Impairments of insulin and glucagon sensitivity in Chinese women with gestational diabetes mellitus.

AIM: To evaluate insulin and glucagon sensitivity in Han Chinese women with and without gestational diabetes mellitus (GDM). METHODS: In total, 81 women with GDM and 81 age-matched healthy controls were evaluated with a 75 g oral glucose tolerance test (OGTT) at gestational weeks 24-28. Plasma glucose concentrations were measured at fasting and 1 h and 2 h post-OGTT. Fasting plasma insulin, glucagon and amino acids were also measured. Insulin and glucagon sensitivity were assessed by the homeostatic model assessment of insulin resistance (HOMA-IR) and glucagon-alanine index, respectively. RESULTS: As expected, plasma glucose concentrations were higher at fasting and 1 h and 2 h post-OGTT in GDM participants (p < .001 each). Both the HOMA-IR and the glucagon-alanine index were higher in GDM participants. There was a weak positive correlation between HOMA-IR and glucagon-alanine index (r = 0.24, p = .0024). Combining the HOMA-IR and the glucagon-alanine index yielded better capacity (area under the curve = 0.878) than either alone (area under the curve = 0.828 for HOMA-IR and 0.751 for glucagon-alanine index, respectively) in differentiating GDM from healthy participants. While the majority of GDM participants (64%) exhibited both reduced insulin and glucagon sensitivity, a third of them presented either reduced insulin (20%) or glucagon (14%) sensitivity alone. HOMA-IR and glucagon-alanine index correlated differentially with fasting glucose, triglycerides, low-density lipoprotein cholesterol, sum of amino acids and hepatic steatosis index. CONCLUSIONS: Impairments of both insulin and glucagon sensitivity occur frequently in Chinese women with GDM, which may, individually or together, drive metabolic derangements in GDM. These observations provide new insights into the pathophysiology of GDM and support the need to target insulin or glucagon resistance, or both, in the management of GDM.

Transcriptome analysis and development of EST-SSR markers in the mushroom Auricularia heimuer.

Auricularia heimuer, the third most frequently cultivated edible mushroom species worldwide, has high medicinal value. However, a shortage of molecular marker hinders the efficiency and accuracy of genetic breeding efforts for A. heimuer. High-throughput transcriptome sequencing data are essential for gene discovery and molecular markers development. This study aimed to clarify the distribution of SSR loci across the A. heimuer transcriptome and to develop highly informative EST-SSR markers. These tools can be used for phylogenetic analysis, functional gene mining, and molecular marker-assisted breeding of A. heimuer. This study used Illumina high-throughput sequencing technology to obtain A. heimuer transcriptome data. The results revealed 37,538 unigenes in the A. heimuer transcriptome. Of these unigenes, 24,777 (66.01%) were annotated via comparison with the COG, Pfam, and NR databases. Overall, 2510 SSRs were identified from the unigenes, including 6 types of SSRs. The most abundant type of repeats were trinucleotides (1425, 56.77%), followed by mononucleotides (391, 15.58%) and dinucleotides (456, 18.17%). Primer pairs for 102 SSR loci were randomly designed for validity confirmation and polymorphism identification; this process yielded 53 polymorphic EST-SSR markers. Finally, 13 pairs of highly polymorphic EST-SSR primers were used to analyze the genetic diversity and population structure of 52 wild A. heimuer germplasms, revealing that the 52 germplasms could be divided into three categories. These results indicated that SSR loci were abundant in types, numbers, and frequencies, providing a potential basis for germplasm resource identification, genetic diversity analysis, and molecular marker-assisted breeding of A. heimuer.

The metabolic role of the CD73/adenosine signaling pathway in HTR-8/SVneo cells: A Double-Edged Sword?

The ecto-5'-nucleotidase (CD73)/adenosine signaling pathway has been reported to regulate tumor epithelial-mesenchymal transition (EMT), migration and proliferation. However, little is known about the metabolic mechanisms underlying its role in trophoblast proliferation and migration. In this study, we aimed to investigate the metabolic role of the CD73/adenosine signaling pathway on the proliferation and migration of trophoblast. We found that CD73 levels were upregulated in preeclamptic placentas compared with the placentas of normotensive pregnant women. EMT and migration of HTR-8/SVneo cells were enhanced when treated with a CD73 inhibitor (100 µM) in vitro. Conversely, excessive adenosine (25 or 50 µM) suppressed trophoblast cell EMT, migration and proliferation. RNA-seq, metabolomics and seahorse findings showed that adenosine treatment resulted in increased expression of PDK1, suppression of aerobic respiration, glycolysis and amino acids synthesis, as well as increased utilization of short-chain fatty acids (SCFAs). Furthermore, the 13C-adenosine isotope tracking experiment demonstrated that adenosine served as a carbon source for the tricarboxylic acid (TCA) cycle. Our results reveal the role of adenosine in regulating trophoblast energy metabolism is like a double-edged sword - either inhibiting aerobic respiration or supplementing carbon sources into metabolic flux. CD73/adenosine signaling regulated trophoblast EMT, migration, and proliferation by modulating energy metabolism. This study indicates that CD73/adenosine signaling potentially plays a role in the occurrence of placenta-derived diseases, including preeclampsia.

Novel insights into toxin changes associated with the growth of Alexandrium pacificum: Revealing active toxin-secretion ability and toxin cell quota variation.

Paralytic shellfish toxins (PSTs) are widely distributed globally and are produced by Alexandrium pacificum in marine system. However, the characteristics of toxins producing and secreting associated with growth phases are still unclear, especially whether A. pacificum has the ability to actively secrete PSTs is controversial. In this study, variation characteristics of intracellular and extracellular PSTs contents associated with A. pacificum growth phases were investigated thoroughly. The results showed that intracellular and extracellular PSTs contents increased sharply during the exponential phase. But during the stationary phase, the intracellular PSTs content increased by only 26 %, and the extracellular PSTs content did not increase significantly. Since the increase in extracellular PSTs content mainly occurred at the exponential phase, when most cells were living, we speculated that active PSTs secretion of living cells might be an important production pathway of extracellular toxins besides leakage from dead cells. Furthermore, toxin cell quota variation associated with the growth phase was analysed. In the exponential phase, the toxin cell quota first increased and then decreased, with a maximum of 19.02 ± 1.80 fmol/cell at 6 d. However, after entering the stationary phase, this value slowly increased again, suggesting that vigilance should be raised for the plateau of Alexandrium blooms. In addition, cells in the exponential phase mainly produced O-sulfated components such as GTX1&4, cells in the stationary phase mainly produced O-sulfate-free components such as GTX5. In this study, the toxigenic rules of A. pacificum were comprehensively uncovered, which provided theoretical guidance for the prevention and mitigation of A. pacificum blooms.

Simulation of New York City's Ventilator Allocation Guideline During the Spring 2020 COVID-19 Surge.

Importance: The spring 2020 surge of COVID-19 unprecedentedly strained ventilator supply in New York City, with many hospitals nearly exhausting available ventilators and subsequently seriously considering enacting crisis standards of care and implementing New York State Ventilator Allocation Guidelines (NYVAG). However, there is little evidence as to how NYVAG would perform if implemented. Objectives: To evaluate the performance and potential improvement of NYVAG during a surge of patients with respect to the length of rationing, overall mortality, and worsening health disparities. Design, Setting, and Participants: This cohort study included intubated patients in a single health system in New York City from March through July 2020. A total of 20 000 simulations were conducted of ventilator triage (10 000 following NYVAG and 10 000 following a proposed improved NYVAG) during a crisis period, defined as the point at which the prepandemic ventilator supply was 95% utilized. Exposures: The NYVAG protocol for triage ventilators. Main Outcomes and Measures: Comparison of observed survival rates with simulations of scenarios requiring NYVAG ventilator rationing. Results: The total cohort included 1671 patients; of these, 674 intubated patients (mean [SD] age, 63.7 [13.8] years; 465 male [69.9%]) were included in the crisis period, with 571 (84.7%) testing positive for COVID-19. Simulated ventilator rationing occurred for 163.9 patients over 15.0 days, 44.4% (95% CI, 38.3%-50.0%) of whom would have survived if provided a ventilator while only 34.8% (95% CI, 28.5%-40.0%) of those newly intubated patients receiving a reallocated ventilator survived. While triage categorization at the time of intubation exhibited partial prognostic differentiation, 94.8% of all ventilator rationing occurred after a time trial. Within this subset, 43.1% were intubated for 7 or more days with a favorable SOFA score that had not improved. An estimated 60.6% of these patients would have survived if sustained on a ventilator. Revising triage subcategorization, proposed improved NYVAG, would have improved this alarming ventilator allocation inefficiency (25.3% [95% CI, 22.1%-28.4%] of those selected for ventilator rationing would have survived if provided a ventilator). NYVAG ventilator rationing did not exacerbate existing health disparities. Conclusions and Relevance: In this cohort study of intubated patients experiencing simulated ventilator rationing during the apex of the New York City COVID-19 2020 surge, NYVAG diverted ventilators from patients with a higher chance of survival to those with a lower chance of survival. Future efforts should be focused on triage subcategorization, which improved this triage inefficiency, and ventilator rationing after a time trial, when most ventilator rationing occurred.

Metabarcoding analysis identifies high diversity of harmful algal bloom species in the coastal waters of the Beibu Gulf.

Harmful algal blooms (HABs) have occurred more frequently in recent years. In this study, to investigate their potential impact in the Beibu Gulf, short-read and long-read metabarcoding analyses were combined for annual marine phytoplankton community and HAB species identification. Short-read metabarcoding showed a high level of phytoplankton biodiversity in this area, with Dinophyceae dominating, especially Gymnodiniales. Multiple small phytoplankton, including Prymnesiophyceae and Prasinophyceae, were also identified, which complements the previous lack of identifying small phytoplankton and those unstable after fixation. Of the top 20 phytoplankton genera identified, 15 were HAB-forming genera, which accounted for 47.3%-71.5% of the relative abundance of phytoplankton. Based on long-read metabarcoding, a total of 147 OTUs (PID > 97%) belonging to phytoplankton were identified at the species level, including 118 species. Among them, 37 species belonged to HAB-forming species, and 98 species were reported for the first time in the Beibu Gulf. Contrasting the two metabarcoding approaches at the class level, they both showed a predominance of Dinophyceae, and both included high abundances of Bacillariophyceae, Prasinophyceae, and Prymnesiophyceae, but the relative contents of the classes varied. Notably, the results of the two metabarcoding approaches were quite different below the genus level. The high abundance and diversity of HAB species were probably due to their special life history and multiple nutritional modes. Annual HAB species variation revealed in this study provided a basis for evaluating their potential impact on aquaculture and even nuclear power plant safety in the Beibu Gulf.

Uncovering the regulation effect of modified clay on toxin production in Alexandrium pacificum: From physiological insights.

As a common dinoflagellate, Alexandrium pacificum can produce paralytic shellfish toxins (PSTs). It can be removed from water by Polyaluminium chloride modified clay (PAC-MC), but it is unclear whether PAC-MC can prevent PSTs content and toxicity from increasing and whether PAC-MC can stimulate PSTs biosynthesis by A. pacificum. Effect of PAC-MC on PSTs and the physiological mechanism were analysed here. The results showed total PSTs content and toxicity decreased respectively by 34.10 % and 48.59 % in 0.2 g/L PAC-MC group at 12 days compared with control group. And the restriction of total PSTs by PAC-MC was mainly achieved via inhibition of algal cell proliferation, by affecting A. pacificum physiological processes and changing phycosphere microbial community. Meanwhile, single-cell PSTs toxicity did not increase significantly throughout the experiment. Moreover, A. pacificum treated with PAC-MC tended to synthesize sulfated PSTs such as C1&2. Mechanistic analysis showed that PAC-MC induced upregulation of sulfotransferase sxtN (related to PSTs sulfation), and functional prediction of bacterial community also showed significant enrichment of "sulfur relay system" after PAC-MC treatment, which might also promote PSTs sulfation. The results will provide theoretical guidance for the application of PAC-MC to field control of toxic Alexandrium blooms.

Mechanisms of Phaeocystis globosa blooms in the Beibu Gulf revealed by metatranscriptome analysis.

The haptophyceae Phaeocystis globosa is a species responsible for harmful algal blooms in the global ocean, forming blooms in the Beibu Gulf annually since 2011. This species can alternate between solitary free-living cells and colonies. Colonies are the dominant morphotype during blooms. To date, the underlying mechanism of P. globosa blooms in the Beibu Gulf is poorly understood. After combining results of ecological surveys, laboratory studies, and metatranscriptome and bioinformatics analyses, it was found that low temperatures, high nitrate, and low organic phosphorus induced P. globosa blooms in the Beibu Gulf. Additionally, the unique genetic and physiological characteristics that allow P. globosa to stand out as a dominant species in such an environment include (1) several genes encoding high-affinity nitrate transport proteins that could be highly expressed under sufficient nitrate conditions; (2) energy metabolism genes involved in photosynthesis and oxidative phosphorylation that were actively expressed at low temperatures to carry out carbon and energy reversion and produce sufficient ATP for various life activities, individually; (3) abundant glycan synthesis genes that were highly expressed at low temperatures, thus synthesizing large quantities of proteoglycans to construct the mucilaginous envelope forming the colony; (4) cells in colonies exhibited active gene expression in DNA replication contributing to a faster growth rate, which could help P. globosa occupy niches quickly; and (5) the energy and material expenditure was redistributed in colonial cells accompanied with chitin filaments and flagella degraded, more expenditure was used for the synthesis of the mucilaginous envelope and the rapid proliferation.

Extraction, physicochemical properties, and antioxidant activity of natural melanin from Auricularia heimuer fermentation.

Introduction: Natural melanin from Auricularia heimuer have numerous beneficial biological properties, which were used as a safe and healthy colorant in several industries. Methods: In this study, single-factor experiments, Box-Behnken design (BBD), and response surface methodology (RSM) were employed to investigate the effects of alkali-soluble pH, acid precipitation pH, and microwave time on the extraction yield of Auricularia heimuer melanin (AHM) from fermentation. Ultraviolet-visible spectrum (UV-Vis), Fourier transform infrared (FT-IR) spectroscopy, scanning electron microscope (SEM), and high-performance liquid chromatography (HPLC) were used to analyze the extracted AHM. The solubility, stability, and antioxidant activities of AHM were also measured. Results: The results showed that alkali-soluble pH, acid precipitation pH, and microwave time significantly affected the AHM yield, with the following optimized microwave-assisted extraction conditions: alkali-soluble pH of 12.3, acid precipitation pH of 3.1, and microwave time of 53 min, resulting in an AHM extraction yield of 0.4042%. AHM exhibited a strong absorption at 210 nm, similar to melanin from other sources. FT-IR spectroscopy also revealed that AHM exhibited the three characteristic absorption peaks of natural melanin. The HPLC chromatogram profile of AHM showed a single symmetrical elution peak with a 2.435 min retention time. AHM was highly soluble in alkali solution, insoluble in distilled water and organic solvents, and demonstrated strong DPPH, OH, and ABTS free radical scavenging activities. Discussion: This study provides technical support to optimize AHM extraction for use in the medical and food industries.

The molecular mechanisms and environmental effects of modified clay control algal blooms in aquacultural water.

Modified clay (MC) technology is an effective method for controlling harmful algal blooms (HABs). Based on field experience, a bloom does not continue after treatment with MC, even though the residual HAB biomass accounts for 20-30% of the initial biomass. Laboratory studies using unialgal cultures have found that MC could inhibit the growth of the residual algal cells to prevent HABs. Nevertheless, the phytoplankton in field waters is diverse. Therefore, unclassified complex mechanisms may exist. To illustrate the molecular mechanisms through which MC controls HABs in the field and verify the previous laboratory findings, a series of experiments and bioinformatics analyses were conducted using bloom waters from aquacultural ponds. The results showed that a 72.29% removal efficiency of algal biomass could effectively control blooms. The metatranscriptomic results revealed that the number of downregulated genes (131,546) was greater than that of upregulated genes (24,318) at 3 h after MC addition. Among these genes, several genes related to DNA replication were downregulated; however, genes involved in DNA repair were upregulated. Metabolism-related pathways were the most significantly upregulated (q < 0.05), including photosynthesis and oxidative phosphorylation. The results also showed that MC reduced most of the biomass of the dominant phytoplankton species, likely by removing apical dominance, which increased the diversity and stability of the phytoplankton community. In addition to reducing the pathogenic bacterial density, MC reduced the concentrations of PO43- (96.22%) and SiO32- (66.77%), thus improving the aquaculture water quality, altering the phytoplankton community structure (the proportion of Diatomea decreased, and that of Chlorophyta increased), and inhibiting phytoplankton growth. These effects hindered the rapid development of large phytoplankton biomasses and allowed the community structure to remain stable, reducing HAB threats. This study illustrates the molecular mechanisms through which MC controls HABs in the field and provides a scientific method for removing HABs in aquacultural waters.

A novel role of FoxO3a in the migration and invasion of trophoblast cells: from metabolic remodeling to transcriptional reprogramming.

BACKGROUND: The forkhead box O3a protein (FoxO3a) has been reported to be involved in the migration and invasion of trophoblast, but its underlying mechanisms unknown. In this study, we aim to explore the transcriptional and metabolic regulations of FoxO3a on the migration and invasion of early placental development. METHODS: Lentiviral vectors were used to knock down the expression of FoxO3a of the HTR8/SVneo cells. Western blot, matrigel invasion assay, wound healing assay, seahorse, gas-chromatography-mass spectrometry (GC-MS) based metabolomics, fluxomics, and RNA-seq transcriptomics were performed. RESULTS: We found that FoxO3a depletion restrained the migration and invasion of HTR8/SVneo cells. Metabolomics, fluxomics, and seahorse demonstrated that FoxO3a knockdown resulted in a switch from aerobic to anaerobic respiration and increased utilization of aromatic amino acids and long-chain fatty acids from extracellular nutrients. Furthermore, our RNA-seq also demonstrated that the expression of COX-2 and MMP9 decreased after FoxO3a knockdown, and these two genes were closely associated with the migration/invasion progress of trophoblast cells. CONCLUSIONS: Our results suggested novel biological roles of FoxO3a in early placental development. FoxO3a exerts an essential effect on trophoblast migration and invasion owing to the regulations of COX2, MMP9, aromatic amino acids, energy metabolism, and oxidative stress.

Establishment and preliminary study of electrophysiological techniques in a typical red tide species.

Electrophysiology studies the electrical properties of cells and tissues including bioelectrical signals and membrane ion channel activities. As an important means to reveal ion channel related physiological functions and the underlying mechanisms, electrophysiological techniques have been widely used in studies of animals, higher plants and algae that are closely related to higher plants. However, few electrophysiological studies have been carried out in red tide organisms, especially in dinoflagellates, which is mainly due to the complex surface structure of dinoflagellate amphiesma. In this study, the surface amphiesma of Alexandrium pacificum, a typical red tide species, was removed by centrifugation, low-temperature treatment and enzymatic treatment. In all three treatments, low-temperature treatment with 4 °C for 2 h had high ecdysis rate and high fixation rate, and the treated cells were easy to puncture, so low-temperature treatment was used as a preprocessing treatment for subsequent current recording. Acquired protoplasts of A. pacificum were identified by calcofluor fluorescence and immobilized by poly-lysine. A modified "puncture" single-electrode voltage-clamp recording was first applied to dinoflagellates, and voltage-gated currents, which had the characteristics of outward K+ current and inward Cl- current, were recorded and confirmed by ion replacement, indicating the voltage-gated currents were mixed. This method can be used as a technical basis for the electrophysiological study of dinoflagellates and provides a new perspective for the study of stress tolerance, red tide succession, and the regulation of physiological function of dinoflagellates.

Simple One-Step and Rapid Patterning of PDMS Microfluidic Device Wettability for PDMS Shell Production.

Double emulsion (DE) droplets with controlled size and internal structure are a promising platform for biological analysis, chemical synthesis, and drug delivery systems. However, to further "democratize" their application, new methods that enable simple and precise spatial patterning of the surface wettability of droplet-generating microfluidic devices are still needed. Here, by leveraging the increase in hydrophilicity of polydimethylsiloxane (PDMS) due to the plasma-treatment used to permanently bond to glass, we developed a one-step method to selectively pattern the wettability of PDMS microfluidic devices for DE generation. Our results show that both Aquapel-treated and 1H,1H,2H,2H-Perfluorodecyltriethoxysilan (PFDTES)-treated devices are functionally showing the generality of our method. With the resulting microfluidic devices, both water-in-oil-in-water (w/o/w) and oil-in-water-in-oil (o/w/o) DE droplets can be produced. Using a PDMS mixture containing cross-linking agents, we formed PDMS microcapsules by solidifying the shell layer of water-in-PDMS-in-water DE droplets. We also characterize the morphological properties of the generated droplets/microcapsules. We anticipate the method developed in this work could be used in a broad range of applications of DE droplets.

Effects of modified clay on the formation of Phaeocystis globosa colony revealed by physiological and transcriptomic analyses.

The harmful algal bloom (HAB) species Phaeocystis globosa is commonly observed in global temperate and tropical oceans, and colonies of P. globosa exhibit a dominant morphotype during blooms. The use of polyaluminium chloride modified clay (PAC-MC) is an effective mitigation strategy for P. globosa blooms. Although previous studies have found that PAC-MC can stimulate P. globosa colony formation at low concentrations and inhibit it at higher concentrations, the underlying mechanisms of these effects are poorly understood. Here, we comprehensively compared the physiochemical indices and transcriptomic response of residual P. globosa cells after treatment with two concentrations of PAC-MC. The results showed that PAC-MC induced oxidative stress, photosynthetic inhibition, and DNA damage in residual cells. Moreover, it could activate antioxidant responses and enhance the repair of photosynthetic structure and DNA damage in cells. The biosynthesis of polysaccharides was enhanced and genes associated with cell motility were down-regulated after treatment with PAC-MC, resulting in the accumulation of colonial matrixes. After treatment with a low concentration of PAC-MC (0.1 g/L), the residual cells were slightly stressed, including physical damage, oxidative stress and other damage, and polysaccharide synthesis was enhanced to promote colony formation to alleviate environmental stress. Moreover, the damage to residual cells was slight; thus, normal cell function provided abundant energy and matter for colony formation. After treatment with a high concentration of PAC-MC (0.5 g/L), the residual cells suffered severe damage, which disrupted normal physiological processes and inhibited cell proliferation and colony formation. The present study elucidated the concentration-dependent mechanism of PAC-MC affecting the formation of P. globosa colonies and provided a reference for the application of PAC-MC to control P. globosa blooms.

A New Species in Pseudophialophora From Wild Rice and Beneficial Potential.

Wild rice (Oryza granulata) is a natural resource pool containing abundant unknown endophytic fungi species. There are few reports on the endophytic fungi in wild rice. Here, one isolate recovered from wild rice roots was identified as a new species Pseudophialophora oryzae sp. nov based on the molecular phylogeny and morphological characteristics. Fluorescent protein-expressing P. oryzae was used to monitor the fungal colonization pattern. Hyphae invaded the epidermis to the inner cortex but not into the root stele. The inoculation of P. oryzae promoted the rice growth, with the growth parameters of chlorophyll content, shoot height, root length, fresh shoot weight, fresh root weight and dry weight increasing by 24.10, 35.32, 19.35, 90.00, 33.3, and 79.17%, respectively. P. oryzae induced up-regulation of nitrate transporter OsPTR9 and potassium transporter OsHAK16 by 7.28 ± 0.84 and 2.57 ± 0.80 folds, promoting nitrogen and potassium elements absorption. In addition, P. oryzae also conferred a systemic resistance against rice blast, showing a 72.65 and 75.63% control rate in sterile plates and potting conditions. This systemic resistance was mediated by the strongly up-regulated expression of resistance-related genes NAC, OsSAUR2, OsWRKY71, EL5, and PR1α. Since P. oryzae can promote rice growth, biomass and induce systemic disease resistance, it can be further developed as a new biogenic agent for agricultural production, providing a new approach for biocontrol of rice blast.

Assessing the Effect of Modified Clay on the Toxicity of Karenia mikimotoi Using Marine Medaka (Oryzias melastigma) as a Model Organism.

Blooms of the toxic dinoflagellate Karenia mikimotoi could threaten the survival of marine life, and modified clay (MC) is considered a promising method for the control of harmful algal blooms. Here, using marine medaka as the model organism, the toxicity of K. mikimotoi before and after MC disposal was investigated. The results showed that only a certain density of intact K. mikimotoi cells could cause obvious damage to fish gills and lead to rapid death. A systematic analysis of morphology, physiology, and molecular biology parameters revealed that the fish gills exhibited structural damage, oxidative damage, osmotic regulation impairment, immune response activation, and signal transduction enhancement. MC can flocculate K. mikimotoi rapidly in water and reduce its toxicity by reducing the density of intact algae cells and hemolytic toxicity. The results indicate that MC is an effective and safe method for controlling K. mikimotoi blooms.

CD39/CD73 Dysregulation of Adenosine Metabolism Increases Decidual Natural Killer Cell Cytotoxicity: Implications in Unexplained Recurrent Spontaneous Abortion.

Unexplained recurrent spontaneous abortion (URSA) is believed to be associated with impaired immunosuppression at the maternal-fetal interface, but the detailed molecular mechanism remains unclear. The ATP-adenosine metabolic pathway regulated by CD39/CD73 has recently been recognized to be important in immunosuppression. This study aimed to investigate the regulation of decidual natural killer (dNK) cells and fetal extravillous trophoblast (EVT) cells by CD39 and CD73 in URSA, as well as the possible regulatory mechanism of CD39/CD73 via the TGF-ß-mTOR-HIF-1α pathway using clinical samples and cell models. Fewer CD39+ and CD73+ cells were found in the URSA decidual and villous tissue, respectively. Inhibition of CD39 on dNK cells transformed the cells to an activated state with increased toxicity and decreased apoptosis, and changed their cytokine secretion, leading to impaired invasion and proliferation of the co-cultured HTR8/SVneo cells. Similarly, inhibition of CD73 on HTR8/SVneo cells decreased the adenosine concentration in the cell culture media, increased the proportion of CD107a+ dNK cells, and decreased the invasion and proliferation capabilities of the HTR8/SVneo cells. In addition, transforming growth factor-ß (TGF-ß) triggered phosphorylation of mammalian target of rapamycin (mTOR) and Smad2/Smad3, which subsequently activated hypoxia-inducible factor-1α (HIF-1α) to induce the CD73 expression on the HTR8/SVneo cells. In summary, reduced numbers of CD39+ and CD73+ cells at the maternal-fetal interface, which may be due to downregulated TGF-ß-mTOR-HIF-1α pathway, results in reduced ATP-adenosine metabolism and increased dNK cytotoxicity, and potentially contributes to URSA occurrences.

Mechanism by Which MC Controls Harmful Algal Blooms Revealed by Cell Morphology of Aureococcus anophagefferens.

On the basis of field experience, a bloom does not continue after treatment with modified clay (MC), even though the residual harmful algal bloom (HAB) biomass accounts for 20-30% of the initial cells. This interesting phenomenon indicates that, in addition to causing flocculation, MC can inhibit the growth of residual cells. Here, from a cell morphology perspective, Aureococcus anophagefferens was used as a model organism to explore this scientific issue and clarify the mechanism by which MC mitigates harmful algal blooms (HABs). The results showed that, at an ~70% removal efficiency, neutral clay (NC) could not effectively inhibit the growth of residual cells, although it caused various forms of damage to residual cells, such as cell deformation, cell breakage, decreased extracellular polysaccharides (EPS), increased cell membrane permeability, and increased cytoplasmic granularity, due to physical collisions. After modification, some physical and chemical properties of the clay particle surface were changed; for example, the surface electrical properties changed from negative to positive, lamellar spacing increased, hardness decreased, adhesion chains increased, adhesion improved, and the number of absorption sites increased, enhancing the occurrence of chemical and electrochemical effects and physical collisions with residual cells, leading to severe cell deformation and chemical cell breakage. Thus, MC effectively inhibited the growth of residual cells and controlled HABs.

Programmed cell death induced by modified clay in controlling Prorocentrum donghaiense bloom.

Modified clay (MC), an effective material used for the emergency elimination of algal blooms, can rapidly reduce the biomass of harmful algal blooms (HABs) via flocculation. After that, MC can still control bloom population through indirect effects such as oxidative stress, which was initially proposed to be related to programmed cell death (PCD) at molecular level. To further study the MC induced cell death in residual bloom organisms, especially identifying PCD process, we studied the physiological state of the residual Prorocentrum donghaiense. The experimental results showed that flocculation changed the physiological state of the residual cells, as evidenced by growth inhibition and increased reactive oxygen species production. Moreover, this research provides biochemical and ultrastructural evidence showing that MC induces PCD in P. donghaiense. Nuclear changes were observed, and increased caspase-like activity, externalization of phosphatidylserine and DNA fragmentation were detected in MC-treated groups and quantified. And the mitochondrial apoptosis pathway was activated in both MC-treated groups. Besides, the features of MC-induced PCD in a unicellular organism were summarized and its concentration dependent manner was proved. All our preliminary results elucidate the mechanism through which MC can further control HABs by inducing PCD and suggest a promising application of PCD in bloom control.

Effects of CEO Identity on Non-family Managers' Pay Dispersion in Family Firms: A Social Comparison Perspective.

The fairness of compensation has been a prominent focus for non-family managers, and pay dispersion, which reflects compensation fairness, has attracted much attention from scholars. Based on social comparison theory, this study investigates the factors that affect the pay dispersion between CEO and non-family managers. In family firms, the role of CEO, which is central in corporate governance, can be filled by either a family or a non-family member. This study provides insights into how the identity of the CEO affects pay dispersion and investigates the moderating effects of CEO tenure and institutional environment. Using the data of Chinese listed family firms from 2009 to 2015, the results show that the presence of non-family CEOs could decrease the pay dispersion between CEO and non-family managers. Empirical evidence also supports that the negative relationship between CEO identity and pay dispersion weakens when CEO tenure increases and the institutional environment matures.