Life-history theory, central to our understanding of diversity in morphology, behaviour and senescence, describes how traits evolve through the optimisation of trade-offs in investment. Despite considerable study, there is only minimal support for trade-offs within species between the two traits most closely linked to fitness – reproductive effort and survival – questioning the theory’s general validity. We used a meta-analysis to separate the effects of individual quality (positive survival/reproduction correlation) from the costs of reproduction (negative survival/reproduction correlation) using studies of reproductive effort and parental survival in birds. Experimental enlargement of brood size caused reduced parental survival. However, the effect size of brood size manipulation was small and opposite to the effect of phenotypic quality, as we found that individuals that naturally produced larger clutches also survived better. The opposite effects on parental survival in experimental and observational studies of reproductive effort provides the first meta-analytic evidence for theory suggesting that quality differences mask trade-offs. Fitness projections using the overall effect size revealed that reproduction presented negligible costs, except when reproductive effort was forced beyond the level observed within species, to that seen between species. We conclude that there is little support for the most fundamental life-history trade-off, between reproductive effort and survival, operating within a population. We suggest that within species, the fitness landscape of the reproduction–survival trade-off is flat until it reaches the boundaries of the between-species fast–slow life-history continuum. Our results provide a quantitative explanation as to why the costs of reproduction are not apparent and why variation in reproductive effort persists within species.

Forest structure analysis and biomass prediction systems are key tools for advancingforest trait-based ecology and management. Surveys using Unmanned Aerial Vehicles(UAV) and Light Detection and Ranging (LiDAR) systems have contributedto this field with increased accuracy in tree phenotyping. Moreover, methods combiningUAV LiDAR surveying and machine learning (ML) have also emerged to enhanceestimates of single tree traits. Here, we utilizeda UAV LiDAR system to survey a Norway spruce forest in Davos, Switzerland, where adetailed field-based inventory served as ground truth data. Our objectives were (i) togain insights into variation and gradients of tree height and (ii)to evaluate whether such insights may prove useful as contextual information toimprove predictions of stem diameter and tree-level biomass. We segmented the pointcloud data scene into individual canopies and treated the LiDAR derived tree height asthe variable of interest.We then used local indicators of spatial association to detect the significant localcontext, and defined tree neighborhoods within the forest. Then,we extracted metricsfromthe neighborhoods and introduced them in a ML regression experiment toevaluate predictions of individual tree diameter.The focus was on comparing performance of tree diameter predictions betweenregression models that either consider neighborhood metrics (i.e. context-awaremodels), or not. Next, AGB was estimated from the tree height derivedfrom theUAV LiDAR survey, the predicted tree diameter and allometry. The benefits ofcontext awareness were assessed in terms of accuracy gained in estimating AGB. Weobtained results of different machine learning methods(i.e. AdaBoost, Lasso and Random Forest) and evaluated these based on nestedcross-validation. We applied this approach to two separate tree data sets within thesame site, one being clustered and continuous, the other discontinuousand scattered in separate sampling plots. In both cases, we found evidence ofenhanced AGB prediction performance in context-aware regressions, where the RMSEwas reduced by 4.0% and by 9.1%, respectively.These findings indicate that gradients in tree heights across the ecosystem may proxyfor local microclimate, edaphic conditions and biotic factors that influence tree growth,which can be leveraged to enhance predictions of AGB. The method proposed is fullynative to UAV LiDAR data.

Abstract Background The onset of severe acute respiratory syndrome coronavirus type 2 at the end of 2019 led to a global pandemic of acute respiratory diseases, commonly known as COVID-19, caused by this highly infectious and pathogenic coronavirus. As members of the Fifth-batch National TCM Medical Team sent by the Affiliated Hospital of Nanjing University of Chinese Medicine to assist Wuhan Jiangxia Mobile Cabin Hospital, it was observed that patients with COVID-19 had an elevated incidence of stroke and are prone to progression. The possible mechanisms included neuroinvasion by the virus, an imbalance between ACE1 and ACE2, hypercoagulability, and a pre-thrombotic state. However, effective treatment options are not yet available. Developed by the Department of Neurology, Affiliated Hospital of Nanjing University of Chinese Medicine, Tongnao Decoction (TND) is a prescribed medication. The chemical components within the TND extract were previously examined using Waters ACQUITY UPLC ultra-performance liquid chromatography. Notably, identified chemical constituents, including curcumin, exhibited protective effects on brain cells. In the current investigation, bioinformatics techniques were employed to mine the GEO database, aiming to assess the functional role and potential action mechanism of curcumin as a therapeutic agent for COVID-19 combined with stroke.Tongnao Decoction Methods The datasets of COVID-19 and stroke were retrieved from the GEO database to identify the differentially intersecting genes (DIGs) between the two diseases. These DIGs were then exposed to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses employing the clusterProfiler to extract TF genes in the Trrust database (TF in TRRUST). Core TF genes were found to be target genes in DEGs-related TF in Stroke and DEGs-related TF in COVID. The overlapping set of these target genes yielded intersected target genes, which were then imported into the DGIdb website for drug prediction. Subsequently, the selected core drugs were subjected to drug validation on the cMAP website. Target prediction was performed on four online platforms: SEA, SwissTargetPrediction, TargetNet, and TCMSP. Subsequently, the obtained results were imported into the String database to create an interaction network comprising core target genes and enriched pathways. Additionally, molecular docking was performed using AutoDock software. Finally, molecular docking scoring was applied to the core targets. Results The intersection of DEGs from stroke dataset GSE16561 with DEGs from COVID dataset GSE211979 yielded 205 intersected genes. These intersected genes, including E2F3, BCL6, ETS2, CEBPD, STAT1, MXD1, NFIL3, HDAC4, MMP9, CD163, FCGR1A, IFIT3, LY96, PLSCR1, TNFSF10:E2F3, BCL6, ETS2, CEBPD, STAT1, MXD1, NFIL3, HDAC4, MMP9, CD163, FCGR1A, IFIT3, LY96, PLSCR1, and TNFSF10, were subjected to GO and KEGG pathway enrichment analyses utilizing the clusterProfiler. Subsequently, the core drug curcumin was selected from the 17 intersected drugs. Curcumin inhibits NF-κb and MAPKs and possesses various pharmacological effects encompassing anti-proliferative, anti-oxidant, anti-inflammatory, and anti-angiogenic effects. The six core targets CCNA2, JAK2, MMP9, PPARG, PTGS2, and STAT3 had molecular docking scores of -2.86, -2.98, -5.01, -2.42, -3.83, and − 2.28, respectively. Conclusion Curcumin, the active ingredient in TND, can effectively intervene in COVID-19 combined with stroke through CCNA2, JAK2, MMP9, PPARG, PTGS2, and STAT3 target pathways, of which the most important target is MMP9.

Trained immunity is the long-term functional reprogramming of innate immune cells, which results in altered responses toward a secondary challenge. Despite indoxyl sulfate (IS) being a potent stimulus associated with chronic kidney disease (CKD)-related inflammation, its impact on trained immunity has not been explored. Here, we demonstrate that IS induces trained immunity in monocytes via epigenetic and metabolic reprogramming, resulting in augmented cytokine production. Mechanistically, the aryl hydrocarbon receptor (AhR) contributes to IS-trained immunity by enhancing the expression of arachidonic acid (AA) metabolism-related genes such as Arachidonate 5-Lipoxygenase (ALOX5) and ALOX5 Activating Protein (ALOX5AP). Inhibition of AhR during IS training suppresses the induction of IS-trained immunity. Monocytes from end-stage renal disease (ESRD) patients have increased ALOX5 expression and after 6-day training, they exhibit enhanced TNF-α and IL-6 production to LPS. Furthermore, healthy control-derived monocytes trained with uremic sera from ESRD patients exhibit increased production of TNF-α and IL-6. Consistently, IS-trained mice and their splenic myeloid cells had increased production of TNF-α after in vivo and ex vivo LPS stimulation compared to that of control mice. These results provide insight into the role of IS in the induction of trained immunity, which is critical during inflammatory immune responses in CKD patients.

The incessant arms race between viruses and hosts has led to numerous evolutionary innovations that shape life’s evolution. During this process, the interactions between viral receptors and viruses have garnered significant interest since viral receptors are cell surface proteins exploited by viruses to initiate infection. Our study sheds light on the arms race between the MDA5 receptor and 5’ppp-RNA virus in a lower vertebrate fish, M. miiuy . Firstly, the frequent and independent loss events of RIG-I in vertebrates prompted us to search for alternative immune substitutes, with homology-dependent genetic compensation response (HDGCR) being the main pathway. Our further analysis suggested that MDA5 of M. miiuy and G. gallus , the homolog of RIG-I, can replace RIG-I in recognizing 5’ppp-RNA virus, which may lead to redundancy of RIG-I and loss from the species genome during evolution. Secondly, as an adversarial strategy, 5’ppp-RNA SCRV can utilize the m 6 A methylation mechanism to degrade MDA5 and weaken its antiviral immune ability, thus promoting its own replication and immune evasion. In summary, our study provides a snapshot into the interaction and coevolution between vertebrate and virus, offering valuable perspectives on the ecological and evolutionary factors that contribute to the diversity of the immune system.

FGF23 via its coreceptor αKlotho (KL) provides critical control of phosphate metabolism, which is altered in rare and very common syndromes, however the spatial-temporal mechanisms dictating renal FGF23 functions remain poorly understood. Thus, developing approaches to modify specific FGF23-dictated pathways has proven problematic. Herein, wild type mice were injected with rFGF23 for 1, 4 and 12h and renal FGF23 bioactivity was determined at single cell resolution. Computational analysis identified distinct epithelial, endothelial, stromal, and immune cell clusters, with differential expressional analysis uniquely tracking FGF23 bioactivity at each time point. FGF23 actions were sex independent but critically relied upon constitutive KL expression mapped within proximal tubule (S1-S3) and distal tubule (DCT/CNT) cell sub-populations. Temporal KL-dependent FGF23 responses drove unique and transient cellular identities, including genes in key MAPK- and vitamin D-metabolic pathways via early- (AP-1-related) and late-phase (EIF2 signaling) transcriptional regulons. Combining ATACseq/RNAseq data from a cell line stably expressing KL with the in vivo scRNAseq pinpointed genomic accessibility changes in MAPK-dependent genes, including the identification of FGF23-dependent EGR1 distal enhancers. Finally, we isolated unexpected crosstalk between FGF23-mediated MAPK signaling and pro-inflammatory TNF receptor activation via NF-κB, which blocked FGF23 bioactivity in vitro and in vivo. Collectively, our findings have uncovered novel pathways at the single cell level that likely influence FGF23-dependent disease mechanisms.

Abstract Objective We aimed to analyze the relationship between non-alcoholic fatty liver and progressive fibrosis and serum 25-hydroxy vitamin D (25(OH)D) in patients with type 2 diabetes mellitus. Methods A total of 184 patients with T2DM who were hospitalized in the Department of Endocrinology of the ShiDong Clinical Hospital between January 2023 and June 2023 were selected.We compared review of anthropometric, biochemical, and inflammatory parameters and non-invasive scores between groups defined by ultrasound NAFLD severity grades.We determine correlation between 25(OH)D and FLI and FIB-4 score respectively. Results Statistically significant differences were seen between BMI, WC, C-peptide levels, FPG, ALT, serum 25(OH)D, TC, HDL, lumbar spine bone density, FLI, and FIB-4 in different degrees of NAFLD. Multivariate logistic regression analysis showed that 25(OH)D (OR = 1.26, p = 0.001), age (OR = 0.93, P < 0.001) and BMI (OR = 1.04, p = 0.007) were independent predictors of NAFLD in patients with T2DM. Conclusions This study revealed the correlation between serum 25(OH)D levels and NAFLD in patients with T2DM. We also demonstrated that serum 25(OH)D levels were negatively correlated with FLI/FIB-4 levels in patients with T2DM with NAFLD, suggesting that vitamin D deficiency may promote hepatic fibrosis progression in T2DM with NAFLD.

Although decarbonylation of carbonyl compounds have attracted much attention for the direct molecular transformations of universal carbonyl moieties into useful compounds, reports on the catalytic decarbonylation of diaryl ketones are scarce. In this study, we successfully developed a catalytic decarbonylation of unstrained diaryl ketone moieties in compounds bearing bidentate directing groups to obtain 2,2′-bipyridyls using a CeO2-supported Cu–Pd alloy nanoparticle catalyst. The catalyst characterization and a series of control experiments revealed that the decarbonylation was efficiently catalyzed by Pd(0) ensembles, which became electron-deficient upon alloying with a small amount of Cu(0) species.

Recent progress in the realm of quantum phenomena holds significant promise for advancing our scientific understanding of consciousness. Traditionally, science and spirituality have been perceived as separate or even contradictory domains. However, the discovery of a non-empirical realm of the universe that doesn’t consist of material things but of forms brings these two distinct disciplines together in consciousness studies. These forms are real, even though they are invisible, because they have the potential to appear in the empirical world and act in it. In this paper, we present arguments regarding the possibility that this empirical world is an emanation out of a cosmic realm of potentiality, whose forms can appear as physical structures in the external world.

We attempt in this article to formulate a conceptual and testable framework weaving Cosmos, Mind and Life into a whole. We build on three recent discoveries, each requiring more evidence: i. The particles of the Standard Model, SU(3) x SU(2) x U(1), are formally capable of collective autocatalysis. This leads us to ask what roles such autocatalysis may have played in Cosmogenesis, and in trying to answer, Why our Laws? Why our Constants? A capacity of the particles of SU(3) x SU(2) x U(1) for collective autocatalysis may be open to experimental test, stunning if confirmed. ii. Reasonable evidence now suggests that matter can expand spacetime.The first issue is to establish the claim that matter expands spacetime at or beyond 5 sigma if that can be done. If true, this process may elucidate Dark Matter, Dark Energy and Inflation and require alteration of Einstein's Field Equations. Cosmology would be transformed. iii. Evidence at 6.49 Sigma suggests that mind can alter the outcome of the two-slit experiment. If widely and independently verified, the foundations of quantum mechanics must be altered. Mind plays a role in the universe. That role may include Cosmic Mind.Our considerations concern: 1. Ontologically Real Potentia and the Unmanifest; 2. Nonlocality as Fundamental; 3. Res potentia, Res extensa, and Actualization; 4. Mind and Qualia, Mind is not in Spacetime; 5. Quantum Vacuum = Potentia not in Spacetime = Mind not in Spacetime; 6. Mind can Actualize Potentia; 7. The emergence of the classical world; 8. Co-evolution of life and ever -more complex matter; 9. Why "My Mind"?; 10. Each embodied mind is coupled bilaterally to the Quantum Vacuum that is Cosmic Mind; 11. Responsible Free Will.We hope we have made progress.