Three-dimensional hPSC-derived lung organoids resemble the fetal lung stage, making them an excellent model for studying human lung development. However, current hPSC-derived lung organoids remain ...incomplete as they lack native lung components such as vasculature, neurons and immune cells. This highlights the need to generate more complex hPSC-derived lung organoids that can faithfully mimic native human lungs for studying human lung development, regeneration, disease modeling and drug screen. In this review, we will discuss the current studies related to the generation of hPSC-derived lung organoids, highlighting how hPSC-derived lung organoids can contribute to the understanding of human lung development. We further focus on potential approaches to generate more complex hPSC-derived lung organoids containing native cellular components. Finally, we discuss the present limitations and potential applications of hPSC-derived lung organoids in the future.
Background/Aims: The present study addressed the potential involvement of microRNAs in acute respiratory distress syndrome (ARDS)-related inflammation and elucidates the underlying molecular ...mechanism. Methods: ARDS rat model was established by lipopolysaccharide, with compromised gas exchange capacity and lung edema. The inflammatory cells from bronchoalveolar lavage fluid (BALF) were profiled with automatic blood cell analyzer. The relative fluorescence intensity of BALF-derived macrophages was analyzed by flow cytometry. The relative microRNA expression was determined using microarray and Taqman assay. The secretory interleukin (IL)-10 was measured by enzyme-linked immunosorbent assay. Luciferase reporter assay was performed to determine the regulatory effects of miR-211 and NF-κB on IL-10 and miR-211 expressions, respectively. Chromatin immunoprecipitation (ChIP) was conducted to detect the direct binding of NK-κB on miR-211 promoter. The protein level was determined by Western blot. Results: The provoked acute inflammation was characterized with increased total cells, macrophages, neutrophils and lymphocytes. The relative expression of miR-211 was aberrantly up-regulated in BALF-derived macrophages from ARDS rats, which was accompanied with reduction of secretory IL-10. We further demonstrated that miR-211 inhibited IL-10 expression by binding to its 3’-UTR. The expression of miR-211 was modulated by NF-κB. Conclusion: Here we elucidated a crucial role of NF-κB/miR-211/IL-10 signaling axis in ARDS-related inflammation.
The Aluminum–Silicon (Al–Si) die-casting alloys, such as the commercial A356 alloy, are expected to be used in heat-sink and the device with high thermal conductivity due to their high production ...efficiency of casting process. These fields also required them to possess sound mechanical properties. To meet these demands, the Strontium (Sr) was often utilized to modify the silicon phase. According to our current work, the secondary dendrite arm spacing of the α-Al grains prominently was decreased when 0.05%–0.25% strontium was added. The decrease of the secondary dendrite arm spacing (SDAS) lead to the enhancement of the mechanical strength as well as the improvement of the thermal and electrical conductivity. When the Sr dosage was 0.15% in the commercial A356 alloy, the strength and the thermal conductivity of the A356 alloy simultaneously reached the maximum value. The improvement of the electrical and thermal conductivity might by contributed by the formation of a good conductor, Al
2
Si
2
Sr phase, on the Si surface. Further investigations suggested that the improvement of thermal conductivity was mainly due to the modification effect of Sr on the eutectic Si phase, which enlarged the specific area between the α-Al/eutectic Si interface. The WDS analysis indicated that the solubility of Si decreased in aluminum matrix by increasing in the Sr dosage. However, the excessive dosage of strontium would result in the coarsening of the modified silicon phase, deteriorating the strength and the thermal and electrical conductivity of the modified A356 alloys.
Graphic Abstract
In this work, the commercial A356 alloy was modified by adding small amounts of strontium (Sr). This kind of aluminum alloy with sound fluidity could be formed by using casting process, and it was potential to be applied in the structural parts. After the Sr modification, the plate-like silicon (Si) phase was transformed to fibrous shape in the raw commercial A356. Meanwhile, it was found that the content of silicon in the Al solid solution was reduced.The XRD and SEM analysis suggested that the Al2Si2Sr phase was formed on the modified silicon phase, which was favorable to the conduction of free electron.
This study aimed to investigate spontaneous hypothermia among emergency trauma patients and develop a predictive model. A cohort of 162 emergency trauma patients was categorized into hypothermic (
= ...61) and control (
= 101) groups, with trauma severity assessed using the modified Glasgow Coma Scale (GCS). Univariate analysis revealed significant differences between the groups in trauma severity, posture, garment wetness, warming measures, pre-hospital fluid resuscitation, and modified GCS scores (
< 0.05). The hypothermic group exhibited lower prothrombin time compared to the control group (
< 0.05). A logistic regression model was constructed, expressed as
= 25.76 − 1.030
+ 0.725
+ 0.922
− 0.750
− 0.57
, and its fit was evaluated using the Hosmer–Lemeshow test. The receiver operating characteristic curve demonstrated an area under the curve of 0.871, with 81.2% sensitivity and 79.5% specificity. The Youden index identified the optimal predictive cut-off at its highest (0.58). Validation results included 86.21% sensitivity, 82.93% specificity, and 84.29% accuracy. Risk factors for spontaneous hypothermia after emergency trauma encompassed trauma severity, posture during consultation, clothing dampness upon admission, warming measures during transfer, pre-hospital fluid resuscitation, and modified GCS scores. The risk prediction model demonstrated high accuracy, enabling effective assessment of spontaneous hypothermia risk in emergency trauma patients and facilitating preventive measures.
The objective of this study was to determine the growth patterns, rates of malnutrition, and factors associated with malnutrition in children born to HIV-infected mothers in western Kenya using data ...from an electronic medical record system.
This study was a retrospective chart review of HIV-infected (HIV+) and-exposed (HEU) children (<5 years) using data collected prospectively in the course of routine clinical care and stored in the electronic medical record system in western Kenya between January 2011 and August 2016. Demographics and anthropometrics were described, with Chi-square testing to compare proportions. Multiple variable logistic regression analysis was used to identify correlates of children being stunted, underweight, and wasted. We also examined growth curves, using a resampling method to compare the areas under the fitted growth curves to compare males/females and HIV+/HEU.
Data from 15,428 children were analyzed. The children were 51.6% (n = 7,955) female, 5.2% (n = 809) orphans, 83.3% (n = 12,851) were HEU, and 16.7% (n = 2,577) were HIV+. For HIV+ children assessed at 24 months, 50.9% (n = 217) were stunted, 26.5% (n = 145) were underweight, and 13.6% (n = 58) were wasted, while 45.0% (n = 577) of HEU children were stunted, 14.8% (n = 255) were underweight, and 5.1% (n = 65) were wasted. When comparing mean z-scores, HIV+ children tended to have larger and earlier dips in z-scores compared to HIV-exposed children, with significant differences found between the two groups (p<0.001). Factors associated with an increased risk of malnutrition included being male, HIV+, and attending an urban clinic. Maternal antiretroviral treatment during pregnancy and mixed feeding at 3 months of age decreased the risk of malnutrition.
HIV+ and HEU children differ in their anthropometrics, with HIV+ children having overall lower z-scores. Continued efforts to develop and implement sustainable and effective interventions for malnutrition are needed for children born to HIV+ mothers.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Bone undergoes constant remodeling of formation by osteoblasts and resorption by osteoclasts. In particular, macrophages have been reported to play an essential role in the regulation of bone ...homeostasis and regeneration. Naringenin, the predominant flavanone in citrus fruits, is reported to exert anti-inflammatory, anti-osteoclastic, and osteogenic effects. However, whether naringenin could modulate the crosstalk between macrophages and osteoblasts/osteoclasts remains to be investigated. In this study, we confirmed that naringenin enhanced osteogenesis and inhibited osteoclastogenesis directly. Naringenin promoted M2 transition and the secretion of osteogenic cytokines including IL-4, IL-10, BMP2, and TGF-β, while suppressing LPS-induced M1 polarization and the production of proinflammatory factors such as TNF-α and IL-1β. In addition, the coculture of primary bone mesenchymal stem cells (BMSCs)/bone marrow monocytes (BMMs) with macrophages showed that the naringenin-treated medium significantly enhanced osteogenic differentiation and impeded osteoclastic differentiation in both inflammatory and non-inflammatory environment. Moreover,
experiments demonstrated that naringenin remarkably reversed LPS-induced bone loss and assisted the healing of calvarial defect. Taken together, naringenin serves as a potential anabolic treatment for pathological bone loss.
Abstract There is increasing evidence that mechanical issues play a vital role in neuron growth and brain development. The importance of this grows as novel devices, whose material properties differ ...from cells, are increasingly implanted in the body. In this work, we studied the mechanical properties of rat brain cells over time and on different materials by using a high throughput magnetic tweezers system. It was found that the elastic moduli of both neurite and soma in networked neurons increased with growth. However, neurites at DIV4 exhibited a relatively high stiffness, which could be ascribed to the high outgrowth tension. The power-law exponents (viscoelasticity) of both neurites and somas of neurons decreased with culture time. On the other hand, the stiffness of glial cells also increased with maturity. Furthermore, both neurites and glia become softer when cultured on compliant substrates. Especially, the glial cells cultured on a soft substrate obviously showed a less dense and more porous actin and GFAP mesh. In addition, the viscoelasticity of both neurites and glia did not show a significant dependence on the substrates' stiffness.
Bud sport is a kind of somatic mutation that usually occurred in apple. 'Red Delicious' is considered to be a special plant material of bud sport, whereas the genetic basis of plant mutants is still ...unknown. In this study, we used whole-genome resequencing and transcriptome sequencing to identify genes related to spur-type and skin-color in the 'Red Delicious' (G0) and its four generation mutants including 'Starking Red' (G1), 'Starkrimson' (G2), 'Campbell Redchief' (G3) and 'Vallee Spur' (G4). The number of single nucleotide polymorphisms (SNPs), insertions and deletions (InDels) and structural variations (SVs) were decreased in four generation mutants compared to G0, and the number of unique SNPs and InDels were over 9-fold and 4-fold higher in G1 versus (vs.) G2 and G2 vs. G3, respectively. Chromosomes 2, 5, 11 and 15 carried the most SNPs, InDels and SVs, while chromosomes 1 and 6 carried the least. Meanwhile, we identified 4,356 variation genes by whole-genome resequencing and transcriptome, and obtained 13 and 16 differentially expressed genes (DEGs) related to spur-type and skin-color by gene expression levels. Among them, DELLA and 4CL7 were the potential genes that regulate the difference of spur-type and skin-color characters, respectively. Our study identified potential genes associated with spur-type and skin-color differences in 'Red Delicious' and its four generation mutants, which provides a theoretical foundation for the mechanism of the apple bud sport.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Electrochemical behavior in aerated 3.5
wt.% NaCl solution of Mg alloy AZ91D anodized or not has been investigated by using electrochemical impedance spectroscopy, potentiodynamic polarization and
E
...corr–
t curve. Their microstructures before and after corrosion have been examined under scanning electron microscope. Testing results from
E
corr–
t and polarization curves indicate that the corrosion behavior of Mg alloy makes significant, characteristic changes due to anodization. Impedance spectra obtained show a regular evolution with exposure time revealing the development of corrosion damage. SEM micrographs confirm that there are pores, defects and microcracks in anodic film which determine the existence of film-vulnerable regions. Electrochemical data are combined with micrographs to explain protection mechanism of anodic film and corrosion mechanism of Mg alloy.
Abstract
Background
Age-associated changes attenuate human blood system functionality through the aging of hematopoietic stem and progenitor cells (HSPCs), manifested in human populations an increase ...in myeloproliferative disease and even leukemia; therefore, study on HSPC senescence bears great significance to treat hematopoietic-associated disease. Furthermore, the mechanism of HSPC aging is lacking, especially the cellular memory mechanism. Here, we not only reported a new HSPC senescence model in vitro, but also propose and verify the cellular memory mechanism of HSPC aging of the Polycomb/Trithorax system.
Methods
HSPCs (Lin
−
c-kit
+
cells) were isolated and purified by magnetic cell sorting (MACS). The proportions and cell cycle distribution of cells were determined by flow cytometry; senescence-related β-galactosidase assay, transmission electron microscope (TEM), and colony-forming unit (CFU)-mix assay were detected for identification of the old HSPC model. Proteomic tests and RNA-seq were applied to analyze differential pathways and genes in the model cells. qPCR, Western blot (WB), and chromatin immunoprecipitation PCR (CHIP-PCR) were used to detect the gene expression of cell memory-related proteins. Knockdown of cell memory-related key genes was performed with shRNA interference.
Results
In the model old HSPCs, β-gal activity, cell cycle, colony-forming ability, aging-related cell morphology, and metabolic pathway were significantly changed compared to the young HSPCs. Furthermore, we found the model HSPCs have more obvious aging manifestations than those of natural mice, and IL3 is the major factor contributing to HSPC aging in the model. We also observed dramatic changes in the expression level of PRC/TrxG complexes. After further exploring the downstream molecules of PRC/TrxG complexes, we found that Uhrf1 and TopII played critical roles in HSPC aging based on the HSPC senescence model.
Conclusions
These findings proposed a new HSPC senescence model in vitro which we forecasted could be used to preliminary screen the drugs of the HSPC aging-related hemopathy and suggested cellular memory mechanism of HSPC aging.
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