Could Chlorella pyrenoidosa be exploited as an alternative nutrition source in aquaculture feed? A study on the nutritional values and anti-nutritional factors.

This work attempted to identify if microalgal biomass can be utilized as an alternative nutrition source in aquaculture feed by analyzing its nutritional value and the anti-nutritional factors (ANFs). The results showed that Chlorella pyrenoidosa contained high-value nutrients, including essential amino acids and unsaturated fatty acids. The protein content in C. pyrenoidosa reached 52.4%, suggesting that microalgal biomass can be a good protein source for aquatic animals. We also discovered that C. pyrenoidosa contained some ANFs, including saponin, phytic acid, and tannins, which may negatively impact fish productivity. The high-molecular-weight proteins in microalgae may not be effectively digested by aquatic animals. Therefore, based on the findings of this study, proper measures should be taken to pretreat microalgal biomass to improve the nutritional value of a microalgae-based fish diet.

hECA: The cell-centric assembly of a cell atlas.

The accumulation of massive single-cell omics data provides growing resources for building biomolecular atlases of all cells of human organs or the whole body. The true assembly of a cell atlas should be cell-centric rather than file-centric. We developed a unified informatics framework for seamless cell-centric data assembly and built the human Ensemble Cell Atlas (hECA) from scattered data. hECA v1.0 assembled 1,093,299 labeled human cells from 116 published datasets, covering 38 organs and 11 systems. We invented three new methods of atlas applications based on the cell-centric assembly: "in data" cell sorting for targeted data retrieval with customizable logic expressions, "quantitative portraiture" for multi-view representations of biological entities, and customizable reference creation for generating references for automatic annotations. Case studies on agile construction of user-defined sub-atlases and "in data" investigation of CAR-T off-targets in multiple organs showed the great potential enabled by the cell-centric ensemble atlas.

Erasing m6A-dependent transcription signature of stress-sensitive genes triggers antidepressant actions.

Emerging evidence has shown that stress responsivity and psychiatric diseases are associated with alterations in N6-methyladenosine (m6A) mRNA epigenetic modifications. Fat mass and obesity-associated protein (FTO) is an m6A demethylase that has been linked to increased body mass and obesity. Here, we show that tricyclic antidepressants (TCAs) with weight-gain side effects, such as imipramine and amitriptyline, directly increased FTO expression and activated its epigenetic function in the ventral tegmental area (VTA). VTA-specific genetic disruption of FTO increased stress vulnerability and abolished the antidepressant activity of TCAs, whereas erasing m6A modification in the VTA by FTO overexpression or cycloleucine led to significant antidepressant activity. Mechanistically, both transcriptome sequencing and quantitative PCR revealed that overexpression of FTO in the VTA decreased the transcription of stress-related neuropeptides, such as cocaine- and amphetamine-regulated transcript peptide and urocortin, in the social defeat model, which was mimicked by imipramine, suggesting an m6A-dependent transcription mechanism of stress-related neuropeptides may underlie the responses to antidepressant. Collectively, our results demonstrate that inhibiting m6A-dependent transcription of stress-related genes may work as a novel antidepressant strategy and highlight a previously unrecognized activator of FTO-dependent epigenetic function that may be used for the treatment of other neurological diseases.

SKF83959, an agonist of phosphatidylinositol-linked dopamine receptors, prevents renewal of extinguished conditioned fear and facilitates extinction.

Fear-related anxiety disorders, such as social phobia and post-traumatic stress disorder, are partly explained by an uncontrollable state of fear. An emerging literature suggests dopamine receptor-1 (D1 receptor) in the amygdala is involved in the regulation of fear memory. An early study has reported that amygdaloid D1 receptor (D1R) is not coupled to the classic cAMP-dependent signal transduction. Here, we investigated whether SKF83959, a typical D1R agonist that mainly activates a D1-like receptor-dependent phosphatidylinositol (PI) signal pathway, facilitates fear extinction and reduces the return of extinguished fear. Interestingly, long-term loss of fearful memories can be induced through a combination of SKF83959 (1 mg/kg/day, i.p., once daily for one week) pharmacotherapy and extinction training. Furthermore, sub-chronic administration of SKF83959 after fear conditioning reduced fear renewal and reinstatement in the mice. We found that the activation D1R and PI signaling in the amygdala was responsible for the effect of SKF83959 on fear extinction. Additionally, SKF83959 significantly promoted the elevation of brain-derived neurotrophic factor (BDNF) expression, possibly by the cAMP response element binding protein (CREB) -directed gene transcription. Given the beneficial effects on extinction, SKF83959 may emerge as a candidate pharmacological approach for improving cognitive-behavioral therapy on fear-related anxiety disorders.

S-methyl-L-cysteine Protects against Antimycin A-induced Mitochondrial Dysfunction in Neural Cells via Mimicking Endogenous Methionine-centered Redox Cycle.

Mitochondrial superoxide overproduction is believed to be responsible for the neurotoxicity associated with neurodegeneration. Mitochondria-targeted antioxidants, such as MitoQ, have emerged as potentially effective antioxidant therapies. Methionine sulfoxide reductase A (MsrA) is a key mitochondrial-localized endogenous antioxidative enzyme and it can scavenge oxidizing species by catalyzing the methionine (Met)-centered redox cycle (MCRC). In this study, we observed that the natural L-Met acted as a good scavenger for antimycin A-induced mitochondrial superoxide overproduction in PC12 cells. This antioxidation was largely dependent on the Met oxidase activity of MsrA. S-methyl-L-cysteine (SMLC), a natural analogue of Met that is abundantly found in garlic and cabbage, could activate the Met oxidase activity of MsrA to scavenge free radicals. Furthermore, SMLC protected against antimycin A-induced mitochondrial membrane depolarization and alleviated 1-methyl-4-phenylpyridinium (MPP+)-induced neurotoxicity. Thus, our data highlighted the possibility for SMLC supplement in the detoxication of mitochondrial damage by activating the Met oxidase activity of MsrA.

Replacement of feed by fresh microalgae as a novel technology to alleviate water deterioration in aquaculture.

The main aim of this work was to evaluate the feasibility of microalgae-assisted aquaculture and explore the relevant mechanisms. In this regard, our work explored the pollution problems in traditional aquaculture and studied the contribution of microalgae to eutrophication control, oxygen gas production and feed replacement. Besides, potential protection mechanisms of microalgae-assisted aquaculture were studied by bacterial community profile analysis and microscope observation. The results showed that microalgae performed well in nutrient assimilation and oxygen production, thus slowing down the eutrophication and preventing oxygen depletion in aquaculture. Study of the mechanisms revealed that microalgae-assisted aquaculture contained much fewer pathogens and a microalgal biofilm was formed to prevent the eutrophication caused by sludge degradation. It is expected that the findings in this work can support the further development of microalgae-assisted aquaculture and promote the industry upgrade.

A novel approach of using zeolite for ammonium toxicity mitigation and value-added Spirulina cultivation in wastewater.

Owning to the ammonium toxicity, some ammonium-rich wastewater may not be used for algae cultivation. To overcome this problem, herein, a novel approach of using zeolite to mitigate ammonium toxicity in wastewater for value-added Spirulina production was proposed. Synthetic zeolite was used as medium for ammonium adsorption in wastewater and subsequently as slow-releaser providing nitrogen to Spirulina growth. The optimal conditions for ammonium adsorption include pH value of 8.0, zeolite dose of 300 g/L, and adsorption time of 9 h. The results showed that in terms of biomass production and ammonium recovery, zeolite-based pretreatment has great advantages over some conventional pretreatment technologies. After algae-assisted desorption treatment, ammonium adsorption capacity of zeolite increased back to 1.21 mg/g. In a real-world application, this work will provide a feasible and sustainable approach to remediate ammonium-rich wastewater, produce value-added Spirulina biomass, and recycle used zeolite, further promoting the industrialization of algae-based wastewater remediation.

High Expression of PLOD1 Drives Tumorigenesis and Affects Clinical Outcome in Gastrointestinal Carcinoma.

BACKGROUND: PLOD1 (procollagen-lysine, 2-oxoglutarate 5-dioxygenase 1) is important for extracellular matrix formation and is involved in various diseases, including cancer; however, its role in gastrointestinal cancer is unclear. In this study, the expression of PLOD1 in gastrointestinal carcinoma and its relationships with patient survival were examined. MATERIALS AND METHODS: Sample expression profiles were downloaded from the Gene Expression Omnibus database and methylation data were obtained from the Cancer Genome Atlas. Correlations between PLOD1 expression and clinicopathological features were analyzed by chi-square tests. Patient survival was evaluated by a Kaplan-Meier analysis. RESULTS: PLOD1 expression was upregulated in gastric cancer and colorectal cancer compared with that in normal tissues. High PLOD1 levels indicated a poor prognosis. The high methylation group had a significantly lower level of PLOD1 expression. CONCLUSION: These results indicated that PLOD1 is highly expressed in gastrointestinal carcinoma and is a potential prognostic marker and therapeutic target. The data also indicate that hypomethylation contributes to PLOD1 upregulation in gastric and colon cancers.

Analgesic effect of total flavonoids from Sanguis draxonis on spared nerve injury rat model of neuropathic pain.

BACKGROUND: Sanguis draxonis (SD) is a kind of red resin obtained from the wood of Dracaena cochinchinensis (Lour.) S. C. Chen (D. cochinchinensis). The active components of total flavonoids from SD (SDF) have analgesic effect. AIM: The aim of this study is to evaluate the analgesic effects and potential mechanism of SDF on mechanical hypersensitivity induced by spared nerve injury (SNI) model of neuropathic pain in the rat. METHODS: SNI model in rats was established and then the rats were treated with SDF intragastric administration for 14 days. Paw withdrawal mechanical threshold (PMWT) in response to mechanical stimulation was measured by von Frey filaments on day 1 before operation and days 1, 3, 5, 7, 9, 11, 14 after operation, respectively. After 14 days, we measured the levels of nitric oxide (NO), nitric oxide synthase (NOS), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) and interleukin-10 (IL-10) in the spinal dorsal horn. In addition, the expression of fibroblast growth factor receptor 3 (FGFR3), phosphorylated cyclic AMP response element-binding protein (p-CREB) and glial fibrillary acidic protein (GFAP) of the spinal dorsal horn was evaluated by western blotting and an immunofluorescence histochemical method, respectively. RESULTS: Intragastric administration of SDF (100, 200, 400 mg/kg) alleviated significantly SNI-induced mechanical hypersensitivity, as PMWT increased in a dose-dependent manner. Moreover, SDF not only reduced the level of NO, NOS, TNF-α and IL-1ß, but also upregulated the level of IL-10 in the spinal dorsal horn of SNI rats. At the same time, SDF (100, 200, 400 mg/kg) could inhibit the expression of FGFR3, GFAP and p-CREB in the spinal dorsal horn. CONCLUSION: SDF has potentially reduced mechanical hypersensitivity induced by SNI model of neuropathic pain which may be attributed to inhibition of astrocytic function (like release pro-inflammatory cytokines) and NO release as well as p-CREB activation in the spinal dorsal horn.

Antidiabetic effect of total flavonoids from Sanguis draxonis in type 2 diabetic rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Sanguis draxonis (SD) is a kind of red resin obtained from the wood of Dracaena cochinchinensis (Lour.) S. C. Chen (Dracaena cochinchinensis). It is a Chinese traditional herb that is prescribed for the handling of diabetic disorders, which is also supported by an array of scientific studies published in recent years. Although chemical constituents of this plant material have also been previously evaluated (Tang et al., 1995; Wei et al., 1998), it still remains poorly understood which constituent is the major contributor to its antidiabetic activities. Moreover, very little is known about the molecular mechanisms underlying antidiabetic activities of SD. Flavonoids exist at a high level in SD. The aim of this study is to evaluate the antidiabetic effects of total flavonoids from SD (SDF) in type 2 Diabetes mellitus (T2DM) rats. MATERIALS AND METHODS: T2DM rats were induced by 4 weeks high-fat diet and a singular injection of streptozotocin (STZ) (35mg/kg). Then T2DM rats were treated with SDF for 21 days, using normal saline as the negative control. For comparison, a standard antidiabetic drug, metformin (200mg/kg), was used as a positive control. Three weeks later, relative biochemical indexes were determined and histopathological examinations were performed to assess the antidiabetic activities of SDF. RESULTS: SDF not only exhibited a significant hypoglycemic activity, but also alleviated dyslipidemia, tissue steatosis, and oxidative stress associated with T2DM. Moreover, considerable pancreatic islet protecting effects could be observed after SDF treatment. Further investigations revealed a potential anti-inflammation activity of SDF by determining serum levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and C-reactive protein (CRP). CONCLUSIONS: This study demonstrates both hypoglycemic and hypolipidemic effects of SDF in T2DM rats, suggesting that flavonoids are the major active ingredients accounting for the antidiabetic activity of SD. Alleviating chronic inflammation responses and protecting pancreatic islets are possible mechanisms involved in the antidiabetic activity of SDF.