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The macroalgal blooms of floating brown algae Sargassum horneri are increasing in the Yellow and East China Seas during the past few years. However, the annual pattern of Sargassum bloom is not well characterized. To study the developing pattern and explore the impacts from hydro-meteorologic environment, high resolution satellite imageries were used to monitor the distribution, coverage and drifting of the pelagic Sargassum rafts in the Yellow and East China Seas from September 2019 to August 2020. Sargassum blooms were detected from October 2019 to June 2020 and presented two successive drifting paths that both initiated from around 37°N. The first path spanned smaller spatial scale and shorter period, starting with a bloom of 3 km2 distribution area near the eastern tip of Shandong Peninsular in late October 2019 and drifted southwards, hit the Pyropia aquaculture area in early January 2020, then vanished in the northwest of East China Sea (ca. 32°N) around end of January. The second path began with a large distribution area of 23 000 km2 east of 123°E in late January 2020, firstly moved southwards in the central Yellow and northern East China Seas (north of 29°N) till late April, then turned northwards with monsoon wind and vanished in mid-June. The mean sea surface temperature of 8°C to 20°C in the Sargassum bloom areas corresponded to in situ observed temperature range for vegetative growth and floating of S. horneri. The surface temperature higher than 22°C in July-September prohibits Sargassum blooming or completing life cycle. The results provide insights to the future management of Sargassum blooms. Further studies are needed to validate the pattern and source of annual Sargassum bloom in the Yellow and East China Seas.

To understand the current status of germplasm resources of Penaeus japonicus, in this study, genetic diversity was analyzed based on morphometric analysis and fluorescent microsatellite markers. For morphometric analysis, the cumulative ratios of the PC1 and PC2 (85.90%) were greater than 75%, which can explain the morphological variation among populations. For microsatellite analysis, the allele number in 10 microsatellite loci ranged from 27 to 53, and the effective allele number ranged from 21 to 42. The observed heterozygosity ranged from 0.463 to 0.983, whereas expected heterozygosity ranged from 0.932 to 0.966, and the average polymorphism information content was 0.947, which indicated a high level of genetic diversity. The unbiased genetic distance among populations ranged from 0.230 to 0.431, and the genetic similarity coefficient ranged from 0.654 to 0.782. Analysis of molecular variance (AMOVA) showed that the genetic variation within individuals was the main source of variation, accounting for 88.55%, and only 1.49% of the genetic variation came from among populations.

Receptor activator of NF-κB (RANK) expression is increased in podocytes of patients with diabetic nephropathy. However, the relevance of RANK to diabetic nephropathy pathobiology remains unclear. Here, to evaluate the role of podocyte RANK in the development of diabetic nephropathy, we generated a mouse model of podocyte-specific RANK depletion (RANK-/-Cre T), and a model of podocyte-specific RANK overexpression (RANK TG), and induced diabetes in these mice with streptozotocin. We found that podocyte RANK depletion alleviated albuminuria, mesangial matrix expansion, and basement membrane thickening, while RANK overexpression aggravated these indices in streptozotocin-treated mice. Moreover, streptozotocin-triggered oxidative stress was increased in RANK overexpression but decreased in the RANK depleted mice. Particularly, the expression of NADPH oxidase 4, and its obligate partner, P22phox, were enhanced in RANK overexpression, but reduced in RANK depleted mice. In parallel, the transcription factor p65 was increased in the podocyte nuclei of RANK overexpressing mice but decreased in the RANK depleted mice. The relevant findings were largely replicated with high glucose-treated podocytes in vitro. Mechanistically, p65 could bind to the promoter regions of NADPH oxidase 4 and P22phox, and increased their respective gene promoter activity in podocytes, dependent on the levels of RANK. Taken together, these findings suggested that high glucose induced RANK in podocytes and caused the increase of NADPH oxidase 4 and P22phox via p65, possibly together with the cytokines TNF- α, MAC-2 and IL-1 β, resulting in podocyte injury. Thus, we found that podocyte RANK was induced in the diabetic milieu and RANK mediated the development of diabetic nephropathy, likely by promoting glomerular oxidative stress and proinflammatory cytokine production.

Cultivating new crop cultivars with multiple abiotic stress tolerances is important for crop production. The abscisic acid‐stress‐ripening (ASR) protein has been shown to confer abiotic stress tolerance in plants. However, the mechanisms of ASR function under stress condition remain largely unclear. In this study, we characterized all ASR family members in common wheat and constitutively overexpressed TaASR1‐D in a commercial hexaploid wheat cultivar Zhengmai 9023. The transgenic wheat plants exhibited increased tolerance to multiple abiotic stresses and increased grain yields under salt stress condition. Overexpression of TaASR1‐D conferred enhanced antioxidant capacity and ABA sensitivity in transgenic wheat plants. Further, RNA in situ hybridization results showed that TaASR1‐D had higher expression levels in the vascular tissues of leaves and the parenchyma cells around the vascular tissues of roots and stems. Yeast one‐hybrid and electrophoretic mobility shift assays revealed that TaASR1‐D could directly bind the specific cis‐elements in the promoters of TaNCED1 and TaGPx1‐D. In conclusion, our findings suggest that TaASR1‐D can be used to breed new wheat cultivars with increased multiple abiotic stress tolerances, and TaASR1‐D enhances abiotic stress tolerances by reinforcing antioxidant capacity and ABA signalling.

Synthesis of septal peptidoglycan (sPG) is crucial for bacterial cell division. FtsW, an indispensable component of the cell division machinery in all walled bacterial species, was recently identified in vitro as a peptidoglycan glycosyltransferase (PGTase). Despite its importance, the septal PGTase activity of FtsW has not been demonstrated in vivo. How its activity is spatiotemporally regulated in vivo has also remained elusive. Here, we confirmed FtsW as an essential septum-specific PGTase in vivo using an N-acetylmuramic acid analogue incorporation assay. Next, using single-molecule tracking coupled with genetic manipulations, we identified two populations of processively moving FtsW molecules: a fast-moving population correlated with the treadmilling dynamics of the essential cytoskeletal FtsZ protein and a slow-moving population dependent on active sPG synthesis. We further identified that FtsN, a potential sPG synthesis activator, plays an important role in promoting the slow-moving population. Our results suggest a two-track model, in which inactive sPG synthases follow the ‘Z-track’ to be distributed along the septum and FtsN promotes their release from the Z-track to become active in sPG synthesis on the slow ‘sPG-track’. This model provides a mechanistic framework for the spatiotemporal coordination of sPG synthesis in bacterial cell division. Single-molecule tracking of the septal peptidoglycan glycosyltransferase FtsW reveals two populations: a fast-moving one that follows treadmilling FtsZ and a slow-moving one that is involved in peptidoglycan synthesis.

The FtsZ protein is a central component of the bacterial cell division machinery. It polymerizes at mid-cell and recruits more than 30 proteins to assemble into a macromolecular complex to direct cell wall constriction. FtsZ polymers exhibit treadmilling dynamics, driving the processive movement of enzymes that synthesize septal peptidoglycan (sPG). Here, we combine theoretical modelling with single-molecule imaging of live bacterial cells to show that FtsZ’s treadmilling drives the directional movement of sPG enzymes via a Brownian ratchet mechanism. The processivity of the directional movement depends on the binding potential between FtsZ and the sPG enzyme, and on a balance between the enzyme’s diffusion and FtsZ’s treadmilling speed. We propose that this interplay may provide a mechanism to control the spatiotemporal distribution of active sPG enzymes, explaining the distinct roles of FtsZ treadmilling in modulating cell wall constriction rate observed in different bacteria., Bacterial protein FtsZ polymerizes at mid-cell and exhibits treadmilling dynamics, driving the movement of enzymes that synthesize septal peptidoglycan. Here, McCausland et al. combine theoretical modelling with single-molecule imaging of bacteria to show that FtsZ treadmilling drives enzyme movement via a Brownian ratchet mechanism.

Extra-intestinal manifestations (EIMs) of the eyes are found in IBD patients, but the underlying pathogenesis remains unknown. To investigate the pathogenesis of IBD-associated retinal dysfunction, chronic colitis was induced in mice by oral administration of dextran sodium sulfate (DSS). Electroretinography (ERG) was performed to evaluate retinal function. Retinal neuron degeneration was analyzed by immunohistochemistry. Colitic mice displayed aberrant amplitudes of ERG a-, b-wave and oscillatory potentials (OP). Importantly, we observed severe degeneration of bipolar and ganglion cells. In contrast, outer retinal neurons (mainly photoreceptor cells) are mildly affected by colitis. Moreover, retinal inflammatory responses were significantly upregulated during colitis, including microglia activation, lymphocyte infiltration and cytokine/chemokine production. Notably, mucosal addressin cell adhesion molecule 1 (MAdCAM-1) was upregulated in retinal microvessels, especially the superficial and deep plexuses, and recruited gut-homing CD4+ T cells to be co-localized with bipolar and ganglion cells during colitis. Expectedly, in vivo depletion of CD4+ T cells or blockade of MAdCAM-1 greatly alleviated colitis-induced retinal inflammatory responses and neuron degeneration. Therefore, our data provide novel insight into the pathogenesis of IBD-associated retinal dysfunction, and targeted immune therapy directly against MAdCAM-1 might provide a novel approach in the management of eye EIM of IBD.

Astaxanthin (AX) is a xanthophyll carotenoid that can effectively inhibit the production of peroxides and thereby protect the body from oxidative damage. In recent years, AX had been shown to have anti-aging properties, both in vivo and in vitro. However, the underlying mechanisms by which AX regulates senescence related proteins and signaling pathways remain unclear. Therefore, we used Caenorhabditis elegans (C. elegans) model binding proteomics to reveal AX anti-aging activity and its molecular mechanism. Our results suggest that AX promotes the health and lifespan of C. elegans by improving mobility, reducing the accumulation of age pigments, and increasing resistance to heat stress. In terms of the underlying mechanism, AX helps prolong the life of worms by regulating AGE-1 in the insulin signaling pathway, promoting the transport of DAF-16 into the nucleus and then up-regulating the expression level of DAF-16's downstream proteins (such as superoxide dismutase [Mn] 2 (SOD-3), heat shock proteins (HSPs), glutathione s-transferase (GST-4), etc.). Furthermore, AX may be a relevant response target for activation of dietary restriction pathways in vivo as a dietary restriction mimic. Meanwhile, proteomics data confirmed that there were 15 proteins enriched in the longevity regulation pathway. AX mainly regulates oxidative stress and the aging process by modulating the insulin signaling pathway around DAF-16 as the "hub". In addition to the insulin signaling pathway, other pathways including dietary restriction, AMP-activated protein kinase (AMPK), and mammal target of rapamycin (mTOR) are also dependent on DAF-16. These findings expand and deepen our knowledge of the underlying mechanism by which AX extends the lifespan of C. elegans.

BACKGROUND As an edible and medicinal herb in Chinese folk medicine, Cyclocarya paliurus (Batal.) Iljinskaja leaves are traditionally widely used in the treatment of metabolic disorders. The vegetable Momordica charantia L. has been consumed worldwide for thousands of years as a traditional drug due to its activities against obesity and diabetes. In view of the therapeutic value of Momordica saponins (MSs) and C. paliurus polysaccharides (CPPs), an independently developed MSs- and CPPs-containing beverage (MC) was evaluated for its efficacy in controlling oxidative stress and obesity in Caenorhabditis elegans. RESULTS First, we found that MC could promote the nuclear localization of DAF-16 and the translation of SOD-3. Further exploring its antioxidant properties, the oxidative stress by-products reactive oxygen species, malondialdehyde, and nonesterified fatty acids were significantly inhibited in C. elegans. Moreover, damage due to diseases related to oxidative stress (age pigments and neurodegenerative diseases) was alleviated. Furthermore, fat accumulation was significantly reduced in normal and high-fat models. Finally, the lipid-lowering effects of MC might involve reductions in the size and number of lipid droplets without impairing basic physiological functions in C. elegans. CONCLUSION These results provide promising data indicating MC as an innovative health beverage for the pharmacological management of oxidative stress and obesity. © 2020 Society of Chemical Industry.

The data of field surveys during 2009 to 2018 was analyzed to understand the seasonality and inter-annual variability of the floating Ulva and Sargassum in the Subei Shoal, the southwestern Yellow Sea of China on decadal scale. The floating Ulva biomass was consistently originated from the central region of the Subei Shoal in middle to late April, increased rapidly, drifted and extended into the offshore water in May and June. The average floating Ulva biomass in the shoal generally increased over the years with evident inter-annual fluctuations. In contrast, pelagic Sargassum was accumulated in the Subei Shoal and formed the spring bloom only in 2013, 2017 and 2018, and the biomass was higher than the co-occurring Ulva during the survey in these three years. Compared to the raft-origin floating Ulva, genesis and development of the pelagic Sargassum was distinct. Based on the current research, the Sargassum biomass was exotic and often initiated in the offshore water in March, and intruded into the shoal in April and May. The analysis on the environmental parameters was inconclusive since multiple anthropogenic and non-indigenous factors could influence the green tides in this region. Further research covering both the East China Sea and the Yellow Sea is needed to trace the origin of the floating Sargassum and to understand the interactions between these two co-occurring seaweeds.

Whether external root resorption is associated with hypoxia in the periodontal ligaments of teeth with severe periodontitis remains unclear. Hypoxia inducible factor-1α (HIF-1α) expression and external resorption sites in the periodontal ligaments of these teeth were observed to elaborate upon the relationship between hypoxia and external root resorption in severe periodontitis. Histological analysis was performed to observe external root resorption. The expressions of HIF-1α and Nuclear factor-activated T cells c1 (NFATc1) in the periodontal ligaments were detected by immunofluorescence, western blotting and real-time PCR. Bone marrow macrophages (BMMs) were stimulated by Porphyromonas gingivalis lipopolysaccharide (Pg.LPS) and cultured under hypoxia in vitro. High levels of HIF-1α and NFATc1 were detected in severe periodontitis. HIF-1α positive-cells were observed in the external resorption sites. Hypoxia promoted Pg.LPS-stimulated osteoclastogenesis of BMMs and bone resorption by the NFATc1 pathway. Increased HIF-1α in severe periodontitis are associated with external root resorption by the NFATc1 pathway.

Osteoporosis is a common metabolic bone disorder in the elderly population. The accumulation of bone microdamage is a critical factor of osteoporotic fracture. Neuropeptide Y (NPY) has been reported to regulated bone metabolism through Y1 receptor (Y1R). In this study the effects and mechanisms of Y1R antagonist on prevention for osteoporosis were characterized. In the clinical experiment, compared with osteoarthritis (OA), osteoporosis (OP) showed significant osteoporotic bone microstructure and accumulation of bone microdamage. NPY and Y1R immunoreactivity in bone were stronger in OP group, and were both correlated with bone volume fraction (BV/TV). In vivo experiment, Y1R antagonist significantly improved osteoporotic microstructure in the ovariectomized (OVX) rats. And Y1R antagonist promoted RUNX2, OPG and inhibit RANKL, MMP9 in bone marrow. In vitro cell culture experiment, NPY inhibited osteogenesis, elevated RANKL/OPG ratio and downregulated the expression of cAMP, p-PKAs and p-CREB in BMSCs, treated with Y1R antagonist or 8-Bromo-cAMP could inhibit the effects of NPY. Together, Y1R antagonist improved the bone microstructure and reduced bone microdamage in OVX rats. NPY-Y1R could inhibit osteoblast differentiation of BMSCs via cAMP/PKA/CREB pathway. Our findings highlight the regulation of NPY-Y1R in bone metabolism as a potential therapy strategy for the prevention of osteoporosis and osteoporotic fracture.

Whether graphene and graphene oxide (GO) would affect the activities of bacteria has been under debate. Nevertheless, how graphene derivatives with biocompatible coatings interact with microorganisms and the underlying mechanisms are important issues for nanobiotechnology, and remain to be further explored. Herein, three new types of nano-GOs functionalized with polyethylene glycol (nGO-PEGs) were synthesized by varying the PEGylation degree, and their effects on Escherichia coli ( E. coli ) were carefully investigated. Interestingly, nGO-PEG (1:1), the one with relatively lower PEGylation degree, could significantly stimulate bacterial growth, whereas as-made GO and the other two nGO-PEGs showed no effect. Further analysis revealed that nGO-PEG (1:1) treatment significantly accelerated FtsZ-ring assembly, shortening Phase 1 in the bacterial cell cycle. Both DNA synthesis and extracellular polymeric substance (EPS) secretion were also dramatically increased. This unique phenomenon suggests promising potentials in microbial engineering as well as in clinical detection of bacterial pathogens. As a proof-of-concept, nGO-PEG (1:1) treatment could remarkably enhance (up to 6-fold) recombinant protein production in engineered bacteria cells. To our best knowledge, this is the first demonstration of functionalized GO as a novel, positive regulator in microbial engineering. Moreover, our work highlights the critical role of surface chemistry in modulating the interactions between nanomaterials and microorganisms.

Background Multidrug-resistant (MDR) Klebsiella pneumoniae infections, from pancreatic infections to bloodstream infections, influence the mortality of patients with acute pancreatitis (AP) on the condition of limited antibiotic choices. The aim of this study was to investigate the predictor of mortality among AP patients complicated with MDR-K. pneumoniae infections. Methods Seventy-one AP patients who occurred MDR-K. pneumoniae infections from August 1st, 2016 to August 1st, 2020 were enrolled. MDR-K. pneumoniae was defined as the K. pneumoniae strain non-susceptible to at least one agent in three or more antimicrobial categories. MDR-K. pneumoniae isolates were confirmed by Vitek-2 system. Antibiotic susceptibility test was carried out using a micro broth dilution method. Clinical characteristics and drug-resistance rates were retrospectively reviewed, and the predictors of mortality were evaluated by univariate and multivariate analyses. Results The mortality rate of AP patients complicated with MDR-K. pneumoniae infections reached 46.5% (33 of 71), and pancreas (n = 53) was the most common site of MDR-K pneumoniae strains. The drug resistance rates of MDR-K. pneumoniae were high to 11 of 12 common antibiotics (more than 50.0%) except of tigecycline (23.9%). The predictor independently associated with mortality was septic shock (hazard ratio 2.959, 95% confidence intervals 1.396 – 6.272, P = 0.005). Conclusions More attention should be paid for pancreatic MDR-K. pneumoniae infections among AP patients The predictor for mortality of AP patients complicated with MDR-K. pneumoniae infection is septic shock. Therefore, further clinical investigations should focus on areas against septic shock.

Green tides caused by the unusual accumulation of high floating Ulva prolifera have occurred regularly in the Yellow Sea since 2007. The primary source of the Yellow Sea green tides is the attached algae on the Pyropia aquaculture rafts in the Subei Shoal. Ulva prolifera and Blidingia (Italic) sp. are the main species observed on Pyropia aquaculture rafts in the Subei Shoal. We found that U. prolifera has strong buoyancy and a rapid growth rate, which may explain why it is the dominant species of green tides that occur in the China's sea area of the Yellow Sea. The growth rate of floating U. prolifera was about 20%–31% d–1, which was much higher than Blidingia (Italic) sp. There were about 1.7 × 104 t of attached algae on the Pyropia aquaculture rafts in May 2012. We found that 39% of attached algae could float when the tide rose in the Subei Shoal, and U. prolifera accounted for 63% of the floating algae. Our analysis estimated that about 4 000 t of attached U. prolifera floated into the surrounding waters of the Subei Shoal during the recycling period of aquaculture rafts. These results suggest that the initial floating biomass of large-scale green tides in the Yellow Sea is determined by the U. prolifera biomass attached to Pyropia aquaculture rafts, further impacting the scale of the green tide.

Astaxanthin (AX) is a red-colored xanthophyll carotenoid with potent antioxidant, anti-inflammatory, and neuroprotective properties. However, the underlying in vivo mechanism by which AX protects the brain from oxidative stress remains unclear. In this study, we investigated the protective effect of AX on brain oxidative damage in a d-galactose-induced rat model of aging. We also explored its possible mechanism of action by analyzing the resulting serum metabolic profiles. Our results showed that AX significantly increased the activities of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) by 26%, 30%, and 53%, respectively. AX also significantly increased the mitochondrial membrane potential by 18% when compared with the model group. Additionally, treatment with AX (15 mg kg-1) increased the activities of respiratory chain complexes I and IV by 50.17% and 122.87%, respectively. Furthermore, AX also improved age-related morphological changes in the cerebral cortex and hippocampus. Significant differences in serum metabolic profiles were observed between the d-galactose and AX treatment groups. AX corrected amino acid metabolic problems by increasing the levels of N-acetyl-l-leucine, N-acetyl-l-tyrosine, and methionine sulfoxide to protect nerve cells. This also allowed AX to regulate the pentose phosphate pathway by acting on ergotoxine, d-xylose-5-phosphoric, and thiamine, to against oxidative stress and apoptosis. Moreover, AX reduced the levels of both hyodeoxycholic acid and chenodeoxycholic acid though the primary bile acid biosynthesis pathway, resulting in improved brain mitochondrial dysfunction. In conclusion, AX likely enhances the brain's antioxidant defenses through these potential metabolic means, enabling the brain to resist mitochondrial dysfunction, improve neuronal damage, and protect the electron transmission of mitochondrial respiratory chain, thus preventing brain aging.

Rosmarinic acid (RA) has a wide range of biological effects, including the antioxidation and antiaging. However, the detailed mechanisms remain unclear but highly attractive. Herein, RA promoted lifespan and motoricity in a dose-dependent manner, and reduced fat store without threatening fertility in Caenorhabditis elegans. In term of antioxidant efficacy, catalase activity, glutathione peroxidas activity, reduced glutathione content, and reduced glutathione/oxidized glutathione ratio were enhanced. And malondialdehyde content was diminished significantly. Moreover, RA increased survival under acute oxidative and thermal stress, and suppressed intestinal lipofuscin accumulation. So the improvement of lifespan mediated by RA could be related with its strong antioxidant properties. Furthermore, RA was absorbed by worms. Further research in pursuit of the mechanism showed that longevity induced by RA was involved with the genes sod-3, sod-5, ctl-1, daf-16, ins-18, skn-1, and sek-1, but was independent of subcellular localization of DAF-16. These findings indicated that RA had a potential for promoting healthy lifespan.

Aims Sphingosine-1-phosphate receptor 2 (S1PR2) is a G-protein-coupled receptor that regulates sphingosine-1-phosphate-triggered cellular response. However, the role of S1PR2 in diabetes-induced glomerular endothelial cell dysfunction remains unclear. This study aims to investigate the effect of S1PR2 blockade on the morphology and function of mitochondria in human renal glomerular endothelial cells (HRGECs). Methods HRGECs were pretreated with a S1PR2 antagonist (JTE-013) or a Rho-associated coiled coil-containing protein kinase 1 (ROCK1) inhibitor (Y27632) for 30 min and then cultured with normal glucose (5.5 mM) or high glucose (30 mM) for 72 h. The protein expression levels of RhoA, ROCK1, and Dynmin-related protein-1(Drp1) were evaluated by immunoblotting; mitochondrial morphology was observed by electron microscopy; intracellular levels of ATP, ROS, and Ca2+ were measured by ATPlite, DCF-DA, and Rhod-2 AM assays, respectively. Additionally, the permeability, apoptosis, and migration of cells were determined to evaluate the effects of S1PR2 and ROCK1 inhibition on high glucose-induced endothelial dysfunction. Results High glucose induced mitochondrial fission and dysfunction, indicated by increased mitochondrial fragmentation, ROS generation, and calcium overload but decreased ATP production. High glucose also induced endothelial cell dysfunction, indicated by increased permeability and apoptosis but decreased migration. However, inhibition of either S1PR2 or ROCK1 almost completely blocked these high glucose-mediated cellular responses. Furthermore, inhibiting S1PR2 resulted in the deceased expression of RhoA, ROCK1, and Drp1 while inhibiting ROCK1 led to the downregulated expression of Drp1. Conclusions S1PR2 antagonist modulates the morphology and function of mitochondria in HRGECs via the positive regulation of the RhoA/ROCK1/Drp1 signaling pathway, suggesting that the S1PR2/ROCK1 pathway may play a crucial role in high glucose milieu. Electronic supplementary material The online version of this article (10.1186/s12882-019-1323-0) contains supplementary material, which is available to authorized users.

The impact of the type of emulsifier used to formulate excipient emulsions on the degradation (D*) and bioaccessibility (B*) of β-carotene in spinach was investigated using a simulated gastrointestinal tract (GIT). Emulsions stabilized by sodium caseinate (SC) were more prone to droplet aggregation than those stabilized by either Tween 20 or octenyl succinic anhydride (OSA)-modified starch. The fraction of β-carotene available for absorption (D* × B*) was also affected by emulsifier type: SC (12.0%) > Tween 20 (5.0%) ≈ OSA stabilized (2.6%) (p

Large-scale green tides caused by Ulva prolifera, occurred for 12 consecutive years in the Yellow Sea of China. To resolve the abrupt shift in species composition between attached and floating macroalgal assemblages, field experiments were conducted from May to July 2017 to quantify the net buoyancy force and compare the floating potential of the common green macroalgae from the red algal seaweed Pyropia yezoensis rafts. At the same time, U. prolifera from different sampling locations were tested to study variable buoyancy of this species and the associated influencing factors. Our results illustrated a stronger positive buoyant force and a proportionally greater buoyancy capacity of U. prolifera, compared to the other co-occurring species. Buoyancy is a dynamic trait and is closely correlated with light intensity, morphology and physiological status. The positive buoyancy of U. prolifera is an important factor that helps explain its predominance in the Yellow Sea's large-scale green tides.

Why do some biological systems and communities persist while others fail? Robustness, a system's stability, and resilience, the ability to return to a stable state, are key concepts that span multiple disciplines within and outside the biological sciences. Discovering and applying common rules that govern the robustness and resilience of biological systems is a critical step toward creating solutions for species survival in the face of climate change, as well as the for the ever-increasing need for food, health, and energy for human populations. We propose that network theory provides a framework for universal scalable mathematical models to describe robustness and resilience and the relationship between them, and hypothesize that resilience at lower organization levels contribute to robust systems. Insightful models of biological systems can be generated by quantifying the mechanisms of redundancy, diversity, and connectivity of networks, from biochemical processes to ecosystems. These models provide pathways towards understanding how evolvability can both contribute to and result from robustness and resilience under dynamic conditions. We now have an abundance of data from model and non-model systems and the technological and computational advances for studying complex systems. Several conceptual and policy advances will allow the research community to elucidate the rules of robustness and resilience. Conceptually, a common language and data structure that can be applied across levels of biological organization needs to be developed. Policy advances such as cross-disciplinary funding mechanisms, access to affordable computational capacity, and the integration of network theory and computer science within the standard biological science curriculum will provide the needed research environments. This new understanding of biological systems will allow us to derive ever more useful forecasts of biological behaviors and revolutionize the engineering of biological systems that can survive changing environments or disease, navigate the deepest oceans, or sustain life throughout the solar system.

The FtsN protein of Escherichia coli and other proteobacteria is an essential and highly conserved bitopic membrane protein that triggers the inward synthesis of septal peptidoglycan (sPG) during cell division. Previous work has shown that the activation of sPG synthesis by FtsN involves a series of interactions of FtsN with other divisome proteins and the cell wall. Precisely how FtsN achieves this role is unclear, but a recent study has shown that FtsN promotes the relocation of the essential sPG synthase FtsWI from an FtsZ-associated track (where FtsWI is inactive) to an sPG-track (where FtsWI engages in sPG synthesis). Whether FtsN works by displacing FtsWI from the Z-track or capturing/retaining FtsWI on the sPG-track is not known. Here we use single-molecule imaging and genetic manipulation to investigate the organization and dynamics of FtsN at the septum and how they are coupled to sPG synthesis activity. We found that FtsN exhibits a spatial organization and dynamics distinct from those of the FtsZ-ring. Single FtsN molecules move processively as a single population with a speed of ∼ 9 nm s-1, similar to the speed of active FtsWI molecules on the sPG-track, but significantly different from the ∼ 30 nm s-1 speed of inactive FtsWI molecules on the FtsZ-track. Furthermore, the processive movement of FtsN is independent of FtsZ’s treadmilling dynamics but driven exclusively by active sPG synthesis. Importantly, only the essential domain of FtsN, a three-helix bundle in the periplasm, is required to maintain the processive complex containing both FtsWI and FtsN on the sPG-track. We conclude that FtsN activates sPG synthesis by forming a processive synthesis complex with FtsWI exclusively on the sPG-track. These findings favor a model in which FtsN captures or retains FtsWI on the sPG-track rather than one in which FtsN actively displaces FtsWI from the Z-track.

Social dominance is a ubiquitous phenomenon among grouped animals and human-being. To date, individual attributes leading it to win in a contest remain elusive. Here, we report that intestinal microbiota discriminated dominants from subordinates. When dysbiosis was induced, rats were predisposed to a subordinate state, while microbiota transplantation can reclaim their dominance. The winning hosts were characterized by core microbes, a majority of which were associated with butyrate production, and sole colonization of Clostridium butyricum was sufficient to restore dominance. Regarding epigenetic aspects, a histone deacetylase, HDAC2, was found to be responsive to varying microbial status, as well as mediate the ensuing competition outcome, however, only in a restricted cell type of medial prefrontal cortex (mPFC). Furthermore, HDAC2 acted by epigenetically modulating synaptic activity, which accounted for social dominance. Together, these findings uncover a new link of commensals with host dominance, providing insight with microbiota-epigenetic mechanisms underlying dominance determination.

BackgroundBacterial proliferation on the endosseous implants surface presents a new threat to the using of the bone implants. Unfortunately, there is no effective constructed antibacterial coating which is bacterial anti-adhesion substrate-independent or have long-term biofilm inhibition functions.MethodsDrug release effect was tested in Chymotrypsin (CMS) solution andS. aureus. We used bacterial inhibition rate assays and protein leakage experiment to analyze the in vitro antibacterial effect of (Montmorillonite/Poly-l-lysine-Chlorhexidine)10[(MMT/PLL-CHX)10] multilayer film. We used the CCK-8 assay to analyze the effect of (MMT/PLL-CHX)10multilayer films on the growth and proliferation of rat osteoblasts. Rat orthopaedic implant-related infections model was constructed to test the antimicrobial activity effect of (MMT/PLL-CHX)10multilayer films in vivo.ResultsIn this study, the (MMT/PLL-CHX)10multilayer films structure were progressively degraded and showed well concentration-dependent degradation characteristics following incubation withStaphylococcus aureusand CMS solution. Bacterial inhibition rate assays and protein leakage experiment showed high levels of bactericidal activity. While the CCK-8 analysis proved that the (MMT/PLL-CHX)10multilayer films possess perfect biocompatibility. It is somewhat encouraging that in the in vivo antibacterial tests, the K-wires coated with (MMT/PLL-CHX)10multilayer films showed lower infections incidence and inflammation than the unmodified group, and all parameters are close to SHAM group.Conclusion(MMT/PLL-CHX)10multilayer films provides a potential therapeutic method for orthopaedic implant-related infections.

The effect of the amount of ice added (20–60%) on the gel properties and water migration of Nemipterus virgatus surimi gel obtained with two-stage heat treatment was studied. The gel strength and water-holding capability (WHC) of the surimi gel with 30% ice added were significantly higher than those of other treatment groups (p &lt, 0.05). The addition of 30% ice was conducive to the increase of protein β-sheet proportion during heat treatment, exposing more reactive sulfhydryl groups. These promoted the combination of protein-protein through disulfide bonds and hydrophobic-hydrophobic interactions, forming an ordered three-dimensional gel network structure. Meanwhile, the increase in hydrogen bonds promoted the protein-water interaction. Low-field nuclear magnetic resonance analysis showed that more bound water was locked in the gel system, reducing the migration of immobile water to free water and finally showing better gel properties. When the amount of ice added was insufficient (20%), the gel structure lacked the support of immobile water, resulting in deterioration of gel strength. However, excessive addition of ice (&gt, 30%) was not conducive to the combination of protein-protein and protein-water, forming a large and rough gel structure, resulting in the migration of immobile water to free water and ultimately exhibited weak gel properties.

The potential impacts of active packaging on the volatile composition of fruits during preservations largely associated with consumers’ acceptance, yet was barely investigated. In this work, a biopolymer-coated polyethylene active film was developed and its effects on qualities and volatile compositions of fruits with different respiration rates were comprehensively investigated. Underlying reasons for the effect of active packaging on volatile composition change of fruits were elucidated through revealing ternary relationship among the packaging-shaped bacterial community, modified atmosphere and volatiles. Off-flavor production was reduced and more sesquiterpenes (α-cubebene, copaene, β-caryophyllene, α-caryophyllene, d-amorphene) were reserved for longan packaged with active film, due to its antimicrobial and moisture absorption ability, as leading contributors to the selective inhibition on spoilage bacteria genera including Zymobacter, Gluconobacter and Pantoea. Whereas volatile profile of strawberry with high respiration rate was more actively affected by the modified atmosphere induced by packaging, instead of the bacterial community, where hypoxia (

Background Hypoxic–ischemic encephalopathy (HIE) is a severe anoxic brain injury that leads to premature mortality or long-term disabilities in infants. Neuroinflammation is a vital contributor to the pathogenic cascade post-HIE and a mediator to secondary neuronal death. As a plasma membrane G-protein-coupled receptor, GPR39, exhibits anti-inflammatory activity in several diseases. This study aimed to explore the neuroprotective function of GPR39 through inhibition of inflammation post-hypoxic–ischemic (HI) injury and to elaborate the contribution of sirtuin 1(SIRT1)/peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α)/nuclear factor, erythroid 2 like 2(Nrf2) in G-protein-coupled receptor 39 (GPR39)-mediated protection. Methods A total of 206 10-day-old Sprague Dawley rat pups were subjected to HIE or sham surgery. TC-G 1008 was administered intranasally at 1 h, 25 h, 49 h, and 73 h post-HIE induction. SIRT1 inhibitor EX527, GPR39 CRISPR, and PGC-1α CRISPR were administered to elucidate the underlying mechanisms. Brain infarct area, short-term and long-term neurobehavioral tests, Nissl staining, western blot, and immunofluorescence staining were performed post-HIE. Results The expression of GPR39 and pathway-related proteins, SIRT1, PGC-1α and Nrf2 were increased in a time-dependent manner, peaking at 24 h or 48-h post-HIE. Intranasal administration of TC-G 1008 reduced the percent infarcted area and improved short-term and long-term neurological deficits. Moreover, TC-G 1008 treatment significantly increased the expression of SIRT1, PGC-1α and Nrf2, but downregulated the expressions of IL-6, IL-1β, and TNF-α. GPR39 CRISPR EX527 and PGC-1α CRISPR abolished GPR39’s neuroprotective effects post-HIE. Conclusions TC-G 1008 attenuated neuroinflammation in part via the SIRT1/PGC-1α/Nrf2 pathway in a neonatal rat model of HIE. TC-G 1008 may be a novel therapeutic target for treatment post-neonatal HIE injury.

Nitrite stress is a major environmental factor that limits aquatic animal growth, reproduction and survival. Even so, some shrimp can withstand somewhat high concentrations of nitrite environment as our previous studies indicated. Therefore, we hypothesized that these shrimps might have specific adaptive strategies to adapt to high concentrations of nitrite environment. To identify the genes and pathways involved in the regulation of nitrite tolerance, we performed comparative transcriptomic analysis in the Litopenaeus vannamei nitrite-tolerant (NT) and nitrite-sensitive (NS) families, and untreated shrimps were used as the control group. After 24 h of nitrite exposure (NaNO2, 112.5 mg/L), a total of 1521 and 868 differentially expressed genes (DEGs) were obtained from NT compared with NS and control group, respectively. Functional enrichment analysis revealed that most of these DEGs were involved in immune defense, energy metabolism processes and endoplasmic reticulum (ER) stress. Nitrite stress significantly enhanced energy metabolism in NT by activating the expression of genes encoding key enzymes in oxidative phosphorylation (OXPHOS) pathway and tricarboxylic acid (TCA) cycle. Furthermore, some DEGs involved in innate immunity- related genes and pathways, and ER stress responses were highly expressed in NT. Therefore, we speculate that accelerated energy metabolism, higher expression of immunity and ER related genes might be the important adaptive strategies for NT in relative to NS under nitrite stress. These results will provide new sights on the potential tolerant molecular mechanisms and the breeding of new varieties of nitrite tolerant L. vannamei, with possible implications for other aquatic animals.

Background Germinal matrix hemorrhage (GMH) is defined by the rupture of immature blood vessels in the germinal matrix, where subsequent hemorrhage enters the subependymal zone and the cerebral lateral ventricles. The consequent blood clot has been identified as the causative factor of secondary brain injury, which triggers a series of complex parallel and sequential harmful mechanisms, including neuroinflammation. The orphan G-protein-coupled receptor 40 (GPR40), a free fatty acid (FFA) receptor 1, has been shown to exert anti-inflammatory effects when activated and improved outcomes in animal models of stroke. We aimed to investigate the anti-inflammatory effects of GPR40 and its underlying mechanisms after GMH. Methods GMH model was induced in 7-day-old rat pups by an intraparenchymal injection of bacterial collagenase. GPR40 agonist, GW9508, was administered intranasally 1 h, 25 h, and 49 h after GMH induction. CRISPR targeting GPR40, PAK4, and KDM6B were administered through intracerebroventricular injection 48 h before GMH induction. Neurologic scores, microglia polarization, and brain morphology were evaluated by negative geotaxis, right reflex, rotarod test, foot fault test, Morris water maze, immunofluorescence staining, Western blots, and nissl staining respectfully. Results The results demonstrated that GW9508 improved neurological and morphological outcomes after GMH in the short (24 h, 48 h, 72h) and long-term (days 21–27). However, the neuroprotective effects of treatment were abolished by GW1100, a selective GPR40 antagonist. GW9508 treatment increased populations of M2 microglia and decreased M1 microglia in periventricular areas 24 h after GMH induction. GW9508 upregulated the phosphorylation of PAK4, CREB, and protein level of KDM6B, CD206, IL-10, which was also met with the downregulation of inflammatory markers IL-1β and TNF-α. The mechanism study demonstrated that the knockdown of GPR40, PAK4, and KDM6B reversed the neuroprotective effects brought on by GW9508. This evidence suggests that GPR40/PAK4/CREB/KDM6B signaling pathway in microglia plays a role in the attenuation of neuroinflammation after GMH. Conclusions In conclusion, the present study demonstrates that the activation of GPR40 attenuated GMH-induced neuroinflammation through the activation of the PAK4/CREB/KDM6B signaling pathway, and M2 microglia may be a major mediator of this effect. Thus, GPR40 may serve as a potential target in the reduction of the inflammatory response following GMH, thereby improving neurological outcomes in the short- and long-term.

In this study, the preventive effect of tangeretin (TAN), a natural flavonoid derivative from citrus fruits, on the dextran sulfate sodium (DSS)-induced colitis in mice was evaluated. Our results showed that dietary TAN (0.04% and 0.08% w/w in the diet) significantly reduced the severity of colitis caused by DSS treatment in mice, evidenced by the increased colon length, the reduced disease activity index, and the attenuated colonic tissue damages. Moreover, dietary TAN inhibited the inflammatory response via down-regulating the overexpression of colonic inflammatory cytokines. Immunohistochemical analysis revealed that the intestinal barrier function was restored by TAN through enhancing claudin-1 and ZO-1 expressions. Additionally, dietary TAN modulated gut microbiota in colitic mice via enhancing gut microbiota diversity, ascending the level of beneficial bacteria, e.g., Lachnospiraceae and Lactobacillaceae, and descending the level of harmful bacteria, e.g., Enterobacteriaceae and Alistipes. Besides, dietary TAN promoted short-chain fatty acids production in DSS-treated mice. Altogether, these findings provided scientific evidence for the rational utilization of TAN as a preventive agent against colonic inflammation and related diseases.

Background Coccidiosis caused by Eimeria stiedae is a widespread and economically significant disease of rabbits. The lack of studies on the life-cycle development and host interactions of E. stiedae at the molecular level has hampered our understanding of its pathogenesis. Methods In this study, we present a comprehensive transcriptome landscape of E. stiedae to illustrate its dynamic development from unsporulated oocysts to sporulated oocysts, merozoites, and gametocytes, and to identify genes related to parasite-host interactions during parasitism using combined PacBio single-molecule real-time and Illumina RNA sequencing followed by bioinformatics analysis and qRT-PCR validation. Results In total, 12,582 non-redundant full-length transcripts were generated with an average length of 1808 bp from the life-cycle stages of E. stiedae. Pairwise comparisons between stages revealed 8775 differentially expressed genes (DEGs) showing highly significant description changes, which compiled a snapshot of the mechanisms underlining asexual and sexual biology of E. stiedae including oocyst sporulation between unsporulated and sporulated oocysts; merozoite replication between sporulated oocysts and merozoites; and gametophyte development and gamete generation between merozoites and gametocytes. Further, 248 DEGs were grouped into nine series clusters and five groups by expression patterns, and showed that parasite–host interaction-related genes predominated in merozoites and gametocytes and were mostly involved in steroid biosynthesis and lipid metabolism and carboxylic acid. Additionally, co-expression analyses identified genes associated with development and host invasion in unsporulated and sporulated oocysts and immune interactions during gametocyte parasitism. Conclusions This is the first study, to our knowledge, to use the global transcriptome profiles to decipher molecular changes across the E. stiedae life cycle, and these results not only provide important information for the molecular characterization of E. stiedae, but also offer valuable resources to study other apicomplexan parasites with veterinary and public significance. Graphical Abstract

Spotted fever group rickettsioses (SFRs) are devastating human infections. Vascular endothelial cells (ECs) are the primary targets of rickettsial infection. Edema resulting from EC barrier dysfunction occurs in the brain and lungs in most cases of lethal SFR, but the underlying mechanisms remain unclear. The aim of the study was to explore the potential role of Rickettsia-infected, EC-derived exosomes (Exos) during infection. Using size exclusion chromatography (SEC), we purified Exos from conditioned, filtered, bacterium-free media collected from Rickettsia parkeri-infected human umbilical vein ECs (HUVECs) (R-ECExos) and plasma of Rickettsia australis- or R. parkeri-infected mice (R-plsExos). We observed that rickettsial infection increased the release of heterogeneous plsExos, but endothelial exosomal size, morphology, and production were not significantly altered following infection. Compared to normal plsExos and ECExos, both R-plsExos and R-ECExos induced dysfunction of recipient normal brain microvascular ECs (BMECs). The effect of R-plsExos on mouse recipient BMEC barrier function is dose dependent. The effect of R-ECExos on human recipient BMEC barrier function is dependent on the exosomal RNA cargo. Next-generation sequencing analysis and stem-loop quantitative reverse transcription-PCR (RT-qPCR) validation revealed that rickettsial infection triggered the selective enrichment of endothelial exosomal mir-23a and mir-30b, which potentially target the endothelial barrier. To our knowledge, this is the first report on the functional role of extracellular vesicles following infection by obligately intracellular bacteria.IMPORTANCE Spotted fever group rickettsioses are devastating human infections. Vascular endothelial cells are the primary targets of infection. Edema resulting from endothelial barrier dysfunction occurs in the brain and lungs in most cases of lethal rickettsioses, but the underlying mechanisms remain unclear. The aim of the study was to explore the potential role of Rickettsia-infected, endothelial cell-derived exosomes during infection. We observed that rickettsial infection increased the release of heterogeneous plasma Exos, but endothelial exosomal size, morphology, and production were not significantly altered following infection. Rickettsia-infected, endothelial cell-derived exosomes induced dysfunction of human recipient normal brain microvascular endothelial cells. The effect is dependent on the exosomal RNA cargo. Next-generation sequencing analysis revealed that rickettsial infection triggered the selective enrichment of endothelial exosomal mir-23a and mir-30b, which potentially target the endothelial barrier. To our knowledge, this is the first report on the functional role of extracellular vesicles following infection by obligately intracellular bacteria.

Strawberry (Fragaria × ananassa Duch.) can be easily propagated with daughter plants or through crown division, which are developed from the axillary bud at the axils of leaves. This study was conducted to investigate the effects of different cytokinins, auxins, and their combinations on the axillary bud growth in strawberry. Four cytokinins (6-benzyladenine, kinetin, zeatin, and thidiazuron (TDZ)) and three auxins (indole-3-acetic acid, indole-3-butyric acid, and naphthaleneacetic acid) at a concentration of 50 mg·L−1 were sprayed on the leaves three times in 10-day intervals. The expression levels of cytokinin, auxin, and meristem-related genes in the crowns were also investigated. The results showed that TDZ was the most effective hormone for the axillary bud growth, and also promoted plant growth. However, chlorophyll, soluble sugar, and starch contents in the leaves were lower after TDZ. TDZ activated the cytokinin signal transduction pathway, while repressing the auxin synthesis genes. Several meristem-related transcription factors were upregulated, which might be essential for the growth of the axillary buds. These results suggested that TDZ can improve the cultivation of strawberry, while further research is needed to explain the effect on phytochemistry.

Background Xylitol, a white or transparent polyol or sugar alcohol, is digestible by colonic microorganisms and promotes the proliferation of beneficial bacteria and the production of short-chain fatty acids (SCFAs), but the mechanism underlying these effects remains unknown. We studied mice fed with 0%, 2% (2.17 g/kg/day), or 5% (5.42 g/kg/day) (weight/weight) xylitol in their chow for 3 months. In addition to the in vivo digestion experiments in mice, 3% (weight/volume) (0.27 g/kg/day for a human being) xylitol was added to a colon simulation system (CDMN) for 7 days. We performed 16S rRNA sequencing, beneficial metabolism biomarker quantification, metabolome, and metatranscriptome analyses to investigate the prebiotic mechanism of xylitol. The representative bacteria related to xylitol digestion were selected for single cultivation and co-culture of two and three bacteria to explore the microbial digestion and utilization of xylitol in media with glucose, xylitol, mixed carbon sources, or no-carbon sources. Besides, the mechanisms underlying the shift in the microbial composition and SCFAs were explored in molecular contexts. Results In both in vivo and in vitro experiments, we found that xylitol did not significantly influence the structure of the gut microbiome. However, it increased all SCFAs, especially propionate in the lumen and butyrate in the mucosa, with a shift in its corresponding bacteria in vitro. Cross-feeding, a relationship in which one organism consumes metabolites excreted by the other, was observed among Lactobacillus reuteri, Bacteroides fragilis, and Escherichia coli in the utilization of xylitol. At the molecular level, we revealed that xylitol dehydrogenase (EC 1.1.1.14), xylulokinase (EC 2.7.1.17), and xylulose phosphate isomerase (EC 5.1.3.1) were key enzymes in xylitol metabolism and were present in Bacteroides and Lachnospiraceae. Therefore, they are considered keystone bacteria in xylitol digestion. Also, xylitol affected the metabolic pathway of propionate, significantly promoting the transcription of phosphate acetyltransferase (EC 2.3.1.8) in Bifidobacterium and increasing the production of propionate. Conclusions Our results revealed that those key enzymes for xylitol digestion from different bacteria can together support the growth of micro-ecology, but they also enhanced the concentration of propionate, which lowered pH to restrict relative amounts of Escherichia and Staphylococcus. Based on the cross-feeding and competition among those bacteria, xylitol can dynamically balance proportions of the gut microbiome to promote enzymes related to xylitol metabolism and SCFAs.

Background Scabies is caused by burrowing of the mite Sarcoptes scabiei into the stratum corneum. Currently, diagnosis via routine skin scraping is very difficult, and information on the allergenic identification of S. scabiei remains limited. Methods We performed comparative analysis of the serological diagnostic potential of recombinant S. scabiei chitinase-like protein-5 (rSsCLP5) and recombinant S. scabiei chitinase-like protein-12 (rSsCLP12) by measuring the levels of serum-specific IgG and IgE antibodies (Abs) as diagnostic markers. In addition, the allergenic characteristics of rSsCLP5 and rSsCLP12 were evaluated using IgE-binding experiments and skin tests. Results The IgE Abs-based indirect enzyme-linked immunosorbent assay (ELISA) methods showed high sensitivity and specificity: the rSsCLP5-based assay had 93.5% sensitivity and 94.4% specificity; the rSsCLP12-based assay had 100% sensitivity and 98.1% specificity. The specific IgE Abs in infested mouse sera could bind rSsCLP5 and rSsCLP12. In skin tests, rabbits in the rSsCLP5 and rSsCLP12 groups and positive control (histamine) groups exhibited allergic reactions. Most test sites in the rSsCLP12 group had edema, bleeding spots, and even ulcers or scabs, but such allergy symptoms were rare in the rSsCLP5 group. Moreover, the allergic history rabbit group had more severe allergic reactions and lower levels of IgE Abs compared to the healthy rabbit group in the same protein group. Conclusions These findings validate the use of IgE Abs to rSsCLP5 and rSsCLP12 as potentially useful markers for diagnosing scabies. Moreover, both rSsCLP5 and rSsCLP12 have allergenic properties, and the potential allergen rSsCLP12 is a stronger allergen than rSsCLP5. Graphical Abstract

Spotted fever group rickettsioses (SFRs) are devastating human infections. Vascular endothelial cells (ECs) are the primary targets of infection. Edema resulting from EC barrier dysfunction occurs in the brain and lungs in most cases of lethal SFR, but the underlying mechanisms remain unclear. The aim of the study is to explore the potential role ofRickettsia(R)-infected, EC-derived exosomes (Exos) during infection. Using size-exclusion chromatography (SEC), we purified Exos from conditioned, filtered, bacteria-free media collected fromR-infected human umbilical vein ECs (HUVECs) (R-ECExos) and plasma ofR-infected mice (R-plsExos). We observed that rickettsial infection increases the release of heterogeneous plsExos, but endothelial exosomal size, morphology, and production were not significantly altered following infection. Compared to normal plsExos and ECExos, bothR-plsExos andR-ECExos induced dysfunction of recipient normal brain microvascular Ecs (BMECs). The effect ofR-plsExos on mouse recipient BMEC barrier function is dose-dependent. The effect ofR-ECExos on human recipient BMEC barrier function is dependent on exosomal RNA cargo. Next-generation sequencing analysis and stem-loop quantitative reverse transcription PCR (RT-qPCR) validation revealed thatRinfection triggered the selective enrichment of endothelial exosomal mir-23a and mir-30b, which target the endothelial barrier. To our knowledge, this is the first report on the functional role of extracellular vesicles following infection by obligately intracellular bacteria.ImportanceSpotted fever group rickettsioses are devastating human infections. Vascular endothelial cells are the primary targets of infection. Edema resulting from endothelial barrier dysfunction occurs in the brain and lungs in most cases of lethal rickettsioses, but the underlying mechanisms remain unclear. The aim of the study is to explore the potential role ofRickettsia-infected, endothelial cell-derived exosomes during infection. We observed that rickettsial infection increases the release of heterogeneous plasma Exos, but endothelial exosomal size, morphology, and production were not significantly altered following infection.Rickettsia-infected, endothelial cell-derived exosomes induced dysfunction of recipient normal brain microvascular endothelial cells. The effect is dependent on exosomal RNA cargo. Next-generation sequencing analysis revealed that rickettsial infection triggered the selective enrichment of endothelial exosomal mir-23a and mir-30b, which target the endothelial barrier. To our knowledge, this is the first report on the functional role of extracellular vesicles following infection by obligately intracellular bacteria.

Coagulopathy is associated with both inflammation and infection, including infection with the novel SARS-CoV-2 (COVID-19). Endothelial cells (ECs) fine tune hemostasis via cAMP-mediated secretion of von Willebrand factor (vWF), which promote the process of clot formation. Theexchangeprotein directlyactivated bycAMP (EPAC) is a ubiquitously expressed intracellular cAMP receptor that plays a key role in stabilizing ECs and suppressing inflammation. To assess whether EPAC could regulate vWF release during inflammation, we utilized ourEPAC1-null mouse model and revealed an increased secretion of vWF in endotoxemic mice in the absence of the EPAC1 gene. Pharmacological inhibition of EPAC1in vitromimicked theEPAC1−/− phenotype. EPAC1 regulated TNFα-triggered vWF secretion from human umbilical vein endothelial cells (HUVECs) in a phosphoinositide 3-kinases (PI3K)/endothelial nitric oxide synthase (eNOS)-dependent manner. Furthermore, EPAC1 activation reduced inflammation-triggered vWF release, bothin vivoandin vitro. Our data delineate a novel regulatory role of EPAC1 in vWF secretion and shed light on potential development of new strategies to controlling thrombosis during inflammation.Key PointPI3K/eNOS pathway-mediated, inflammation-triggered vWF secretion is the target of the pharmacological manipulation of the cAMP-EPAC system.

Stroke, a lethal neurological disease, accounts for a grave economic burden on society. Despite extensive basic and clinical studies on stroke prevention, a precise effective treatment approach for stroke at this stage remains unavailable. The majority of our body's gut microbiota plays a vital role in food digestion, immune regulation, and nervous system development, which is highly associated with the development of some diseases. Multiple clinical studies have documented variation in the composition of gut microbiota between stroke patients and healthy counterparts. Moreover, the intervention of intestinal symbiotic microorganisms via several mechanisms plays an active role in stroke prognosis. In the prevention and treatment of stroke, the gut microbiota gives off a seductive glow, this is a promising therapeutic target. This paper summarizes the current knowledge of stroke and gut microbiota, and systematically describes the possible mechanisms of interaction between stroke and gut microbiota, the relationship between stroke-related risk factors and gut microbiota, and the treatment of gut flora using microorganisms. Thus, it could valuably elucidate the correlation of gut microbiota with stroke incidence, providing stroke researchers with a new strategy for stroke prevention and treatment by regulating gut microbiota.

Massive floating green macroalgae have formed harmful green tides in the Yellow Sea since 2007. To study the early development and the associated environmental factors for the green tide, a field survey was carried out in the Subei Shoal, southwestern Yellow Sea. Multiple species were identified in both floating green macroalgae and micro-propagules , while their abundances showed distinct spatial variations. The floating macroalgal biomass was widespread in the northern Subei Shoal and most abundant at 34°N. Ulva prolifera dominated (91.2% in average) the floating macroalgae, and the majority (88.5%) of U. prolifera was the ‘floating type’. In comparison, the micro-propagules were most abundant around the aquaculture rafts, and decreased significantly with the distance to the rafts. The dominant species of micro-propagules was U. linza (48.5%), followed by U. prolifera (35.1%). Their distinct distribution patterns and species diversity suggested little direct contribution of micro-propagules for the floating macroalgae. The spatial variation of the floating macroalgae was probably a combined result from the biomass source and environmental factors, while the abundance of micro-propagules was closely associated with the rafts. A positive correlation between the floating macroalgae and DO was observed and suggested active photosynthesis of the initial biomass in Subei Shoal. This study revealed specific distributional pattern and relationships among the floating macroalgae, micro-propagules and the environmental factors in the source region, which helps understanding the early blooming dynamics of the green tides in Yellow Sea.

HU (Histone-like protein from Escherichia coli strain U93) is the most conserved nucleoid-associated protein in eubacteria, but how it impacts global chromosome organization is poorly understood. Using single-molecule tracking, we demonstrate that HU exhibits nonspecific, weak, and transitory interactions with the chromosomal DNA. These interactions are largely mediated by three conserved, surface-exposed lysine residues (triK), which were previously shown to be responsible for nonspecific binding to DNA. The loss of these weak, transitory interactions in a HUα(triKA) mutant results in an over-condensed and mis-segregated nucleoid. Mutating a conserved proline residue (P63A) in the HUα subunit, deleting the HUβ subunit, or deleting nucleoid-associated naRNAs, each previously implicated in HU's high-affinity binding to kinked or cruciform DNA, leads to less dramatically altered interacting dynamics of HU compared to the HUα(triKA) mutant, but highly expanded nucleoids. Our results suggest HU plays a dual role in maintaining proper nucleoid volume through its differential interactions with chromosomal DNA. On the one hand, HU compacts the nucleoid through specific DNA structure-binding interactions. On the other hand, it decondenses the nucleoid through many nonspecific, weak, and transitory interactions with the bulk chromosome. Such dynamic interactions may contribute to the viscoelastic properties and fluidity of the bacterial nucleoid to facilitate proper chromosome functions.

Eimeria stiedai is an apicomplexan protozoan parasite that invades the liver and bile duct epithelial cells in rabbits and causes severe hepatic coccidiosis, resulting in significant economic losses in the domestic rabbit industry. Hepatic coccidiosis lacks the typical clinical symptoms and there is a lack of effective premortem tools to timely diagnose this disease. Therefore, in the present study we cloned and expressed the two microneme proteins i.e., microneme protein 1 (EsMIC1) and microneme protein 3 (EsMIC3) from E. stiedai and used them as recombinant antigens to develop a serodiagnostic method for an effective diagnosis of hepatic coccidiosis. The cDNAs encoding EsMIC1 and EsMIC3 were cloned and the mRNA expression levels of these two genes at different developmental stages of E. stiedai were determined by quantitative real-time PCR analysis (qRT-PCR). The immunoreactivity of recombinant EsMIC1 (rEsMIC1) and EsMIC3 (rEsMIC3) proteins were detected by Western blotting, and indirect enzyme-linked immunosorbent assays (ELISAs) based on these two recombinant antigens were established to evaluate their serodiagnostic potential. Our results showed that the proteins encoded by the ORFs of EsMIC1 (711 bp) and EsMIC3 (891 bp) were approximately 25.89 and 32.39 kDa in predicted molecular weight, respectively. Both EsMIC1 and EsMIC3 showed the highest mRNA expression levels in the merozoites stage of E. stiedai. Western blotting analysis revealed that both recombinant proteins were recognized by E. stiedai positive sera, and the indirect ELISAs using rEsMIC1 and rEsMIC3 were developed based on their good immunoreactivity, with 100% (48/48) sensitivity and 97.9% (47/48) specificity for rEsMIC1 with 100% (48/48) sensitivity and 100% (48/48) specificity for rEsMIC3, respectively. Moreover, rEsMIC1- and rEsMIC3-based indirect ELISA were able to detect corresponding antibodies in sera at days 6, 8, and 10 post E. stiedai infection, with the highest positive diagnostic rate (62.5% (30/48) for rEsMIC1 and 66.7% (32/48) for rEsMIC3) observed at day 10 post infection. Therefore, both EsMIC1 and EsMIC3 can be used as potential serodiagnostic candidate antigens for hepatic coccidiosis caused by E. stiedai.

Recently, aberrant expression of miR‐876‐5p has been reported to participate in the progression of several human cancers. However, the expression and function of miR‐876‐5p in osteosarcoma (OS) are still unknown. Here, we found that the expression of miR‐876‐5p was significantly down‐regulated in OS tissues compared to para‐cancerous tissues. Clinical association analysis indicated that underexpression of miR‐876‐5p was positively correlated with advanced clinical stage and poor differentiation. More importantly, OS patients with low miR‐876‐5p level had a significant shorter overall survival compared to miR‐876‐5p high‐expressing patients. In addition, gain‐ and loss‐of‐function experiments demonstrated that miR‐876‐5p restoration suppressed whereas miR‐876‐5p knockdown promoted cell proliferation, migration and invasion in both U2OS and MG63 cells. In vivo studies revealed that miR‐876‐5p overexpression inhibited tumour growth of OS in mice. Mechanistically, miR‐876‐5p reduced c‐Met abundance in OS cells and inversely correlated c‐Met expression in OS tissues. Herein, c‐Met was recognized as a direct target of miR‐876‐5p using luciferase reporter assay. Notably, c‐Met restoration rescued miR‐876‐5p attenuated the proliferation, migration and invasion of OS cells. In conclusion, these findings indicate that miR‐876‐5p may be used as a potential therapeutic target and promising biomarker for the diagnosis and prognosis of OS.

This paper investigates the two problems of generalized chaotic synchronization. In one case, the Chen system is treated as the drive system and the controlled Rucklidge system as the response system. In the other case, we choose the Rucklidge system as the drive system and the controlled Chen system as the response system. For each case, a scalar control input and a state transformation are proposed by using the differential geometric approach when a simple condition holds. Under the scalar control input and the state transformation, the trajectory of the response system can track the trajectory of the drive system no matter what initial values of the two systems. The two generalized synchronizations realized in this paper reveal the Rucklidge system and the Chen system are similar in some sense although their system equations are quite different. Finally, several numerical simulations are studied to demonstrate the control schemes given in this paper.

A water-soluble polysaccharide named CYP-1 was isolated from Chinese yam. CYP-1 was characterized as a mannoglucan having a backbone consisting predominately of 1,4-α-linked Glcp branched at O-2, O-3, and O-6 position by t-α-linked Manp with a molecular weight of 2.86 kDa. CYP-1 could inhibit the overproduction of pro-inflammatory cytokines (such as TNF-α and IL-1β) in LPS-induced RAW 264.7 cells and DSS-induced colitis mice. Oral administration of CYP-1 dramatically alleviated colonic pathological damage, suppressed the activation of colonic inflammatory signaling pathways (such as NF-κB and NLRP3 inflammasome), recovered the mRNA expression of junctional proteins (such as ZO-1, claudin-1, occludin, and connexin-43), and modulated the gut microbiota by decreasing the abundances of Alistipes, Helicobacter, and an unidentified Enterobacteriaceae, in DSS-induced colitis mice. Overall, the present study elucidated that a new polysaccharide structure CYP-1 from Chinese yam and its therapeutic potential as a prebiotic for the prevention of inflammatory bowel disease.

A small armed dinoflagellate bloomed in the aquaculture ponds off the coast of Liaodong Bay, Bohai Sea of China, resulting in heavy mortalities of the cultured prawns (Penaeus japonicus) and larvae of Chinese mitten handed crabs (Eriocheir sinensis). The bloom-forming species was successfully isolated, and cellular morphology of the specimen was consequently investigated through light, fluorescent and electron microscopy. The small ((14.4±1.6) μm in length) ellipsoid cells show typical Heterocapsa thecal plate arrangement (Po, cp, 5′, 3a, 7′′, 6c, 5s, 5′′′, 2′′′′). The episome is evidently bigger than the hyposome. One to three spherical pyrenoids are located above or beside the large elongated nucleus. The body scale is characterized by a triangle basal plate with one central upright and nine peripheral spines. Above all, Heterocapsa bohaiensis could be distinguished from other Heterocapsa species by the combination of the cell size, morphology, cellular structure and body scale. Sequence analyses of both ITS and LSU regions reveal the significant genetic divergence between H. bohaiensis and other established species in this genus, further supporting novelty of this species. Noticeably, different sample treatment methods resulted in morphological variation of the apical pore complex (APC) of H. bohaiensis, which needs to be taken into account in future study.

Box jellyfish Chiropsoides buitendijki from the coastal zone along the Andaman Sea, southwestern Thailand are characterized by a box-shaped body with unilateral branched tentacles and lack of interradial furrows. Tentacular banding was first reported in the present study with 1–3–2–3–2–3–2–3–1 patterns (1–major band, 2–thicker minor band and 3–thinner minor band). The DNA sequences of 18 S ribosomal RNA genes indicated that the specimen examined were genetically similar to C. buitendijki that was previously identified from the Nam Bor Bay, Phuket, Thailand, and distinct to the other known taxa in the order Chirodropida. In addition, a significant genetic divergence based on 16S mitochondrial gene was observed within the C. buitendijki samples. This indicates a population genetic differentiation but needs further confirmation.

Background Podocyte apoptosis is important mechanism that leading to proteinuria in Diabetic nephropathy (DN), but the underling mechanisms that cause podocyte apoptosis in DN are not very clear. We have recently demonstrated that RhoA, a small GTPase protein, effectively protected podocyte apoptosis induced by LPS and ADR in vitro. However, the potential role of RhoA in DN is unknown. Methods and results Conditionally immortalized mouse podocyte cells, C57BL/KsJ, db/db diabetic mice, and renal biopsies from patients with DN were used for study. The treatment of podocytes with high glucose (HG) for 48h significantly induced cell apoptosis and decreased RhoA expression and its activity. The expression of RhoA was also decreased in glomerular podocytes of db/db mice and patients with DN. Knockdown of RhoA by siRNA contributed in the apoptosis of podocyte and induced proteinuria in db/db mice. Beyond the increased pro-apoptotic Bax and the decreased anti-apoptotic Bcl-2, RhoA knockdown also inhibited the expression of a nuclear protein of YAP in podocyte. Over expression active form of YAP completely abolished the apoptosis of podocyte induced by RhoA knockdown. Conclusion RhoA plays a critical role in DN probably by mediating the podocyte apoptosis through YAP. RhoA may be a novel molecular target for the treatment of DN.

A novel pyrone derivative (1) bearing two fused five-member rings, together with two new naphthalenone derivatives (2, 3), as well as two known compounds (4, 5) were obtained from the endophytic fungus Fusarium sp. HP-2, which was isolated from "Qi-Nan" agarwood. The structures of the new compounds were elucidated by analysis of 1D and 2D NMR, and by HRESIMS spectra, as well as by comparison with the literature. Bioactivity results indicated that compound 3 showed weak acetylcholinesterase inhibitory activity.

e-Polylysine-loaded chitosan-sodium alginate nanoparticles (e-PL NPs) were synthesized and characterized in terms of particle size distribution, surface morphology, thermal properties and structure, respectively. Their antibacterial activity on Escherichia coli, Bacillus subtilis, Staphylococcus aureus and Micrococcus luteus were studied. The e-PL NPs were well dispersed as spherical particles within the range of 200–500 nm. In vitro release studies showed an initial burst release of e-PL from the nanoparticles followed by a sustained release. The minimum inhibitory concentrations (MIC) of e-PL NPs against four test bacteria were 7.81 μg/mL (E. coli), 31.25 μg/mL (B. subtilis), 15.63 μg/mL (S. aureus) and 38.67 μg/mL (M. luteus), respectively. The bacteriostatic activity of e-PL NPs was three times higher (P