Simultaneous inorganic nitrogen and phosphate removal by aerobic-heterotrophic fungus Fusarium keratoplasticum FSP1: Performance, pathway and application.

Fungi with multiple contaminant removal function have rarely been studied. Here, a novel fungal strain Fusarium keratoplasticum FSP1, which was isolated from halophilic granular sludge, is reported for first time to perform simultaneous nitrogen and phosphate removal. The strain showed wide adaptability under C/N ratios of 30-35, salinities of 0 %-3 % (m/v), and pH of 7.5-9.5. The maximum removal rates of ammonium, nitrate and nitrite were 4.43, 4.01 and 2.97 mg N/L/h. The nitrogen balance, enzyme activity and substrate conversion experiments demonstrated a single strain FSP1 can assimilate inorganic nitrogen and convert inorganic nitrogen to gaseous nitrogen through heterotrophic nitrification or aerobic denitrification. About 39 %-42 % of the degraded phosphorus was in the extracellular polymeric substances (EPS). Orthophosphate was the main phosphorus species in the cell, whereas phosphate monoester and diester were in the EPS. The novel strain FSP1 is a potential candidate for wastewater treatment.

Screening of anti-cancer compounds from Vaccariae Semen by lung cancer A549 cell fishing and UHPLC-LTQ Orbitrap MS.

Vaccariae Semen, derived from the dried ripe seed of Vaccaria segetalis (Neck.) Garcke, has various therapeutic characteristics in traditional Chinese medicine (TCM), containing promoting blood circulation and unblocking meridians. It exhibits significant anti-cancer activity and is therapeutically utilized to treat and reduce chemotherapy adverse effects in cancer patients, notably those with lung cancer. However, the active ingredients responsible for its anti-lung cancer efficacy remain unknown. In this study, we used A549 cell fishing in conjunction with UHPLC-LTQ Orbitrap MS to screen for anti-lung cancer active components in Vaccariae Semen. The cell counting Kit-8 (CCK-8) assay revealed that the n-butanol extract substantially reduced A549 cell growth. Through the cell fishing assay, we found 14 A549 cell-binding compounds in the n-butanol extract, all of which were identified as triterpenoid saponins. The total saponins of Vaccariae Semen were subsequently purified using macroporous adsorption resin (MAR), and they showed a significant inhibitory effect on the proliferation of A549 lung cancer cells, as well as alterations in cell morphology, apoptosis, and fragmentation. In conclusion, saponins were discovered as the key active components responsible for the anti-lung cancer activity of Vaccariae Semen.

Identification of in vivo metabolites of Citri Sarcodactylis Fructus by UHPLC-Q/Orbitrap HRMS.

INTRODUCTION: Citri Sarcodactylis Fructus has the effects of relieving cough, removing phlegm, and reducing asthma, but little is known about the metabolic and distribution of its chemical constituents in vivo. Therefore, it is necessary to study the metabolism of Citri Sarcodactylis Fructus in vivo. OBJECTIVE: We aimed to (1) analyze the distribution of prototype compounds and metabolites of the chemical constituents of Citri Sarcodactylis Fructus in rat and (2) infer the metabolites and metabolic pathways of the chemical constituents. MATERIALS AND METHODS: A C18 column (3 × 100 mm, 2.6 µm) was used. The mobile phase was water containing 0.1% formic acid (eluent A) and acetonitrile containing 0.1% formic acid (eluent B) at a discharge rate of 0.3 mL/min. Mass spectra of biological samples were collected in electrospray ionization (ESI) positive ion mode in the m/z 100-1500 scan range. The obtained biological samples were then subjected to chemical analysis, including plasma, urine, feces, and heart, liver, spleen, lungs, kidneys, stomach, and small intestine tissues. Prototype compounds and metabolites were identified. RESULTS: In all, 40 prototype compounds and 78 metabolites, including 26 phase I metabolites and 52 phase II metabolites, were identified using UHPLC-Q/Orbitrap HRMS. Eight possible metabolic pathways (reduction, hydrolysis, dehydration, methylation, hydroxylation, sulfation, glucuronidation, and demethylation) were proposed. The prototype compounds were predominantly distributed in lung tissues. The metabolites were mainly distributed in plasma and kidney tissues. CONCLUSION: We systematically investigated the metabolites of Citri Sarcodactylis Fructus in vivo. We suggest metabolic pathways that might be relevant for further metabolic studies and screening of active ingredients of Citrus Sarcodactylis Fructus in vivo.

Effects of Tai Chi on working memory in older adults: evidence from combined fNIRS and ERP.

Objective: The study aimed to investigate the effects of a 12-week Tai Chi exercise intervention on working memory in older adults using ERP-fNIRS. Method: Fifty older adults were randomly assigned to either an experimental group receiving a 12-week Tai Chi exercise intervention or a control group receiving regular daily activities. Working memory was assessed using the n-back task before and after the intervention, and spatial and temporal components of neural function underlying the n-back task were measured using ERP-fNIRS. Results: The experimental group demonstrated significant improvements in reaction time and accuracy on the 2-back task and showed higher activation levels in the R-DLPFC. Additionally, the Tai Chi group displayed significant increases in P3 amplitude in the overall n-back task. Conclusion: These findings suggest that Tai Chi interventions can enhance working memory in older adults, as evidenced by increasing neural activity and improving HbO in the R-DLPFC during the 2-back task.

Natural Products-Based Botanical Bactericides Discovery: Novel Abietic Acid Derivatives as Anti-Virulence Agents for Plant Disease Management.

The discovery of natural product-based pesticides is critical for agriculture. In this work, a series of novel tricyclic diterpenoid derivatives decorated with an amino alcohol moiety were elaborately prepared from natural abietic acid, and their antibacterial behavior was explored. Bioassay results indicated that compound C2 exhibited the most promising bioactivity (EC50 = 0.555 µg mL-1) against Xanthomonas oryzae pv. oryzae (Xoo), about 73 times higher than the effect of commercial thiodiazole copper (TC). Results of in vivo bioassays showed that compound C2 displayed significantly higher control of rice bacterial leaf blight (curative activity: 63.8%; protective activity: 58.4%) than TC (curative activity: 43.6%; protective activity: 40.8%), and their bioactivity could be improved maximally 16% by supplementing the auxiliaries. Antibacterial behavior suggested that compound C2 could suppress various virulence factors. Overall, these findings suggested that new botanical bactericide candidates could control intractable plant bacterial diseases by suppressing virulence factors.

Lentinuses A-B, two alkaloids from the marine-derived fungus Lentinus sajor-caju with potent anti-pulmonary fibrosis activity.

By adding natural amino acids into the medium as sole nitrogen source, twenty-four compounds, including two new alkaloids lentinuses A-B (1-2) with a rare oxazinone core in marine natural products, one new natural product 3-acetamido-4-phenylfurazan (3), 9ß-ergosterol (22) were firstly discovered from a marine fungus, and twenty known compounds (4-21, 23-24) were isolated from the marine-derived fungus Lentinus sajor-caju. The chemical structures of all these compounds were elucidated by HRMS, NMR spectroscopy and X-ray diffraction. Compounds 1-24 were evaluated for their inhibitory activity against TGF-ß1-induced collagen accumulation in human fetal lung fibroblasts (HFL1). Compounds 2, 3, 12, 22, and 23 showed potent activity against TGF-ß1-induced collagen accumulation and low toxicity to HFL1 cells. The binding mode of lentinus B (2) with TGF-ß1 receptor was then performed by using Schrödinger software, and the result showed that lentinus B possesses a strong binding force such as hydrogen bonding and hydrophobic interactions to the protein, which may provide a theoretical basis to design more potent anti-fibrotic drugs in the future.

Targeting NAD+: is it a common strategy to delay heart aging?

Heart aging is the main susceptible factor to coronary heart disease and significantly increases the risk of heart failure, especially when the aging heart is suffering from ischemia-reperfusion injury. Numerous studies with NAD+ supplementations have suggested its use in anti-aging treatment. However, systematic reviews regarding the overall role of NAD+ in cardiac aging are scarce. The relationship between NAD+ signaling and heart aging has yet to be clarified. This review comprehensively summarizes the current studies on the role of NAD+ signaling in delaying heart aging from the following aspects: the influence of NAD+ supplementations on the aging heart; the relationship and cross-talks between NAD+ signaling and other cardiac aging-related signaling pathways; Importantly, the therapeutic potential of targeting NAD+ in delaying heart aging will be discussed. In brief, NAD+ plays a vital role in delaying heart aging. However, the abnormalities such as altered glucose and lipid metabolism, oxidative stress, and calcium overload could also interfere with NAD+ function in the heart. Therefore, the specific physiopathology of the aging heart should be considered before applying NAD+ supplementations. We believe that this article will help augment our understanding of heart aging mechanisms. In the meantime, it provides invaluable insights into possible therapeutic strategies for preventing age-related heart diseases in clinical settings.

A Lycium barbarum extract inhibits ß-amyloid toxicity by activating the antioxidant system and mtUPR in a Caenorhabditis elegans model of Alzheimer's disease.

Lycium barbarum, a traditional Chinese medicine, has been shown to have antioxidant properties and has a protective effect in many diseases related to oxidative stress, such as neurodegenerative diseases, cardiovascular diseases, and cancer. Although the neuroprotective effects of L. barbarum extract (LBE) have been reported in several studies, the underlying molecular mechanisms are still unclear. In this study, the transgenic Caenorhabditis elegans strain CL2006 was used to investigate the function and molecular mechanism of an LBE in Alzheimer's disease (AD). LBE had high antioxidant potential and effectively delayed Aß-induced paralysis in the CL2006 strain. LBE inhibited the production of excessive reactive oxygen species by inducing the SKN-1-mediated antioxidant system, thereby inhibiting the generation of Aß and inhibiting mitochondrial damage. Importantly, LBE reduced Aß levels by inducing FSHR-1-mediated activation of the mtUPR. Therefore, our study not only reveals a new mechanism of LBE in the treatment of AD but also identifies a novel strategy for the treatment of AD by enhancing the mtUPR.

Capsella bursa-pastoris (L.) Medic. extract alleviate cataract development by regulating the mitochondrial apoptotic pathway of the lens epithelial cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Capsella bursa-pastoris (L.) Medic. (CBP) is a cruciferous plant valuable in reducing fever, improving eyesight and calming the liver. This herb was recorded in the Compendium of Materia Medica for cataract treatment. AIM OF THE STUDY: To determine the effects and mechanism of CBP on cataract prevention and treatment using a selenite cataract model. MATERIALS AND METHODS: The main compounds in CBP extract were analyzed by UPLC, 1H-NMR and 13C-NMR spectroscopic techniques. Flavonoids formed a significant proportion of its compounds, thus necessitating an evaluation of their inhibitory effects on the development of cataract using a selenite cataract model. The protective effects of CBP flavonoids (CBPF) against oxidative damage and the modulation of mitochondrial apoptotic pathway were subsequently verified on H2O2-treated SRA01/04 lens epithelial cells. RESULTS: CBPF significantly alleviated the development of cataract by decreasing the MDA level and increasing the GSH-Px and SOD levels in the lens. It also inhibited H2O2-induced apoptosis in SRA01/04 cells, increased the expression of Bcl-2 protein and decreased the expressions of Caspase-3 and Bax proteins. CONCLUSION: CBPF exerts a significant preventive effect on cataract development by regulating the mitochondrial apoptotic pathway of the lens epithelial cells. It is thus a potent traditional Chinese medicine (TCM) whose application should be further developed for the clinical treatment of cataract.

[Yishen Tonglong Decoction inhibits the epithelial-mesenchymal transition and Ras/ERK signaling pathway in human prostate cancer DU-145 cells].

Objective: To observe the effect of Yishen Tonglong Decoction (YTD) on the epithelial-mesenchymal transition (EMT) and Ras/ERK signaling pathway in human PCa DU-145 cells and explore its action mechanism. METHODS: We treated human PCa DU-145 cells with normal plasma (the blank control) or plasma containing 5% (low-dose), 10% (medium-dose) and 15% (high-dose) YTD. After intervention, we examined the proliferation of the DU-145 cells in different groups with CCK-8 and their apoptosis by Annexin V/PI double staining. We detected the cell cycle by PI assay, the invasion and migration of the cells using the Transwell chamber and scratch test, and the expressions of the proteins and genes related to the EMT and Ras/ERK signaling pathways in the cells by Western blot and RT-PCR. RESULTS: Compared with the blank control group, high-, medium- and low-dose YTD significantly inhibited the proliferation of the PCa DU-145 cells, decreased their adherence and growth (P < 0.05, P < 0.01), promoted their apoptosis (P < 0.01), regulated their cell cycles (P < 0.05, P < 0.01), and reduced their in vitro invasion and migration abilities (P < 0.05), all in a dose-dependent manner. The results of Western blot and RT-PCR revealed down-regulated protein and mRNA expressions of N-cadherin, zinc finger transcription factor (Snail), Ras, p-ERK1/2 and ERK1/2, but up-regulated protein and mRNA expressions of E-cadherin in the PCa DU-145 cells treated with YTD (P < 0.05, P < 0.01). CONCLUSIONS: Yishen Tonglong Decoction can effectively inhibit the proliferation, promote the apoptosis, regulate the cell cycle and suppress the invasion and migration abilities and EMT process of human PCa DU-145 cells. The mechanism of Yishen Tonglong Decoction acting on PCa may be associated with its inhibitory effect on the EMT process and expression of the Ras/ERK signaling pathway in PCa cells./.

[Research progress on rutin derivatives].

Compounds derived from natural products present satisfactory efficacy in disease prevention and treatment. The use of chemical substances in plants to promote healthhas increasingly attracted people's attention. Rutin, a typical flavonoid, is mainly found in various vegetables, fruits and Chinese herbal medicines. As a natural antioxidant, it features many pharmacological activities, such as anti-inflammation, anti-virus, anti-tumor, and prevention and treatment of cardiovascular and cerebrovascular diseases. However, the low bioavailability and poor water solubility limit its clinical application. In view of this, its structure is optimized and modified to afford rutin derivatives with good solubility, high bioavailability, stable metabolism and small toxic side effects. So far, a large number of rutin ethers, esters, and complexes have been synthesized and undergone activity testing. This paper reviews the structural modification of rutin in recent years, and the obtained derivatives have excellent properties and significant biological activity.

[Expression profiling and functional verification of flavonoid 3'-hydroxylase gene from leaves of Euryale ferox].

Leaves of Euryale ferox are rich in anthocyanins. Anthocyanin synthesis is one of the important branches of the flavonoid synthesis pathway, in which flavonoid 3'-hydroxylase(F3'H) can participate in the formation of important intermediate products of anthocyanin synthesis. According to the data of E. ferox transcriptome, F3'H cDNA sequence was cloned in the leaves of E. ferox and named as EfF3'H. The correlation between EfF3'H gene expression and synthesis of flavonoids was analyzed by a series of bioinforma-tics tools and qRT-PCR. Moreover, the biological function of EfF3'H was verified by the heterologous expression in yeast. Our results showed that EfF3'H comprised a 1 566 bp open reading frame which encoded a hydrophilic transmembrane protein composed of 521 amino acid residues. It was predicted to be located in the plasma membrane. Combined with predictive analysis of conserved domains, this protein belongs to the cytochrome P450(CYP450) superfamily. The qRT-PCR results revealed that the expression level of EfF3'H was significantly different among different cultivars and was highly correlated with the content of related flavonoids in the leaves. Eukaryotic expression studies showed that EfF3'H protein had the biological activity of converting kaempferol to quercetin. In this study, EfF3'H cDNA was cloned from the leaves of E. ferox for the first time, and the biological function of the protein was verified. It provi-ded a scientific basis for further utilizing the leaves of E. ferox and laid a foundation for the further analysis of the biosynthesis pathway of flavonoids in medicinal plants.

Two new polycyclic polyprenylated acylphloroglucinols derivatives from Hypericum acmosepalum.

Polycyclic polyprenylated acylphloroglucinols (PPAPs) were mainly obtained from the plants of Hypericum genus of Guttiferae family, and possessed intriguing chemical structures and appealing biological activities. Two new PPAPs derivatives, hyperacmosin C (1) and hyperacmosin D (2) were isolated from H. acmosepalum. Their structures were established by NMR, HREIMS, and experimental electronic circular dichroism spectra. Besides, compound 1 showed significant hepatoprotective activity at 10 µM against paracetamol-induced HepG2 cell damage and compound 2 could moderately increase the relative glucose consumption.

Precision Redox: The Key for Antioxidant Pharmacology.

Significance: The redox balance of cells provides a stable microenvironment for biological macromolecules to perform their physiological functions. As redox imbalance is closely related to the occurrence and development of a variety of diseases, antioxidant therapies are an attractive option. However, redox-based therapeutic strategies have not yet shown satisfactory results. To find the key reason is of great significance. Recent Advances: We emphasize the precise nature of redox regulation and elucidate the importance and necessity of precision redox strategies from three aspects: differences in redox status, differences in redox function, and differences in the effects of redox therapy. We then propose the "5R" principle of precision redox in antioxidant pharmacology: "Right species, Right place, Right time, Right level, and Right target." Critical Issues: Redox status must be considered in the context of species, time, place, level, and target. The function of a biomacromolecule and its cellular signaling role are closely dependent on redox status. Accurate evaluation of redox status and specific interventions are critical for the success of redox treatments. Precision redox is the key for antioxidant pharmacology. The precise application of antioxidants as nutritional supplements is also key to the general health of the population. Future Directions: Future studies to develop more accurate methods for detecting redox status and accurately evaluating the redox state of different physiological and pathological processes are needed. Antioxidant pharmacology should consider the "5R" principle rather than continuing to apply global nonspecific antioxidant treatments. Antioxid. Redox Signal. 34, 1069-1082.

Expression profiling and functional verification of flavonoid 3'-hydroxylase gene from leaves of Euryale ferox / 中国中药杂志

Leaves of Euryale ferox are rich in anthocyanins. Anthocyanin synthesis is one of the important branches of the flavonoid synthesis pathway, in which flavonoid 3'-hydroxylase(F3'H) can participate in the formation of important intermediate products of anthocyanin synthesis. According to the data of E. ferox transcriptome, F3'H cDNA sequence was cloned in the leaves of E. ferox and named as EfF3'H. The correlation between EfF3'H gene expression and synthesis of flavonoids was analyzed by a series of bioinforma-tics tools and qRT-PCR. Moreover, the biological function of EfF3'H was verified by the heterologous expression in yeast. Our results showed that EfF3'H comprised a 1 566 bp open reading frame which encoded a hydrophilic transmembrane protein composed of 521 amino acid residues. It was predicted to be located in the plasma membrane. Combined with predictive analysis of conserved domains, this protein belongs to the cytochrome P450(CYP450) superfamily. The qRT-PCR results revealed that the expression level of EfF3'H was significantly different among different cultivars and was highly correlated with the content of related flavonoids in the leaves. Eukaryotic expression studies showed that EfF3'H protein had the biological activity of converting kaempferol to quercetin. In this study, EfF3'H cDNA was cloned from the leaves of E. ferox for the first time, and the biological function of the protein was verified. It provi-ded a scientific basis for further utilizing the leaves of E. ferox and laid a foundation for the further analysis of the biosynthesis pathway of flavonoids in medicinal plants.

Research progress on rutin derivatives / 中国中药杂志

Compounds derived from natural products present satisfactory efficacy in disease prevention and treatment. The use of chemical substances in plants to promote healthhas increasingly attracted people's attention. Rutin, a typical flavonoid, is mainly found in various vegetables, fruits and Chinese herbal medicines. As a natural antioxidant, it features many pharmacological activities, such as anti-inflammation, anti-virus, anti-tumor, and prevention and treatment of cardiovascular and cerebrovascular diseases. However, the low bioavailability and poor water solubility limit its clinical application. In view of this, its structure is optimized and modified to afford rutin derivatives with good solubility, high bioavailability, stable metabolism and small toxic side effects. So far, a large number of rutin ethers, esters, and complexes have been synthesized and undergone activity testing. This paper reviews the structural modification of rutin in recent years, and the obtained derivatives have excellent properties and significant biological activity.

Yishen Tonglong Decoction inhibits the epithelial-mesenchymal transition and Ras/ERK signaling pathway in human prostate cancer DU-145 cells / 中华男科学杂志

Objective@#To observe the effect of Yishen Tonglong Decoction (YTD) on the epithelial-mesenchymal transition (EMT) and Ras/ERK signaling pathway in human PCa DU-145 cells and explore its action mechanism.@*METHODS@#We treated human PCa DU-145 cells with normal plasma (the blank control) or plasma containing 5% (low-dose), 10% (medium-dose) and 15% (high-dose) YTD. After intervention, we examined the proliferation of the DU-145 cells in different groups with CCK-8 and their apoptosis by Annexin V/PI double staining. We detected the cell cycle by PI assay, the invasion and migration of the cells using the Transwell chamber and scratch test, and the expressions of the proteins and genes related to the EMT and Ras/ERK signaling pathways in the cells by Western blot and RT-PCR.@*RESULTS@#Compared with the blank control group, high-, medium- and low-dose YTD significantly inhibited the proliferation of the PCa DU-145 cells, decreased their adherence and growth (P < 0.05, P < 0.01), promoted their apoptosis (P < 0.01), regulated their cell cycles (P < 0.05, P < 0.01), and reduced their in vitro invasion and migration abilities (P < 0.05), all in a dose-dependent manner. The results of Western blot and RT-PCR revealed down-regulated protein and mRNA expressions of N-cadherin, zinc finger transcription factor (Snail), Ras, p-ERK1/2 and ERK1/2, but up-regulated protein and mRNA expressions of E-cadherin in the PCa DU-145 cells treated with YTD (P < 0.05, P < 0.01).@*CONCLUSIONS@#Yishen Tonglong Decoction can effectively inhibit the proliferation, promote the apoptosis, regulate the cell cycle and suppress the invasion and migration abilities and EMT process of human PCa DU-145 cells. The mechanism of Yishen Tonglong Decoction acting on PCa may be associated with its inhibitory effect on the EMT process and expression of the Ras/ERK signaling pathway in PCa cells./.

Preparative Separation of Flavonoids from Goji Berries by Mixed-Mode Macroporous Adsorption Resins and Effect on Aß-Expressing and Anti-Aging Genes.

Flavonoids are the main constituents of Goji berries and have good biological and pharmacological activities. The mixed-mode macroporous adsorption resins (MARs) for purification of flavonoids from Goji berries through computer-assisted calculation of the molecular size of flavonoids and the precise matching of MAR physical and chemical properties was firstly developed in the present study. Ten varieties of MARs with suitable molecular dimensions and polarities were used for investigating the adsorption/desorption behaviors of the flavonoids. Both AUKJ-1 and BWKX-1 showed higher separation efficiency than other MARs and then were mixed in different ratios to constitute a mixed-mode macroporous adsorption resin to obtain the optimal adsorption phase. Under optimal conditions, total flavonoid content of purified flavonoid (p-FLA) extract increased from 0.97% to 36.88% after one purification. The p-FLA extract from Goji berries significantly improved the expression of six genes with anti-aging effects and played an important role in aging-related Alzheimer's disease by down-regulating Aß expression.

Arsenic trioxide ameliorates experimental autoimmune encephalomyelitis in C57BL/6 mice by inducing CD4+ T cell apoptosis.

BACKGROUND: Multiple sclerosis (MS) is an immune-mediated disease of the central nervous system characterized by severe white matter demyelination. Because of its complex pathogenesis, there is no definite cure for MS. Experimental autoimmune encephalomyelitis (EAE) is an ideal animal model for the study of MS. Arsenic trioxide (ATO) is an ancient Chinese medicine used for its therapeutic properties with several autoimmune diseases. It is also used to inhibit acute immune rejection due to its anti-inflammatory and immunosuppressive properties. However, it is unclear whether ATO has a therapeutic effect on EAE, and the underlying mechanisms have not yet been clearly elucidated. In this study, we attempted to assess whether ATO could be used to ameliorate EAE in mice. METHODS: ATO (0.5 mg/kg/day) was administered intraperitoneally to EAE mice 10 days post-immunization for 8 days. On day 22 post-immunization, the spinal cord, spleen, and blood were collected to analyze demyelination, inflammation, microglia activation, and the proportion of CD4+ T cells. In vitro, for mechanistic studies, CD4+ T cells were sorted from the spleen of naïve C57BL/6 mice and treated with ATO and then used for an apoptosis assay, JC-1 staining, imaging under a transmission electron microscope, and western blotting. RESULTS: ATO delayed the onset of EAE and alleviated the severity of EAE in mice. Treatment with ATO also attenuated demyelination, alleviated inflammation, reduced microglia activation, and decreased the expression levels of IL-2, IFN-γ, IL-1ß, IL-6, and TNF-α in EAE mice. Moreover, the number and proportion of CD4+ T cells in the spinal cord, spleen, and peripheral blood were reduced in ATO-treated EAE mice. Finally, ATO induced CD4+ T cell apoptosis via the mitochondrial pathway both in vitro and in vivo. Additionally, the administration of ATO had no adverse effect on the heart, liver, or kidney function, nor did it induce apoptosis in the spinal cord. CONCLUSIONS: Overall, our findings indicated that ATO plays a protective role in the initiation and progression of EAE and has the potential to be a novel drug in the treatment of MS.

Bottom-up and top-down effects on phytoplankton communities in two freshwater lakes.

The relative importance of bottom-up versus top-down effects in aquatic ecosystems remains a longstanding and ongoing controversy. To investigate these effects on phytoplankton communities in freshwater lakes, phytoplankton and zooplankton were sampled, and physical-chemical variables were measured during spring and summer in two important freshwater lakes in northern China: Nansi Lake and Dongping Lake. The redundancy analysis results showed that phytoplankton density and biomass were regulated by physical-chemical variables (bottom-up effects) and predation (top-down effects) together, and the former was more prominent in both lakes. However, the correlation analysis indicated that the top-down effects of zooplankton on phytoplankton were not significant in spring and summer in both lakes, while the bottom-up regulation of physical-chemical variables on phytoplankton had different patterns in the two lakes. In Nansi Lake, the bottom-up effects of physical-chemical variables on phytoplankton were weaker in summer than that in spring due to the abundant nutrients in summer. In Dongping Lake, the bottom-up effects of physical-chemical on phytoplankton were significant both in spring and summer, and the dominant bottom-up control factor shifted from total nitrogen in spring to total phosphorus in summer, with an increased ratio of nitrogen to phosphorus due to changes in limiting factors. In the two studied lakes, with fish culture, the bottom-up effects of phytoplankton on zooplankton were more important than the top-down effects of zooplankton on phytoplankton. These results demonstrate the interactions between phytoplankton and zooplankton and highlight the importance of phytoplankton regulation in freshwater lakes, which has implications for the effective management of freshwater lake ecosystems.