Orally administered selenium-containing α-D-1,6-glucan and α-D-1,6-glucan relief early cognitive deficit in APP/PS1 mice.

Alzheimer's disease (AD) is a complex, progressive and deadly disorder that exhibits various typical pathological characteristics. Till now no effective treatment has been found that can prevent or reverse AD. Here, the effects of 2 months of treatment with α-D-1,6-glucan (CPA) and selenium-containing α-D-1,6-glucan (Se-CPA) on early cognitive dysfunction and neuropathology were explored in the 3-month-old APP/PS1 transgenic mouse. The results of the Morris water maze and open-field test revealed that Se-CPA exerted more significant effects than CPA in improving cognitive function and depressive-like behavior by attenuating the oxidative stress, decreasing serum LPS level, downregulating the inflammation of astrocytes and microglia through inhibiting the activation of NLRP3 inflammasome, mitigating neuronal cells loss and improving synaptic plasticity. Moreover, Se-CPA exerted beneficial effects on reshaping gut microbiome by increasing the microbial α-diversity, enhancing the proportion of beneficial bacteria such as Akkermansia muciniphila and promoting the SCFAs concentration. These findings provide evidence that Se-CPA might be a potentially viable compound for AD prevention.

Long-Term Krill Oil Administration Alleviated Early Mild Cognitive Impairment in APP/PS1 Mice.

SCOPE: Alzheimer's disease is an age-dependent neurodegenerative disorder. Mounting studies focus on the improvement of advanced cognitive impairment by dietary nutrients. Krill oil (KO), a rich source of DHA/EPA and astaxanthin, is effective in improving cognitive function. The study mainly investigates the protective effects of long-term KO administration on early cognitive impairment. METHODS AND RESULTS: Results show that 2 months KO administration (50 and 100 mg kg-1 BW) can dramatically promote learning and memory abilities. Mechanism studies demonstrate that KO reduces amyloid ß concentration by regulating the amyloidogenic pathway, inhibits neuro-inflammation via regulating TLR4-NLRP3 signaling pathway, and prevents neuron injure. KO supplementation also enhances gut barrier integrity, reduces serum lipopolysaccharide leakage, and alters the gut microbiota by reducing Helicobacteraceae, Lactobacillaceae proportion, increasing Dubosiella and Akkermansia relative abundance. Particularly, a significant increase of isovaleric acid, propionic acid, and acetic acid levels is observed after KO supplementation. Correlation analysis shows that short-chain fatty acids (SCFAs), gut microbiota, and cognitive function are strongly correlated. CONCLUSIONS: The results reveal that KO relieves early mild cognitive impairment possibly for its role in mediating the gut microbiome-SCFAs-brain axis. Thus, KO may provide potential intervention strategies to prevent cognitive impairment in the early stages through the microbiota-gut-brain axis.

Saccharina japonica Ethanol Extract Ameliorates Dextran Sulfate Sodium-Induced Colitis via Reshaping Intestinal Microenvironment and Alleviating Inflammatory Response.

Saccharina japonica belongs to brown macro-alga with various potential health benefits; its antioxidant and anti-inflammatory activities indicate the potential to improve inflammatory bowel diseases. Here, the potential anti-colitis effect of Saccharina japonica extract (SJE) was evaluated on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) in C57B/L6 mice. The mice were treated with mesalazine (MES) and various doses of SJE by gavage for 14 days. Results showed that both MES and SJE treatment decreased the disease activity index scores, relieving the short colon. SJE increased the occludin and zonula occludens-1 levels, and the beneficial effects were better than MES. MES and SJE exerted similar effects in decreasing inflammatory cytokines and oxidative stress. Moreover, SJE reshaped the intestinal microbiota by increasing α-diversity and reducing plenty of harmful bacteria. Dietary SJE was significant to relieving the reduction in short-chain fatty acids. The results revealed the protective effect of SJE on colitis and potential mechanisms, which is important for the rational use of SJE in UC prevention.

Cloning and Characterization of Fructose-1,6-Bisphosphate Aldolase from Euphausia superba.

Fructose-1,6-bisphosphate aldolase (EC 4.1.2.13) is a highly conserved enzyme that is involved in glycolysis and gluconeogenesis. In this study, we cloned the fructose-1,6-bisphosphate aldolase gene from Euphausia superba (EsFBA). The full-length cDNA sequence of EsFBA is 1098 bp long and encodes a 365-amino-acid protein. The fructose-1,6-bisphosphate aldolase gene was expressed in Escherichia coli (E. coli). A highly purified protein was obtained using HisTrap HP affinity chromatography and size-exclusion chromatography. The predicted three-dimensional structure of EsFBA showed a 65.66% homology with human aldolase, whereas it had the highest homology (84.38%) with the FBA of Penaeus vannamei. Recombinant EsFBA had the highest activity at 45 °C and pH 7.0 in phosphate buffer. By examining the activity of metal ions and EDTA, we found that the effect of metal ions and EDTA on EsFBA's enzyme activity was not significant, while the presence of borohydride severely reduced the enzymatic activity; thus, EsFBA was confirmed to be a class I aldolase. Furthermore, targeted mutations at positions 34, 147, 188, and 230 confirmed that they are key amino acid residues for EsFBA.

An aptamer and flower-shaped AuPtRh nanoenzyme-based colorimetric biosensor for the detection of profenofos.

In this work, a simple, sensitive and selective colorimetric method was established for the detection of profenofos. Firstly, novel flower-shaped AuPtRh trimetallic nanospheres were synthesized via a simple one-pot method, and had outstanding peroxidase catalytic activity. AuPtRh nanospheres with a great specific surface area were linked with an aptamer via Au-S and Pt-S bonds to specifically recognize profenofos. A graphene oxide grafted stainless-steel mesh (SSM-GO) was prepared to be a carrier and the aptamer-AuPtRh was nonspecifically adsorbed on the surface of SSM-GO, which was to be the capture probe for the detection of profenofos in real samples. They were characterized and confirmed by transmission electron microscopy, atomic force microscopy, etc. Through the investigation of the catalytic performance on the basis of the Michaelis equation, the Vmax of AuPtRh nanospheres was 22.27 × 10-8 M s-1, and Km was 0.6632 mM, which indicated that the affinity of AuPtRh nanospheres was relatively higher than that of horseradish peroxidase and Au NPs. In the presence of profenofos, the aptamer-AuPtRh would specifically combine with profenofos, which would further detach from SSM-GO. Then, it was introduced into the 3,3',5,5'-tetramethylbenzidine/H2O2 (TMB/H2O2) system to form blue oxTMB. The linear range of this colorimetric biosensor was 1-300 ng L-1 and the limit of detection was 0.725 ng L-1. It also had good recovery and anti-interference ability in real samples, which provided a new strategy for the rapid detection of pesticides.

Halophilic bacteria as starter cultures: A new strategy to accelerate fermentation and enhance flavor of shrimp paste.

Retaining the traditional flavor while shortening the fermentation cycle is the current research focus for shrimp paste fermentation technology. The present study investigated the effect of combined use of halophilic bacteria as starters on the sensory and flavor characteristics of rapidly fermented shrimp paste. Sensory evaluation indicated that the starter-inoculated samples had high texture, appearance, and overall quality scores. Headspace gas chromatography-ion mobility spectrometry/mass spectrometry (HS-GC-IMS/MS) identified 95 volatile compounds, the fingerprint profiles of the starter-inoculated samples were similar to those of the traditional sample. Notably, the content of benzaldehyde, phenylethylaldehyde, and 3-methylbutyraldehyde increased significantly in the starter-inoculated samples (p < 0.05), which may provide an intense malt, caramel, and pleasant odor. Although the content of certain flavor substances in the starter-inoculated samples was lower than those of traditional sample, the use significantly reduced the fermentation time and mimicked the flavor profile of traditional shrimp paste to some extent.

α-D-1,6-glucan from Castanea mollissima Blume alleviates dextran sulfate sodium-induced colitis in vivo.

A homogenous α-D-1,6-glucan (CPA) was extracted from Castanea mollissima Blume. The effect of CPA on ameliorating dextran sulfate sodium induced colitis was investigated. CPA repressed TNF-α and IL-1ß level in LPS stimulated RAW264.7 cells. After the intragastric administration of CPA (200 or 400 mg/kg/day), the colon length and body weights of mice with colitis increased and the disease activity index reduced. CPA alleviated colon tissue damage by elevating ZO-1 and occludin protein levels and regulating TNF-α and IL-1ß by inhibiting the protein expression of NLPR3 and NF-κB p65. The abundance of Bacteroidetes and Firmicutes was altered and short-chain fatty acid (SCFA) levels, especially propionic, butyric, and isovaleric acids increased significantly. These results indicated that CPA could alleviate colitis by protecting mucosal barriers, reducing inflammation, and regulating intestinal microbiota and SCFA levels. Thus, CPA can be developed as a functional food for the prevention and treatment of colitis.

Identification of novel paralytic shellfish toxin binding protein via homology modeling and molecular docking.

A paralytic shellfish toxin binding protein (PST-BP) was extracted and purified from the viscera of oyster (Crassostrea hongkongensis) that accumulates paralytic shellfish toxin (PST), and the amino acid sequence of the protein was detected via HPLC-MS-MS. The structure of the PST-BP was built by homology modeling, and the interaction between PST and PST-BP was studied using molecular docking. The results showed that the purity of PST-BP was more than 99.8% after the purification. The PST-BP carried a molecular weight of 33.5 kDa and sequence alignment revealed its high sequence similarities with glyceraldehyde-3-phosphate-dehydrogenase (GAPDH). It has been shown that 99.9% of the amino acid residues in the PST-BP homology model are within a reasonable range, which exceeds the 90% threshold requirement for residuals in high-quality model structures. The molecular docking results revealed that Arg, Asp, Lys, Ala, Ser, Gln, Gly, Trp, Asn, Met, and Pro were identified as the major interacting amino acids residues between PST-BP and PST.

Versatile Bilayer Hydrogel for Wound Dressing through PET-RAFT Polymerization.

Multifunctional hydrogel-based wound dressings have been explored for decades due to their huge potential in multifaceted medical intervention to wound healing. However, it is usually not easy to fabricate a single hydrogel with all of the desirable functions at one time. Herein, a bilayer model with an outer layer for hydrogel wound dressing was proposed. The inner layer (Hm-PNn) was a hybrid hydrogel prepared by N-isopropylacrylamide and chitosan-N-2-hydroxypropyl trimethylammonium chloride (HACC), and the outer layer (PVAo-PAmp) was prepared by polyvinyl alcohols and acrylamide. The two hydrogel layers of the bilayer model were covalently connected with excellent interfacial strength by photoinduced electron/energy transfer-reversible addition-fragmentation chain transfer (PET-RAFT) polymerization. The outer layer exposed to the ambient environment exhibited good stretchability and toughness, while the inner-layer hydrogel adhered to the skin exhibited excellent softness, antibacterial activity, thermoresponsivity, and biocompatibility. In particular, the inner layer of a hydrogel demonstrated excellent antibacterial capability toward both Staphylococcus aureus as Gram-positive bacteria and Escherichia coli as Gram-negative bacteria. Cell cytotoxicity showed that the cell viability of all Hm-PNn layer hydrogels exceeds 80%, confirming that the hydrogels bear excellent biocompatibility. In vivo experimental results indicated that the Hm-PNn/PVAo-PAmp bilayer hydrogel has a significant effect on the acceleration of wound healing, which was demonstrated in a full-thickness skin defect model showing improved collagen disposition and granulation tissue thickness. With these results, the established multifunctional bilayer hydrogel exhibits potential as an excellent wound dressing for wound healing applications, especially for open and infected traumas.

Orally administered melanin from Sepiapharaonis ink ameliorates depression-anxiety-like behaviors in DSS-induced colitis by mediating inflammation pathway and regulating apoptosis.

The effects of intestinal inflammation on the brain and behavior have received a lot of attention. Melanin (MSI) from Sepiapharaonis ink as an emerging functional food, it exhibited a significant protective effect on dextran sulfate sodium (DSS) induced colitis in previous study. In present study, C57BL/6J mice were free to drink 2.5% DSS solution to establish the colitis model. During the DSS treatment, mice were orally administrated with MSI once per day (75, 150, and 300 mg/kg, respectively). The results showed that MSI treatment ameliorated the depression and anxiety symptoms of colitis mice. Further mechanism studies indicated that MSI alleviated inflammatory response by adjusting cytokines TNF-α, IL-1ß, IFN-γ, and IL-10, and proteins NLRP3/ASC/caspase-1 inflammasome), inhibited the activation of microglia, restored brain synaptic density, reduced oxidative stress (SOD, MDA) and regulated apoptosis (tunel staining, caspase-3). MSI could modulate depression-anxiety states by targeting inflammation, nerve tissue, oxidative stress and apoptosis. MSI administration could serve as an emerging blue food and nutrition strategy for the prevention of digestive tract inflammation and behavioral disorders.

Ink melanin from Sepiapharaonis ameliorates colitis in mice via reducing oxidative stress, andprotecting the intestinal mucosal barrier.

Melanin is the major component from Sepiapharaonis ink (MSI), and its anti-inflammatory and antioxidant activities indicate the potential for improvement of inflammatory bowel diseases. The study aimed to investigate how orally-administered MSI on alleviating the dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) and the potential mechanisms. We found that MSI significantly improved DSS-induced weight loss, colon shortening, hematochezia, DAI score, histopathology, and antioxidant indices (SOD and MDA). Further analysis demonstrated that MSI could significantly down-regulate the expression of pro-inflammatory cytokines (TNF-α, IL-1ß and IFN-γ) and up-regulate the concentration of anti-inflammatory cytokine IL-10 by regulating TLR4/NF-κB and NLRP3/ASC/Caspase-1 signal pathway. Moreover, tight junction proteins in melanin groups were also maintained by ZO-1 and occludin expressions. In addition, MSI also regulated cellular apoptosis by reducing the expression of pro-apoptosis protein Caspase-3. Interestingly, MSI treatments increased the proportion of dominant bacteria (such as Bacteroidetes and Clostridium) and the abundance of community (alpha diversity, ß-diversity, etc.), which significantly balanced microbiota in a dose-dependent manner. In conclusion, oral administration of MSI alleviated DSS-induced colitis by modulating inflammatory cytokines and oxidation stress, maintaining the mucosal barrier, and reverting microbiota changes.

Supplementary selenium in the form of selenylation α-D-1,6-glucan ameliorates dextran sulfate sodium induced colitis in vivo.

The deficiency of selenium has been found in clinical IBD patients and supplementation selenium is recognized as beneficial for colitis treatment. In this study, an organic selenium compound-selenylation α-D-1,6-glucan (sCPA) was prepared, and the effect of sCPA on DSS induced colitis mice was investigated. The results suggested that sCPA prevented the weight loss, colon length shortening, and stool loose of colitis mice. It protected colon mucosal barrier by promoting tight junction protein ZO-1 and Occludin expression. Moreover, sCPA reduced oxidative stress via regulating SOD and MDA levels, and decreased the contents of inflammatory proteins NF-κB and NLRP3 and adjusted TNF-α, IFN-γ, IL-1ß, and IL-10 inflammatory cytokines. Furthermore, sCPA repaired intestinal microbiota composition especially Bacteroidetes, Firmicutes, Proteobacteria, and Actinobacteria that altered by DSS in colitis mice. Meanwhile, SCFAs produced by gut microbiota were restored by sCPA close to the level in the normal group. In conclusion, these findings indicated that the sCPA might be a potential dietary selenium supplementation for the prevention and treatment of colitis.

Extraction of Chitin From Shrimp Shell by Successive Two-Step Fermentation of Exiguobacterium profundum and Lactobacillus acidophilus.

As an environmentally friendly and efficient method, successive two-step fermentation has been applied for extracting chitin from shrimp shells. To screen out the microorganisms for fermentation, a protease-producing strain, Exiguobacterium profundum, and a lactic acid-producing strain, Lactobacillus acidophilus, were isolated from the traditional fermented shrimp paste. Chitin was extracted by successive two-step fermentation with these two strains, and 85.9 ± 1.2% of protein and 95 ± 3% of minerals were removed. The recovery and yield of chitin were 47.82 and 16.32%, respectively. Fourier transform infrared spectroscopy, X-ray diffraction, and scanning electron microscopy (SEM) were used to characterize the chitin. The crystallinity index was 54.37%, and the degree of deacetylation was 3.67%, which was lower than that of chitin extracted by the chemical method. These results indicated that successive two-step fermentation using these two bacterial strains could be applied to extract chitin. This work provides a suitable strategy for developing an effective method to extract chitin by microbial fermentation.

Orally Administered DHA-Enriched Phospholipids and DHA-Enriched Triglyceride Relieve Oxidative Stress, Improve Intestinal Barrier, Modulate Inflammatory Cytokine and Gut Microbiota, and Meliorate Inflammatory Responses in the Brain in Dextran Sodium Sulfate Induced Colitis in Mice.

SCOPE: Studies based on DHA/EPA supplementation in animal models of inflammatory bowel disease (IBD) reveal controversial results. It is speculated that different forms of DHA may explain the controversial results. Therefore, the effects of DHA-enriched phospholipids (DHA-PL) and DHA-enriched triglyceride (DHA-TG) on IBD are compared. METHODS AND RESULTS: Male C57BL6/J mice are given DHA-PL and DHA-TG for 14 consecutive days, and receive ad libitum a 3.0% dextran sodium sulfate solution on the eighth day to establish IBD model. The results show that both DHA-PL and DHA-TG can reverse the colitis pathological process by decreasing the disease activity indexes (DAI), raising the colon length, suppressing the intestinal permeability, suppressing the oxidative stress, down-regulating pro-inflammatory factors, up-regulating anti-inflammatory factor in colon tissues. DHA-PL and DHA-TG also regulate the composition of gut microbiota via decreasing of the abundance Bacteroidetes and Firmicutes, and DHA-TG increases the abundance of Odoribacter. Importantly, DHA-PL and DHA-TG obviously attenuate the activation of microglia. CONCLUSIONS: DHA-PL shows outstanding advantages in regulating oxidative stress, inflammatory responses, and intestinal barrier permeability. The current research indicates that the existence of DHA affects the improvement, DHA in phospholipid form could be a more effective choice for nutritional intervention to prevent and treat colitis.

The complete mitochondrial genome of Sporobolus alterniflorus (loisel.) P.M. Peterson & Saarela (Poaceae) and phylogenetic analysis.

The complete mitochondrial genome of Sporobolus alterniflorus was a circular molecule of 566,328 bp in length and encoded 64 genes, including 35 protein-coding genes, 24 tRNA genes, and 5 rRNA genes. The most common initiated codon was ATG and the most common termination codon was CAT. The overall A + T content was 55.96%. The phylogenomic analysis revealed that Sporobolus alterniflorus have a closest phylogenetic relationship with Sorghum bicolor.

Effect of carboxymethyl chitosan on the detoxification and biotransformation of paralytic shellfish toxins in oyster Ostrea rivularis.

Economic bivalve ingested toxic algae causes frequent human poisoning events. To explore new compounds that can accelerate the depuration of toxins in shellfish, we investigated the detoxification of the paralytic shellfish toxins (PSTs) and the biotransformation pathway of PSTs during detoxification by the application of three treatments to a toxic bloom, Alexandrium minutum (A. minutum). The detoxification effect of Platymonas subcordiformis (PS) mixed with carboxymethyl chitosan (CMC) group is significantly better than the starving group in each oyster tissues. The toxicity of viscera which occupied 78.95% of total toxicity reduced to 155 MU/100g after 13 days' depuration experiment. And adding CMC could significantly achieve rapid detoxification and effectively reduce the STX to 0.07 µmol/100 g in viscera. Meanwhile, PSTs underwent biotransformation during the depuration process, which mainly manifested as GTX1/4→GTX2/3→STX, GTX2→dcGTX2. This study explored a new strategy for toxin depuration in shellfish.

Construction of an electrochemical sensor with graphene aerogel doped with ZrO2 nanoparticles and chitosan for the selective detection of luteolin.

A simple, fast and sensitive method for the detection of luteolin is proposed based on the chitosan/reduced graphene oxide aerogel with dispersed ZrO2 nanoparticles modified glassy carbon electrode (ZrO2/CS/rGOA-GCE) as an electrochemical sensor. The ZrO2/CS/rGOA composite was prepared by one pot synthesis from a mixture of GO, CS and zirconyl chloride octahydrate, and subsequently be freeze-dried. Scanning electron microscope images showed a typical thin, wrinkled and fluctuant morphology of graphene nanosheets and the polymerized CS and ZrO2 nanoparticles deposited on the surface of rGOA. Cyclic voltammetry and differential pulse voltammetry were used to measure the electrochemical response of ZrO2/CS/rGOA composite-based biosensor towards luteolin at the working potential window (-0.8-0.8 V). The improved performance of this biosensor was attributed to efficient electron transfer and large surface area of 3D rGOA, and high specific activity of Zr towards adjacent hydroxyl groups. Under optimized conditions, the analytical performance of this method towards luteolin was investigated with a detection limit of 1 nM and a linear range from 5 nM to 1000 nM.. Finally, the ZrO2/CS/rGOA-GCE electrochemical method coupled with solid phase extraction was used for the detection of luteolin in real samples. Recoveries of  spiked samples with different concentrations were in the range 78.6-103.3% with a relative RSD lower than 12.0%. Graphical abstract Schematic representation of the preparation of the ZrO2 nanoparticles and chitosan doped graphene aerogel modified electrode. The electrode was employed for the detection of luteolin coupled with the solid-phase extraction technique.

Saccharina japonica Ethanol Extract Ameliorates Depression/Anxiety-Like Behavior by Inhibiting Inflammation, Oxidative Stress, and Apoptosis in Dextran Sodium Sulfate Induced Ulcerative Colitis Mice.

Saccharina japonica is a common marine vegetable in East Asian markets and has a variety of health benefits. This study was focused on the anti-depressant/anxiety effects of Saccharina japonica ethanol extract (SJE) on dextran sodium sulfate (DSS)-induced mice and its potential mechanism in their brain. Male C57BL/6 mice were treated with mesalazine and various doses of SJE (1, 2, and 4 g/kg body weight) for 2 weeks, followed by DSS treatment at the second week. The DSS-induced mice showed depression/anxiety-like behavior, which included shorter path length in the open field test and longer immobility time in the tail suspension test. L-SJE alleviated the depression-like behaviors. In the DSS-induced mice, reduced synaptic plasticity activated microglia, increased proinflammatory cytokines, decreased anti-inflammatory cytokine, and increased expression levels of Toll-like receptors-4, nuclear factor kappa-B, NOD-like receptors 3, apoptosis-associated speck-like protein, and Caspase-1 were observed, most of which were alleviated by SJE treatment. Furthermore, all the SJE groups could significantly enhance superoxide dismutase activity, while the L-SJE treatment decreased the contents of malondialdehyde, and the H-SJE treatment inhibited apoptosis. All these results showed that the SJE might serve as a nutritional agent for protecting the brain in ulcerative colitis mice.

Effect of the structural characterization of the fungal polysaccharides on their immunomodulatory activity.

The immunomodulatory effects of the four extracellular polysaccharides, namely WPA, WPB, AP2A, and TP1A, which were isolated from the fermented broth of Aspergillus aculeatus, A. terreus and Trichoderma sp. KK19L1, were investigated in vitro. WPA, WPB, AP2A, and TP1A were not toxic to RAW264.7 cells. These polysaccharides enhanced cell viability. WPA, WPB, AP2A, and TP1A showed increased immunomodulatory effect by strengthening the phagocytic activity and enhancing the release of NO, TNF-α and IL-6 from RAW264.7 cells. WPA, WPB, AP2A, and TP1A exhibited different immunomodulatory activity in vitro due to their different structural characterizations, and their immunoregulatory effects decreased successively in the following order: WPA, WPB, AP2A, and TP1A. The extracellular polysaccharides WPA, WPB, AP2A, and TP1A had potent immunomodulatory effects and could be used as potential immunomodulatory agents in the fields of functional food and medicine.

Biocompatibility of Alexandrium minutum in the growth and paralytic shellfish toxins production under five cultivation methods.

This study evaluated the performance of an easy-cultivation device for the mass culture of Alexandrium minutum (A. minutum), a dinoflagellate that produces paralytic shellfish toxins (PSTs). Five culture conditions including three different sizes of containers (250 mL conical flask, 500 mL beaker, and 20 L jar) in two different environments (out-incubator and incubator) were compared in terms of growth and PSTs production. Compared with the incubator environment, the out-incubator environment had more fluctuations in temperature and light intensity. Results showed that the cell densities of A. minutum increased in all groups, especially in the conical flask (I, out-incubator, 6.29×106 cells/mL) and the beaker (IV, incubator, 7.28×106 cells/mL). When cultured in the 20 L jar under out-incubator condition, the algae had the lowest cell density (2.82×106 cells/mL) but the highest toxicity (93.42 ± 2.55×10-6 MU/cell). The negative correlation between average growth rate and single-cell toxicity could be explained by biocompatibility, thereby indicating that the low growth rate led to high toxicity. HPLC-FLD showed that the cellular toxicity increased due to the quantitative increase in GTX1/4, which are the more toxic derivatives. The PSTs types consistently contained GTX1/4 and GTX2/3. The differences in algae growth and toxin-production could be due to changes in bacteria (out-incubator) and CO2 (incubator) with vessel size. The effects of environmental factors on algae are strain specific. The out-incubator device can be applied for large-scale cultivation of A. minutum considering the algae density and toxin-producing ability.