Lysozyme 1 Inflamed CCR2+ Macrophages Promote Obesity-Induced Cardiac Dysfunction.

BACKGROUND: Macrophages are key players in obesity-associated cardiovascular diseases, which are marked by inflammatory and immune alterations. However, the pathophysiological mechanisms underlying macrophage's role in obesity-induced cardiac inflammation are incompletely understood. Our study aimed to identify the key macrophage population involved in obesity-induced cardiac dysfunction and investigate the molecular mechanism that contributes to the inflammatory response. METHODS: In this study, we used single-cell RNA-sequencing analysis of Cd45+CD11b+F4/80+ cardiac macrophages to explore the heterogeneity of cardiac macrophages. The CCR2+ (C-C chemokine receptor 2) macrophages were specifically removed by a dual recombinase approach, and the macrophage CCR2 was deleted to investigate their functions. We also performed cleavage under target and tagmentation analysis, chromatin immunoprecipitation-polymerase chain reaction, luciferase assay, and macrophage-specific lentivirus transfection to define the impact of lysozyme C in macrophages on obesity-induced inflammation. RESULTS: We find that the Ccr2 cluster undergoes a functional transition from homeostatic maintenance to proinflammation. Our data highlight specific changes in macrophage behavior during cardiac dysfunction under metabolic challenge. Consistently, inducible ablation of CCR2+CX3CR1+ macrophages or selective deletion of macrophage CCR2 prevents obesity-induced cardiac dysfunction. At the mechanistic level, we demonstrate that the obesity-induced functional shift of CCR2-expressing macrophages is mediated by the CCR2/activating transcription factor 3/lysozyme 1/NF-κB (nuclear factor kappa B) signaling. Finally, we uncover a noncanonical role for lysozyme 1 as a transcription activator, binding to the RelA promoter, driving NF-κB signaling, and strongly promoting inflammation and cardiac dysfunction in obesity. CONCLUSIONS: Our findings suggest that lysozyme 1 may represent a potential target for the diagnosis of obesity-induced inflammation and the treatment of obesity-induced heart disease.

Fish microplastic ingestion may induce tipping points of aquatic ecosystems.

Microplastics can be ingested by a wide range of aquatic animals. Extensive studies have demonstrated that microplastic ingestion-albeit often not lethal-can affect a range of species life-history traits. However, it remains unclear how the sublethal effects of microplastics on individual levels scale up to influence ecosystem-level dynamics through cascading trophic interactions. Here we employ a well-studied, empirically fed three-species trophic chain model, which was parameterized to mimic a common type of aquatic ecosystems to examine how microplastic ingestion by fish on an intermediate trophic level can produce cascading effects on the species at both upper and lower trophic levels. We show that gradually increasing microplastics in the ingested substances of planktivorous fish may cause population structure effects such as skewed size distributions (i.e. reduced average body length vs. increased maximal body size), and induce abrupt declines in fish biomass and reproduction. Our model analysis demonstrates that these abrupt changes correspond to an ecosystem-level tipping point, crossing which difficult-to-reverse ecosystem degradation can happen. Importantly, microplastic pollution may interact with other anthropogenic stressors to reduce safe operating space of aquatic ecosystems. Our work contributes to better understanding complex effects of microplastic pollution and anticipating tipping points of aquatic ecosystems in a changing world. It also calls attention to an emerging threat that novel microplastic contaminants may lead to unexpected and abrupt degradation of aquatic ecosystems, and invites systematic studies on the ecosystem-level consequences of microplastic exposure.

Association between organophosphorus insecticides exposure and osteoarthritis in patients with arteriosclerotic cardiovascular disease.

BACKGROUND: Organic phosphorus insecticides (OPPs) are a class of environmental pollutants widely used worldwide with potential human health risks. We aimed to assess the association between exposure to OPPs and osteoarthritis (OA) particularly in participants with atherosclerotic cardiovascular disease (ASCVD). METHODS: Participants' information was obtained from data in the National Health and Nutrition Examination (NHANES). Weighted logistic regression models were utilized to detect associations between OPPs metabolites and OA. Restricted cubic spline plots (RCS) were drawn to visualize the dose-response relationship between each metabolite and OA prevalence. Weighted quantile sum (WQS) regression and Bayesian kernel-machine regression (BKMR), were applied to investigate the joint effect of mixtures of OPPs on OA. RESULTS: A total of 6871 samples were included in our study, no significant associations between OPPs exposure and OA incidence were found in whole population. However, in a subset of 475 individuals with ASCVD, significant associations between DMP (odds ratio [OR] as a continuous variable = 1.22, 95% confidence interval [CI]: 1.07,1.28), DEP ((odds ratio [OR] of the highest tertile compared to the lowest = 2.43, 95% confidence interval [CI]: 1.21,4.86), and OA were observed. DMP and DEP showed an increasing dose-response relationship to the prevalence of OA, while DMTP, DETP, DMDTP and DEDTP showed a nonlinear relationship. Multi-contamination modeling revealed a 1.34-fold (95% confidence intervals:0.80, 2.26) higher prevalence of OA in participants with high co-exposure to OPPs compared to those with low co-exposure, with a preponderant weighting (0.87) for the dimethyl dialkyl phosphate metabolites (DMAPs). The BKMR also showed that co-exposure of mixed OPPs was associated with an increased prevalence of OA, with DMP showing a significant dose-response relationship. CONCLUSION: High levels of urine dialkyl phosphate metabolites (DAP) of multiple OPPs are associated with an increased prevalence of OA in patients with ASCVD, suggesting the need to prevent exposure to OPPs in ASCVD patients to avoid triggering OA and further avoid the occurrence of cardiovascular events caused by OA.

Transcriptomic Analysis Under Drought and Salt Stress Provides Insight into Genes Putatively Involved in Ginsenoside Biosynthesis in Panax japonicus Meyer.

Panax japonicus Meyer, a perennial herb of the dicotyledonaceae family Araliaceae, is a rare folk traditional Chinese medicine, known as "the king of herbal medicine" in China. To understand the genes involved in secondary pathways under drought and salt stress, the transcriptomic analysis of P. japonicus is of vital importance. The transcriptome of underground rhizomes, stems, and leaves under drought and salt stress in P. japonicus were performed using the Illumina HiSeq platform. After de novo assembly of transcripts, expression profiling and identified differentially expressed genes (DEGs) were performed. Furthermore, putative functions of identified DEGs correlated with ginsenoside in P. japonicus were explored using Gene Ontology terms and Kyoto Encyclopedia of Genes and Genome (KEGG) pathway enrichment analysis. A total of 221,804 unigenes were obtained from the transcriptome of P. japonicus. The further analysis revealed that 10,839 unigenes were mapped to 91 KEGG pathways. Furthermore, a total of two metabolic pathways of P. japonicus in response to drought and salt stress related to triterpene saponin synthesis were screened. The sesquiterpene and triterpene metabolic pathways were annotated and finally putatively involved in ginsenoside content and correlation analysis of the expression of these genes were analyzed to identify four genes, ß-amyrin synthase, isoprene synthase, squalene epoxidase, and 1-deoxy-D-ketose-5-phosphate synthase, respectively. Our results paves the way for screening highly expressed genes and mining genes related to triterpenoid saponin synthesis. It also provides valuable references for the study of genes involved in ginsenoside biosynthesis and signal pathway of P. japonicus.

Gestational Diabetes Mellitus-Induced Milk Fat Globule Membrane Protein Changes of Human Mature Milk Based on TMT Proteomic Analysis.

Breastfeeding by mothers with gestational diabetes mellitus (GDM) has been shown to reduce maternal insulin demands and diminish the risks of diabetes in infants, leading to improved long-term health outcomes. Milk fat globule membrane (MFGM) proteins play a crucial role in influencing the immunity and cognitive development of infants. Understanding the alterations in MFGM proteins in breastmilk from mothers with GDM is essential for enhancing their self-efficacy and increase breastfeeding rates. The objective of this study is to investigate and compare MFGM proteins in milk from mothers with GDM and without based on tandem mass tag (TMT) labeling and liquid chromatography tandem mass spectrometry (LC-MS) techniques. A total of 5402 proteins were identified, including 4 upregulated proteins and 24 downregulated proteins. These significantly altered proteins were found to be associated with human diseases, cellular processes, and metabolism pathways. Additionally, the oxidative phosphorylation pathway emerged as the predominant pathway through Gene Set Enrichment Analysis (GSEA) involving all genes.

Why are biodiversity-ecosystem functioning relationships so elusive? Trophic interactions may amplify ecosystem function variability.

The relationship between biodiversity and ecosystem functions (BEFs) has attracted great interest. Studies on BEF have so far focused on the average trend of ecosystem function as species diversity increases. A tantalizing but rarely addressed question is why large variations in ecosystem functions are often observed across systems with similar species diversity, likely obscuring observed BEFs. Here we use a multi-trophic food web model in combination with empirical data to examine the relationships between species richness and the variation in ecosystem functions (VEFs) including biomass, metabolism, decomposition, and primary and secondary production. We then probe the mechanisms underlying these relationships, focusing on the role of trophic interactions. While our results reinforce the previously documented positive BEF relationships, we found that ecosystem functions exhibit significant variation within each level of species richness and the magnitude of this variation displays a hump-shaped relationship with species richness. Our analyses demonstrate that VEFs is reduced when consumer diversity increases through elevated nonlinearity in trophic interactions, and/or when the diversity of basal species such as producers and decomposers decreases. This explanation is supported by a 34-year empirical food web time series from the Gulf of Riga ecosystem. Our work suggests that biodiversity loss may not only result in ecosystem function decline, but also reduce the predictability of functions by generating greater function variability among ecosystems. It thus helps to reconcile the debate on the generality of positive BEF relationships and to disentangle the drivers of ecosystem stability. The role of trophic interactions and the variation in their strengths mediated by functional responses in shaping ecosystem function variation warrants further investigations and better incorporation into biodiversity-ecosystem functioning research.

Medium and long-term radiographic and clinical outcomes of Dynesys dynamic stabilization versus instrumented fusion for degenerative lumbar spine diseases.

BACKGROUND: Dynesys stabilization (DS) is utilized to preserve mobility at the instrumental segments and prevent adjacent segment pathology in clinical practice. However, the advantages of DS method in medium and long-term follow-up remain controversial. OBJECTIVE: To compare the radiographic and clinical outcomes between DS and instrumented fusion in the treatment of degenerative lumbar spine disease with or without grade I spondylolisthesis with a minimum follow-up period of 2 years. METHODS: We conducted a comprehensive search of PubMed, EMBASE, Cochrane, and Web of Science databases, Chinese National Knowledge Databases, and Wanfang Database for potentially eligible articles. Clinical outcomes were assessed in terms of VAS and ODI scores, screw loosening and breakage, and surgical revision. Radiographic outcomes were assessed in terms of postoperative range of movement (ROM) and disc heigh. Moreover, adjacent segment degeneration (ASDeg) and adjacent segment disease (ASDis) were evaluated. RESULTS: Seventeen studies with 1296 patients were included in the meta-analysis. The DS group was associated with significantly lower postoperative VAS scores for low-back and leg pain, and lower rate of surgical revision than the fusion group. Moreover, the Dynesys group showed significantly less ASDeg than the fusion group but showed no significant advantage over the fusion group in terms of preventing ASDis. Additionally, the ROM at the stabilized segments of the fusion group decreased significantly and that at the adjacent segments increased significantly compared with those of the DS group. CONCLUSION: DS showed comparable clinical outcomes and provided benefits in preserving the motion at the stabilized segments, thus limiting the hypermobility at the adjacent segments and preventing ASDeg compared with the fusion method in degenerative disease with or without grade I spondylolisthesis.

Gallic acid improves the metformin effects on diabetic kidney disease in mice.

OBJECTIVES: Metformin is an antidiabetic agent that is used as the first-line treatment of type 2 diabetes mellitus. Gallic acid is a type of phenolic acid that has been shown to be a potential drug candidate to treat diabetic kidney disease, an important complication of diabetes. We aimed to test whether a combination of gallic acid and metformin can exert synergetic effect on diabetic kidney disease in diabetic mice model. METHODS: Streptozotocin (65 mg/kg) intraperitoneal injection was used to induce diabetic kidney disease in mice. The diabetic mice were treated with saline (Vehicle), gallic acid (GA) (30 mg/kg), metformin (MET) (200 mg/kg), or the combination of gallic acid (30 mg/kg) and metformin (200 mg/kg) (GA + MET). RESULTS: Our results demonstrated that compared to the untreated diabetic mice, all three strategies (GA, MET, and GA + MET) exhibited various effects on improving renal morphology and functions, reducing oxidative stress in kidney tissues, and restoring AMP-activated protein kinase (AMPK)/silent mating type information regulation 2 homolog 1 (SIRT1) signaling in kidney tissues of diabetic mice. Notably, the combination strategy (GA + MET) provided the most potent renal protection effects than any single strategies (GA or MET). CONCLUSION: Our results support the hypothesis that gallic acid might serve as a potential supplement to metformin to enhance the therapeutical effect of metformin.

Sacubitril/valsartan attenuates myocardial ischemia/reperfusion injury via inhibition of the GSK3ß/NF-κB pathway in cardiomyocytes.

In ischemia/reperfusion (I/R) injury, both inflammation and apoptosis play a vital role, and the inhibition of excessive inflammation and apoptosis show substantial clinical potential in the treatment of I/R disease. The role of sacubitril/valsartan (SAC/VAL)-a first-in-class angiotensin receptor-neprilysin inhibitor (ARNI)-in inflammation regulation and apoptosis in the context of I/R injury needs to be further explored. In this study, we investigate the short- and long-term effects of SAC/VAL administration in treating adult murine I/R injury both in vivo and in vitro. Our results verified that the application of SAC/VAL could reduce infarct size and suppress apoptosis and the inflammatory response in the acute phase post I/R. Long-term application of SAC/VAL for four weeks significantly improved ventricular function and reversed pathological ventricular remodeling. Mechanistically, SAC/VAL treatment induces the inhibition of the GSK3ß-mediated NF-κB pathway through synergistically blocking angiotensin 1 receptor (AT1R) and activating natriuretic peptide receptor (NPR). In summary, we reported the therapeutic role of SAC/VAL in regulating the GSK3ß/NF-κB signaling pathway to suppress the inflammatory response and apoptosis, thereby reducing cardiac dysfunction and remodeling post I/R.

Self-Maintenance of Cardiac Resident Reparative Macrophages Attenuates Doxorubicin-Induced Cardiomyopathy Through the SR-A1-c-Myc Axis.

RATIONALE: Doxorubicin-induced cardiomyopathy (DiCM) is a primary cause of heart failure and mortality in cancer patients, in which macrophage-orchestrated inflammation serves as an essential pathological mechanism. However, the specific roles of tissue-resident and monocyte-derived macrophages in DiCM remain poorly understood. OBJECTIVE: Uncovering the origins, phenotypes, and functions of proliferative cardiac resident macrophages and mechanistic insights into the self-maintenance of cardiac macrophage during DiCM progression. METHODS AND RESULTS: Mice were administrated with doxorubicin to induce cardiomyopathy. Dynamic changes of resident and monocyte-derived macrophages were examined by lineage tracing, parabiosis, and bone marrow transplantation. We found that the monocyte-derived macrophages primarily exhibited a proinflammatory phenotype that dominated the whole DiCM pathological process and impaired cardiac function. In contrast, cardiac resident macrophages were vulnerable to doxorubicin insult. The survived resident macrophages exhibited enhanced proliferation and conferred a reparative role. Global or myeloid specifically ablation of SR-A1 (class A1 scavenger receptor) inhibited proliferation of cardiac resident reparative macrophages and, therefore, exacerbated cardiomyopathy in DiCM mice. Importantly, the detrimental effect of macrophage SR-A1 deficiency was confirmed by transplantation of bone marrow. At the mechanistic level, we show that c-Myc (Avian myelocytomatosis virus oncogene cellular homolog), a key transcriptional factor for the SR-A1-P38-SIRT1 (Sirtuin 1) pathway, mediated the effect of SR-A1 in reparative macrophage proliferation in DiCM. CONCLUSIONS: The SR-A1-c-Myc axis may represent a promising target to treat DiCM through augmentation of cardiac resident reparative macrophage proliferation.

Trade-off between climatic and human population impacts on Aedes aegypti life history shapes its geographic distribution.

The annual death statistics due to vector-borne diseases transmitted by Aedes mosquitoes cause a still growing concern for the public health in the affected regions. An improved understanding of how climatic and population changes impact the spread of Aedes aegypti will help estimate the future populations exposure and vulnerability, and is essential to the improvement of public health preparedness. We apply an empirically well-investigated process-based mathematical model based on the life cycle of the mosquito to assess how climate scenarios (Representative Concentration Pathways (RCP)) and population scenarios (Shared Socioeconomic Pathways (SSP)) will affect the growth and potential distribution of this mosquito in China. Our results show that the risk area is predicted to expand considerably, increasing up to 21.46% and 24.75% of China's land area in 2050 and 2070, respectively, and the new added area lies mainly in the east and center of China. The population in the risk area grows substantially up to 2050 and then drops down steadily. However, these predicted changes vary noticeably among different combinations between RCPs and SSPs with the RCP2.6*SSP4 yielding the most favorable scenario in 2070, representing approximately 14.11% of China's land area and 113 cities at risk, which is slightly lower compared to 2019. Our results further reveal that there is a significant trade-off between climatic and human population impacts on the spreading of Aedes aegypti, possibly leading to an overestimation (underestimation) in sparsely (densely) populated areas if the populations impact on the mosquito's life history is unaccounted for. These results suggest that both climate and population changes are crucial factors in the formation of the populations exposure to Aedes-borne virus transmission in China, however, a reduced population growth rate may slow down the spread of this mosquito by effectively counteracting the climate warming impacts.

Performance enhancement of polyurethane foam applied to optical fiber microphones.

The application of polyurethane foam to optical fiber microphone sensitization is proposed. In this experiment, the Michelson interference system is used, and polyurethane foam is coated on the optical fiber of the signal arm. By changing the optical fiber material of the signal arm and the reference arm, four sets of comparative experiments are designed to test the sensitivity of the optical microphone. Through a scanning electron microscope (SEM) test and a pore size distribution test, the porous structure and non-closed cell structure characteristics, pore size range, etc., of the polyurethane foam were determined. The average sound absorption coefficient of the polyurethane foam is 0.66 through the sound absorption coefficient and sound insulation test. The sound absorption coefficient of each frequency band is above 0.2, the sound insulation is below 30 dB, and the overall sound insulation performance is poor, which can be regarded as an ideal sound absorption material. The sound-absorbing effect of polyurethane foam is better than that of nylon tight-packed materials in the frequency range of 500-2800 Hz, and it has a significant sensitization effect in this frequency band. In the frequency band above 2800 Hz, the sound-absorbing effect of nylon tight-packed optical fiber is better than that of polyurethane foam, and the optimal combination is determined by lateral comparison as signal arm (nylon tight-packed fiber + polyurethane foam) + reference arm (bare fiber). Finally, with different coating thicknesses as variables, the results show that the optical fiber microphone has the best sound collection effect when the coating thickness of polyurethane foam is 1.5 cm.

Screening for obstructive sleep apnoea in patients with serious mental illness.

OBJECTIVE: Patients with serious mental illness (SMI) are at increased risk of obstructive sleep apnoea (OSA). Despite this, OSA is frequently under-recognised in the psychiatric population. This study describes the results of OSA screening in SMI patients. METHOD: Patients with SMI attending a metropolitan mental health clinic were screened for OSA using the OSA50, STOP-BANG Questionnaire (SBQ), Epworth Sleep Score (ESS) and the Pittsburgh Sleep Quality Index (PSQI). They were then offered diagnostic sleep testing via ResMed ApneaLinkTM and polysomnography. RESULTS: Of the 65 patients recruited, 65% had a primary diagnosis of schizophrenia or schizoaffective disorder, 85% were on antipsychotic medications and the majority were obese. Approximately 50% of patients reported poor sleep quality via the PSQI, in contrast to 12% with elevated daytime sleepiness via the ESS. 46% of our cohort were at risk of OSA due to an elevated OSA50 or SBQ. Of the five patients who agreed to proceed to diagnostic sleep testing, three were diagnosed with OSA. CONCLUSION: A high proportion of patients with psychiatric illness are at risk of sleep-disordered breathing. Sleep dissatisfaction is high. The low uptake of sleep investigation requires improved patient engagement to improve OSA diagnosis in this high-risk group.

[Research progress of Angelicae Sinensis Radix and predictive analysis on its quality markers].

Angelicae Sinensis Radix, as a medicinal and edible Chinese medicinal herb, is widely used in clinical practice. It is mainly cultivated in Minxian, Tanchang, Zhangxian and Weiyuan counties of Gansu province. In recent years, with the comprehensive and in-depth study of Angelicae Sinensis Radix in China and abroad, its chemical composition, pharmacological effects and application and development have attracted much attention. In this study, the chemical composition, traditional efficacy, and modern pharmacological effects of Angelicae Sinensis Radix were summarized. On this basis, combined with the core concept of quality markers(Q-markers), the Q-markers of Angelicae Sinensis Radix were discussed from the aspects of mass transfer and traceability and chemical composition specificity, availability, and measurability, which provided scientific basis for the quality evaluation of Angelicae Sinensis Radix.

Spatial drivers of instability in marine size-spectrum ecosystems.

Size-spectrum models are a recent class of models describing the dynamics of a whole community based on a description of individual organisms. The models are motivated by marine ecosystems where they cover the size range from multicellular plankton to the largest fish. We propose to extend the size-spectrum model with spatial components. The spatial dynamics is governed by a random motion and a directed movement in the direction of increased fitness, which we call 'fitness-taxis'. We use the model to explore whether spatial irregularities of marine communities can occur due to the internal dynamics of predator-prey interactions and spatial movements. This corresponds to a pattern-formation analysis generalized to an entire ecosystem but is not limited to one prey and one predator population. The analyses take the form of Fourier analysis and numerical experiments. Results show that diffusion always stabilizes the equilibrium but fitness-taxis destabilizes it, leading to non-stationary spatially inhomogeneous population densities, which are travelling in size. However, there is a strong asymmetry between fitness-induced destabilizing effects and diffusion-induced stabilizing effects with the latter dominating over the former. These findings reveal that fitness taxis acts as a possible mechanism behind pattern formations in ecosystems with high diversity of organism sizes, which can drive the emergence of spatial heterogeneity even in a spatially homogeneous environment.

Design and perspective of amorphous metal nanoparticles from laser synthesis and processing.

Amorphous metal nanoparticles (A-NPs) have aroused great interest in their structural disordering nature and combined downsizing strategies (e.g. nanoscaling), both of which are beneficial for highly strengthened properties compared to their crystalline counterparts. Conventional synthesis strategies easily induce product contamination and/or size limitations, which largely narrow their applications. In recent years, laser ablation in liquid (LAL) and laser fragmentation in liquid (LFL) as "green" and scalable colloid synthesis methodologies have attracted extensive enthusiasm in the production of ultrapure crystalline NPs, while they also show promising potential for the production of A-NPs. Yet, the amorphization in such methods still lacks sufficient rules to follow regarding the formation mechanism and criteria. To that end, this article reviews amorphous metal oxide and carbide NPs from LAL and LFL in terms of NP types, liquid selection, target elements, laser parameters, and possible formation mechanism, all of which play a significant role in the competitive relationship between amorphization and crystallization. Furthermore, we provide the prospect of laser-generated metallic glass nanoparticles (MG-NPs) from MG targets. The current and potential applications of A-NPs are also discussed, categorized by the attractive application fields e.g. in catalysis and magnetism. The present work aims to give possible selection rules and perspective on the design of colloidal A-NPs as well as the synthesis criteria of MG-NPs from laser-based strategies.

Phytochemical Profile and Anti-Inflammatory Activity of the Fraction from Artemisia lavandulaefolia.

Artemisia lavandulaefolia, a traditional herbal medicine, has been utilized as anti-inflammatory and analgesia agent in clinic. Bioassay-guided fractionation resulted in a fraction (ALDF) with anti-inflammatory effect obtained from A. lavandulaefolia. Its main constituents were analyzed and identified by UPLC-ESI-Q-TOF-MS technology. ALDF showed the strong inhibitory activity on the nitrogen oxide (NO) production in LPS-induced RAW 264.7 macrophages with an IC50 value of 1.64±0.41 µg/mL. Further results displayed that ALDF also significantly suppressed the secretion of key pro-inflammatory mediators, including tumor necrosis factor-α (TNF-α), prostaglandin E2 (PGE2 ) and interleukin-1ß (IL-1ß), and the increase of the inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein expression induced by LPS stimulation. Mechanism study indicated that ALDF was able to block NF-κB signaling pathway through inhibiting IκB and p65 phosphorylation, as well as NF-κB p65 nuclear translocation. Furthermore, in vivo results in mice revealed that treatments with ALDF evoked significant inhibition on ear edema induced by xylene and on the writhing responses induced by acetic acid. These results suggest that ALDF holds great potential in the prevention and treatment of inflammatory disorders.

YAP/TEAD3 signal mediates cardiac lineage commitment of human-induced pluripotent stem cells.

Cardiomyocytes differentiated from human-induced pluripotent stem cells (hiPSCs) hold great potential for therapy of heart diseases. However, the underlying mechanisms of its cardiac differentiation have not been fully elucidated. Hippo-YAP signal pathway plays important roles in cell differentiation, tissue homeostasis, and organ size. Here, we identify the role of Hippo-YAP signal pathway in determining cardiac differentiation fate of hiPSCs. We found that cardiac differentiation of hiPSCs were significantly inhibited after treatment with verteporfin (a selective and potent YAP inhibitor). During hiPSCs differentiation from mesoderm cells (MESs) into cardiomyocytes, verteporfin treatment caused the cells retained in the earlier cardiovascular progenitor cells (CVPCs) stage. Interestingly, during hiPSCs differentiation from CVPC into cardiomyocytes, verteporfin treatment induced cells dedifferentiation into the earlier CVPC stage. Mechanistically, we found that YAP interacted with transcriptional enhanced associate domain transcription factor 3 (TEAD3) to regulate cardiac differentiation of hiPSCs during the CVPC stage. Consistently, RNAi-based silencing of TEAD3 mimicked the phenotype as the cells treated with verteporfin. Collectively, our study suggests that YAP-TEAD3 signaling is important for cardiomyocyte differentiation of hiPSCs. Our findings provide new insight into the function of Hippo-YAP signal in cardiovascular lineage commitment.

Iron Homeostasis Determines Fate of Human Pluripotent Stem Cells Via Glycerophospholipids-Epigenetic Circuit.

Iron homeostasis is crucial for a variety of biological processes, but the biological role of iron homeostasis in pluripotent stem cells (PSCs) remains largely unknown. The present study aimed to determine whether iron homeostasis is involved in maintaining the pluripotency of human PSCs (hPSCs). We found that the intracellular depletion of iron leads to a rapid downregulation of NANOG and a dramatic decrease in the self-renewal of hPSCs as well as spontaneous and nonspecific differentiation. Moreover, long-term depletion of iron can result in the remarkable cell death of hPSCs via apoptosis and necrosis pathways. Additionally, we found that the depletion of iron increased the activity of lipoprotein-associated phospholipase A2 (LP-PLA2) and the production of lysophosphatidylcholine, thereby suppressing NANOG expression by enhancer of zeste homolog 2-mediated trimethylation of histone H3 lysine 27. Consistently, LP-PLA2 inhibition abrogated iron depletion-induced loss of pluripotency and differentiation. Altogether, the findings of our study demonstrates that iron homeostasis, acting through glycerophospholipid metabolic pathway, is essential for the pluripotency and survival of hPSCs. Stem Cells 2019;37:489-503.

Trait-based food web model reveals the underlying mechanisms of biodiversity-ecosystem functioning relationships.

The concept of biodiversity-ecosystem functioning (BEF) has been studied over the last three decades using experiments, theoretical models and more recently observational data. While theoretical models revealed that species richness is the best metric summarizing ecosystem functioning, it is clear that ecosystem function is explained by other variables besides species richness. Additionally, theoretical models rarely focus on more than one ecosystem function, limiting ecosystem functioning to biomass or production. There is a lack of theoretical background to verify how other components of biodiversity and species interactions support ecosystem functioning. Here, using simulations from a food web model based on a community assembly process and a trait-based approach, we test how species biodiversity, food web structure and predator-prey interactions determine several ecosystem functions (biomass, metabolism, production and productivity). Our results demonstrate that the relationship between species richness and ecosystem functioning depends on the type of ecosystem function considered and the importance of diversity and food web structure differs across functions. Particularly, we show that dominance plays a major role in determining the level of biomass, and it is at least as important as the number of species. We find that dominance occurs in the food web when species do not experience strong predation. By manipulating the structure of the food web, we show that species using a wider trait space (generalist communities) result in more connected food webs and generally reach the same level of functioning with less species. The model shows the importance of generalist versus specialist communities on BEF relationships, and as such, empirical studies should focus on quantifying the importance of diet/habitat use on ecosystem functioning. Our study provides a better understanding of BEF underlying mechanisms and generates research hypotheses that can be considered and tested in observational studies. We recommend that studies investigating links between biodiversity and ecosystem functions should include metrics of dominance, species composition, trophic structure and possibly environmental trait space. We also advise that more effort should be made into calculating several ecosystem functions and properties with data from natural multitrophic systems.