movimento Celular , Colangiocarcinoma/patologia , Colangiocarcinoma/metabolismo , Colangiocarcinoma/genética , Regulação Neoplásica da Expressão Gênica , Complexo Repressor Polycomb 1/metabolismo , Complexo Repressor Polycomb 1/genética , Fator de Transcrição STAT3/metabolismo
3.
J Proteome Res ; 23(8): 3460-3468, 2024 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-39013122

RESUMO

Neonatal respiratory distress syndrome (NRDS) is one of the most severe respiratory disorders in preterm infants (PTIs) due to immature lung development. To delineate the serum metabolic alterations and gut microbiota variations in NRDS and assess their implications on neonatal development, we enrolled 13 NRDS neonates and 12 PTIs and collected fecal and serum specimens after birth. Longitudinal fecal sampling was conducted weekly for a month in NRDS neonates. NRDS neonates were characterized by notably reduced gestational ages and birth weights and a higher rate of asphyxia at birth relative to PTIs. Early postnatal disturbances in tryptophan metabolism were evident in the NRDS group, concomitant with elevated relative abundance of Haemophilus, Fusicatenibacter, and Vibrio. Integrative multiomics analyses revealed an inverse relationship between tryptophan concentrations and Blautia abundance. At one-week old, NRDS neonates exhibited cortisol regulation anomalies and augmented hepatic catabolism. Sequential microbial profiling revealed distinct gut microbiota evolution in NRDS subjects, characterized by a general reduction in potentially pathogenic bacteria. The acute perinatal stress of NRDS leads to mitochondrial compromise, hormonal imbalance, and delayed gut microbiota evolution. Despite the short duration of NRDS, its impact on neonatal development is significant and requires extended attention.


Assuntos
Fezes , Microbioma Gastrointestinal , Recém-Nascido Prematuro , Síndrome do Desconforto Respiratório do Recém-Nascido , Humanos , Recém-Nascido , Síndrome do Desconforto Respiratório do Recém-Nascido/microbiologia , Síndrome do Desconforto Respiratório do Recém-Nascido/metabolismo , Fezes/microbiologia , Feminino , Masculino , Idade Gestacional , Triptofano/metabolismo , Triptofano/sangue , Hidrocortisona/sangue
4.
Diabetologia ; 67(4): 738-754, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38236410

RESUMO

AIMS/HYPOTHESIS: Sodium-glucose co-transporter 2 (SGLT2) inhibitors (SGLT2i) are antihyperglycaemic drugs that protect the kidneys of individuals with type 2 diabetes mellitus. However, the underlying mechanisms mediating the renal benefits of SGLT2i are not fully understood. Considering the fuel switches that occur during therapeutic SGLT2 inhibition, we hypothesised that SGLT2i induce fasting-like and aestivation-like metabolic patterns, both of which contribute to the regulation of metabolic reprogramming in diabetic kidney disease (DKD). METHODS: Untargeted and targeted metabolomics assays were performed on plasma samples from participants with type 2 diabetes and kidney disease (n=35, 11 women) receiving canagliflozin (CANA) 100 mg/day at baseline and 12 week follow-up. Next, a systematic snapshot of the effect of CANA on key metabolites and pathways in the kidney was obtained using db/db mice. Moreover, the effects of glycine supplementation in db/db mice and human proximal tubular epithelial cells (human kidney-2 [HK-2]) cells were studied. RESULTS: Treatment of DKD patients with CANA for 12 weeks significantly reduced HbA1c from a median (interquartile range 25-75%) of 49.0 (44.0-57.0) mmol/mol (7.9%, [7.10-9.20%]) to 42.2 (39.7-47.7) mmol/mol (6.8%, [6.40-7.70%]), and reduced urinary albumin/creatinine ratio from 67.8 (45.9-159.0) mg/mmol to 47.0 (26.0-93.6) mg/mmol. The untargeted metabolomics assay showed downregulated glycolysis and upregulated fatty acid oxidation. The targeted metabolomics assay revealed significant upregulation of glycine. The kidneys of db/db mice undergo significant metabolic reprogramming, with changes in sugar, lipid and amino acid metabolism; CANA regulated the metabolic reprogramming in the kidneys of db/db mice. In particular, the pathways for glycine, serine and threonine metabolism, as well as the metabolite of glycine, were significantly upregulated in CANA-treated kidneys. Glycine supplementation ameliorated renal lesions in db/db mice by inhibiting food intake, improving insulin sensitivity and reducing blood glucose levels. Glycine supplementation improved apoptosis of human proximal tubule cells via the AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway. CONCLUSIONS/INTERPRETATION: In conclusion, our study shows that CANA ameliorates DKD by inducing fasting-like and aestivation-like metabolic patterns. Furthermore, DKD was ameliorated by glycine supplementation, and the beneficial effects of glycine were probably due to the activation of the AMPK/mTOR pathway.


Assuntos
Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , Inibidores do Transportador 2 de Sódio-Glicose , Camundongos , Animais , Humanos , Feminino , Canagliflozina/farmacologia , Canagliflozina/uso terapêutico , Diabetes Mellitus Tipo 2/metabolismo , Nefropatias Diabéticas/metabolismo , Reprogramação Metabólica , Proteínas Quinases Ativadas por AMP/metabolismo , Transportador 2 de Glucose-Sódio/metabolismo , Estivação , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/metabolismo , Rim/metabolismo , Jejum , Serina-Treonina Quinases TOR/metabolismo , Glicina/metabolismo , Mamíferos/metabolismo
5.
J Transl Med ; 22(1): 225, 2024 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-38429794

RESUMO

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is becoming increasingly prevalent worldwide, emerging as a significant health issue on a global scale. Berberine exhibits potential for treating NAFLD, but clinical evidence remains inconclusive. This meta-analysis was conducted to assess the efficacy and safety of berberine for treating NAFLD. METHODS: This study was registered with PROSPERO (No. CRD42023462338). Identification of randomized controlled trials (RCTs) involved searching 6 databases covering the period from their initiation to 9 September 2023. The primary outcomes comprised liver function markers such as glutamyl transpeptidase (GGT), alanine transaminase (ALT), aspartate transaminase (AST), lipid indices including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C), homeostasis model assessment for insulin resistance (HOMA-IR) and body mass index (BMI). Review Manager 5.4 and STATA 17.0 were applied for analysis. RESULTS: Among 10 RCTs involving 811 patients, berberine demonstrated significant reductions in various parameters: ALT (standardized mean difference (SMD) = - 0.72), 95% confidence interval (Cl) [- 1.01, - 0.44], P < 0.00001), AST (SMD = - 0.79, 95% CI [- 1.17, - 0.40], P < 0.0001), GGT (SMD = - 0.62, 95% CI [- 0.95, - 0.29], P = 0.0002), TG (SMD = - 0.59, 95% CI [- 0.86, - 0.31], P < 0.0001), TC(SMD = - 0.74, 95% CI [- 1.00, - 0.49], P < 0.00001), LDL-C (SMD = - 0.53, 95% CI [- 0.88, - 0.18], P = 0.003), HDL-C (SMD = - 0.51, 95% CI [- 0.12, 1.15], P = 0.11), HOMA-IR (SMD = - 1.56, 95% CI [- 2.54, - 0.58], P = 0.002), and BMI (SMD = - 0.58, 95% CI [- 0.77, - 0.38], P < 0.00001). Importantly, Berberine exhibited a favorable safety profile, with only mild gastrointestinal adverse events reported. CONCLUSION: This meta-analysis demonstrates berberine's efficacy in improving liver enzymes, lipid profile, and insulin sensitivity in NAFLD patients. These results indicate that berberine shows promise as an adjunct therapy for NAFLD. Trial registration The protocol was registered with PROSPERO (No. CRD42023462338). Registered on September 27, 2023.


Assuntos
Berberina , Resistência à Insulina , Hepatopatia Gordurosa não Alcoólica , Humanos , Berberina/efeitos adversos , HDL-Colesterol , LDL-Colesterol , Lipídeos , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Resultado do Tratamento , Triglicerídeos
6.
Glob Chang Biol ; 30(4): e17264, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38556774

RESUMO

Nutrient enrichment often alters the biomass and species composition of plant communities, but the extent to which these changes are reversible after the cessation of nutrient addition is not well-understood. Our 22-year experiment (15 years for nutrient addition and 7 years for recovery), conducted in an alpine meadow, showed that soil nitrogen concentration and pH recovered rapidly after cessation of nutrient addition. However, this was not accompanied by a full recovery of plant community composition. An incomplete recovery in plant diversity and a directional shift in species composition from grass dominance to forb dominance were observed 7 years after the nutrient addition ended. Strikingy, the historically dominant sedges with low germination rate and slow growth rate and nitrogen-fixing legumes with low germination rate were unable to re-establish after nutrient addition ceased. By contrast, rapid recovery of aboveground biomass was observed after nutrient cessation as the increase in forb biomass only partially compensated for the decline in grass biomass. These results indicate that anthropogenic nutrient input can have long-lasting effects on the structure, but not the soil chemistry and plant biomass, of grassland communities, and that the recovery of soil chemical properties and plant biomass does not necessarily guarantee the restoration of plant community structure. These findings have important implications for the management and recovery of grassland communities, many of which are experiencing alterations in resource input.


Assuntos
Pradaria , Plantas , Biomassa , Poaceae , Solo/química , Nitrogênio/análise , Nutrientes
7.
BMC Endocr Disord ; 24(1): 223, 2024 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-39448988

RESUMO

BACKGROUND: This study aimed to compare the diagnostic accuracy of four indicators, including waist-to-height ratio (WHTR), vascular adiposity index (VAI), TG/HDL-C, and BMI/HDL-C for metabolic syndrome (MS) in Chinese adults aged 40 years and above. Additionally, the study aimed to develop an efficient diagnostic model displayed by a nomogram based on individual's BMI and circulating HDL-C level. METHODS: A cross-sectional study was conducted on 699 participants aged 40 years and above. Quartiles of BMI/HDL-C, TG/HDL-C, VAI, and WHTR were used as independent variables, and metabolic syndrome was used as the dependent variable. Logistic regression was conducted to explore the impact of each parameter on the risk of MS. The areas under the receiver operating characteristics were compared to determine the accuracy of the indicators in diagnosing MS in the participants. Logistic regression was run to construct the nomograms, and the performance of the nomogram was assessed by a calibration curve. RESULTS: MS subjects had higher levels of BMI, BFM, PBF, VFA, AMC, WC, SCR, TG, and insulin, but lower LDH and HDL-C levels than the subjects without MS. The BMI/HDL-C ratio was positively correlated with the prevalence of MS and its components. The final diagnostic model included five variables: gender, BFM, WC, TG, and BMI/HDL-C. The model showed good calibration and discrimination power with an AUC of 0.780. The cut-off value for the nomogram was 0.623 for diagnosing MS. CONCLUSIONS: BMI/HDL-C ratio was an independent risk factor for MS in Chinese adults. BMI/HDL-C was significantly correlated with MS and its components. BMI/HDL-C was the most powerful diagnostic indicator compared to other indicators, including TG/HDL-C, VAI and WHTR for diagnosing MS. The nomogram drawn based on the diagnostic model provided a practical tool for diagnosing MS in Chinese adults.


Assuntos
Índice de Massa Corporal , HDL-Colesterol , Diagnóstico Precoce , Síndrome Metabólica , Humanos , Síndrome Metabólica/diagnóstico , Síndrome Metabólica/sangue , Síndrome Metabólica/epidemiologia , Estudos Transversais , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , HDL-Colesterol/sangue , China/epidemiologia , Fatores de Risco , Idoso , Nomogramas , Biomarcadores/sangue , População do Leste Asiático
8.
Surg Endosc ; 38(3): 1637-1646, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38286835

RESUMO

BACKGROUND: Nonradiation, digital cholangioscope (DCS)-assisted endoscopic intervention for cholelithiasis has not been widely performed. For this study, we aimed to report the feasibility, efficacy, and safety of an established DCS-guided lithotomy procedure. METHODS: Data relating to biliary exploration, stone clearance, adverse events, and follow-up were obtained from 289 patients. The choledocholithiasis-related outcomes via the DCS-guided procedure were subsequently compared to those via conventional endoscopic retrograde cholangiopancreatography (ERCP). RESULTS: Biliary access was achieved in 285 patients. The technical success rate for the exploration of the common bile duct, the cystic stump, the hilar ducts, and secondary radicals was 100%. Moreover, the success rates were 98.4%, 61.7%, and 20.7%, for the exploration of the cystic duct, complete cystic duct, and gallbladder, respectively. Suspicious or confirmed suppurative cholecystitis, cholesterol polyps, and hyperplastic polyps were detected in 42, 23, and 5 patients, respectively. Stone clearance was achieved in one session in 285 (100%), 11 (100%), 13 (100%), 7 (100%), 6 (100%), and 3 (14.3%) patients with choledocholithiasis and hepatolithiasis, cystic duct stump stones, nondiffuse located intrahepatic lithiasis, a single cystic duct stone, a single gallbladder stone, and diffuse located intrahepatic lithiasis, respectively. Complete stone clearance for diffuse intrahepatic lithiasis was achieved in 19 (90.5%) patients, and fractioned re-lithotomy was performed in 16 (76.2%) patients. One patient developed mild acute cholangitis, and 12 developed mild pancreatitis. Stones recurred in one patient. Compared with conventional ERCP, DCS-guided lithotomy has the advantages of clearing difficult-to-treat choledocholithiasis and revealing concomitant biliary lesions, and this technique has fewer complications and a decreased risk of stone recurrence. CONCLUSIONS: The technical profile, efficacy, and safety of nonradiation-guided and DCS-guided lithotomy are shown in this study. We provide a feasible modality for the endoscopic removal of cholelithiasis.


Assuntos
Cálculos , Coledocolitíase , Litíase , Hepatopatias , Humanos , Coledocolitíase/cirurgia , Vesícula Biliar , Estudos de Viabilidade , Resultado do Tratamento , Colangiopancreatografia Retrógrada Endoscópica/métodos , Estudos Retrospectivos
9.
Nucleic Acids Res ; 50(19): 10869-10881, 2022 10 28.
Artigo em Inglês | MEDLINE | ID: mdl-36243974

RESUMO

Cancer is a disease of gene dysregulation, where cells acquire somatic and epigenetic alterations that drive aberrant cellular signaling. These alterations adversely impact transcriptional programs and cause profound changes in gene expression. Interpreting somatic alterations within context-specific transcriptional programs will facilitate personalized therapeutic decisions but is a monumental task. Toward this goal, we develop a partially interpretable neural network model called Chromatin-informed Inference of Transcriptional Regulators Using Self-attention mechanism (CITRUS). CITRUS models the impact of somatic alterations on transcription factors and downstream transcriptional programs. Our approach employs a self-attention mechanism to model the contextual impact of somatic alterations. Furthermore, CITRUS uses a layer of hidden nodes to explicitly represent the state of transcription factors (TFs) to learn the relationships between TFs and their target genes based on TF binding motifs in the open chromatin regions of tumor samples. We apply CITRUS to genomic, transcriptomic, and epigenomic data from 17 cancer types profiled by The Cancer Genome Atlas. CITRUS predicts patient-specific TF activities and reveals transcriptional program variations between and within tumor types. We show that CITRUS yields biological insights into delineating TFs associated with somatic alterations in individual tumors. Thus, CITRUS is a promising tool for precision oncology.


Assuntos
Aprendizado Profundo , Neoplasias , Humanos , Cromatina/genética , Neoplasias/genética , Medicina de Precisão , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
10.
Molecules ; 29(19)2024 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-39407653

RESUMO

Chlormequat chloride (CCC), as a commonly used plant growth regulator in the production of rhizomatous medicinal herbs, can effectively control the bolting phenomenon in Angelica sinensis, significantly increasing the yield of underground rhizomes (medicinal part). However, its specific effects on the intrinsic quality of Angelica sinensis, especially medicinal components, require further investigation. The objective of this study is to conduct a thorough examination of CCC residue and its influence on the yield and medicinal components of Angelica sinensis. By spraying different concentrations of CCC on Angelica sinensis, we systematically monitored the final yield of Angelica sinensis Radix (ASR) in each treatment group and the residual concentration of CCC in ASR. Using UPLC-QTOF-MS technology, we conducted an in-depth analysis of the metabolic profile of ASR. Subsequently, UFLC-MS/MS was employed to accurately quantify the changes in the content of nine key active components in ASR. The results of this study indicate that the application of CCC significantly improves the yield of ASR, with the best effect observed at 0.1 g/L, resulting in a yield increase of 24.8%. Meanwhile, the residual amount of CCC in ASR is positively correlated with the application concentration, with the residual levels as high as 7.12 mg/kg in the high-concentration treatment group. Metabolomic analysis preliminarily identified 21 chemical components in ASR, including four organic acids and 13 phthalides. It is worth noting that the quantitative analysis results indicate significant changes in active components such as butylphthalide, Z-ligustilide, and ferulic acid after the application of CCC. Specifically, high-concentration CCC significantly increased the content of butylphthalide and levistolide A, while low-concentration CCC significantly promoted the accumulation of coniferyl ferulate and senkyunolide A, accompanied by a significant decrease in Z-ligustilide and ferulic acidy. In conclusion, while CCC use can increase yield, the associated increase in residues and imbalanced composition ratios may threaten the quality and safety of ASR. Therefore, it is crucial to control the amount of CCC used rationally to balance yield enhancement and quality assurance.


Assuntos
Angelica sinensis , Clormequat , Espectrometria de Massas em Tandem , Angelica sinensis/química , Clormequat/farmacologia , Clormequat/análise , Cromatografia Líquida de Alta Pressão , Ácidos Cumáricos/análise , Rizoma/química , 4-Butirolactona/análogos & derivados , 4-Butirolactona/farmacologia , 4-Butirolactona/análise , Benzofuranos/farmacologia , Benzofuranos/análise , Benzofuranos/química , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Reguladores de Crescimento de Plantas/farmacologia
11.
J Med Virol ; 95(6): e28887, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37341527

RESUMO

The highly contagious SARS-CoV-2 and its associated disease (COVID-19) are a threat to global public health and economies. To develop effective treatments for COVID-19, we must understand the host cell types, cell states and regulators associated with infection and pathogenesis such as dysregulated transcription factors (TFs) and surface proteins, including signaling receptors. To link cell surface proteins with TFs, we recently developed SPaRTAN (Single-cell Proteomic and RNA-based Transcription factor Activity Network) by integrating parallel single-cell proteomic and transcriptomic data based on Cellular Indexing of Transcriptomes and Epitopes by sequencing (CITE-seq) and gene cis-regulatory information. We apply SPaRTAN to CITE-seq data sets from patients with varying degrees of COVID-19 severity and healthy controls to identify the associations between surface proteins and TFs in host immune cells. Here, we present COVID-19db of Immune Cell States (https://covid19db.streamlit.app/), a web server containing cell surface protein expression, SPaRTAN-inferred TF activities, and their associations with major host immune cell types. The data include four high-quality COVID-19 CITE-seq data sets with a toolset for user-friendly data analysis and visualization. We provide interactive surface protein and TF visualizations across major immune cell types for each data set, allowing comparison between various patient severity groups for the discovery of potential therapeutic targets and diagnostic biomarkers.


Assuntos
COVID-19 , Fatores de Transcrição , Humanos , Fatores de Transcrição/metabolismo , SARS-CoV-2/metabolismo , Proteômica , Regulação da Expressão Gênica
12.
Neuropathol Appl Neurobiol ; 49(1): e12855, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36259948

RESUMO

AIMS: The study was designed to explore the role of apolipoprotein E (ApoE) deficiency concomitant with dietary docosahexaenoic acid (DHA) treatment on brain ß-amyloid (Aß) and lipid levels. METHOD: A 5-month dietary DHA intervention was conducted in ApoE-deficient (ApoE-/- ) mice and wild-type C57BL/6J (C57 wt) mice. The Morris water maze test was performed to assess the behaviour of the animals. The cortical contents of soluble Aß1-40 and Aß1-42 were detected by enzyme-linked immunosorbent assay (ELISA). Cortical fatty acid levels were detected by gas chromatography. Gene and protein expression of molecules associated with cerebral Aß and lipid metabolism were measured using real-time polymerase chain reaction (PCR), Western blot and histological methods. RESULTS: DHA treatment increased the content of cortical DHA and n-3 polyunsaturated fatty acids (n-3 PUFAs) but decreased the ratio of n-6/n-3 PUFAs in ApoE-/- mice; whereas the content of cortical DHA and n-3 PUFAs in C57 wt mice remained unchanged after DHA treatment. Cerebral Fabp5 and Cd36 gene expression were significantly downregulated in DHA-fed C57 wt mice; cerebral Cd36 and Scarb1 gene expression were significantly upregulated, whereas Fabp5 gene expression was downregulated in DHA-fed ApoE-/- mice. In comparison with C57 wt mice, the content of cortical soluble Aß1-42 , total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) increased, whereas the level of high-density lipoprotein cholesterol (HDL-C) decreased in ApoE-/- mice. Interestingly, these differences were significantly reversed by DHA dietary treatment. CONCLUSION: DHA intervention has discrepant impacts on cerebral lipids, fatty acid transporter expression and soluble Aß levels in ApoE-/- and C57 wt mice, suggesting the modifying role of ApoE status on the responses of cerebral lipids and Aß metabolism to DHA treatment.


Assuntos
Ácidos Docosa-Hexaenoicos , Ácidos Graxos , Camundongos , Animais , Ácidos Docosa-Hexaenoicos/metabolismo , Ácidos Docosa-Hexaenoicos/farmacologia , Ácidos Graxos/metabolismo , Camundongos Endogâmicos C57BL , Apolipoproteínas E/genética , Colesterol
13.
Mol Ecol ; 32(13): 3747-3762, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37060060

RESUMO

The processes governing soil bacteria biogeography are still not fully understood. It remains unknown how the importance of environmental filtering and dispersal differs between bacterial taxonomic and functional biogeography, and whether their importance is scale-dependent. We sampled soils across the Tibet plateau, with distances among plots ranging from 20 m to 1550 km. Taxonomic composition of bacterial community was characterized by 16S amplicon sequencing and functional community composition by qPCR targeting 9 functional groups involved in N dynamics. Factors representing climate, soil and plant community were measured to assess different facets of environmental dissimilarity. Both bacterial taxonomic and functional dissimilarities were more related to abiotic dissimilarity than biotic (vegetation) dissimilarity or distance. Taxonomic dissimilarity was mostly explained by differences in soil pH and mean annual temperature (MAT), while functional dissimilarity was linked to differences in soil N and P availabilities and N:P ratio. Soil pH and MAT remained the main determinants of taxonomic dissimilarity across spatial scales. In contrast, the explanatory variables of N-related functional dissimilarity varied across the scales, with soil moisture and organic matter having the highest role across short distances (<~330 km), and available P, N:P ratio and distance being important over long distances (>~660 km). Our results demonstrate how biodiversity dimension (taxonomic versus functional aspects) and spatial scale influence the factors driving soil bacterial biogeography.


Assuntos
Microbiologia do Solo , Solo , Tibet , Solo/química , Bactérias/genética , Biodiversidade , Plantas
14.
Opt Express ; 31(3): 4553-4568, 2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36785420

RESUMO

We present and investigate a hybrid laser-based method of surface shaping for damage mitigation on fused silica surfaces. Damage sites were removed and precisely shaped into an optically-benign cone by a procedure of femtosecond laser ablation with a subsequent CO2 laser polishing process. The morphology of the cone rim was quantitatively predicted by a numerical model. Since the heat-affected zone (HAZ) of the laser polishing process was effectively confined by the optimization of ablation parameters, the dimensions of the raised rim were reduced by an order of magnitude. The intensity of the on-axis hotspot was positively related to the dimensions of the raised rim, and thus an inapparent downstream intensification was achieved by the rim reduction. Laser-induced damage threshold (LIDT) of the cone was tested to be ∼14 J/cm2 on the input surface. Therefore, the presented method is appropriate to mitigate damage and also provides a promising approach to manufacturing functional microstructures for high-power applications.

15.
Langmuir ; 39(32): 11294-11303, 2023 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-37534406

RESUMO

As a promising photocatalyst material, g-C3N4 has great application potential in energy production and environmental improvement. In this work, surface-modified g-C3N4 nanosheets with excellent stability and high photocatalytic activity were successfully synthesized by physical steam activation. The charge transfer rate of carbon nitride was improved due to the synergistic effect of nitrogen defect and oxygen doping caused by steam activation. Meanwhile, the specific surface area and pore volume of the optimized sample reached 124.3 m2 g-1 and 0.42 cm3 g-1, respectively, which increased the exposed reaction sites of reactants, enhancing the photocatalytic activity of g-C3N4. In addition, this novel g-C3N4 displayed a great H2 evolution rate of 5889.39 µmol h-1 g-1 with a methylene blue degradation rate up to 6.52 × 10-3 min-1, which was 3.7 and 2.1 times of original g-C3N4, respectively. This study provided a simple and economical method to develop a highly efficient g-C3N4 photocatalyst for solar energy conversion.

16.
Langmuir ; 39(19): 6924-6931, 2023 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-37129080

RESUMO

Carbon-based supercapacitors with high performance have a wide foreground among various energy storage devices. In this work, wood-based hollow carbon spheres (WHCS) were prepared from liquefied wood through the processes of emulsification, curing, carbonization, and activation. Then, the hydrodeposition method was used to introduce nickel sulfide (NiS) to the surface of the microspheres, obtaining NiS/WHCS as the supercapacitor electrode. The results show that NiS/WHCS microspheres exhibited a core-shell structure and flower-like morphology with a specific surface (307.55 m2 g-1) and a large total pore volume (0.14 cm3 g-1). Also, the capacitance could be up to 1533.6 F g-1 at a current density of 1 A g-1. In addition, after 1000 charge/discharge cycles, the specific capacitance remained at 72.8% at the initial current density of 5 A g-1. Hence, NiS/WHCS with excellent durability and high specific capacitance is a potential candidate for electrode materials.

17.
Langmuir ; 39(37): 13325-13334, 2023 09 19.
Artigo em Inglês | MEDLINE | ID: mdl-37612781

RESUMO

Titanium carbide MXene quantum dots (MQDs) possess intrinsic regulatory properties and selective toxicity to cancer cells. Here, MDQs were selected for the modification of hydroxyapatite (HA) microspheres, and MXene quantum dots-modified hydroxyapatite (MQDs-HA) hollow microspheres with controllable shapes and sizes were prepared as bone drug carriers. The results show that the prepared MQDs-HA hollow microspheres had a large BET surface area (231.2 m2/g), good fluorescence, and low toxicity. In addition, MQDs-HA showed a mild storage-release behavior and good responsiveness of pH and near-infrared (NIR). Thus, the MQDs-HA hollow microspheres have broad application prospects in the field of drug delivery and photothermal therapy.


Assuntos
Portadores de Fármacos , Pontos Quânticos , Portadores de Fármacos/toxicidade , Microesferas , Pontos Quânticos/toxicidade , Durapatita/toxicidade , Concentração de Íons de Hidrogênio
18.
Mol Biol Rep ; 50(9): 7783-7796, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37480509

RESUMO

DNA methylation and demethylation are widely acknowledged epigenetic phenomena which can cause heritable and phenotypic changes in functional genes without changing the DNA sequence. They can thus affect phenotype formation in medicinal plants. However, a comprehensive review of the literature summarizing current research trends in this field is lacking. Thus, this review aims to provide an up-to-date summary of current methods for the detection of 5-mC DNA methylation, identification and analysis of DNA methyltransferases and demethyltransferases, and regulation of DNA methylation in medicinal plants. The data showed that polyploidy and environmental changes can affect DNA methylation levels in medicinal plants. Changes in DNA methylation can thus regulate plant morphogenesis, growth and development, and formation of secondary metabolites. Future research is required to explore the mechanisms by which DNA methylation regulates the accumulation of secondary metabolites in medicinal plants.


Assuntos
Plantas Medicinais , Plantas Medicinais/genética , Metilação de DNA/genética , Metilases de Modificação do DNA , Epigenômica , Desmetilação
19.
Clin Lab ; 69(7)2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-37436385

RESUMO

BACKGROUND: The aim of the study was to investigate the clinical and laboratory characteristics of IgM primary plasma cell leukemia. METHODS: We retrospectively analyzed a case of clinical and laboratory characteristics of IgM primary plasma cell leukemia and review related literature of patient with primary plasma cell leukemia. RESULTS: Laboratory tests: Alanine aminotransferase 128 U/L, Aspartate aminotransferase 245 U/L, Globulin 47.8 g/L, Lactate dehydrogenase 1,114 U/L, Creatinine 111.7 mol/L, Serum calcium 2.47 mmol/L, ß2 microglobulin 8.52 µg/mL, Immunoglobulin G 31.41 g/L, D-dimer 2.34 mg/L, Prothrombin time 13.6 seconds Fibrinogen 2 g/L, White blood cell 7.38 x 109/L, Red blood cell 3.46 x 1012/L, Hemoglobin 115 g/L, Platelet 7 x 109/L, and 12% Primitive naive cells can be seen in peripheral blood smear. Bone marrow smear: Accounted for 52% of original cells, the cell size, shape is irregular, the edge is not neat, the cell quality is rich, stained gray blue, cytoplasmic staining uneven, some devouring blood cells can be seen in the cytoplasm or unknown substance, the nucleus shape is irregular, visible distortion and fold, is visible on the part of the nuclei cavitation sample inclusions, chromatin is meticulous, partly visible large nucleoli. Flow cytometry results showed abnormal cell group held 23.85% of nuclear cells, expression of CD38, CD138, CD117, cKappa, partly CD20, weak expressing CD45, not express CD27, CD19, CD56, CD200, CD81, cLambda. It was a monoclonal plasma cell with an abnormal phenotype, consistent with a plasma cell tumor. Immunofixation electrophoresis results showed that the serum M protein was 22.80 g/L, which was IgG-κ type, the serum free KAP light chain was 232.69 mg/L, the serum free LAM light chain was 5.37 mg/L, and the rFLC (κ-FLC: λFLC) was 43.33. The diagnosis was primary plasmacytic leukemia of light chain type. CONCLUSIONS: Primary plasma cell leukemia (pPCL) is a rare and highly aggressive plasma cell malignancy. Laboratory staff should pay more attention to and recognize the pleomorphic morphology of neoplastic plasma cells, which can enable timely clinical development of bone marrow smear, biopsy, flow cytometry, and cytogenetic tests providing help in early diagnosis and treatment.


Assuntos
Leucemia Plasmocitária , Neoplasias de Plasmócitos , Humanos , Leucemia Plasmocitária/diagnóstico , Leucemia Plasmocitária/genética , Leucemia Plasmocitária/patologia , Estudos Retrospectivos , Antígenos CD19 , Imunoglobulina M
20.
Nucleic Acids Res ; 49(17): 9633-9647, 2021 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-34500467

RESUMO

The identity and functions of specialized cell types are dependent on the complex interplay between signaling and transcriptional networks. Recently single-cell technologies have been developed that enable simultaneous quantitative analysis of cell-surface receptor expression with transcriptional states. To date, these datasets have not been used to systematically develop cell-context-specific maps of the interface between signaling and transcriptional regulators orchestrating cellular identity and function. We present SPaRTAN (Single-cell Proteomic and RNA based Transcription factor Activity Network), a computational method to link cell-surface receptors to transcription factors (TFs) by exploiting cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) datasets with cis-regulatory information. SPaRTAN is applied to immune cell types in the blood to predict the coupling of signaling receptors with cell context-specific TFs. Selected predictions are validated by prior knowledge and flow cytometry analyses. SPaRTAN is then used to predict the signaling coupled TF states of tumor infiltrating CD8+ T cells in malignant peritoneal and pleural mesotheliomas. SPaRTAN enhances the utility of CITE-seq datasets to uncover TF and cell-surface receptor relationships in diverse cellular states.


Assuntos
Perfilação da Expressão Gênica , Proteômica , Receptores de Superfície Celular/metabolismo , Fatores de Transcrição/metabolismo , Biologia Computacional/métodos , Regulação da Expressão Gênica , Humanos , Leucócitos Mononucleares/metabolismo , Mesotelioma/metabolismo , Transdução de Sinais
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