Fucoidan Improves D-Galactose-Induced Cognitive Dysfunction by Promoting Mitochondrial Biogenesis and Maintaining Gut Microbiome Homeostasis.

Recent studies have indicated that fucoidan has the potential to improve cognitive impairment. The objective of this study was to demonstrate the protective effect and possible mechanisms of fucoidan in D-galactose (D-gal)-induced cognitive dysfunction. Sprague Dawley rats were injected with D-galactose (200 mg/kg, sc) and administrated with fucoidan (100 mg/kg or 200 mg/kg, ig) for 8 weeks. Our results suggested that fucoidan significantly ameliorated cognitive impairment in D-gal-exposed rats and reversed histopathological changes in the hippocampus. Fucoidan reduced D-gal-induced oxidative stress, declined the inflammation level and improved mitochondrial dysfunction in hippocampal. Fucoidan promoted mitochondrial biogenesis by regulating the PGC-1α/NRF1/TFAM pathway, thereby improving D-gal-induced mitochondrial dysfunction. The regulation effect of fucoidan on PGC-1α is linked to the upstream protein of APN/AMPK/SIRT1. Additionally, the neuroprotective action of fucoidan could be related to maintaining intestinal flora homeostasis with up-regulation of Bacteroidota, Muribaculaceae and Akkermansia and down-regulation of Firmicutes. In summary, fucoidan may be a natural, promising candidate active ingredient for age-related cognitive impairment interventions.

Differential interference effects of thermal pollution on the induced defense of different body-sized cladocerans.

Climate warming influences the biological activities of aquatic organisms, including feeding, growth, and reproduction, thereby affecting predator-prey interactions. This study explored the variation in thermal sensitivity of anti-predator responses in two cladoceran species with varying body sizes, Daphnia pulex and Ceriodaphnia cornuta. These species were cultured with or without the fish (Rhodeus ocellatus) kairomone at temperatures of 15, 20, 25, and 30 °C for 15 days. Results revealed that cladocerans of different body sizes exhibited varying responses to fish kairomones in aspects such as individual size, first-brood neonate size, total offspring number, average brood size, growth rate, and reproductive effort. Notably, low temperature differently affected defense responses in cladocerans of different body sizes. Both high and low temperatures moderated the intensity of the kairomone-induced response on body size at maturity. Additionally, low temperature reversed the reducing effect of fish kairomone on the total offspring number, average brood size, and reproductive effort in D. pulex. Conversely, it enhanced the increasing effect of fish kairomone on these parameters in C. cornuta. These results suggest that inducible anti-predator responses in cladocerans are modifiable by temperature. The differential effects of fish kairomones on various cladocerans under temperature influence offer crucial insights for predicting changes in predator-prey interactions within freshwater ecosystems under future climate conditions.

Folic Acid Rescues Dopaminergic Neurons in MPTP-Induced Mice by Inhibiting the NLRP3 Inflammasome and Ameliorating Mitochondrial Impairment.

Parkinson's disease (PD) is marked by the degeneration of dopaminergic neurons of the substantia nigra (SN), with neuroinflammation and mitochondrial dysfunction being key contributors. The neuroprotective potential of folic acid (FA) in the dopaminergic system of PD was assessed in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model. MPTP (20 mg/kg of body weight) was administered to C57BL/6J mice to simulate PD symptoms followed by FA treatment (5 mg/kg of body weight). Behavioral tests, pole, rotarod, and open-field tests, evaluated motor function, while immunohistochemistry, ELISA, RT-qPCR, and Western blotting quantified neuroinflammation, oxidative stress markers, and mitochondrial function. FA supplementation considerably improved motor performance, reduced homocysteine levels and mitigated oxidative damage in the SN. The FA-attenuated activation of the NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome lessened glial cell activity and reduced neuroinflammation. At the molecular level, FA reduced DNA damage, downregulated phosphorylated p53, and induced the expression of peroxisome proliferator-activated receptor α coactivator 1α (PGC-1α), enhancing mitochondrial function. Therefore, FA exerts neuroprotection in MPTP-induced PD by inhibiting neuroinflammation via NLRP3 inflammasome suppression and promoting mitochondrial integrity through the p53-PGC-1α pathway. Notable limitations of our study include its reliance on a single animal model and the incompletely elucidated mechanisms underlying the impact of FA on mitochondrial dynamics. Future investigations will explore the clinical utility of FA and its molecular mechanisms, further advancing it as a potential therapeutic for managing and delaying the progression of PD.

Bifidobacterium animalis subsp. lactis F1-7 Alleviates Lipid Accumulation in Atherosclerotic Mice via Modulating Bile Acid Metabolites to Downregulate Intestinal FXR.

The dysfunction of intestinal microbiota and bile acid metabolism is related to the pathogenesis of atherosclerosis. This study we explored the mechanism of Bifidobacterium animalis subsp. lactis F1-7 (Bif. animalis F1-7), improving atherosclerosis by regulating the bile acid metabolism and intestinal microbiota in the ApoE-/- mice. The Bif. animalis F1-7 effectively reduced aortic plaque accumulation and improved the serum and liver lipid levels in atherosclerotic mice. The untargeted metabolomics revealed that Bif. animalis F1-7 reduced the glycine-conjugated bile acids and the levels of differential metabolite lithocholic acid (LCA) significantly. Downregulation of LCA decreased the intestinal levels of the farnesoid X-activated receptor (FXR) and regulated the bile acid metabolism through the FXR/FGF15/CYP7A1 pathway. Furthermore, the 16srRNA gene sequencing analysis revealed that structural changes in intestinal microbiota with an increase in the abundance of Bifidobacterium, Lactobacillus, Faecalibaculum, Desulfovibrio, and a decrease in Dubosiella, Clostridium_sensu_stricto_1, and Turicibacter following the Bif. animalis F1-7 intervention. Correlation analysis showed that the changes in intestinal microbiota mentioned above were significantly correlated with bile acid metabolism in atherosclerotic mice. In conclusion, this study sheds light on the mechanisms by which Bif. animalis F1-7 regulates atherosclerosis.

Two Stable Bifunctional Zinc Metal-Organic Frameworks with Luminescence Detection of Antibiotics and Proton Conduction.

Functionalized crystalline solids based on metal-organic frameworks (MOFs) enable efficient luminescence detection and high proton conductivity, making them crucial in the realms of environmental monitoring and clean energy. Here, two structurally and functionally distinct zinc-based MOFs, [Zn(TTDPa)(bodca)]·H2O (1) and [Zn(TTDPb)(bodca)]·H2O (2), were successfully designed and synthesized using 3,6-di(pyridin-4-yl)thieno[3,2-b]thiophene (TTDPa) and 2,5-di(pyridin-4-yl)thieno[3,2-b]thiophene (TTDPb) as ligands, in the presence of bicyclo[2.2.2]octane-1,4-dicarboxylic acid (H2bodca). Both 1 and 2 display a three-dimensional (3D) structure with 5-fold interpenetration, and notably, 2 forms a larger one-dimensional pore measuring 17.16 × 10.81 Å2 in size. Fluorescence experiments demonstrate that 1 and 2 can function as luminescent sensors for nitrofurantoin (NFT) and nitrofurazone (NFZ) with low detection limits, remarkable selectivity, and good recyclability. A comprehensive analysis was conducted to investigate the differing sensing effects of compounds 1 and 2 and to explore potential sensing mechanisms. Additionally, at 328 K and 98% relative humidity, 1 and 2 exhibit proton conductivity values of 2.13 × 10-3 and 4.91 × 10-3 S cm-1, respectively, making them suitable proton-conducting materials. Hence, the integration of luminescent sensing and proton conductivity in monophasic 3D Zn-MOFs holds significant potential for application in intelligent multitasking devices.

Puerarin: A review of its mechanisms of action and clinical studies in ophthalmology.

BACKGROUND: Pueraria is the common name of the dried root of either Pueraria montana var. lobata (Willd.) Maesen & S.M.Almeida ex Sanjappa & Predeep (syn. Pueraria lobata (Willd.) Ohwi) or Pueraria montana var. thomsonii (Benth.) M.R.Almeida (syn. Pueraria thomsonii Benth.). Puerarin is a C-glucoside of the isoflavone daidzein extracted from Pueraria. It has been widely investigated to explore its therapeutic role in eye diseases and the molecular mechanisms. PURPOSE: To collect the available literature from 2000 to 2022 on puerarin in the treatment of ocular diseases and suggest the future required directions to improve its medicinal value. METHOD: The content of this review was obtained from databases such as Web of Science, PubMed, Google Scholar, China National Knowledge Infrastructure (CNKI), and the Wanfang Database. RESULTS: The search yielded 428 articles, of which 159 articles were included after excluding duplicate articles and articles related to puerarin but less relevant to the topic of the review. In eleven articles, the bioavailability of puerarin was discussed. Despite puerarin possesses diverse biological activities, its bioavailability on its own is poor. There are 95 articles in which the therapeutic mechanisms of puerarin in ocular diseases was reported. Of these, 54 articles discussed the various signalling pathways related to occular diseases affected by puerarin. The other 41 articles discussed specific biological activities of puerarin. It plays a therapeutic role in ophthalmopathy via regulating nuclear factor kappa-B (NF-ĸB), mitogen-activated protein kinases (MAPKs), PI3K/AKT, JAK/STAT, protein kinase C (PKC) and other related pathways, affecting the expression of tumour necrosis factor α (TNF-α), interleukin-1ß (IL-1ß), intercellular adhesion molecule-1 (ICAM-1), monocyte chemoattractant protein-1 (MCP-1), superoxide dismutase (SOD), B-cell lymphoma-2 (Bcl-2) and other cytokines resulting in anti-inflammatory, antioxidant and anti-apoptotic effects. The clinical applications of puerarin in ophthalmology were discussed in 25 articles. Eleven articles discussed the toxicity of puerarin. The literature suggests that puerarin has a good curative effect and can be used safely in clinical practice. CONCLUSION: This review has illustrated the diverse applications of puerarin acting on ocular diseases and suggested that puerarin can be used for treating diabetic retinopathy, retinal vascular occlusion, glaucoma and other ocular diseases in the clinic. Some ocular diseases are the result of the combined action of multiple factors, and the effect of puerarin on different factors needs to be further studied to improve a more complete mechanism of action of puerarin. In addition, it is necessary to increase the number of subjects in clinical trials and conduct clinical trials for other ocular diseases. The information presented here will guide future research studies.

Whole-genome survey and phylogenetic analysis of Gadus macrocephalus.

Gadus macrocephalus (Pacific cod) is an economically important species on the northern coast of the Pacific. Although numerous studies on G. macrocephalus exist, there are few reports on its genomic data. Here, we used whole-genome sequencing data to elucidate the genomic characteristics and phylogenetic relationship of G. macrocephalus. From the 19-mer frequency distribution, the genome size was estimated to be 658.22 Mb. The heterozygosity, repetitive sequence content and GC content were approximately 0.62%, 27.50% and 44.73%, respectively. The draft genome sequences were initially assembled, yielding a total of 500,760 scaffolds (N50 = 3565 bp). A total of 789,860 microsatellite motifs were identified from the genomic data, and dinucleotide repeat was the most dominant simple sequence repeat motif. As a byproduct of whole-genome sequencing, the mitochondrial genome was assembled to investigate the evolutionary relationships between G. macrocephalus and its relatives. On the basis of 13 protein-coding gene sequences of the mitochondrial genome of Gadidae species, the maximum likelihood phylogenetic tree showed that complicated relationships and divergence times among Gadidae species. Demographic history analysis revealed changes in the G. macrocephalus population during the Pleistocene by using the pairwise sequentially Markovian coalescent model. These findings supplement the genomic data of G. macrocephalus, and make a valuable contribution to the whole-genome studies on G. macrocephalus.

SepNet: A neural network for directionally correlated data.

Multi-dimensional tensor data appear in diverse settings, including multichannel signals, spectrograms, and hyperspectral data from remote sensing. In many cases, these data are directionally correlated, i.e. the correlation between variables from different dimensions is significantly weaker than the correlation between variables from the same dimension. Convolutional neural networks are readily applicable to directionally correlated data but are often inefficient, as they impose many unnecessary connections between neurons. Here we propose a novel architecture, SepNet, specifically for directionally correlated datasets. SepNet uses directional operators to extract directional features from each dimension separately, followed by a linear operator along the depth to generate higher-level features from the directional features. Experiments on two representative directionally correlated datasets showed that SepNet improved network efficiency up to 100-fold while maintaining high accuracy comparable with state-of-the-art convolutional neural network models. Furthermore, SepNet can be flexibly constructed with minimal restriction on the output shape of each layer. These results reveal the potential of data-specific architecting of neural networks.

RFC1 80G>A is a genetic determinant of methotrexate efficacy in rheumatoid arthritis: a human genome epidemiologic review and meta-analysis of observational studies.

OBJECTIVE: Associations have been reported between candidate genes and the response to methotrexate (MTX) in rheumatoid arthritis (RA) patients, but most of the studies have been small and have yielded conflicting results. This study was undertaken to provide a systematic review of all genetic variant associations with MTX efficacy and toxicity, and to conduct a meta-analysis evaluating the most commonly studied single-nucleotide polymorphism for which prior cumulative analysis has been lacking. METHODS: A systematic review and meta-analysis were performed to identify genetic variant associations with MTX efficacy and toxicity. Studies were identified from the Medline, EMBase, HuGENet Navigator, and Cochrane Library databases through December 2012, and from the 2009-2011 abstracts of the American College of Rheumatology and the European League Against Rheumatism annual meeting proceedings. Additional unpublished genotype data from a Canadian cohort of patients with early RA were also included. RESULTS: Among the 87 identified studies examining genetic associations with MTX efficacy and toxicity, the reduced folate carrier 1 gene (RFC1) variant 80G>A (Arg(27) His, rs1051266) was selected for random-effects meta-analysis. RFC1 80G>A was associated with MTX efficacy in both the recessive model (odds ratio [OR] 1.42, 95% confidence interval [95% CI] 1.04-1.93) and the additive model (OR 1.28, 95% CI 1.10-1.49). Restriction of the sensitivity analyses to studies that involved Caucasian subjects only and that used similar outcome measures (MTX failure versus nonfailure) maintained and improved the associations in both models. No significant association between RFC1 80G>A and MTX toxicity was detected. CONCLUSION: In these analyses of available data from observational studies, RFC1 80G>A was found to be associated with MTX efficacy, but not toxicity, in RA patients. This variant merits further prospective analysis as a potential predictor of MTX efficacy. Variability in the definitions of response in pharmacogenetic studies is a source of data heterogeneity that should be addressed.