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1.
Artigo em Inglês | MEDLINE | ID: mdl-38563796

RESUMO

OBJECTIVE: To investigate the relationship between anti-Müllerian hormone (AMH) level and early pregnancy loss in patients who underwent their first embryo transfer by hormone replacement therapy-frozen-thawed embryo transfer (HRT-FET) and analyze the threshold effect. METHODS: A retrospective cohort analysis was performed on pregnant women undergoing HRT-FET at the Reproductive Medical Center of Henan Provincial People's Hospital from January 2016 to December 2021. The patients were divided into four groups based on AMH concentration according to the Poseidon criteria: group A (≤1 µg/L), group B (1-≤2 µg/L), group C (2-≤6 µg/L), and group D (>6 µg/L). Univariate analysis, multivariate logistic regression analysis, smooth curve fitting, and threshold effect analysis were applied to investigate the influence of AMH on the outcome of early pregnancy loss in in vitro fertilization/intracytoplasmic sperm injection and HRT-FET cycles. RESULTS: Of the 6597 pregnant women, early pregnancy loss occurred in 893, giving an early pregnancy loss rate of 13.54%. Univariate regression analysis demonstrated that age, female body mass index, AMH, antral follicle count, endometrial thickness at endometrial transformation day, total retrieved oocyte number, number of pregnancies, duration of infertility, type of infertility, and the number of embryos transferred were all factors influencing the early pregnancy loss rate (P < 0.050). Multivariate logistic regression analysis, after adjusting for confounders, further stratified the analysis of patients of different ages. With group A as the control group, the results showed that when age was younger than 35 years, the pregnancy loss rates in groups B, C, and D were lower than that in group A, with statistical significance (P < 0.050); when age was 35 years or older, there was no statistically significant difference in outcome indicators between the groups (P > 0.050). A threshold effect analysis revealed that the AMH threshold was 2.83 µg/L. When the AMH concentration was less than 2.83 µg/L, the early pregnancy loss rate decreased significantly with increasing AMH concentration; the early pregnancy loss rate decreased by 21% for each unit increase in AMH (odds ratio 0.79; 95% confidence interval 0.71-0.88; P < 0.001); when the AMH concentration was 2.83 µg/L or more, there was no statistical difference in the change in early pregnancy loss rate (odds ratio 1.01; 95% confidence interval 0.99-1.03; P = 0.383). CONCLUSION: For pregnant women after their first embryo transfer, there is a curvilinear relationship between the influences of AMH levels on early pregnancy loss rates in patients younger than 35 years. When the AMH level was less than 2.83 µg/L, the early pregnancy loss rate declined significantly with increasing AMH levels.

2.
Hortic Res ; 11(4): uhae036, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38595909

RESUMO

Transcription factors with basic helix-loop-helix (bHLH) structures regulate plant growth, epidermal structure development, metabolic processes, and responses to stress extensively. Sea lavender (Limonium bicolor) is a recretohalophyte with unique salt glands in the epidermis that make it highly resistant to salt stress, contributing to the improvement of saline lands. However, the features of the bHLH transcription factor family in L. bicolor are largely unknown. Here, we systematically analyzed the characteristics, localization, and phylogenetic relationships of 187 identified bHLH family genes throughout the L. bicolor genome, as well as their cis-regulatory promoter elements, expression patterns, and key roles in salt gland development or salt tolerance by genetic analysis. Nine verified L. bicolor bHLH genes are expressed and the encoded proteins function in the nucleus, among which the proteins encoded by Lb2G14060 and Lb1G07934 also localize to salt glands. Analysis of CRISPR-Cas9-generated knockout mutants and overexpression lines indicated that the protein encoded by Lb1G07934 is involved in the formation of salt glands, salt secretion, and salt resistance, indicating that bHLH genes strongly influence epidermal structure development and stress responses. The current study lays the foundation for further investigation of the effects and functional mechanisms of bHLH genes in L. bicolor and paves the way for selecting salt-tolerance genes that will enhance salt resistance in crops and for the improvement of saline soils.

3.
Plant Physiol ; 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38588029

RESUMO

Salt gland is an epidermal Na+ secretory structure that enhances salt resistance in the recretohalophyte sea lavender (Limonium bicolor). To elucidate the salt gland development trajectory and related molecular mechanisms, we performed single-cell RNA sequencing of L. bicolor protoplasts from young leaves at salt gland initiation and differentiation stages. Dimensionality reduction analyses defined 19 transcriptionally distinct cell clusters, which were assigned into four broad populations-promeristem, epidermis, mesophyll, and vascular tissue-verified by in situ hybridization. Cytokinin was further proposed to participate in salt gland development by the expression patterns of related genes and cytological evidence. By comparison analyses of scRNA-seq with exogenous application of 6-benzylaminopurine, we delineated five salt gland development-associated sub-clusters and defined salt gland specific differentiation trajectories from sub-clusters 8, 4, or 6 to sub-cluster 3 and 1. Additionally, we validated the participation of TRIPTYCHON and the interacting protein Lb7G34824 in salt gland development, which regulated the expression of cytokinin metabolism and signaling related genes such as GLABROUS INFLORESCENCE STEMS 2 to maintain cytokinin homeostasis during salt gland development. Our results generated a gene expression map of young leaves at single-cell resolution for the comprehensive investigation of salt gland determinants and cytokinin participation that helps elucidate cell fate determination during epidermis formation and evolution in recretohalophytes.

4.
Environ Sci Technol ; 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38629869

RESUMO

Exposure to hexavalent chromium damages genetic materials like DNA and chromosomes, further elevating cancer risk, yet research rarely focuses on related immunological mechanisms, which play an important role in the occurrence and development of cancer. We investigated the association between blood chromium (Cr) levels and genetic damage biomarkers as well as the immune regulatory mechanism involved, such as costimulatory molecules, in 120 workers exposed to chromates. Higher blood Cr levels were linearly correlated with higher genetic damage, reflected by urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) and blood micronucleus frequency (MNF). Exploratory factor analysis revealed that both positive and negative immune regulation patterns were positively associated with blood Cr. Specifically, higher levels of programmed cell death protein 1 (PD-1; mediated proportion: 4.12%), programmed cell death ligand 1 (PD-L1; 5.22%), lymphocyte activation gene 3 (LAG-3; 2.11%), and their constitutive positive immune regulation pattern (5.86%) indirectly positively influenced the relationship between blood Cr and urinary 8-OHdG. NOD-like receptor family pyrin domain containing 3 (NLRP3) positively affected the association between blood Cr levels and inflammatory immunity. This study, using machine learning, investigated immune regulation and its potential role in chromate-induced genetic damage, providing insights into complex relationships and emphasizing the need for further research.

5.
Front Immunol ; 15: 1374236, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38605948

RESUMO

Despite undeniable advances in modern medicine, lung cancer still has high morbidity and mortality rates. Lung cancer is preventable and treatable, and it is important to identify new risk factors for lung cancer, especially those that can be treated or reversed. Obstructive sleep apnea (OSA) is a very common sleep-breathing disorder that is grossly underestimated in clinical practice. It can cause, exacerbate, and worsen adverse outcomes, including death and various diseases, but its relationship with lung cancer is unclear. A possible causal relationship between OSA and the onset and progression of lung cancer has been established biologically. The pathophysiological processes associated with OSA, such as sleep fragmentation, intermittent hypoxia, and increased sympathetic nervous excitation, may affect normal neuroendocrine regulation, impair immune function (especially innate and cellular immunity), and ultimately contribute to the occurrence of lung cancer, accelerate progression, and induce treatment resistance. OSA may be a contributor to but a preventable cause of the progression of lung cancer. However, whether this effect exists independently of other risk factors is unclear. Therefore, by reviewing the literature on the epidemiology, pathogenesis, and treatment of lung cancer and OSA, we hope to understand the relationships between the two and promote the interdisciplinary exchange of ideas between basic medicine, clinical medicine, respiratory medicine, sleep medicine, and oncology.


Assuntos
Neoplasias Pulmonares , Apneia Obstrutiva do Sono , Humanos , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/etiologia , Neoplasias Pulmonares/terapia , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/epidemiologia , Apneia Obstrutiva do Sono/terapia , Fatores de Risco , Sistema Nervoso Simpático , Hipóxia/complicações
6.
PLoS One ; 19(4): e0301420, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38593140

RESUMO

The COVID-19 pandemic has been present globally for more than three years, and cross-border transmission has played an important role in its spread. Currently, most predictions of COVID-19 spread are limited to a country (or a region), and models for cross-border transmission risk assessment remain lacking. Information on imported COVID-19 cases reported from March 2020 to June 2022 was collected from the National Health Commission of China, and COVID-19 epidemic data of the countries of origin of the imported cases were collected on data websites such as WHO and Our World in Data. It is proposed to establish a prediction model suitable for the prevention and control of overseas importation of COVID-19. Firstly, the SIR model was used to fit the epidemic infection status of the countries where the cases were exported, and most of the r2 values of the fitted curves obtained were above 0.75, which indicated that the SIR model could well fit different countries and the infection status of the region. After fitting the epidemic infection status data of overseas exporting countries, on this basis, a SIR-multiple linear regression overseas import risk prediction combination model was established, which can predict the risk of overseas case importation, and the established overseas import risk model overall P <0.05, the adjusted R2 = 0.7, indicating that the SIR-multivariate linear regression overseas import risk prediction combination model can obtain better prediction results. Our model effectively estimates the risk of imported cases of COVID-19 from abroad.


Assuntos
COVID-19 , Humanos , COVID-19/epidemiologia , SARS-CoV-2 , Pandemias , China/epidemiologia , Modelos Lineares
7.
Environ Pollut ; 349: 123947, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38608856

RESUMO

There is sufficient evidence suggesting that exposure to hexavalent chromium [Cr(VI)] can cause a decline in lung function and the onset of lung diseases. However, no studies have yet explored the underlying mechanisms of these effects from various perspectives such as systemic inflammation, oxidative stress, and cellular senescence, simultaneously. This cross-sectional study was conducted among 304 workers engaged in chromate production and processing in China. Urine was used for detection of 8-hydroxy-2'-deoxyguanosine (8-OHdG) and 8-iso-prostaglandin F2α (8-iso-PGF2α), while RNA and DNA extraction from peripheral blood cells was used for detection of mRNA, telomere length, and ribosomal DNA copy numbers (rDNA CNs). A 2.7-fold elevation in blood chromate (Cr) corresponded to a 7.86% (95% CI: 2.57%, 13.42%) rise in urinary 8-OHdG and a 4.14% (0.02%, 8.42%) increase in urinary 8-iso-PGF2α, indicating that exposure to chromates can cause oxidative stress. Furthermore, strong correlations emerged between blood Cr concentration and mRNA levels of P16, P21, TP53, and P15 in the cellular senescence pathway. Simultaneously, a 2.7-fold elevation in blood Cr associated with a -5.47% (-8.72%, -2.1%) change in telomere length, while rDNA CNs (5S, 5.8S, 18S, and 28S) changed by -3.91% (-7.99%, 0.34%), -9.4% (-15.73%, -2.6%), -8.06% (-14.01%, -1.69%), and -5.86% (-10.67%, -0.78%), respectively. Structural equation model highlighted that cellular senescence exerted significant indirect effects on Cr(VI)-associated lung function decline, with a mediation proportion of 23.3%. This study provided data supporting for 8-iso-PGF2α, telomere length, and rDNA CNs as novel biomarkers of chromate exposure, emphasizing the significant role of cellular senescence in the mechanism underlying chromate-induced lung function decline.

8.
Intern Emerg Med ; 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38607541
9.
J Neuroinflammation ; 21(1): 101, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38632579

RESUMO

BACKGROUND: Increased neuroinflammation in brain regions regulating sympathetic nerves is associated with hypertension. Emerging evidence from both human and animal studies suggests a link between hypertension and gut microbiota, as well as microbiota-derived metabolites short-chain fatty acids (SCFAs). However, the precise mechanisms underlying this gut-brain axis remain unclear. METHODS: The levels of microbiota-derived SCFAs in spontaneously hypertensive rats (SHRs) were determined by gas chromatography-mass spectrometry. To observe the effect of acetate on arterial blood pressure (ABP) in rats, sodium acetate was supplemented via drinking water for continuous 7 days. ABP was recorded by radio telemetry. The inflammatory factors, morphology of microglia and astrocytes in rostral ventrolateral medulla (RVLM) were detected. In addition, blood-brain barrier (BBB) permeability, composition and metabolomics of the gut microbiome, and intestinal pathological manifestations were also measured. RESULTS: The serum acetate levels in SHRs are lower than in normotensive control rats. Supplementation with acetate reduces ABP, inhibits sympathetic nerve activity in SHRs. Furthermore, acetate suppresses RVLM neuroinflammation in SHRs, increases microglia and astrocyte morphologic complexity, decreases BBB permeability, modulates intestinal flora, increases fecal flora metabolites, and inhibits intestinal fibrosis. CONCLUSIONS: Microbiota-derived acetate exerts antihypertensive effects by modulating microglia and astrocytes and inhibiting neuroinflammation and sympathetic output.


Assuntos
Hipertensão , Microbiota , Humanos , Ratos , Animais , Ratos Endogâmicos SHR , Doenças Neuroinflamatórias , Hipertensão/metabolismo , Pressão Sanguínea , Bulbo/metabolismo , Acetatos/farmacologia
10.
J Environ Sci (China) ; 143: 224-234, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38644019

RESUMO

Hexavalent chromium and its compounds are prevalent pollutants, especially in the work environment, pose a significant risk for multisystem toxicity and cancers. While it is known that chromium accumulation in the liver can cause damage, the dose-response relationship between blood chromium (Cr) and liver injury, as well as the possible potential toxic mechanisms involved, remains poorly understood. To address this, we conducted a follow-up study of 590 visits from 305 participants to investigate the associations of blood Cr with biomarkers for liver injury, including serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), and direct bilirubin (DBIL), and to evaluate the mediating effects of systemic inflammation. Platelet (PLT) and the platelet-to-lymphocyte ratio (PLR) were utilized as biomarkers of systemic inflammation. In the linear mixed-effects analyses, each 1-unit increase in blood Cr level was associated with estimated effect percentage increases of 0.82% (0.11%, 1.53%) in TBIL, 1.67% (0.06%, 3.28%) in DBIL, 0.73% (0.04%, 1.43%) in ALT and 2.08% (0.29%, 3.87%) in AST, respectively. Furthermore, PLT mediated 10.04%, 11.35%, and 10.77% increases in TBIL, DBIL, and ALT levels induced by chromate, respectively. In addition, PLR mediated 8.26% and 15.58% of the association between blood Cr and TBIL or ALT. These findings shed light on the mechanisms underlying blood Cr-induced liver injury, which is partly due to worsening systemic inflammation.


Assuntos
Cromatos , Cromo , Inflamação , Humanos , Cromo/toxicidade , Cromo/sangue , Inflamação/sangue , Masculino , Cromatos/toxicidade , Cromatos/sangue , Adulto , Feminino , Pessoa de Meia-Idade , Biomarcadores/sangue , Exposição Ocupacional/efeitos adversos , Alanina Transaminase/sangue , Doença Hepática Induzida por Substâncias e Drogas/sangue , Aspartato Aminotransferases/sangue , Poluentes Ambientais/sangue , Poluentes Ambientais/toxicidade
11.
Cell Biol Toxicol ; 40(1): 16, 2024 03 13.
Artigo em Inglês | MEDLINE | ID: mdl-38472656

RESUMO

Intervertebral disc degeneration (IVDD) is an aging disease that results in a low quality of life and heavy socioeconomic burden. The mitochondrial unfolded protein response (UPRmt) take part in various aging-related diseases. Our research intents to explore the role and underlying mechanism of UPRmt in IVDD. Nucleus pulposus (NP) cells were exposed to IL-1ß and nicotinamide riboside (NR) served as UPRmt inducer to treat NP cells. Detection of ATP, NAD + and NADH were used to determine the function of mitochondria. MRI, Safranin O-fast green and Immunohistochemical examination were used to determine the degree of IVDD in vivo. In this study, we discovered that UPRmt was increased markedly in the NP cells of human IVDD tissues than in healthy controls. In vitro, UPRmt and mitophagy levels were promoted in NP cells treated with IL-1ß. Upregulation of UPRmt by NR and Atf5 overexpression inhibited NP cell apoptosis and further improved mitophagy. Silencing of Pink1 reversed the protective effects of NR and inhibited mitophagy induced by the UPRmt. In vivo, NR might attenuate the degree of IDD by activating the UPRmt in rats. In summary, the UPRmt was involved in IVDD by regulating Pink1-induced mitophagy. Mitophagy induced by the UPRmt might be a latent treated target for IVDD.


Assuntos
Degeneração do Disco Intervertebral , Mitofagia , Animais , Humanos , Ratos , Fatores Ativadores da Transcrição/metabolismo , Fatores Ativadores da Transcrição/farmacologia , Apoptose , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Degeneração do Disco Intervertebral/metabolismo , Mitocôndrias/metabolismo , Proteínas Quinases/metabolismo , Qualidade de Vida , Ratos Sprague-Dawley
12.
Artigo em Inglês | MEDLINE | ID: mdl-38507171

RESUMO

Gastric cancer (GC) is a malignant tumor with global incidence and death ranking fifth and fourth, respectively. GC patients nevertheless have a poor prognosis despite the effectiveness of more advanced chemotherapy and surgical treatment options. The second most frequently mutated gene in GC is PI3Kalpha, a confirmed oncogene that results in abnormal PI3K/AKT/mTOR signaling, causing enhanced translation, proliferation, and survival, and is mutated in 7-25% of GC patients. The protein PI3Kalpha was targeted in the present study by utilizing machine learning (ML), molecular docking, and simulation. A total of 9214 molecules from the DrugBank database were chosen for the first screening. A training set for 6770 compounds tested against PI3Kalpha was assessed to create a quantitative structure-activity relationship-based machine learning model using five different classification algorithms: random forest, random tree, J48 pruned tree, decision stump, and REPTree. Furthermore, consideration was given to the random forest classifier for screening based on its performance index (Kappa statistics, ROC, and MCC). Overall, 1539 of the 9214 drug bank compounds were predicted to be active. Thereafter, three pharmacological filters, Lipinski's rule, Ghose filter, and Veber rule, were applied to test the drug-like properties of the screened compounds. Twenty-six of 1593 compounds showed excellent drug-like properties and were further considered for molecular docking. Thereafter, two compounds were screened as hits because they possessed the molecular docked position with the lowest binding energy and an excellent bonding profile. The binding stability of the selected compounds was further assessed through molecular dynamics simulations for up to 100 ns. Furthermore, compound 1-(3-(2,4-dimethylthiazol-5-YL)-4-oxo-2,4-dihydroindeno[1,2-C]pyrazol-5-YL)-3-(4-methylpiperazin-1-YL) urea was selected as a potential hit in the final screening by analyzing a number of parameters, including the Rg, RMSD, RMSF, H bonding, and SASA profile. Therefore, we conclude that compound 1-(3-(2, 4-dimethylthiazol-5-YL)-4-oxo-2,4-dihydroindeno[1,2-C]pyrazol-5-YL)-3-(4-methylpiperazin-1-YL) urea has efficient inhibitory potential against PI3Kalpha protein and could be utilized for the development of effective drugs against GC.

13.
Sensors (Basel) ; 24(6)2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38544264

RESUMO

Imaging using scattering media is a very important yet challenging technology. As one of the most widely used scattering imaging methods, speckle autocorrelation technology has important applications in several fields. However, traditional speckle autocorrelation imaging methods usually use iterative phase recovery algorithms to obtain the Fourier phase of hidden objects, posing issues such as large data calculation volumes and uncertain reconstruction results. Here, we propose a single-shot scattering imaging method based on the bispectrum truncation method. The bispectrum analysis is utilized for hidden object phase recovery, the truncation method is used to avoid the computation of redundant data when calculating the bispectrum data, and the method is experimentally verified. The experimental results show that our method does not require uncertain iterative calculations and can reduce the bispectrum data computation by more than 80% by adjusting the truncation factor without damaging the imaging quality, which greatly improves imaging efficiency. This method paves the way for rapid imaging through scattering media and brings benefits for imaging in dynamic situations.

14.
Food Sci Nutr ; 12(3): 2068-2080, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38455195

RESUMO

Studies suggest that mangiferin (MAF) has good therapeutic effects on chronic bronchitis and hepatitis. Also, it is one of the antiviral ingredients in Anemarrhena asphodeloides Bunge. However, its effect on the LPS-induced inflammation and intestinal flora during sepsis remains unclear yet. In the present study, LPS-stimulated inflammation RAW264.7 cells and LPS-induced sepsis mice were used to evaluate the efficacy of MAF in vitro and in vivo. 16S rDNA sequencing was performed to analyze the characteristics of intestinal flora of the sepsis mice. It has been demonstrated that MAF (12.5 and 25 µg/mL) significantly inhibited protein expressions of TLR4, MyD88, NF-κB, and TNF-α in the LPS-treated cells and reduced the supernatant TNF-α and IL-6 levels. In vivo, MAF (20 mg/kg) markedly protected the sepsis mice and reduced the serum TNF-α and IL-6 levels. Also, MAF significantly downregulated the protein expressions of TLR4, NF-κB, and MyD88 in the livers. Importantly, MAF significantly attenuated the pathological injuries of the livers and small intestines. Further, MAF significantly increased proportion of Bacteroidota and decreased the proportions of Firmicutes, Desulfobacterota, Actinobacteriota, and Proteobacteria at phylum level, and it markedly reduced the proportions of Escherichia-Shigella, Pseudoalteromonas, Staphylococcus at genus level. Moreover, MAF affects some metabolism-related pathways such as citrate cycle (TCA cycle), lipoic acid metabolism, oxidative phosphorylation, bacterial chemotaxis, fatty acid biosynthesis, and peptidoglycan biosynthesis of the intestinal flora. Thus, it can be concluded that MAF as a treatment reduces the inflammatory responses in vitro and in vivo by inhibiting the TLR4/ MyD88/NF-κB pathway, and corrects intestinal flora imbalance during sepsis to some degree.

15.
Sci Rep ; 14(1): 7473, 2024 03 29.
Artigo em Inglês | MEDLINE | ID: mdl-38553555

RESUMO

Orexin signaling plays a facilitatory role in respiration. Abnormalities in orexin levels correlate with disordered breathing patterns and impaired central respiratory chemoreception. Nucleus tractus solitarii (NTS) neurons expressing the transcription factor Phox2b contribute to the chemoreceptive regulation of respiration. However, the extent to which orexinergic signaling modulates respiratory activity in these Phox2b-expressing NTS neurons remains unclear. In the present study, the injection of orexin A into the NTS significantly increased the firing rate of the phrenic nerve. Further analysis using fluorescence in situ hybridization and immunohistochemistry revealed that orexin 1 receptors (OX1Rs) were primarily located in the ventrolateral subdivision of the NTS and expressed in 25% of Phox2b-expressing neurons. Additionally, electrophysiological recordings showed that exposure to orexin A increased the spontaneous firing rate of Phox2b-expressing neurons. Immunostaining experiments with cFos revealed that the OX1R-residing Phox2b-expressing neurons were activated by an 8% CO2 stimulus. Crucially, OX1R knockdown in these NTS neurons notably blunted the ventilatory response to 8% CO2, alongside an increase in sigh-related apneas. In conclusion, orexinergic signaling in the NTS facilitates breathing through the activation of OX1Rs, which induces the depolarization of Phox2b-expressing neurons. OX1Rs are essential for the involvement of Phox2b-expressing NTS neurons in the hypercapnic ventilatory response.


Assuntos
Dióxido de Carbono , Núcleo Solitário , Núcleo Solitário/metabolismo , Orexinas/metabolismo , Hibridização in Situ Fluorescente , Respiração
16.
Cell Rep ; 43(3): 113930, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38507412

RESUMO

Oligodendrocyte progenitor cells (OPCs) differentiate into myelin-producing cells and modulate neuronal activity. Defects in OPC development are associated with neurological diseases. N6-methyladenosine (m6A) contributes to neural development; however, the mechanism by which m6A regulates OPC development remains unclear. Here, we demonstrate that PRRC2B is an m6A reader that regulates OPC development and myelination. Nestin-Cre-mediated Prrc2b deletion affects neural stem cell self-renewal and glial differentiation. Moreover, the oligodendroglia lineage-specific deletion of Prrc2b reduces the numbers of OPCs and oligodendrocytes, causing hypomyelination and impaired motor coordination. Integrative methylated RNA immunoprecipitation sequencing, RNA sequencing, and RNA immunoprecipitation sequencing analyses identify Sox2 as the target of PRRC2B. Notably, PRRC2B, displaying separate and cooperative functions with PRRC2A, stabilizes mRNA by binding to m6A motifs in the coding sequence and 3' UTR of Sox2. In summary, we identify the posttranscriptional regulation of PRRC2B in OPC development, extending the understanding of PRRC2 family proteins and providing a therapeutic target for myelin-related disorders.


Assuntos
Células Precursoras de Oligodendrócitos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Oligodendroglia/metabolismo , Bainha de Mielina/metabolismo , Neurogênese , Diferenciação Celular/genética
17.
Anal Chem ; 96(14): 5375-5383, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38523323

RESUMO

Lipids play a significant role in life activities and participate in the biological system through different pathways. Although comprehensive two-dimensional liquid chromatography-mass spectrometry (2DLC-MS) has been developed to profile lipid abundance changes, lipid identification and quantification from 2DLC-MS data remain a challenge. We created Lipid Wizard, open-source software for lipid assignment and isotopic peak stripping of the 2DLC-MS data. Lipid Wizard takes the peak list deconvoluted from the 2DLC-MS data as input and assigns each isotopic peak to the lipids recorded in the LIPID MAPS database by precursor ion m/z matching. The matched lipids are then filtered by the first-dimension retention time (1D RT), followed by the second-dimension retention time (2D RT), where the 2D RT of each lipid is predicted using an equivalent carbon number (ECN) model. The remaining assigned lipids are used for isotopic peak stripping via an iterative linear regression. The performance of Lipid Wizard was tested using a set of lipid standards and then applied to study the lipid changes in the livers of mice (fat-1) fed with alcohol.


Assuntos
Lipídeos , 60705 , Camundongos , Animais , Lipídeos/análise , Software , Fígado/química , Bases de Dados Factuais
18.
ACS Omega ; 9(9): 10426-10439, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38463325

RESUMO

Gas drainage with bedding boreholes is an efficient method for preventing gas and achieving coal and gas comining in underground mining engineering. An underground pressurized drilling method is proposed to maintain the borehole stability. However, the presence of natural fractures in coal seams poses challenges during pressurized drilling. Therefore, it is crucial to establish a low-leadage degradable drilling fluid system that minimizes coal seam damage. In this study, a degradable drilling fluid system was developed based on the characteristics of coal seams. The performance and influencing factors of the drilling fluid and the degrading capability of cellulase were examined. Moreover, the damage of the drilling fluid on fractured coal seams was investigated using core flow test methods. The results showed that additives significantly improved the rheology, filtration, and inhibition of the drilling fluid. The drilling fluid system exhibited excellent stability, rheological properties, low filtration, and sealing performance in coal seam environments. However, drilling fluid invasion and mud cake blockage negatively affected gas flow in fractured coal seams, and a higher content of filtrate reducer hindered the recovery of the gas flow rate. Cellulase was used to degrade polymers and alleviate the challenge of mud cake removal after drilling. Research on the influencing factors of cellulase indicates that the degradation efficiency of cellulase enzymes is influenced by the temperature, pH, salinity, and solid-phase content. For polluted coal samples, the gas flow rate significantly recovered after treatment with a cellulase solution. This study provides insights into a degradable drilling fluid system that can enhance underground pressurized drilling methods and minimize reservoir damage.

19.
Spectrochim Acta A Mol Biomol Spectrosc ; 313: 124151, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38492464

RESUMO

Herein, we fabricate a melamine modified metal organic framework-199 composite (MOF-199@melamine), of which the structure is affected by the dynamics of the guest H2O molecule with significant color change. It realizes the visualized quantitative detection of water in a variety of organic solvents within 30 s. Moreover, DMF restored the original structure by replacing H2O molecules, realizing the regeneration of the materials. On this basis, PTFE-MOF-199@melamine test paper is developed to portably detect water content in organic solvents (maximum 0 %-98 % (v/v) water content) and ambient relative humidity (11-85 %). The test paper can be recycled four times with a regeneration rate higher than 90 %. The results are expected to solve the problems of existed electrochemical or fluorescence strategy such as the complicated operation process and signal output/reading system.

20.
Front Pharmacol ; 15: 1308733, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38434710

RESUMO

Acute kidney injury (AKI) is a global health problem, given its substantial morbidity and mortality rates. A better understanding of the mechanisms and factors contributing to AKI has the potential to guide interventions aimed at mitigating the risk of AKI and its subsequent unfavorable outcomes. Endoplasmic reticulum stress (ERS) is an intrinsic protective mechanism against external stressors. ERS occurs when the endoplasmic reticulum (ER) cannot deal with accumulated misfolded proteins completely. Excess ERS can eventually cause pathological reactions, triggering various programmed cell death (autophagy, ferroptosis, apoptosis, pyroptosis). This article provides an overview of the latest research progress in deciphering the interaction between ERS and different programmed cell death. Additionally, the report consolidates insights into the roles of ERS in AKI and highlights the potential avenues for targeting ERS as a treatment direction toward for AKI.

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