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1.
Cell ; 187(11): 2855-2874.e19, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38657603

RESUMO

Progress in understanding early human development has been impeded by the scarcity of reference datasets from natural embryos, particularly those with spatial information during crucial stages like gastrulation. We conducted high-resolution spatial transcriptomics profiling on 38,562 spots from 62 transverse sections of an intact Carnegie stage (CS) 8 human embryo. From this spatial transcriptomic dataset, we constructed a 3D model of the CS8 embryo, in which a range of cell subtypes are identified, based on gene expression patterns and positional register, along the anterior-posterior, medial-lateral, and dorsal-ventral axis in the embryo. We further characterized the lineage trajectories of embryonic and extra-embryonic tissues and associated regulons and the regionalization of signaling centers and signaling activities that underpin lineage progression and tissue patterning during gastrulation. Collectively, the findings of this study provide insights into gastrulation and post-gastrulation development of the human embryo.


Assuntos
Embrião de Mamíferos , Gastrulação , Regulação da Expressão Gênica no Desenvolvimento , Imageamento Tridimensional , Humanos , Embrião de Mamíferos/metabolismo , Transcriptoma/genética , Gástrula/metabolismo , Gástrula/embriologia , Transdução de Sinais , Linhagem da Célula , Perfilação da Expressão Gênica , Padronização Corporal/genética
2.
bioRxiv ; 2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38260472

RESUMO

Many neurodevelopmental defects are linked to perturbations in genes involved in housekeeping functions, such as those encoding ribosome biogenesis factors. However, how reductions in ribosome biogenesis can result in tissue and developmental specific defects remains a mystery. Here we describe new allelic variants in the ribosome biogenesis factor AIRIM primarily associated with neurodevelopmental disorders. Using human cerebral organoids in combination with proteomic analysis, single-cell transcriptome analysis across multiple developmental stages, and single organoid translatome analysis, we identify a previously unappreciated mechanism linking changes in ribosome levels and the timing of cell fate specification during early brain development. We find ribosome levels decrease during neuroepithelial differentiation, making differentiating cells particularly vulnerable to perturbations in ribosome biogenesis during this time. Reduced ribosome availability more profoundly impacts the translation of specific transcripts, disrupting both survival and cell fate commitment of transitioning neuroepithelia. Enhancing mTOR activity by both genetic and pharmacologic approaches ameliorates the growth and developmental defects associated with intellectual disability linked variants, identifying potential treatment options for specific brain ribosomopathies. This work reveals the cellular and molecular origins of protein synthesis defect-related disorders of human brain development. Highlights: AIRIM variants reduce ribosome levels specifically in neural progenitor cells. Inappropriately low ribosome levels cause a transient delay in radial glia fate commitment.Reduced ribosome levels impair translation of a selected subset of mRNAs.Genetic and pharmacologic activation of mTORC1 suppresses AIRIM-linked phenotypes.

3.
Methods Mol Biol ; 2767: 1-18, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37351840

RESUMO

Under certain culture conditions, naive human pluripotent stem cells can generate human blastocyst-like structures (called human blastoids). Human blastoids serve as an accessible model for human blastocysts and are amenable for large-scale production. Here, we describe a detailed step-by-step protocol for the robust and high-efficient generation of human blastoids from naive human pluripotent stem cells.


Assuntos
Células-Tronco Pluripotentes , Humanos , Blastocisto , Diferenciação Celular
4.
Cell ; 186(26): 5859-5875.e24, 2023 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-38052213

RESUMO

Embryogenesis necessitates harmonious coordination between embryonic and extraembryonic tissues. Although stem cells of both embryonic and extraembryonic origins have been generated, they are grown in different culture conditions. In this study, utilizing a unified culture condition that activates the FGF, TGF-ß, and WNT pathways, we have successfully derived embryonic stem cells (FTW-ESCs), extraembryonic endoderm stem cells (FTW-XENs), and trophoblast stem cells (FTW-TSCs) from the three foundational tissues of mouse and cynomolgus monkey (Macaca fascicularis) blastocysts. This approach facilitates the co-culture of embryonic and extraembryonic stem cells, revealing a growth inhibition effect exerted by extraembryonic endoderm cells on pluripotent cells, partially through extracellular matrix signaling. Additionally, our cross-species analysis identified both shared and unique transcription factors and pathways regulating FTW-XENs. The embryonic and extraembryonic stem cell co-culture strategy offers promising avenues for developing more faithful embryo models and devising more developmentally pertinent differentiation protocols.


Assuntos
Embrião de Mamíferos , Células-Tronco Embrionárias , Animais , Técnicas de Cocultura , Macaca fascicularis , Células-Tronco Embrionárias/metabolismo , Diferenciação Celular , Endoderma/metabolismo , Linhagem da Célula
5.
Cell Stem Cell ; 30(9): 1246-1261.e9, 2023 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-37683605

RESUMO

Recent advances in human blastoids have opened new avenues for modeling early human development and implantation. One limitation of our first protocol for human blastoid generation was relatively low efficiency. We now report an optimized protocol for the efficient generation of large quantities of high-fidelity human blastoids from naive pluripotent stem cells. This enabled proteomics analysis that identified phosphosite-specific signatures potentially involved in the derivation and/or maintenance of the signaling states in human blastoids. Additionally, we uncovered endometrial stromal effects in promoting trophoblast cell survival, proliferation, and syncytialization during co-culture with blastoids and blastocysts. Side-by-side single-cell RNA sequencing revealed similarities and differences in transcriptome profiles between pre-implantation blastoids and blastocysts, as well as post-implantation cultures, and uncovered a population resembling early migratory trophoblasts during co-culture with endometrial stromal cells. Our optimized protocol will facilitate broader use of human blastoids as an accessible, perturbable, scalable, and tractable model for human blastocysts.


Assuntos
Implantação do Embrião , Transdução de Sinais , Humanos , Blastocisto , Sobrevivência Celular , Trofoblastos
6.
Plant Physiol Biochem ; 201: 107894, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37482030

RESUMO

Suaeda salsa is remarkable for its high oil content and abundant unsaturated fatty acids. In this study, the regulatory networks on fatty acid and lipid metabolism were constructed by combining the de novo transcriptome and lipidome data. Differentially expressed genes (DEGs) associated with lipids biosynthesis pathways were identified in the S. salsa transcriptome. DEGs involved in fatty acid and glycerolipids were generally up-regulated in leaf tissues. DEGs for TAG assembly were enriched in developing seeds, while DEGs in phospholipid metabolic pathways were enriched in root tissues. Polar lipids were extracted from S. salsa tissues and analyzed by lipidomics. The proportion of galactolipid MGDG was the highest in S. salsa leaves. The molar percentage of PG was high in the developing seeds, and the other main phospholipids had higher molar percentage in roots of S. salsa. The predominant C36:6 molecular species indicates that S. salsa is a typical 18:3 plant. The combined transcriptomic and lipidomic data revealed that different tissues of S. salsa were featured with DEGs associated with specific lipid metabolic pathways, therefore, represented unique lipid profiles. This study will be helpful on understanding lipid metabolism pathway and exploring the key genes involved in lipid synthesis in S. salsa.


Assuntos
Chenopodiaceae , Metabolismo dos Lipídeos , Metabolismo dos Lipídeos/genética , Perfilação da Expressão Gênica , Transcriptoma , Chenopodiaceae/metabolismo , Ácidos Graxos/metabolismo
7.
Mediators Inflamm ; 2023: 9077787, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37197571

RESUMO

Background: Neonatal sepsis is an extremely dangerous and fatal disease among neonates, and its timely diagnosis is critical to treatment. This research is aimed at evaluating the clinical significance of the lymphocyte-to-C-reactive protein ratio (LCR) as an early sepsis indicator in neonates with suspected sepsis. Methods: Between January 2016 and December 2021, 1269 neonates suspected of developing sepsis were included in this research. Among them, sepsis was diagnosed in 819 neonates, with 448 severe cases, as per the International Pediatric Sepsis Consensus. Data related to clinical and laboratory tests were obtained via electronic medical records. LCR was calculated as total lymphocyte (109 cells/L)/C-reactive protein (mg/L). Multivariate logistic regression analysis was employed to evaluate the effectiveness of LCR as an independent indicator for determining sepsis in susceptible sepsis neonates. Receiver operating characteristic (ROC) curve analysis was conducted for investigating the diagnostic significance of LCR in sepsis. When suitable, the statistical tool SPSS 24.0 was used for statistical analyses. Results: LCR decreased significantly in the control, mild, and severe sepsis groups. Further analyses exhibited that there was a substantially greater incidence of sepsis in neonates in the low-LCR group (LCR ≤ 3.94) as opposed to the higher LCR group (LCR > 3.94) (77.6% vs. 51.4%, p < 0.001). Correlation analysis indicated a substantial negative association of LCR with procalcitonin (r = -0.519, p < 0.001) and hospital stay duration (r = -0.258, p < 0.001). Multiple logistic regression analysis depicted LCR as an independent indicator for identifying sepsis and severe cases of this disease. ROC curve analysis indicated the optimal cutoff value of LCR in identifying sepsis to be 2.10, with 88% sensitivity and 55% specificity. Conclusions: LCR has proven to be a potentially strong biomarker capable of identifying sepsis in a timely manner in neonates suspected to have the disease.


Assuntos
Proteína C-Reativa , Sepse , Humanos , Recém-Nascido , Biomarcadores , Proteína C-Reativa/metabolismo , Calcitonina , Estudos Retrospectivos , Curva ROC , Sepse/diagnóstico
8.
Cell ; 186(10): 2092-2110.e23, 2023 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-37172563

RESUMO

The third and fourth weeks of gestation in primates are marked by several developmental milestones, including gastrulation and the formation of organ primordia. However, our understanding of this period is limited due to restricted access to in vivo embryos. To address this gap, we developed an embedded 3D culture system that allows for the extended ex utero culture of cynomolgus monkey embryos for up to 25 days post-fertilization. Morphological, histological, and single-cell RNA-sequencing analyses demonstrate that ex utero cultured monkey embryos largely recapitulated key events of in vivo development. With this platform, we were able to delineate lineage trajectories and genetic programs involved in neural induction, lateral plate mesoderm differentiation, yolk sac hematopoiesis, primitive gut, and primordial germ-cell-like cell development in monkeys. Our embedded 3D culture system provides a robust and reproducible platform for growing monkey embryos from blastocysts to early organogenesis and studying primate embryogenesis ex utero.


Assuntos
Embrião de Mamíferos , Desenvolvimento Embrionário , Animais , Macaca fascicularis , Blastocisto , Organogênese , Primatas
9.
Cell Stem Cell ; 30(5): 611-616.e7, 2023 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-37146582

RESUMO

Understanding the mechanisms of blastocyst formation and implantation is critical for improving farm animal reproduction but is hampered by a limited supply of embryos. Here, we developed an efficient method to generate bovine blastocyst-like structures (termed blastoids) via assembling bovine trophoblast stem cells and expanded potential stem cells. Bovine blastoids resemble blastocysts in morphology, cell composition, single-cell transcriptomes, in vitro growth, and the ability to elicit maternal recognition of pregnancy following transfer to recipient cows. Bovine blastoids represent an accessible in vitro model for studying embryogenesis and improving reproductive efficiency in livestock species.


Assuntos
Blastocisto , Trofoblastos , Gravidez , Feminino , Bovinos , Animais , Implantação do Embrião , Desenvolvimento Embrionário , Células-Tronco , Técnicas de Cultura de Células
10.
bioRxiv ; 2023 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-36945498

RESUMO

Faithful embryogenesis requires precise coordination between embryonic and extraembryonic tissues. Although stem cells from embryonic and extraembryonic origins have been generated for several mammalian species(Bogliotti et al., 2018; Choi et al., 2019; Cui et al., 2019; Evans and Kaufman, 1981; Kunath et al., 2005; Li et al., 2008; Martin, 1981; Okae et al., 2018; Tanaka et al., 1998; Thomson et al., 1998; Vandevoort et al., 2007; Vilarino et al., 2020; Yu et al., 2021b; Zhong et al., 2018), they are grown in different culture conditions with diverse media composition, which makes it difficult to study cross-lineage communication. Here, by using the same culture condition that activates FGF, TGF-ß and WNT signaling pathways, we derived stable embryonic stem cells (ESCs), extraembryonic endoderm stem cells (XENs) and trophoblast stem cells (TSCs) from all three founding tissues of mouse and cynomolgus monkey blastocysts. This allowed us to establish embryonic and extraembryonic stem cell co-cultures to dissect lineage crosstalk during early mammalian development. Co-cultures of ESCs and XENs uncovered a conserved and previously unrecognized growth inhibition of pluripotent cells by extraembryonic endoderm cells, which is in part mediated through extracellular matrix signaling. Our study unveils a more universal state of stem cell self-renewal stabilized by activation, as opposed to inhibition, of developmental signaling pathways. The embryonic and extraembryonic stem cell co-culture strategy developed here will open new avenues for creating more faithful embryo models and developing more developmentally relevant differentiation protocols.

11.
Theranostics ; 13(2): 596-610, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36632223

RESUMO

Rationale: Prostate cancer metastasizes to the bone with the highest frequency and exhibits high resistance to 177Lu-prostate-specific membrane antigen (PSMA) radioligand therapy. Little is known about bone metastatic prostate cancer (mPCa) resistance to radiation. Methods: We filtered the metastatic eRNA using RNA-seq, MeRIP-seq, RT-qPCR and bioinformation. Western blot, RT-qPCR, CLIP, co-IP and RNA pull-down assays were used for RNA/protein interaction, RNA or protein expression examination. MTS assay was used to determine cell viability in vitro, xenograft assay was used to examine the tumor growth in mice. Results: In this study, we screened and identified bone-specific N6 adenosine methylation (m6A) on enhancer RNA (eRNA) that played a post-transcriptional functional role in bone mPCa and was correlated with radiotherapy (RT) resistance. Further data demonstrated that RNA-binding protein KHSRP recognized both m6A at eRNA and m6Am at 5'-UTR of mRNA to block RNA degradation from exoribonuclease XRN2. Depletion of the MLXIPe/KHSRP/PSMD9 regulatory complex inhibited tumor growth and RT sensitization of bone mPCa xenograft in vitro and in vivo. Conclusions: Our findings indicate that a bone-specific m6A-modified eRNA plays a vital role in regulating mPCa progression and RT resistance and might be a novel specific predictor for cancer RT.


Assuntos
Neoplasias Ósseas , Neoplasias da Próstata , RNA , Tolerância a Radiação , Animais , Humanos , Masculino , Camundongos , Neoplasias Ósseas/genética , Neoplasias Ósseas/radioterapia , Neoplasias Ósseas/secundário , Metilação , Próstata/patologia , Neoplasias da Próstata/genética , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/patologia
12.
Contrast Media Mol Imaging ; 2022: 8433489, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35992543

RESUMO

Purpose: To dig the PD-L1 rs2890658 polymorphism with susceptibility of non-small-cell lung cancer (NSCLC) in northern China. Patients and Methods. There were 600 NSCLC patients and 600 age and sex matched controls from the same ethnic origin recruited in the present research. Polymerase chain reaction-restriction fragment length polymorphism method genotyped PD-L1 rs2890658 polymorphism. PubMed and Embase were searched to get eligible literature for meta-analysis. The association between PD-L1 rs2890658 polymorphism and NSCLC risk was calculated with odds ratio and 95% confidence interval. Results: It is more likely that individuals who have CC genotype and C allele are 2.15 and 1.41 times to develop NSCLC compared with individuals with AA genotype and A allele, respectively. Meta-analysis showed that the individuals who have C allele and CA genotype increased the risk of suffering from NSCLC. Conclusion: PD-L1 rs2890658 polymorphism increased NSCLC risk in northern China population and it might predict the occurrence of NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Antígeno B7-H1/genética , Carcinoma Pulmonar de Células não Pequenas/epidemiologia , Carcinoma Pulmonar de Células não Pequenas/genética , China/epidemiologia , Predisposição Genética para Doença/genética , Humanos , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/genética , Polimorfismo de Nucleotídeo Único
13.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 53(4): 682-687, 2022 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-35871741

RESUMO

Objective: To explore the risk factors of abdominal aortic enlargement (AAE) after thoracic endovascular aortic repair using two-stent graft implantation (TEVAR-TSI) for Stanford type B aortic dissection. Methods: The clinical and imaging data of patients who underwent TEVAR-TSI for Stanford type B aortic dissection in the First Affiliated Hospital of Hebei North University from January 2013 through September 2020 were retrospectively collected and analyzed. CT angiography (CTA) scans were performed before the procedure. Follow-up CTA scans were scheduled and performed in 1, 3, 6, and 12 months after the procedure and annually thereafter. The primary outcome was AAE. The risk factors of AAE after TEVAR-TSI were selected and survival analysis and multivariate logistic regression were conducted accordingly. Results: A total of 146 patients were regularly followed up at our hospital, with the median followup time of the entire cohort being 48 months (ranging from 12 to 84 months). During the followup period after TEVAR-TSI, the incidence of AAE was 19.9% (29/146). A total of 29 patients developed AAE (the AAE group), while 117 patients did not develop AAE (the non-AAE group). There were a total of 27 deaths, including 13 in the non-AAE group versus 14 in the AAE group. Distal aortic reoperation was performed on 10 patients, including 4 in the non-AAE group versus 6 in the AAE group. The cumulative long-term survival and freedom from distal aortic reoperation of the non-AAE group were both significantly better those of the AAE group ( P<0.05). Logistic multivariate regression analysis showed that independent risk factors of AAE after TEVAR-TSI included the following, partial thrombosis of the false lumen (odds ratio [ OR]=4.090, 95% confidence interval [ CI]: 1.539-10.867, P=0.005), the longer cumulative diameter of residual intimal tear above the level of the lowest renal arteries ( OR=1.290, 95% CI: 1.164-1.429, P=0.000), and shorter cumulative diameter of residual intimal tear below the level of the lowest renal arteries ( OR=0.487, 95% CI: 0.270-0.878, P=0.017). Conclusion: The prognosis of patients who developed AAE after TEVAR-TSI was not good. During followup visits, as precautions against the development of AAE, close attention should be paid to partial thrombosis of the false lumen, cumulative diameter of residual intimal tear above the level of the lowest renal arteries, and cumulative diameter of residual intimal tear below the level of the lowest renal arteries.


Assuntos
Aneurisma da Aorta Torácica , Dissecção Aórtica , Implante de Prótese Vascular , Procedimentos Endovasculares , Trombose , Dissecção Aórtica/etiologia , Dissecção Aórtica/cirurgia , Aneurisma da Aorta Torácica/cirurgia , Aortografia/métodos , Prótese Vascular , Implante de Prótese Vascular/efeitos adversos , Procedimentos Endovasculares/efeitos adversos , Análise Fatorial , Humanos , Estudos Retrospectivos , Fatores de Risco , Stents/efeitos adversos , Trombose/etiologia , Trombose/cirurgia , Resultado do Tratamento
14.
Genes (Basel) ; 13(6)2022 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-35741773

RESUMO

Phospholipase C is an enzyme that catalyzes the hydrolysis of glycerophospholipids and can be classified as phosphoinositide-specific PLC (PI-PLC) and non-specific PLC (NPC), depending on its hydrolytic substrate. In maize, the function of phospholipase C has not been well characterized. In this study, the phospholipase C inhibitor neomycin sulfate (NS, 100 mM) was applied to maize seedlings to investigate the function of maize PLC. Under the treatment of neomycin sulfate, the growth and development of maize seedlings were impaired, and the leaves were gradually etiolated and wilted. The analysis of physiological and biochemical parameters revealed that inhibition of phospholipase C affected photosynthesis, photosynthetic pigment accumulation, carbon metabolism and the stability of the cell membrane. High-throughput RNA-seq was conducted, and differentially expressed genes (DEGS) were found significantly enriched in photosynthesis and carbon metabolism pathways. When phospholipase C activity was inhibited, the expression of genes related to photosynthetic pigment accumulation was decreased, which led to lowered chlorophyll. Most of the genes related to PSI, PSII and TCA cycles were down-regulated and the net photosynthesis was decreased. Meanwhile, genes related to starch and sucrose metabolism, the pentose phosphate pathway and the glycolysis/gluconeogenesis pathway were up-regulated, which explained the reduction of starch and total soluble sugar content in the leaves of maize seedlings. These findings suggest that phospholipase C plays a key role in photosynthesis and the growth and development of maize seedlings.


Assuntos
Plântula , Zea mays , Carbono/metabolismo , Neomicina/metabolismo , Fotossíntese/genética , Amido/metabolismo , Fosfolipases Tipo C/genética , Fosfolipases Tipo C/metabolismo
15.
J Inflamm Res ; 15: 2313-2321, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35437348

RESUMO

Purpose: Previous studies have demonstrated that procalcitonin and albumin have a close correlation with sepsis. However, the role of procalcitonin (PCT) to albumin (ALB) ratio (PAR) in sepsis was still unclear, especially in neonates. Thus, this study aimed to investigate the association between PAR and neonatal sepsis. Patients and Methods: A total of 1,196 neonates with suspected sepsis were included in this study. Neonates were divided into control group and sepsis group, according to whether they were diagnosed with sepsis. Neonates with sepsis were further divided into mild sepsis and severe sepsis group according to the severity of sepsis. PAR was calculated as serum PCT (ng/mL)/ALB (mg/mL). All statistical analyses were performed using the statistical package SPSS 24.0, as appropriate. Results: Compared with the control group, neonates with sepsis had a higher PAR. PAR also showed a significant gradual increase in the control, mild sepsis, and severe sepsis groups (P<0.001). Correlation analysis showed that there was a strong positive correlation between PAR and hsCRP, neonatal sequential organ failure assessment score (nSOFA), and prolonged length of hospital stay (P<0.001). On multiple logistic regression, higher PAR was independently associated with the presence and severity of neonatal sepsis. According to the receiver operating characteristic curve analysis, a PAR ≥0.065 had 64% sensitivity and 72% specificity in predicting the presence of neonatal sepsis (area under curve (AUC)=0.72, 95% CI=0.69-0.75, P<0.001) and a PAR≥0.070 had 69% sensitivity and 63% specificity in predicting the presence of severe sepsis (AUC=0.71, 95% CI=0.68-0.74, P<0.001). Conclusion: PAR is significantly higher in neonates with sepsis and correlated with the severity of the disease. Increased PAR is an independent predictor useful for identifying the presence and severity of neonatal sepsis.

16.
J Inflamm Res ; 15: 6923-6930, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36605131

RESUMO

Purpose: Previous studies have demonstrated that interleukin-18 (IL-18) levels were elevated in adult patients with sepsis. However, its role in neonatal sepsis remains unknown. The current research was conducted to assess the clinical value of serum IL-18 level as a candidate biomarker in neonatal sepsis diagnosis and prediction of mortality. Patients and Methods: From July 2022 to September 2022, we prospectively enrolled 91 septic neonates and 31 non-sepsis neonates in the intensive care unit of neonates at Henan Children's Hospital in Zhengzhou, China. Neonatal peripheral blood serum was collected at admission and levels of serum IL-18 were assessed. Employing multivariate logistic regression analysis, the evaluation of the potential of IL-18 as an independent biomarker for sepsis was executed. Furthermore, employing the receiver operating characteristic (ROC) curve analysis, the diagnostic value of IL-18 in sepsis and the ability of IL-18 in predicting the mortality of neonatal sepsis was measured. The statistical package SPSS 24.0 was employed to conduct all statistical analyses. Results: Serum IL-18 levels in neonates in the sepsis group were elevated compared to the control group, reaching the highest levels in the non-survival sepsis group (P < 0.001). Correlation analysis exhibited a positive relationship between IL-18 levels and age, body temperature, respiratory rate, and C-reactive protein levels. IL-18 was identified as an independent biomarker in identifying sepsis (OR = 4.747, 95% CI 1.493-15.092, P = 0.008) by multiple logistic regression. ROC curve analysis exhibited that IL-18 was good in identifying neonatal sepsis (area under curve (AUC) = 0.77, 95% CI = 0.68-0.85, P < 0.001) and predicting neonatal mortality (AUC = 0.80, 95% CI = 0.63-0.96, P = 0.003). Conclusion: IL-18 was a potential biomarker for identifying neonatal sepsis and neonatal mortality prediction.

18.
J Inflamm Res ; 14: 3207-3215, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34285544

RESUMO

PURPOSE: Previous studies have reported that C-reactive protein-to-albumin ratio (CAR) was a risk factor for sepsis in adults. However, little is known regarding the role of CAR in neonates with sepsis. The aim of this study was to explore the relationship between CAR and neonatal sepsis. PATIENTS AND METHODS: In this research, from January 2016 to February 2020, a total of 1076 neonates were enrolled at Henan Children's Hospital in China. Complete clinical and laboratory data were collected. To identify the potential independent risk factor for neonatal sepsis, multivariate logistic regression analysis was performed. Receiver operating characteristic (ROC) curve analysis was used to evaluate the prediction accuracy of CAR in identifying neonatal sepsis. RESULTS: CAR levels were higher in neonates with sepsis and showed a gradual increase among the control group, mild sepsis group and severe sepsis group. The prevalence of neonates with overall sepsis, mild sepsis and severe sepsis increased significantly from CAR tertile 1 to tertile 3. Multiple logistic regression analysis showed that CAR was an independent risk factor for the presence of sepsis (OR = 10.144, 95% CI 4.151-24.790, P < 0.001) and severe sepsis (OR = 1.876, 95% CI 1.562-2.253, P < 0.001). ROC curve analysis showed that CAR had a well discriminatory power in predicting sepsis (area under curve (AUC) = 0.74, 95% CI, 0.71-0.77, P < 0.001) and severe sepsis (AUC = 0.70, 95% CI, 0.67-0.74, P < 0.001). CONCLUSION: CAR was an independent predictor for the presence and severity of neonatal sepsis.

19.
Front Plant Sci ; 12: 639132, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33936129

RESUMO

Low temperature is one of the major abiotic stresses that restrict the growth and development of maize seedlings. Membrane lipid metabolism and remodeling are key strategies for plants to cope with temperature stresses. In this study, an integrated lipidomic and transcriptomic analysis was performed to explore the metabolic changes of membrane lipids in the roots of maize seedlings under cold stress (5°C). The results revealed that major extraplastidic phospholipids [phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidic acid (PA), and phosphatidylinositol (PI)] were dominant membrane lipids in maize root tissues, accounting for more than 70% of the total lipids. In the transcriptome data of maize roots under cold stress, a total of 189 lipid-related differentially expressed genes (DEGs) were annotated and classified into various lipid metabolism pathways, and most of the DEGs were enriched in the "Eukaryotic phospholipid synthesis" (12%), "Fatty acid elongation" (12%), and "Phospholipid signaling" (13%) pathways. Under low temperature stress, the molar percentage of the most abundant phospholipid PC decreased around 10%. The significantly up-regulated expression of genes encoding phospholipase [phospholipase D (PLD)] and phosphatase PAP/LPP genes implied that PC turnover was triggered by cold stress mainly via the PLD pathway. Consequently, as the central product of PC turnover, the level of PA increased drastically (63.2%) compared with the control. The gene-metabolite network and co-expression network were constructed with the prominent lipid-related DEGs to illustrate the modular regulation of metabolic changes of membrane lipids. This study will help to explicate membrane lipid remodeling and the molecular regulation mechanism in field crops encountering low temperature stress.

20.
Front Plant Sci ; 12: 635327, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33790924

RESUMO

Plants are frequently confronted by diverse environmental stress, and the membrane lipids remodeling and signaling are essential for modulating the stress responses. Saline-alkaline stress is a major osmotic stress affecting the growth and development of crops. In this study, an integrated transcriptomic and lipidomic analysis was performed, and the metabolic changes of membrane lipid metabolism in maize (Zea mays) roots under saline-alkaline stress were investigated. The results revealed that phospholipids were major membrane lipids in maize roots, and phosphatidylcholine (PC) accounts for approximately 40% of the total lipids. Under 100 mmol NaHCO3 treatment, the level of PC decreased significantly (11-16%) and the parallel transcriptomic analysis showed an increased expression of genes encoding phospholipase A and phospholipase D/non-specific phospholipase C, which suggested an activated PC turnover under saline-alkaline stress. The plastidic galactolipid synthesis was also activated, and an abnormal generation of C34:6 galactolipids in 18:3 plants maize implied a plausible contribution from the prokaryotic pathway, which could be partially supported by the up-regulated expression of three putative plastid-localized phosphatidic acid phosphatase/lipid phosphate phosphatase. A comprehensive gene-metabolite network was constructed, and the regulation of membrane lipid metabolism under saline-alkaline stress in maize was discussed.

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