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1.
Heliyon ; 10(7): e29062, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38601693

RESUMO

Background: The role of Ferroptosis in the course of sepsis-induced myopathy is yet unclear. The objective of our work is to identify key genes connected with Ferroptosis in sepsis-induced myopathy and investigate possible pharmaceutical targets related to this process. This research aims to provide new insights into the management of sepsis-induced myopathy. Methods: We got the GSE13205 dataset from the Gene Expression Omnibus (GEO) and extracted Ferroptosis-associated genes from the FerrDb database. After conducting a functional annotation analysis of these genes, we created a protein-protein interaction network using Cytoscape software to identify important genes. Subsequently, we employed CMap to investigate prospective pharmaceuticals that could target these crucial genes. Results: A total of 61 genes that are expressed differently (DEGs) have been found concerning Ferroptosis. These genes are involved in a wide range of biological functions, including reacting to signals from outside the cell and the availability of nutrients, programmed cell death, controlling apoptosis, and responding to peptides, chemical stressors, and hormones. The KEGG pathway study revealed that these pathways are involved in Ferroptosis, autophagy, P53 signaling, PI3K-Akt signaling, mTOR signaling, HIF-1 signaling, endocrine resistance, and different tumorigenic processes. In addition, we created a network that shows the simultaneous expression of important genes and determined the top 10 medications that have the potential to treat sepsis-induced myopathy. Conclusion: The bioinformatics research undertaken sheds insight into the probable role of Ferroptosis-associated genes in sepsis-induced myopathy. The identified critical genes show potential as therapeutic targets for treating sepsis-induced myopathy, offering opportunities for the development of tailored medicines.

2.
BMC Psychiatry ; 24(1): 273, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38609907

RESUMO

BACKGROUND: Extensive literature revealed that childhood trauma serves as a significant risk factor for developing psychotic-like experiences (PLEs) among the general population. Resilience has been regarded as a protective factor against PLEs. However, it remains unclear what role resilience plays in the relationship between childhood trauma and PLEs. METHODS: A total of 4302 college students completed the web-based survey in January 2021. Participants completed self-report measures of sample characteristics variables, childhood trauma, and PLEs. Moderation and mediation analyses were adopted to examine the associations linking childhood trauma, resilience, and PLEs. RESULTS: PLEs were positively associated with childhood trauma while negatively associated with resilience. Resilience played a partially mediating role in the relationship between childhood trauma and PLEs. Additionally, resilience moderated the association of childhood trauma with PLEs. CONCLUSIONS: These findings indicated that resilience plays a crucial role in mediating the relationship between childhood trauma and PLEs, suggesting the potential clinical implication of enhancing resilience for the prevention and intervention of PLEs among college students.


Assuntos
Experiências Adversas da Infância , Transtornos Mentais , Resiliência Psicológica , Humanos , Fatores de Proteção , Estudantes
3.
Heliyon ; 10(8): e28960, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38628773

RESUMO

Background: Major depressive disorder (MDD) was involved in widely transcriptional changes in central and peripheral tissues. While, previous studies focused on single tissues, making it difficult to represent systemic molecular changes throughout the body. Thus, there is an urgent need to explore the central and peripheral biomarkers with intrinsic correlation. Methods: We systematically retrieved gene expression profiles of blood and anterior cingulate cortex (ACC). 3 blood datatsets (84 MDD and 88 controls) and 6 ACC datasets (100 MDD and 100 controls) were obtained. Differential expression analysis, RobustRankAggreg (RRA) analysis, functional enrichment analysis, immune associated analysis and protein-protein interaction networks (PPI) were integrated. Furthermore, the key genes were validated in an independent ACC dataset (12 MDD and 15 controls) and a cohort with 120 MDD and 117 controls. Results: Differential expression analysis identified 2211 and 2021 differential expressed genes (DEGs) in blood and ACC, respectively. RRA identified 45 and 25 robust DEGs in blood and ACC based on DEGs, and all of them were closely associated with immune cells. Functional enrichment results showed both the robust DEGs in blood and ACC were enriched in humoral immune response. Furthermore, PPI identified 8 hub DEGs (CD79A, CD79B, CD19, MS4A1, PLP1, CLDN11, MOG, MAG) in blood and ACC. Independent ACC dataset showed the area under the curve (AUC) based on these hub DEGs was 0.77. Meanwhile, these hub DEGs were validated in the serum of MDD patients, and also showed a promising diagnostic power. Conclusions: The biomarker panel based on hub DEGs yield a promising diagnostic efficacy, and all of these hub DEGs were strongly correlated with immunity. Humoral immune response may be the key link between the brain and blood in MDD, and our results may provide further understanding for MDD.

4.
Front Psychiatry ; 15: 1366311, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38596637

RESUMO

Introduction: Schizophrenia is a complex psychiatric disorder, of which molecular pathogenesis remains largely unknown. Accumulating evidence suggest that gut microbiota may affect brain function via the complex gut-brain axis, which may be a potential contributor to schizophrenia. However, the alteration of gut microbiota showed high heterogeneity across different studies. Therefore, this study aims to identify the consistently altered gut microbial taxa associated with schizophrenia. Methods: We conducted a systematic search and synthesis of the up-to-date human gut microbiome studies on schizophrenia, and performed vote counting analyses to identify consistently changed microbiota. Further, we investigated the effects of potential confounders on the alteration of gut microbiota. Results: We obtained 30 available clinical studies, and found that there was no strong evidence to support significant differences in α-diversity and ß-diversity between schizophrenic patients and healthy controls. Among 428 differential gut microbial taxa collected from original studies, we found that 8 gut microbial taxa were consistently up-regulated in schizophrenic patients, including Proteobacteria, Gammaproteobacteria, Lactobacillaceae, Enterobacteriaceae, Lactobacillus, Succinivibrio, Prevotella and Acidaminococcus. While 5 taxa were consistently down-regulated in schizophrenia, including Fusicatenibacter, Faecalibacterium, Roseburia, Coprococcus and Anaerostipes. Discussion: These findings suggested that gut microbial changes in patients with schizophrenia were characterized by the depletion of anti-inflammatory butyrate-producing genera, and the enrichment of certain opportunistic bacteria genera and probiotics. This study contributes to further understanding the role of gut microbiota in schizophrenia, and developing microbiota-based diagnosis and therapy for schizophrenia.

5.
J Environ Manage ; 357: 120713, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38552520

RESUMO

With the continuous advancement of urban renewal, the application of recycled aggregates (RA) is a win-win measure to solve the treatment of construction waste and provide the required building materials. However, the existence of a large amount of old adhesive mortar (OAM) makes it difficult for RA to equivalently replace natural aggregates (NA) due to their higher water absorption and crushing index, as well as a lower apparent density. From the published literature on enhancing RA, the most mature and easiest method for construction is physical enhancement technology. Therefore, through a review of recent related researches, this article summarizes and compares the modification effects of mechanical grinding technology, traditional heating and grinding technology, and microwave heating technology on the physical properties of RA, including water absorption, apparent density, and crushing value. The related modification mechanisms were discussed. Additionally, the impacts of different physical enhancement technologies on the environment and economy effects are assessed from the perspectives of carbon emissions and cost required during processing. Based on multi-criteria analysis, microwave heating technology is more efficient and cleaner, which is the most recommended in the future.


Assuntos
Resíduos Industriais , Reciclagem , Resíduos Industriais/análise , Reciclagem/métodos , Materiais de Construção , Água , Desempenho Físico Funcional
6.
Front Physiol ; 15: 1304829, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38455845

RESUMO

Introduction: Precise classification has an important role in treatment of pressure injury (PI), while current machine-learning or deeplearning based methods of PI classification remain low accuracy. Methods: In this study, we developed a deeplearning based weighted feature fusion architecture for fine-grained classification, which combines a top-down and bottom-up pathway to fuse high-level semantic information and low-level detail representation. We validated it in our established database that consist of 1,519 images from multi-center clinical cohorts. ResNeXt was set as the backbone network. Results: We increased the accuracy of stage 3 PI from 60.3% to 76.2% by adding weighted feature pyramid network (wFPN). The accuracy for stage 1, 2, 4 PI were 0.870, 0.788, and 0.845 respectively. We found the overall accuracy, precision, recall, and F1-score of our network were 0.815, 0.808, 0.816, and 0.811 respectively. The area under the receiver operating characteristic curve was 0.940. Conclusions: Compared with current reported study, our network significantly increased the overall accuracy from 75% to 81.5% and showed great performance in predicting each stage. Upon further validation, our study will pave the path to the clinical application of our network in PI management.

8.
ASAIO J ; 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38483814

RESUMO

Extracorporeal membrane oxygenation (ECMO) is often associated with disturbances in acid/base status that can be triggered by the underlying pathology or the ECMO circuit itself. Extracorporeal membrane oxygenation is known to cause hypocapnia, but the impact of reduced partial pressure of carbon dioxide (pCO2) on biomarkers of tissue perfusion during veno-arterial (VA)-ECMO has not been evaluated. To study the impact of low pCO2 on perfusion indices in VA-ECMO, we placed Sprague-Dawley rats on an established VA-ECMO circuit using either an oxygen/carbon dioxide mixture (O2 95%, CO2 5%) or 100% O2 delivered through the oxygenator (n = 5 per cohort). Animals receiving 100% O2 developed a significant VA CO2 difference (pCO2 gap) and rising blood lactate levels that were inversely proportional to the decrease in pCO2 values. In contrast, pCO2 gap and lactate levels remained similar to pre-ECMO baseline levels in animals receiving the O2/CO2 mixture. More importantly, there was no significant difference in venous oxygen saturation (SvO2) between the two groups, suggesting that elevated blood lactate levels observed in the rats receiving 100% O2 were a response to oxygenator induced hypocapnia and alkaline pH rather than reduced perfusion or underlying tissue hypoxia. These findings have implications in clinical and experimental extracorporeal support contexts.

9.
Psychol Res Behav Manag ; 17: 755-764, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38434956

RESUMO

Background: Depressive symptoms are common among HIV-positive men who have sex with men (MSM). This study aims to explore (1) the relationship between family functioning and depressive symptoms and (2) the mediating roles of stigma and resilience in the relationship among HIV-positive MSM. Methods: We used data from a cross-sectional study of a convenience sample in Hunan Province, China, conducted in 2019. The data analysis included 191 HIV-positive MSM with an average age of 26.98 years. All participants completed self-report questionnaires on demographic variables, family functioning, stigma, resilience, and depressive symptoms. Results: Better family functioning was significantly associated with lower depressive symptoms. Both stigma (Indirect effect = -0.04, 95% CI, -0.10 ~ -0.001) and resilience (Indirect effect = -0.06, 95% CI, -0.12 ~ -0.01) were significant partial mediators in the relationship between family functioning and depressive symptoms. A parallel and chain mediating role of stigma and resilience in the relationship between family functioning and depressive symptoms was also supported (Indirect effect = -0.03, 95% CI, -0.08 ~ -0.01). Conclusion: Improving family functioning is crucial for alleviating depressive symptoms among HIV-positive MSM in China. Depression assessment and reduction should be an integral part of prevention and treatment programs targeting stigma and resilience.

10.
Psychol Res Behav Manag ; 17: 799-811, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38434958

RESUMO

Background: Current psychotic-like experiences (PLEs) are prevalent among adolescents. However, epidemiological data on the prevalence rate of current PLEs among college students and its clinical correlates are scarce and limited. To address this study gap, this study aimed to investigate the prevalence and correlates of current PLEs among Chinese college students. Methods: A cross-sectional study was designed with a sample of 18,578 college students in China. Each participant completed a survey on social-demographic characteristics variables, PLEs, sleep disturbance, depression, anxiety, and suicidal ideation. Logistic regression analyses were conducted to explore the influential factors for PLEs among all participants and suicidal ideation among those with PLEs. Results: Among Chinese college students, 40.3% of the participants reported having at least one PLE in the past month, while 7.5% had frequent PLEs. Males, age, residence location in town, left-behind experiences, poor family economic status, chronic physical illness, family history of mental disorder, BMI ≥ 28 [obesity], sleep disturbance, depression, anxiety, and suicidal ideation were independent correlates for frequent PLEs. Furthermore, the prevalence of suicidal ideation among participants with frequent PLEs was 32.1%. Lower grades, sleep disturbance, depression, and anxiety were independent predictors of suicidal ideation among college students who experience PLEs frequently. Conclusion: Current PLEs are widespread among Chinese college students. Suicidal ideation is largely prevalent among individuals who suffer frequent PLEs, suggesting that special measures and attention should be provided to these students based on relevant factors to prevent their suicidal ideation and behavior.

11.
Eur Neuropsychopharmacol ; 83: 11-18, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38490016

RESUMO

Long-acting injectable antipsychotics (LAIs) are primarily used for relapse prevention, but in some settings and situations, they may also be useful for acute treatment of schizophrenia. We conducted a systematic review and frequentist network meta-analysis of randomized-controlled trials (RCTs), focusing on adult patients in the acute phase of schizophrenia. Interventions were risperidone, paliperidone, aripiprazole, olanzapine, and placebo, administered either orally or as LAI. We synthesized data on overall symptoms, complemented by 17 other efficacy and tolerability outcomes. Confidence in the evidence was assessed with the Confidence-in-Network-Meta-Analysis-framework (CINeMA). We included 115 RCTs with 25,550 participants. All drugs were significantly more efficacious than placebo with the following standardized mean differences and their 95 % confidence intervals: olanzapine LAI -0.66 [-1.00; -0.33], risperidone LAI -0.59[-0.73;-0.46], olanzapine oral -0.55[-0.62;-0.48], aripiprazole LAI -0.54[-0.71; -0.37], risperidone oral -0.48[-0.55;-0.41], paliperidone oral -0.47[-0.58;-0.37], paliperidone LAI -0.45[-0.57;-0.33], aripiprazole oral -0.40[-0.50; -0.31]. There were no significant efficacy differences between LAIs and oral formulations. Sensitivity analyses of the primary outcome overall symptoms largely confirmed these findings. Moreover, some side effects were less frequent under LAIs than under their oral counterparts. Confidence in the evidence was moderate for most comparisons. LAIs are efficacious for acute schizophrenia and may have some benefits compared to oral formulations in terms of side effects. These findings assist clinicians with insights to weigh the risks and benefits between oral and injectable agents when treating patients in the acute phase.

12.
Proc Natl Acad Sci U S A ; 121(13): e2306814121, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38513102

RESUMO

Triple-negative breast cancer (TNBC) is a subtype of breast cancer with aggressive behavior and poor prognosis. Current therapeutic options available for TNBC patients are primarily chemotherapy. With our evolving understanding of this disease, novel targeted therapies, including poly ADP-ribose polymerase (PARP) inhibitors, antibody-drug conjugates, and immune-checkpoint inhibitors, have been developed for clinical use. Previous reports have demonstrated the essential role of estrogen receptor ß (ERß) in TNBC, but the detailed molecular mechanisms downstream ERß activation in TNBC are still far from elucidated. In this study, we demonstrated that a specific ERß agonist, LY500307, potently induces R-loop formation and DNA damage in TNBC cells. Subsequent interactome experiments indicated that the residues 151 to 165 of U2 small nuclear RNA auxiliary factor 1 (U2AF1) and the Trp439 and Lys443 of ERß were critical for the binding between U2AF1 and ERß. Combined RNA sequencing and ribosome sequencing analysis demonstrated that U2AF1-regulated downstream RNA splicing of 5-oxoprolinase (OPLAH) could affect its enzymatic activity and is essential for ERß-induced R-loop formation and DNA damage. In clinical samples including 115 patients from The Cancer Genome Atlas (TCGA) and 32 patients from an in-house cohort, we found a close correlation in the expression of ESR2 and U2AF1 in TNBC patients. Collectively, our study has unraveled the molecular mechanisms that explain the therapeutic effects of ERß activation in TNBC, which provides rationale for ERß activation-based single or combined therapy for patients with TNBC.


Assuntos
Processamento Alternativo , Benzopiranos , Receptor beta de Estrogênio , Estruturas R-Loop , Fator de Processamento U2AF , Neoplasias de Mama Triplo Negativas , Humanos , Receptor beta de Estrogênio/agonistas , Receptor beta de Estrogênio/metabolismo , Fator de Processamento U2AF/química , Fator de Processamento U2AF/genética , Fator de Processamento U2AF/metabolismo , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/metabolismo , Terapia Combinada , Células MDA-MB-231 , Processamento Alternativo/efeitos dos fármacos , Benzopiranos/farmacologia , Benzopiranos/uso terapêutico , Ligação Proteica , Sítios de Ligação
13.
Mol Ther Nucleic Acids ; 35(1): 102137, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38384444

RESUMO

Decoy oligodeoxynucleotides (ODNs) allow targeting undruggable transcription factors, such as STAT3, but their limited potency and lack of delivery methods hampered translation. To overcome these challenges, we conjugated a STAT3-specific decoy to thalidomide, a ligand to cereblon in E3 ubiquitin ligase complex, to generate a proteolysis-targeting chimera (STAT3DPROTAC). STAT3DPROTAC downregulated STAT3 in target cells, but not STAT1 or STAT5. Computational modeling of the STAT3DPROTAC ternary complex predicted two surface lysines, K601 and K626, in STAT3 as potential ubiquitination sites. Accordingly, K601/K626 point mutations in STAT3, as well as proteasome inhibition or cereblon deletion, alleviated STAT3DPROTAC effect. Next, we conjugated STAT3DPROTAC to a CpG oligonucleotide targeting Toll-like receptor 9 (TLR9) to generate myeloid/B cell-selective C-STAT3DPROTAC. Naked C-STAT3DPROTAC was spontaneously internalized by TLR9+ myeloid cells, B cells, and human and mouse lymphoma cells but not by T cells. C-STAT3DPROTAC effectively decreased STAT3 protein levels and also STAT3-regulated target genes critical for lymphoma cell proliferation and/or survival (BCL2L1, CCND2, and MYC). Finally, local C-STAT3DPROTAC administration to human Ly3 lymphoma-bearing mice triggered tumor regression, while control C-STAT3D and C-SCR treatments had limited effects. Our results underscore the feasibility of using a PROTAC strategy for cell-selective, decoy oligonucleotide-based STAT3 targeting of and potentially other tumorigenic transcription factors for cancer therapy.

14.
Artigo em Inglês | MEDLINE | ID: mdl-38411725

RESUMO

PURPOSE: In China, individuals with substance use disorders (SUD) face severe stigma, but reliable stigma assessment tool is lacking. Therefore, this study aimed to validate the Chinese version of the Substance Use Stigma Mechanism Scale (SU-SMS-C) and set its cut-off point. METHODS: We recruited 1005 individuals with SUDs from Chinese rehabilitation centers. These participants completed a battery of questionnaires that included the SU-SMS-C, The Multidimensional Scale of Perceived Social Support (MSPSS), Center for Epidemiologic Studies Depression Scale (CES-D), General Self-Efficacy Scale (GSES), and Perceived Devaluation and Discrimination (PDD). Confirmatory factor analysis was used to assess the construct validity of the scale. Additionally, the Naive Bayes classifier was used to establish the cut-off point for the SU-SMS-C. We additionally explored the correlation between patient demographic characteristics and stigma. RESULTS: A confirmatory factor analysis was utilized, revealing a second-order five-factor model. Based on the Naive Bayes classifier, the area under the receiver operating characteristic (AUCROC) of 0.746, the cut-off point for the SU-SMS-C was established at 44.5. The prevalence of stigma observed in the study population was 49.05%. Significant disparities were observed in the distribution of stigma across genders, with males experiencing more pronounced stigma than females. Moreover, patients consuming different primary substances reported diverse levels of stigma. Notably, those primarily using heroin endured a higher degree of stigma than users of other substances. CONCLUSION: The study is the first to identify a cut-off point for the SU-SMS-C by Naive Bayes classifier, bridging a major gap in stigma measurement research. SU-SMS-C may help treat and manage SUDs by reducing stigma.

15.
Postgrad Med J ; 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38366645

RESUMO

BACKGROUND: Multiple displaced rib fractures often result in a poor prognosis. Open reduction and internal fixation has been shown to provide benefits for patients with displaced rib fractures and flail chest. Nevertheless, for patients who are unwilling or unsuitable for surgery, the therapeutic options are limited. We developed a novel plastic vacuum device for rib fractures external stabilization. This study aims to compare the therapeutic efficacy of this device against a traditional chest strap in polytrauma patients with multiple rib fractures. METHODS: A retrospective investigation was conducted on polytrauma patients with multiple rib fractures admitted to our trauma center between March 2020 and March 2023. Patients were categorized into two groups: vacuum external fixation and chest strap. Comparative analysis was conducted on baseline parameters, injury characteristics, and clinical outcomes between the two groups. RESULTS: In this study, 54 patients were included, with 28 receiving chest strap and 26 undergoing vacuum external fixation. Results showed that, at 3 days and 7 days postintervention, the vacuum external fixation group had significantly lower visual analog scale scores during deep breathing and coughing (P < .05). Vacuum external fixation also reduced pleural drainage duration and volume, as well as lowered the risk of pneumonia and other complications (P < .05). Furthermore, the vacuum external fixation group demonstrated notable improvements in vital capacity, tidal volume, blood-gas test results, and a shorter hospital length of stay. CONCLUSIONS: According to the study findings, vacuum external fixation appears to offer benefits to patients with multiple rib fractures, potentially reducing the risk of complications and improving overall clinical outcomes.

16.
Sleep ; 47(3)2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38230742

RESUMO

STUDY OBJECTIVES: Sleep disturbance may cause suicidal ideation (SI). This study aimed to examine their co-occurrence rate among adolescents and investigate whether psychotic-like experiences (PLEs) mediate this association. METHODS: A total of 17 722 Chinese adolescents were included in this two-wave longitudinal study. The baseline survey (time 1, T1) was conducted between April 21 and May 12, 2021, and the follow-up survey (time 2, T2) was implemented between December 17 and 26, 2021. At T1, participants completed questionnaires to assess their sleep disturbance, sleep duration, PLEs, SI, depressive symptoms, and sociodemographic characteristics. At T2, participants reported their PLEs, SI, and negative life events. RESULTS: The SI prevalence decreased from 20.2% (T1) to 18.4% (T2). Participants with SI showed significantly higher prevalence of sleep disturbance and short sleep duration compared to those without SI. Baseline sleep disturbance and short sleep duration were both associated with the increased risk of SI 6 months later. These longitudinal links were mediated by PLEs, independent of baseline covariates and negative life events. CONCLUSIONS: These findings provide a novel insight into the mechanism linking sleep problems and suicidality, and stress the significance of assessing and addressing sleep problems and PLEs for adolescent suicide prevention and intervention.


Assuntos
Transtornos Psicóticos , Transtornos do Sono-Vigília , Humanos , Adolescente , Ideação Suicida , Estudos Longitudinais , Inquéritos e Questionários , Transtornos do Sono-Vigília/complicações , Transtornos do Sono-Vigília/epidemiologia , Sono , Transtornos Psicóticos/complicações , Transtornos Psicóticos/epidemiologia
17.
Genome Med ; 16(1): 2, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38167466

RESUMO

BACKGROUND: Pituitary neuroendocrine tumors (PitNETs) are one of the most common types of intracranial tumors. Currently, the cellular characteristics of normal pituitary and various other types of PitNETs are still not completely understood. METHODS: We performed single-cell RNA sequencing (scRNA-seq) on 4 normal samples and 24 PitNET samples for comprehensive bioinformatics analysis. Findings regarding the function of PBK in the aggressive tumor cells were validated by siRNA knockdown, overexpression, and transwell experiments. RESULTS: We first constructed a reference cell atlas of the human pituitary. Subsequent scRNA-seq analysis of PitNET samples, representing major tumor subtypes, shed light on the intrinsic cellular heterogeneities of the tumor cells and tumor microenvironment (TME). We found that the expression of hormone-encoding genes defined the major variations of the PIT1-lineage tumor cell transcriptomic heterogeneities. A sub-population of TPIT-lineage tumor cells highly expressing GZMK suggested a novel subtype of corticotroph tumors. In immune cells, we found two clusters of tumor-associated macrophages, which were both highly enriched in PitNETs but with distinct functional characteristics. In PitNETs, the stress response pathway was significantly activated in T cells. While a majority of these tumors are benign, our study unveils a common existence of aggressive tumor cells in the studied samples, which highly express a set of malignant signature genes. The following functional experiments confirmed the oncogenic role of selected up-regulated genes. The over-expression of PBK could promote both tumor cell proliferation and migration, and it was also significantly associated with poor prognosis in PitNET patients. CONCLUSIONS: Our data and analysis manifested the basic cell types in the normal pituitary and inherent heterogeneity of PitNETs, identified several features of the tumor immune microenvironments, and found a novel epithelial cell sub-population with aggressive signatures across all the studied cases.


Assuntos
Neoplasias Encefálicas , Tumores Neuroendócrinos , Humanos , Tumores Neuroendócrinos/genética , Células Epiteliais , Proliferação de Células , Perfilação da Expressão Gênica , Microambiente Tumoral/genética
18.
Nat Commun ; 15(1): 128, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38167856

RESUMO

The demand for milk has increased globally, accompanied by an increase in waste milk. Here, we provide an artificial humification technology to recycle waste milk into an agricultural nano-fertilizer. We use KOH-activated persulfate to convert waste milk into fulvic-like acid and humic-like acid. We mix the product with attapulgite to obtain a slow-release nano fulvic-like acid fertilizer. We apply this nano-fertilizer to chickweeds growing in pots, resulting in improved yield and root elongation. These results indicate that waste milk could be recycled for agricultural purposes, however, this nano-fertilizer needs to be tested further in field experiments.


Assuntos
Fertilizantes , Resíduos , Animais , Fertilizantes/análise , Leite/química , Agricultura/métodos , Solo
20.
Antioxidants (Basel) ; 13(1)2024 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-38247520

RESUMO

The redox potential plays a critical role in sustaining the stability of gut microbiota. This study measured the fecal redox potential in healthy and diarrheal pigs using direct and dilution methods and investigated their correlation with microbiota. The results showed that the fluctuations in the redox potential of healthy pig feces were consistent using two different methods and the two methods are equivalent based on an equivalence test. The redox potential was positively correlated with the number of fungi and negatively related to the total bacteria. The relative or absolute abundances of many bacteria at the phyla and genus levels were associated with redox potential. In diarrheal pigs, the potentiometric trends of the two methods demonstrated an opposing pattern and the correlation with total bacteria was reversed. Precipitously elevated redox potential was detected post-diarrhea using dilution methods. The absolute abundance of Escherichia-Shigella and Fuurnierella was positively correlated with redox potential, while both relative and absolute abundances of Limosilactobacillus were positively correlated. These results suggest that both methods are suitable for detecting gut redox potential in healthy pigs, while the dilution method is more suitable for diarrheal pigs. The findings on the correlation of Limosilactobacillus, Prevotella, and Escherichia-Shigella with redox potential offer novel insights for targeted modulation of intestinal health.

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