Transplantation Experiments Research Articles

Functional differences between herbs and woody species in a semiarid Mediterranean plant community: A whole‐plant perspective on growth, nutrient‐use and size

Abstract Despite decades of research, a comprehensive understanding of trait coordination at the whole‐plant level remains elusive. Furthermore, while the link between above‐ground growth rates and leaf traits related to nutrient use is well established, much less is known about the below‐ground compartment. Herbs and woody species exhibit distinct above‐ground growth and nutrient‐use strategies, but whether these differences extend to root traits below‐ground remains unclear. We carried out a common garden experiment with 23 perennials (7 herbs and 16 woody species) coexisting in a Mediterranean shrubland and measured 17 above‐ground and below‐ground traits related to growth, nutrient use and size. We analysed the links between growth rate and nutrient use focusing especially on roots and considering potential differences between herbs and woody species. We also combined plant size data from experimental juveniles and field‐sampled adults to determine the effects of life stage on whole‐plant phenotypic integration. We found a significant relationship between growth rates (both above‐ground and below‐ground) and root nutrient‐use strategies. Root diameter was negatively associated to growth rate only in herbs. Specific root area and root tissue density were positively and negatively correlated with growth rate, respectively, in both herbs and woody species. Moreover, we found significant differences in roots traits between herbs and woody species. Plant growth rate and root nutrient‐use strategies were both positively associated to plant size (height and above‐ground diameter) in juveniles, while a negative relationship was observed in adults. Our work provides insights on the links between whole‐plant growth rate and nutrient‐use strategies in species from a dry Mediterranan shrubland. Specifically, we show that whole‐plant growth rate is strongly associated to root traits, with more acquisitive root nutrient‐use strategies related to faster growth rates, which in turn translated to greater plant size in juveniles but smaller in adults. Our results also highlight root functional differences and contrasting patterns of whole‐plant phenotypic integration between herbs and woody species, offering deeper insights into species coexistence in species‐rich dry Mediterranean environments. Read the free Plain Language Summary for this article on the Journal blog.

Low-intensity pulsed ultrasound combined with microbubble mediated JNK/c-Jun pathway to reverse multidrug resistance in triple-negative breast cancer

To investigate the effects of low-intensity pulsed ultrasound combined with microbubble (LIPUS-MB) mediated JNK/c-Jun pathway reversal on multidrug resistance in triple-negative breast cancer and the underlying mechanisms. An orthogonal experiment was designed to screen for the optimal parameters of LIPUS-MB in MDA-MB-231/DOX cells. The CCK-8 assay was used to determine the drug resistance of the cells and to measure their proliferation activity and resistance reversal efficiency at the optimal parameters. Hoechst 33,342 staining and Annexin V-FITC/PI staining were employed to detect cell morphological changes and apoptosis, respectively. The MDA-MB-231/DOX models of transplanted tumor were established in BALB/c. The impact of LIPUS-MB on allograft tumor growth was observed in vivo. Immunohistochemistry was employed to investigate the expression of P-gp, ABCG2, and Ki-67 in tumor tissues, while western blot was utilized to assess the protein expression of P-gp, ABCG2, JNK, p-JNK, c-Jun, p-c-Jun, Bcl-2 and Bax in both MDA-MB-231/DOX cells and allograft tumor tissues. The optimal LIPUS-MB parameters for MDA-MB-231/DOX cells are the microbubble concentration of 20%, ultrasound intensity of 1.0 W/cm2, and irradiation time of 60 s. The drug resistance index of MDA-MB-231/DOX cells is 19.17. Following the optimal parameter application, the IC50 value of the cells decreases by 5.71-fold, with a reversal efficiency of 87.03%, and a simultaneous decrease in cell proliferation activity. Compared with other groups, the DOX + LIPUS-MB group displayed the highest incidence of apoptotic nuclear morphology, and the greatest quantity of cellular apoptosis and the most pronounced decrease in the expression levels of P-gp, ABCG2, p-JNK, p-c-Jun, and Bcl-2 proteins within the cells. Conversely, the expression levels of Bax proteins reach the highest levels (all P < 0.05). Furthermore, in vivo subcutaneous tumor transplantation experiments in nude mice revealed that the DOX + LIPUS-MB group exhibited smaller tumor growth rate, volume and the expression of P-gp, ABCG2, and Ki-67 compared to the DOX + LIPUS group, indicating the most pronounced inhibitory effect on tumor growth and it significantly inhibited tumor proliferation, promoted its apoptosis. In conclusion, following parameter optimization, LIPUS-MB was found to reduce the drug resistance of MDA-MB-231/DOX cells. The underlying mechanism may involve the downregulation of P-gp and ABCG2 proteins expression through the modulation of the JNK/c-Jun pathway by LIPUS-MB, thereby inhibiting cell proliferation activity and promoting apoptosis, and enhancing the in vivo anti-tumor effect of DOX, thus reversing multidrug resistance in triple-negative breast cancer.

ApoE Receptor-2 R952Q Variant in Macrophages Elevates Soluble LRP1 to Potentiate Hyperlipidemia and Accelerate Atherosclerosis in Mice.

apoER2 (apolipoprotein E receptor-2) is a transmembrane receptor in the low-density lipoprotein receptor (LDLR) family with unique tissue expression. A single-nucleotide polymorphism that encodes the R952Q sequence variant has been associated with elevated plasma cholesterol levels and increased myocardial infarction risk in humans. The objective of this study was to delineate the mechanism underlying the association between the apoER2 R952Q variant and increased atherosclerosis risk. An apoER2 R952Q mouse model was generated using a CRISPR/Cas9 strategy, intercrossed with LDLR knockout mice, followed by feeding a Western-type high-fat high-cholesterol diet for 16 weeks. Atherosclerosis was investigated by immunohistology. Plasma lipids and lipid distributions among the various lipoprotein classes were analyzed by colorimetric assay. Tissue-specific effects of the R952Q sequence variant on atherosclerosis were analyzed by bone marrow transplant studies. sLRP1 (soluble low-density lipoprotein receptor-related protein 1) was measured in plasma and conditioned media from bone marrow-derived macrophages by ELISA and GST-RAP (glutathione S-transferase-receptor-associated protein) pull-down, respectively. P38 MAPK (mitogen-activated protein kinase) phosphorylation in VLDL (very-low-density lipoprotein)-treated macrophages was determined by Western blot analysis. Consistent with observations in humans with this sequence variant, the apoER2 R952Q mutation exacerbated diet-induced hypercholesterolemia, via impediment of plasma triglyceride-rich lipoprotein clearance, to accelerate atherosclerosis in Western diet-fed LDLR knockout mice. Reciprocal bone marrow transplant experiments revealed that the apoER2 R952Q mutation in bone marrow-derived cells instead of non-bone marrow-derived cells was responsible for the increase in hypercholesterolemia and atherosclerosis. Additional data showed that the apoER2 R952Q mutation in macrophages promotes VLDL-induced LRP1 (low-density lipoprotein receptor-related protein 1) shedding in a p38 MAPK-dependent manner. The apoER2 R952Q mouse model recapitulates characteristics observed in human disease. The underlying mechanism is that the apoER2 R952Q mutation in macrophages exacerbates VLDL-stimulated sLRP1 production in a p38 MAPK-dependent manner, resulting in its competition with cell surface LRP1 to impede triglyceride-rich lipoprotein clearance, thereby resulting in increased hypercholesterolemia and accelerated atherosclerosis.

Coral performance is comparable when transplanted to disparate reef sites despite divergent histories of reef decline and recovery

As coral reefs degrade worldwide, researchers and managers need to determine whether corals can acclimatize to altered local conditions or whether their fixed phenotypes prevent coral persistence under these new environmental conditions. Fixed phenotypes could produce environmental mismatches that reduce population connectivity and exacerbate decline in the near-term, but a capacity for acclimatization could be harnessed in both passive and proactive coral restoration efforts. Here, we conducted a reciprocal transplant experiment in Mo‘orea, French Polynesia, to test how intraspecific performance of 2 common coral species (Acropora hyacinthus and Pocillopora verrucosa) varied between a neighboring forereef and backreef that differed dramatically in trajectories of coral loss, resilience over decadal time scales, and cover of corals versus competing macroalgae. We also tested how corals responded to 2 common stressors—corallivory and macroalgal competition—and how this varied as a function of transplant location and the area of origin. Growth and survival of both coral species were affected by macroalgal competition, corallivory, transplant location, or some combination thereof, but we found limited evidence that the habitat of origin significantly impacted intraspecific performance. These results suggest that acclimatization capacity may outweigh local adaptation for these common reef-building species and could be leveraged to facilitate coral restoration.

Long-term safety of photobiomodulation exposure to beta cell line and rat islets in vitro and in vivo

This study evaluates the safety and potential benefits of PBM on pancreatic beta cells and islets. PBM was applied to insulin-secreting cell lines (MIN6) and rat pancreatic islets using a 670 nm light source, continuous output, with a power density of 2.8 mW/cm², from 5 s to several 24 h. Measure of cell viability, insulin secretion, mitochondrial function, ATP content, and cellular respiration were assessed. Additionally, a diabetic rat model is used for islet transplantation (pre-conditioning with PBM or not) experiments. Short and long-term PBM exposure did not affect beta cell islets viability, insulin secretion nor ATP content. While short-term PBM (2 h) increases superoxide ion content, this was not observed for long exposure (24 h). Mitochondrial respirations were slightly decreased after PBM. In the islet transplantation model, both pre-illuminated and non-illuminated islets improved metabolic control in diabetic rats with a safety profile regarding the post-transplantation period. In summary, for the first time, long-term PBM exhibited safety in terms of cell viability, insulin secretion, energetic profiles in vitro, and post-transplantation period in vivo. Further investigation is warranted to explore PBM’s protective effects under conditions of stress, aiding in the development of innovative approaches for cellular therapy.

Pulmonary Flora-Derived Lipopolysaccharide Mediates Lung-Brain Axis through Activating Microglia Involved in Polystyrene Microplastic-Induced Cognitive Dysfunction.

Microplastics (MPs) have been detected in the atmospheric and the human respiratory system, indicating that the respiratory tract is a significant exposure route for MPs. However, the effect of inhaled MPs on cognitive function has not been adequately studied. Here, a C57BL/6 J mouse model of inhalation exposure to polystyrene MPs (PS-MPs, 5 µm, 60 d) is established by intratracheal instillation. Interestingly, in vivo fluorescence imaging and transmission electron microscopy reveal that PS-MPs do not accumulate in the brain. However, behavioral experiments shows that cognitive function of mice is impaired, accompanied by histopathological damage of lung and brain tissue. Transcriptomic studies in hippocampal and lung tissue have demonstrated key neuroplasticity factors as well as cognitive deficits linked to lung injury, respectively. Mechanistically, the lung-brain axis plays a central role in PS-MPs-induced neurological damage, as demonstrated by pulmonary flora transplantation, lipopolysaccharide (LPS) intervention, and cell co-culture experiments. Together, inhalation of PS-MPs reduces cognitive function by altering the composition of pulmonary flora to produce more LPS and promoting M1 polarization of microglia, which provides new insights into the mechanism of nerve damage caused by inhaled MPs and also sheds new light on the prevention of neurotoxicity of environmental pollutants.

Ellagic Acid Protects against Alcohol-Related Liver Disease by Modulating the Hepatic Circadian Rhythm Signaling through the Gut Microbiota-NPAS2 Axis.

Alcohol-related liver disease (ALD) encompasses a spectrum of hepatic disorders resulting from alcohol abuse, which constitutes the predominant etiology of morbidity and mortality associated with hepatic pathologies globally. Excessive alcohol consumption disrupts the integrity of the intestinal barrier and perturbs the balance of gut microbiota, thereby facilitating the progression of ALD. Ellagic acid (EA) has been extensively reported to be an effective intervention for alleviating liver symptoms. However, the target molecules of EA in improving ALD and its underlying mechanism remain elusive. First, our study indicates that EA ameliorated ALD through the hepatic circadian rhythm signaling by up-regulating neuronal PAS domain protein 2 (NPAS2). Furthermore, analysis of the intestinal microbiome showed that EA significantly enhanced the abundance of beneficial bacteria, which was positively correlated with NPAS2 expression and negatively correlated with liver injury. Finally, antibiotic treatment and fecal microbiota transplantation (FMT) experiments established a causal relationship between the reshaped microbiota and NPAS2 in the amelioration of ALD. In summary, our study demonstrates novel evidence that EA attenuated ALD by modulating the hepatic circadian rhythm signaling pathway via the gut microbiota-NPAS2 axis, providing valuable insights for EA and microbiome-targeted interventions against ALD.

Plant responses to urban gradients: Extinction, plasticity, adaptation

Abstract Biodiversity‐oriented urban management and planning require information on the drivers of wildlife composition and ecosystem function within cities. Urban landscapes impose environmental gradients along which species may be filtered away, or respond by showing adaptive variation in functional trait values. Such trait variation may in turn be due to a species' phenotypic plasticity, or a consequence of microevolution leading to local adaptation. This study investigates three possible plant responses to urban environmental gradients, with different evolutionary consequences: extinction, plasticity and adaptation. We assessed whether individual functional traits (LMA—leaf mass per area, plant height and flower length), population performance traits (seed mass and germination rate), as well as species frequency in the plant community, responded to gradients in mowing frequency, soil fertility and structure, temperature and surrounding mean building height, among four herbaceous plant species present in the metropolitan area of Strasbourg. Using a common garden experiment, we tested whether the observed trait variation was hereditary, and may thus constitute evidence for local adaptation. Our results detected the three types of expected responses. Plantago lanceolata is plastic to urban gradients, and Trifolium pratense showed both plastic and hereditary responses. Dactylis glomerata and Medicago lupulina showed all three responses: they both declined under increasing mowing frequency, were plastic to surrounding mean building height, and showed hereditary responses to different urban gradients. Urban management and planning therefore impact on the evolutionary capabilities of plants in cities. In the case of management this is highlighted by the detected trends in species' traits and frequency in response to mowing. The consequences of urban planning are evidenced by mean building height eliciting most often plastic and adaptive responses. Synthesis. Herbaceous plants often change their morphology in response to urban conditions: grass cutting, altered soils, warmer temperatures and being surrounded by tightly packed buildings. These changes are sometimes hereditary, which suggests that city management and planning affect the ability of plants to survive and evolve in urban environments.

A field study of the molecular response of brown macroalgae to heavy metal exposure: An (epi)genetic approach

Our understanding of the relative contribution of genetic and epigenetic mechanisms to organismal response to stress is largely biased towards specific taxonomic groups (e.g. seed plants) and environmental stresses (e.g. drought and salinity). In previous work, we found intraspecific differences in heavy metal (HM) uptake capacity in the brown macroalgae Fucus vesiculosus. The molecular mechanisms underlying these differences, however, remained unknown. Here, we evaluated the concentrations of HMs, and characterized the genetic (single nucleotide polymorphisms) and epigenetic (cytosine DNA methylation) variability in reciprocal transplants of F. vesiculosus between two polluted and two unpolluted sites on the NW Spanish coast after 90 days. Genetic and epigenetic differentiation did not explain the phenotypic differentiation observed, possibly due to the combined effect of multiple environmental factors acting on the algae in their natural habitats. Nonetheless, we provide further evidence of intraspecific genetic differentiation in F. vesiculosus at short spatial scales, as well as first evidence of population-specific epigenetic changes in brown macroalgae in response to changes in environmental conditions (i.e. transplantation ex situ). We propose that both genetic and, to some extent, epigenetic mechanisms might impinge upon the adaptive potential of this species to environmental change, but this needs to be further addressed.

Differential responses in recovery, growth and survival between intertidal and subtidal corals after acute thermal stress

Sea temperature increases may compromise ecological restoration as a tool for recovering degraded coral reefs. A potential solution may lay within using corals with naturally higher thermal resilience, such as intertidal corals. This study aimed at comparing thermal resilience, growth and survival between intertidal and subtidal corals in a reciprocal transplant experiment. Sixty coral nurseries were installed in a shallow coral reef area in Kenya: half were placed in the intertidal zone and half in the subtidal zone. At both zones, intertidal and subtidal Pocillopora cf. damicornis coral fragments were cultured in equal proportions, resulting in 15 replicate nurseries for four treatments. After an initial culture phase of 1 month in situ, six nurseries per treatment were thermally stressed ex situ by exposing corals for 5 days to a temperature of 32 °C (3 °C above summer maximum), after which they were returned in situ to recover. Fragment brightness was measured as the response variable to thermal stress. Intertidal and subtidal corals increased brightness (i.e., bleached) at a similar rate, but during recovery intertidal corals returned quicker to their original brightness in both culture environments. Coral growth was highest for intertidal corals in the intertidal zone during cooler months and was highest for subtidal corals in the subtidal zone during peak temperatures. Intertidal corals transplanted to the subtidal zone registered the lowest survival. Thus, intertidal corals display higher thermal resilience through quicker recovery, but potential trade-offs require further investigation before these corals can be used as a climate-proof broodstock for reef restoration.

Conditional over-expression of heme-oxygenase 1 in myelomonocytic cells reduces AngII-induced hypertension and vascular inflammation in mice

Abstract Background Systemic arterial Hypertension is one of the most important risk factor responsible for morbidity and mortality world-wide. Angiotensin II (Ang II), a potent vasoconstrictor and key player in the renin-angiotensin-aldosterone system (RAAS) is responsible for vascular dysfunction, inflammation, and tissue damage. Heme oxygenase-1 (HO-1) overexpression may confer antioxidant and anti-inflammatory properties in Ang II-induced hypertension through its action on heme catabolism, generating carbon monoxide (CO), ferritin and biliverdin/bilirubin by the action of biliverdin reductase A (BLVRA). Methods and results Male 9–12-weeks-old HO-1indxLySMCre/wt and LySMCre/wt mice were infused with AngII (1mgAngII/Day/Kg) for 7 days to induce hypertension and compared to sham treatment. Blood pressure monitoring by tail-cuff method, and endothelium-dependent vasodilator studies via organ chamber system using acetylcholine (ACh) in isolated aortic segments (~4 mm), revealed that overexpression of HO-1 in myeloid cells resulted in decreased systolic blood pressure and improved endothelial function in AngII-infused HO-1indxLySMCre/wt mice compared to controls. Concurrently, increased BLVRA expression in liver tissue and elevated plasma bilirubin levels were detected by transcriptome analysis and high-performance liquid chromatography, respectively. These results were supported by a reduction in the expression of inducible cytokines and cell adhesion molecules (CAMs) in the aorta, assessed using qPCR. Bone marrow transplant experiments demonstrated that bone marrow from LysMcre mice in HO-1indxLySMCre/wt mice abrogated the protective effect of HO-1, resulting in endothelial damage and increased blood pressure, potentially due to decreased liver BLVRA expression and the accumulation of bone marrow-derived cells in the vessel wall in response to AngII. Additionally, adeno-associated viral vector (AAV) transfection targeting specifically BLVRA activity in liver lead to an increase in blood pressure values and worse endothelium relaxation, in parallel with higher oxidative stress and the blood neutrophils concentration, as assessed in whole blood by using oxidative burst method and blood count system respectively. Conclusion The overexpression of HO-1 in myeloid cells confers anti-inflammatory protection in AngII-induced arterial hypertension in mice. Myeloid cells bone marrow-derived overexpressing HO-1 regulate the differentiation and infiltration of pro-inflammatory immune cells in the vasculature. BLVRA expression and bilirubin levels downstream of HO-1 play a critical role in protecting against vascular damage by reducing leukocyte infiltration.

The evolution of thermal performance curves in fungi farmed by attine ant mutualists in aboveground or belowground microclimates.

Fungi are abundant and ecologically important at a global scale, but little is known about whether their thermal adaptations are shaped by biochemical constraints (i.e. the Hotter is Better Model, HBM) or evolutionary tradeoffs (i.e., the Specialist Generalist Model, SGM). We tested these hypotheses by generating thermal performance curves (TPCs) of fungal cultivars farmed by six species of Panamanian fungus-farming 'attine' ants. These fungi represent evolutionary transitions in farming strategies as four cultivars are farmed by ants belowground at stable temperatures near 25°C and two cultivars are farmed aboveground at variable temperatures. We generated TPCs using a common garden experiment confining fungal isolates to different temperatures and then used a Bayesian hierarchical modeling approach to compare competing temperature sensitivity models. Some thermal performance traits differed consistently across farming strategies, with aboveground cultivars having: 1) higher tolerance to low temperatures (CTLmin) and 2) higher maximum growth rate at the optimal temperature (rmax). However, two core assumptions shared by the HBM or SGM were not supported as aboveground cultivars did not show systematic increases in either their optimal temperature (Topt) or thermal tolerance breadth. These results harness ant farming systems as long-term natural experiments to decouple the effects of environmental thermal variation and innate physiological temperature sensitivity on fungal thermal evolution. The results have clear implications for predicting climate warming induced breaking points in animal-microbe mutualisms.

Surprisingly wide climatic niche breadth of a relict mountain species raises hope for survival under climate change

AbstractAimsWe assessed the juvenile climatic niche breadth of a relict mountain species by comparing field observations and transplant experiments within and beyond the elevational limits of its distribution range.LocationLebanon – Near East – Mediterranean region.MethodsWe studied the survival and growth of the Cedar of Lebanon (Cedrus libani) to determine the lower and upper elevational range limits of its juvenile stage through an experimental setup with and without water supplementation and with potentially competing species as a control. The experiment included eight common gardens at elevations ranging from 110 to 2330 m, within and far beyond the warm and cold limits of Cedar distribution observed under natural conditions.ResultsWe observed unexpectedly high survival and growth rates of Cedar at elevations well below the range of its natural distribution in Lebanon. Below the observed warm limit, water stress at very low elevations and competition at low and medium elevations limited juvenile survival. In contrast, cold temperature and water stress limited survival at elevations slightly above the observed upper natural limit. The experimental setup demonstrated that the elevation range suitable for Cedar growth and survival was twice as wide as the range within which Cedar is observed under natural conditions.Main ConclusionsHigh survival rates experimentally observed beyond the warm limit of the natural distribution range of the Cedar of Lebanon raise hope for its resilience to ongoing climate warming. If this pattern were frequent among montane species, it would challenge predictions of massive extinction with climate change and pave the way for promoting adaptive actions such as competition management to improve their survival.

A mammalian herbivore selects local and cooler provenance trees in a restoration common garden experiment: implications for community‐assisted migration efforts

Rapid changes in climate have the potential to alter habitats faster than evolution may respond, leading to maladapted tree populations. Assisted migration may help foundation tree species persist in future climates by identifying populations and genotypes that are robust to expected climate change‐induced alterations. Importantly, community‐assisted migration accounts for impacts of those populations and genotypes on the broader community, including herbivores, often adapted to local plants. These impacts have been examined in arthropod communities, but few studies have assessed mammals, and fewer still have leveraged an experimental design to disentangle genetic contributions to herbivore selection among genotypes and populations. We tested whether North American porcupine (Erethizon dorsatum) browsing on Fremont cottonwood (Populus fremontii) is under genetic control in a common garden to uncouple genetic and environmental contributions on browse selection. Porcupines selected trees from climatically similar and cooler areas, where trees from cooler climates suffered greater than 2× more herbivory than trees from warmer areas. Plant genotype was a significant factor for selection, with the most heavily browsed genotype having greater than 10× more herbivory than the least browsed. Broad‐sense heritability of porcupine tree selection was H2B = 0.27 among genotypes, indicating a genetic component to tree defenses against porcupine herbivory that can be predicted by source population climate. Our results have important implications for future mammalian herbivore populations, should climate change render local tree genotypes maladaptive. We recommend assisted migration efforts plant stock from areas up to 3°C warmer and climatically similar areas to maintain productivity and mammalian herbivore browsing.

A Global Experience of Donation after Circulatory Death for Pediatric Lung Transplantation.

Donation after circulatory death (DCD) lung transplantation has increased, but there is limited data in children. We sought to characterize the international experience of pediatric DCD lung transplant (LT) in comparison to donation after brain death (DBD) to address extreme donor organ shortages in children needing LT. Using the International Society for Heart and Lung Transplantation (ISHLT) Thoracic Organ Transplant Registry, 1453 children (<18yo) LT recipients from January 2004 to June 2018 were identified: 34 (3%) were DCD and 1419 (97%) were DBD recipients. Post-transplant outcomes were compared between groups. Propensity score method was used to derive matched cohorts and were compared between groups. DCD and DBD recipients were of similar age, with cystic fibrosis being the most frequent indication for LT in both groups (64.5% vs. 57.5%, respectively). Kaplan-Meier analysis demonstrated similar survival between DCD and DBD cohorts, whereas propensity score-matched recipients also identified similar post-transplant survival in both groups (P=0.098). Secondary analysis found that DCD LT recipients had a longer post-transplant length of hospital stay (unmatched cohorts: 36.5d vs. 20d, p=0.022; matched cohort: 26d vs. 19d, p=0.016), and shorter time to acute cellular rejection (ACR) (unmatched cohorts: 248d vs. 560d, p=0.039; matched cohorts: 248d vs. 1650d,p=0.059). Due to DCD being a key contributor to the increasing number of lung transplants being performed worldwide, the results of this analysis support this organ donation approach in children requiring LT, which would increase access to donor organs. The identification of a potential shorter time to ACR needs further exploration as more DCD pediatric LTs are performed.

Kui-Jie-Ling capsule inhibits ulcerative colitis by modulating inflammation and gut microbiota.

Kui-Jie-Ling capsule (Kui-Jie-Ling) is a hospital preparation for ulcerative colitis (UC) in China. This study aimed at evaluating the protective effects and mechanisms of Kui-Jie-Ling and Kui-Jie-Ling combined with adalimumab on UC induced by dextran sulfate sodium (DSS). Network pharmacology was combined with an animal experiment to reveal the targets of Kui-Jie-Ling alleviating UC. The UC model was established by drinking 2.5% DSS solution for 7days. On the second day, the mice in the Kui-Jie-Ling group were orally administered with Kui-Jie-Ling (1.5 and 3.0g/kg) daily for seven consecutive days, and the mice in the combination group were orally administered with Kui-Jie-Ling (3.0g/kg) once a day for seven consecutive days and received one subcutaneous injection of adalimumab. The disease activity index, the colon length, the spleen index, the cytokines, the colon, the short-chain fatty acid content, and the gut microbiota in the colon were analyzed. The role of gut microbiota against UC was verified by fecal microbiota transplantation experiments. The animal study's results were consistent with the network pharmacology analysis, which reflected that Kui-Jie-Ling alleviated UC via multi-pathway. Kui-Jie-Ling ameliorated UC by inhibiting the formation of neutrophil extracellular traps (NETs), regulating inflammatory factors through the lipopolysaccharide-toll-like receptor 4/nuclear factor kappa B and interleukin-23-Janus kinase 2/signal transducer and activator of transcription 3 signaling pathway, and restoring intestinal homeostasis. These studies provided the experimental basis for the clinical administration of Kui-Jie-Ling and Kui-Jie-Ling combined with adalimumab against UC.

Predicting rapid adaptation in time from adaptation in space: A 30-year field experiment in marine snails

Predicting the outcomes of adaptation is a major goal of evolutionary biology. When temporal changes in the environment mirror spatial gradients, it opens up the potential for predicting the course of adaptive evolution over time based on patterns of spatial genetic and phenotypic variation. We assessed this approach in a 30-year transplant experiment in the intertidal snail Littorina saxatilis . In 1992, snails were transplanted from a predation-dominated environment to one dominated by wave action. On the basis of spatial patterns, we predicted transitions in shell size and morphology, allele frequencies at positions throughout the genome, and chromosomal rearrangement frequencies. Observed changes closely agreed with predictions and transformation was both dramatic and rapid. Hence, adaptation can be predicted from knowledge of the phenotypic and genetic variation among populations.

Impact of Viruses on Prokaryotic Communities and Greenhouse Gas Emissions in Agricultural Soils.

Viruses are abundant and ubiquitous in soil, but their importance in modulating greenhouse gas (GHG) emissions in terrestrial ecosystems remains largely unknown. Here, various loads of viral communities are introduced into paddy soils with different fertilization histories via a reciprocal transplant approach to study the role of viruses in regulating greenhouse gas emissions and prokaryotic communities. The results showed that the addition of viruses has a strong impact on methane (CH4) and nitrous oxide (N2O) emissions and, to a minor extent, carbon dioxide (CO2) emissions, along with dissolved carbon and nitrogen pools, depending on soil fertilization history. The addition of a high viral load resulted in a decrease in microbial biomass carbon (MBC) by 31.4%, with changes in the relative abundance of 16.6% of dominant amplicon sequence variants (ASVs) in comparison to control treatments. More specifically, large effects of viral pressure are observed on some specific microbial communities with decreased relative abundance of prokaryotes that dissimilate sulfur compounds and increased relative abundance of Nanoarchaea. Structural equation modeling further highlighted the differential direct and indirect effects of viruses on CO2, N2O, and CH4 emissions. These findings underpin the understanding of the complex microbe-virus interactions and advance current knowledge on soil virusecology.

Distinct muscle regenerative capacity of human induced pluripotent stem cell-derived mesenchymal stromal cells in Ullrich congenital muscular dystrophy model mice

BackgroundUllrich congenital muscular dystrophy (UCMD) is caused by a deficiency in type 6 collagen (COL6) due to mutations in COL6A1, COL6A2, or COL6A3. COL6 deficiency alters the extracellular matrix structure and biomechanical properties, leading to mitochondrial defects and impaired muscle regeneration. Therefore, mesenchymal stromal cells (MSCs) that secrete COL6 have attracted attention as potential therapeutic targets. Various tissue-derived MSCs exert therapeutic effects in various diseases. However, no reports have compared the effects of MSCs of different origins on UCMD pathology.MethodsTo evaluate which MSC population has the highest therapeutic efficacy for UCMD, in vivo (transplantation of MSCs to Col6a1-KO/NSG mice) and in vitro experiments (muscle stem cell [MuSCs] co-culture with MSCs) were conducted using adipose tissue-derived MSCs, bone marrow-derived MSCs, and xeno-free-induced iPSC-derived MSCs (XF-iMSCs).ResultsIn transplantation experiments on Col6a1-KO/NSG mice, the group transplanted with XF-iMSCs showed significantly enhanced muscle fiber regeneration compared to the other groups 1 week after transplantation. At 12 weeks after transplantation, only the XF-iMSCs transplantation group showed a significantly larger muscle fiber diameter than the other groups without inducing fibrosis, which was observed in the other transplantation groups. Similarly, in co-culture experiments, XF-iMSCs were found to more effectively promote the fusion and differentiation of MuSCs derived from Col6a1-KO/NSG mice than the other primary MSCs investigated in this study. Additionally, in vitro knockdown and supplementation experiments suggested that the IGF2 secreted by XF-iMSCs promoted MuSC differentiation.ConclusionXF-iMSCs are promising candidates for promoting muscle regeneration while avoiding fibrosis, offering a safer and more effective therapeutic approach for UCMD than other potential therapies.

Quality diversity of three calcium-rich Primulina vegetables: A comprehensive analysis of calcium content, metabolite profiles, taste characteristics, and medicinal potential

Primulina plants native to karst regions are exceptionally rich in calcium and have been developed into high‑calcium leafy vegetables. However, limited knowledge of their metabolites, taste characteristics, and potential medicinal value restricts further genetic improvements. This study conducted a comprehensive analysis on three breeding species of Primulina vegetables. Common garden experiment demonstrated significant calcium enrichment capability, with calcium content ranging from 204.45 to 391.52 mg/100 g. Through widely-targeted metabolomics, 1121 metabolites were identified within these Primulina vegetables. Furthermore, comparative analysis identified 976 differentially accumulated metabolites across nine comparison groups, driven mainly by flavonoids, phenolic acids, and lipids. Integration of electronic tongue analysis and metabolomics revealed taste profiles and identified 17 key candidate compounds related to taste. Based on network pharmacology analysis, 32 active ingredients were found in Primulina vegetables, which highlighted potential medicinal value. These findings provide a data-driven foundation for breeding programs aimed at enhancing nutritional and flavor traits.