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Frontiers in Plant Science 2024In crops like wheat, terminal drought is one of the principal stress factors limiting productivity in rain-fed systems. However, little is known about root development...
In crops like wheat, terminal drought is one of the principal stress factors limiting productivity in rain-fed systems. However, little is known about root development after heading, when water uptake can be critical to wheat crops. The impact of water-stress on root growth was investigated in two wheat cultivars, Scout and Mace, under well-watered and post-anthesis water stress in three experiments. Plants were grown outside in 1.5-m long pots at a density similar to local recommended farming practice. Differences in root development were observed between genotypes, especially for water stress conditions under which Scout developed and maintained a larger root system than Mace. While under well-watered conditions both genotypes had shallow roots that appeared to senesce after heading, a moderate water stress stimulated shallow-root growth in Scout but accelerated senescence in Mace. For deep roots, post-heading biomass growth was observed for both genotypes in well-watered conditions, while under moderate water stress, only Scout maintained net growth as Mace deep roots senesced. Water stress of severe intensity affected both genotypes similarly, with root senescence at all depths. Senescence was also observed above ground. Under well-watered conditions, Scout retained leaf greenness (i.e. stay-green phenotype) for slightly longer than Mace. The difference between genotypes accentuated under moderate water stress, with rapid post-anthesis leaf senescence in Mace while Scout leaf greenness was affected little if at all by the stress. As an overall result, grain biomass per plant ('yield') was similar in the two genotypes under well-watered conditions, but more affected by a moderate stress in Mace than Scout. The findings from this study will assist improvement in modelling root systems of crop models, development of relevant phenotyping methods and selection of cultivars with better adaptation to drought.
PubMed: 38911974
DOI: 10.3389/fpls.2024.1351436 -
Frontiers in Immunology 2024Exacerbations of chronic obstructive pulmonary disease (COPD) increase mortality risk and can lead to accelerated loss of lung function. The increased inflammatory...
INTRODUCTION
Exacerbations of chronic obstructive pulmonary disease (COPD) increase mortality risk and can lead to accelerated loss of lung function. The increased inflammatory response during exacerbations contributes to worsening of airflow limitation, but whether it also impacts epithelial repair is unclear. Therefore, we studied the effect of the soluble factor micro-environment during COPD exacerbations on epithelial repair using an exacerbation cocktail (EC), composed of four factors that are increased in COPD lungs during exacerbations (IL-1β, IL-6, IL-8, TNF-α).
METHODS
Mouse organoids (primary CD31-CD45-Epcam+ cells co-cultured with CCL206 fibroblasts) were used to study epithelial progenitor behavior. Mature epithelial cell responses were evaluated using mouse precision cut lung slices (PCLS). The expression of epithelial supportive factors was assessed in CCL206 fibroblasts and primary human lung fibroblasts.
RESULTS
EC exposure increased the number and size of organoids formed, and upregulated , and expression in day 14 organoids. In PCLS, EC imparted no effect on epithelial marker expression. Pre-treatment of CCL206 fibroblasts with EC was sufficient to increase organoid formation. Additionally, the expression of , and was increased in CCL206 fibroblasts from EC treated organoids, but these factors individually did not affect organoid formation or size. However, TGF-α downregulated expression and upregulated expression in day 14 organoids.
CONCLUSIONS
EC exposure stimulates organoid formation and growth, but it alters epithelial differentiation. EC changes the epithelial progenitor support function of fibroblasts which contributes to observed effects on epithelial progenitors.
Topics: Animals; Pulmonary Disease, Chronic Obstructive; Humans; Mice; Fibroblasts; Epithelial Cells; Organoids; Cytokines; Lung; Cells, Cultured; Disease Progression; Respiratory Mucosa; Mice, Inbred C57BL
PubMed: 38911863
DOI: 10.3389/fimmu.2024.1346491 -
Frontiers in Immunology 2024Bone regeneration is a complex pathophysiological process determined by molecular, cellular, and biomechanical factors, including immune cells and growth factors.... (Review)
Review
Bone regeneration is a complex pathophysiological process determined by molecular, cellular, and biomechanical factors, including immune cells and growth factors. Fracture healing usually takes several weeks to months, during which patients are frequently immobilized and unable to work. As immobilization is associated with negative health and socioeconomic effects, it would be desirable if fracture healing could be accelerated and the healing time shortened. However, interventions for this purpose are not yet part of current clinical treatment guidelines, and there has never been a comprehensive review specifically on this topic. Therefore, this narrative review provides an overview of the available clinical evidence on methods that accelerate fracture healing, with a focus on clinical applicability in healthy patients without bone disease. The most promising methods identified are the application of axial micromovement, electromagnetic stimulation with electromagnetic fields and direct electric currents, as well as the administration of growth factors and parathyroid hormone. Some interventions have been shown to reduce the healing time by up to 20 to 30%, potentially equivalent to several weeks. As a combination of methods could decrease the healing time even further than one method alone, especially if their mechanisms of action differ, clinical studies in human patients are needed to assess the individual and combined effects on healing progress. Studies are also necessary to determine the ideal settings for the interventions, i.e., optimal frequencies, intensities, and exposure times throughout the separate healing phases. More clinical research is also desirable to create an evidence base for clinical guidelines. To make it easier to conduct these investigations, the development of new methods that allow better quantification of fracture-healing progress and speed in human patients is needed.
Topics: Humans; Fracture Healing; Animals; Fractures, Bone; Bone Regeneration; Magnetic Field Therapy
PubMed: 38911851
DOI: 10.3389/fimmu.2024.1384783 -
ACS Omega Jun 2024The separation of xenon/krypton gas mixtures is a valuable but challenging endeavor in the gas industry due to their similar physical characteristics and closely sized...
The separation of xenon/krypton gas mixtures is a valuable but challenging endeavor in the gas industry due to their similar physical characteristics and closely sized molecules. To address this, we investigated the effectiveness of the hydrate-based gas separation method for mixed Xe-Kr gas via molecular dynamics (MD) simulations. The formation process of hydrates facilitates the encapsulation of guest molecules within hydrate cages, offering a potential strategy for gas separation. Higher temperatures and pressures are advantageous for accelerating the hydrate growth rate. The final occupancy of guest molecules and empty cages within 5, 56, and all hydrate cages were thoroughly examined. An increase in the pressure and temperature enhanced the occupancy rates of Xe in both 5 and 56 cages, whereas elevated pressure alone improved the occupancy of Kr in 56 cages. However, the impact of temperature and pressure on Kr occupancy within 5 cages was found to be minimal. Elevated temperature and pressure resulted in a reduced occupancy of empty cages. Predominantly, 56 cages were occupied by Xe, whereas Kr showed a propensity to occupy the 5 cages. With increasing simulated pressure, the final occupancy of Xe molecules in all cages rose from 0.37 to 0.41 for simulations at 260 K, while the final occupancy of empty cages decreased from 0.24 to 0.2.
PubMed: 38911791
DOI: 10.1021/acsomega.4c00108 -
Ecology and Evolution Jun 2024Ecosystem services offered by urban forests must be proactively managed to remain diverse and sustainable. Recent research findings deserve a systematic synthesis to...
Ecosystem services offered by urban forests must be proactively managed to remain diverse and sustainable. Recent research findings deserve a systematic synthesis to elucidate inherent knowledge structures and dynamics. This study focused on the urban tree diversity theme from 2000 to 2022. Web of Science Core Collection database provided bibliometric details on academic publications. The data-driven quantitative analysis explored research quantities, emphasis, trends, patterns, linkages, and impacts by countries, institutions, authors, journals, and citations. Publications and research topics have expanded continually, with accelerated growth in recent years. Research activities, outputs and interactions demonstrated conspicuous spatial clustering. A few countries, institutions and researchers generated a notable proportion of publications. Their scholarly contributions were visualized in knowledge graphs as complex networks of nodes and inter-node links. Keyword analysis generated a network to indicate research hotspots and frontiers to steer and prioritize future studies. Recent findings affirmed that cities can harbor substantial tree diversity due to enhanced habitat heterogeneity and successful species adaptation. Aligning tree traits with environmental conditions and management objectives can improve benefits. Urbanization can filter tree traits to shape community assemblages through stressors: habitat degradation, fragmentation and loss, in conjunction with pollution, climate change, and introduced species. Diversity preservation strategies include protecting remnant natural vegetation, connecting green spaces, and restoring complex canopy geometry and biomass structure. The emerging frontiers are marked by modeling future species distributions, leveraging technologies like remote sensing, linking ecology with human values, and committing to community-based stewardship. Management can be upgraded by interdisciplinary perspectives integrating ecological science and social engagement. The findings highlight the need for biodiversity enrichment anchored by native species, trait-matched assemblages, adaptive policies, and community participation to create livable-green cities. This review synthesizes key advances in urban tree ecology and biodiversity research to inform the planning and stewardship of resilient urban forests.
PubMed: 38911495
DOI: 10.1002/ece3.11630 -
Regenerative Therapy Jun 2024Nosocomial infections caused by multidrug-resistant are a considerable public health threat, requiring innovative therapeutic approaches.
BACKGROUND
Nosocomial infections caused by multidrug-resistant are a considerable public health threat, requiring innovative therapeutic approaches.
OBJECTIVES
This study explored preconditioning mesenchymal stem cells (MSCs) with the antimicrobial peptide Nisin to enhance their antibacterial properties while maintaining regenerative capacity.
METHODS
Human MSCs were preconditioned with varying concentrations of Nisin (0.1-1000 IU/mL) to determine an optimal dose. MSCs preconditioned with Nisin were characterized using microscopy, flow cytometry, gene expression analysis, and functional assays. The effects of preconditioning on the viability, phenotype, differentiation capacity, antimicrobial peptide expression, and antibacterial activity of MSCs against were tested . The therapeutic efficacy was evaluated by topically applying conditioned media from Nisin-preconditioned versus control MSCs to infected wounds in a rat model, assessing bacterial burden, healing, host response, and survival.
RESULTS
An optimal Nisin dose of 500 IU/mL was identified, which increased MSC antibacterial gene expression and secretome activity without compromising viability or stemness. Nisin-preconditioned MSCs showed upregulated expression of LL37 and hepcidin. Conditioned media from Nisin-preconditioned MSCs exhibited about 4-fold more inhibition of growth compared to non-preconditioned MSCs. In the wound infection model, the secretome of Nisin-preconditioned MSCs suppressed bacterial load, accelerated wound closure, modulated inflammation, and improved survival compared to standard MSC treatments.
CONCLUSION
This study explores the effect of preconditioning MSCs with the antimicrobial peptide Nisin on enhancing their antibacterial properties while maintaining regenerative capacity. Secreted factors from Nisin-preconditioned MSCs have the potential to attenuate infections and promote healing . The approach holds translational promise for managing antibiotic-resistant infections and warrants further development. Preconditioned MSCs with Nisin may offer innovative, multifaceted therapies for combating nosocomial pathogens and promoting tissue regeneration.
PubMed: 38911027
DOI: 10.1016/j.reth.2024.05.015 -
BMC Geriatrics Jun 2024The accelerated growth of older individuals worldwide has increased the number of patients presenting with fragility hip fractures. Having a hip fracture can cause...
BACKGROUND
The accelerated growth of older individuals worldwide has increased the number of patients presenting with fragility hip fractures. Having a hip fracture can cause excess mortality, and patients with hip fracture have a higher risk of death than those without hip fracture. Most studies have treated hip fracture as a single, homogeneous condition, but hip fracture includes two major anatomic types: intertrochanteric fracture and femoral neck fracture. Few studies have specifically evaluated 1-year mortality risk in older individuals with femoral intertrochanteric fracture. The aim of this study was to evaluate 1-year mortality and factors associated with mortality in older individuals with femoral intertrochanteric fracture.
METHODS
A retrospective review was conducted of 563 patients ≥ 65 years old who underwent surgery for femoral intertrochanteric fractures at our institution between January 2010 and August 2018. Patient demographics, comorbidities, and treatment were collected by retrospective chart review. Age, sex, Body Mass Index (BMI), American Society of Anesthesiologists (ASA) classification, Charlson comorbidity index (CCI), Arbeitsgemeinschaft Für Osteosynthesefragen (AO) fracture classification, haemoglobin value at admission, time to surgery, operation time, and intraoperative blood loss were risk factors to be tested. Multivariable logistic regression was used to evaluate associations between variables and death.
RESULTS
Among the 563 patients, 49 died within 1 year after surgery, and the 1-year mortality rate was 8.7%. Multivariate analysis identified age > 80 years (OR = 4.038, P = 0.011), haemoglobin < 100 g/l (OR = 2.732, P = 0.002), ASA score ≥ 3 (OR = 2.551, P = 0.005), CCI ≥ 3 (OR = 18.412, P = 0.018) and time to surgery > 14 d (OR = 3.907, P = 0.030) as independent risk factors for 1-year mortality. Comorbidities such as myocardial infarction and chronic pulmonary disease were associated with 1-year mortality after adjusting for age > 80 years and time to surgery > 14 days.
CONCLUSIONS
Patients over 80 years old with haemoglobin < 100 g/l, ASA score ≥ 3, CCI ≥ 3, and multiple comorbidities, especially myocardial infarction and chronic pulmonary disease before surgery, are at a higher risk of 1-year mortality. Doctors should pay more attention to these vulnerable patients, and a surgical delay greater than 14 days should be avoided.
Topics: Humans; Male; Female; Aged; Retrospective Studies; Hip Fractures; China; Aged, 80 and over; Risk Factors; Tertiary Care Centers; Risk Assessment
PubMed: 38909190
DOI: 10.1186/s12877-024-05159-y -
Cell Death & Disease Jun 2024TBX3 behaves as a tumor suppressor or oncoprotein across cancer. However, TBX3 function remains undetermined in intrahepatic cholangiocarcinoma (iCCA), a deadly primary...
TBX3 behaves as a tumor suppressor or oncoprotein across cancer. However, TBX3 function remains undetermined in intrahepatic cholangiocarcinoma (iCCA), a deadly primary liver malignancy with few systemic treatment options. This study sought to investigate the impact of TBX3 on iCCA. We found that overexpression of TBX3 strongly inhibited human iCCA cell growth. In the Akt/FBXW7ΔF mouse iCCA model, overexpression of Tbx3 reduced cholangiocarcinogenesis in vivo, while inducible genetic knockout of Tbx3 accelerated iCCA growth. RNA-seq identified MAD2L1 as a downregulated gene in TBX3-overexpressing cells, and ChIP confirmed that TBX3 binds to the MAD2L1 promoter. CRISPR-mediated knockdown of Mad2l1 significantly reduced the growth of two iCCA models in vivo. Finally, we found that TBX3 expression is upregulated in ~20% of human iCCA samples, and its high expression is associated with less proliferation and better survival. MAD2L1 expression is upregulated in most human iCCA samples and negatively correlated with TBX3 expression. Altogether, our findings suggest that overexpression of TBX3 suppresses CCA progression via repressing MAD2L1 expression.
Topics: Cholangiocarcinoma; T-Box Domain Proteins; Humans; Animals; Mice; Bile Duct Neoplasms; Carcinogenesis; Cell Line, Tumor; Gene Expression Regulation, Neoplastic; Cell Proliferation
PubMed: 38909034
DOI: 10.1038/s41419-024-06839-8 -
Cancer Letters Jun 2024Although survival from breast cancer has dramatically increased, many will develop recurrent, metastatic disease. Unfortunately, survival for this stage of disease...
Although survival from breast cancer has dramatically increased, many will develop recurrent, metastatic disease. Unfortunately, survival for this stage of disease remains very low. Activating the immune system has incredible promise since it has the potential to be curative. However, immune checkpoint blockade (ICB) which works through T cells has been largely disappointing for metastatic breast cancer. One reason for this is a suppressive myeloid immune compartment that is unaffected by ICB. Cholesterol metabolism and proteins involved in cholesterol homeostasis play important regulatory roles in myeloid cells. Here, we demonstrate that NR0B2, a nuclear receptor involved in negative feedback of cholesterol metabolism, works in several myeloid cell types to impair subsequent expansion of regulatory T cells (T); T being a subset known to be highly immune suppressive and associated with poor therapeutic response. Within myeloid cells, NR0B2 serves to decrease many aspects of the inflammasome, ultimately resulting in decreased IL1β; IL1β driving T expansion. Importantly, mice lacking NR0B2 exhibit accelerated tumor growth. Thus, NR0B2 represents an important node in myeloid cells dictating ensuing T expansion and tumor growth, thereby representing a novel therapeutic target to re-educate these cells, having impact across different solid tumor types. Indeed, a paper co-published in this issue demonstrates the therapeutic utility of targeting NR0B2.
PubMed: 38908543
DOI: 10.1016/j.canlet.2024.217042 -
International Journal of Biological... Jun 2024While it is known that calcium phosphate (CaP) minerals deposit in elastin-rich medial layers of arteries during medial calcification, their nucleation and growth sites...
While it is known that calcium phosphate (CaP) minerals deposit in elastin-rich medial layers of arteries during medial calcification, their nucleation and growth sites are still debated. Neutral carbonyl groups and carboxylate groups are possible candidates. Also, while it is known that elastin degradation leads to calcification, it is unclear whether this is due to formation of new carboxylate groups or elastin fragmentation. In this work, we disentangle effects of carboxylate groups and particle size on elastin calcification; in doing so, we shed light on CaP mineralization sites on elastin. We find carboxylate groups accelerate calcification only in early stages; they mainly function as Ca ion chelation sites but not calcification sites. Their presence promotes formation (likely on Ca ions adsorbed on nearby carbonyl groups) of CaP minerals with high calcium-to-phosphate ratio as intermediate phases. Larger elastin particles calcify slower but reach similar amounts of CaP minerals in late stages; they promote direct formation of hydroxyapatite and CaP minerals with low calcium-to-phosphate ratio as intermediate phases. This work provides new perspectives on how carboxylate groups and elastin particle size influence calcification; these parameters can be tuned to study the mechanism of medial calcification and design drugs to inhibit the process.
PubMed: 38906359
DOI: 10.1016/j.ijbiomac.2024.133267