Two-Dimensional Spin-Crossover Molecular Solid Solutions with Tunable Transition Temperatures across 90 K.

Spin-crossover (SCO) materials exhibit remarkable potential as bistable switches in molecular devices. However, the spin transition temperatures (Tc) of known compounds are unable to cover the entire ambient temperature spectrum, largely limiting their practical utility. This study reports an exemplary two-dimensional SCO solid solution system, [FeIII(H0.5LCl)2-2x(H0.5LF)2x]·H2O (H0.5LX = 5-X-2-hydroxybenzylidene-hydrazinecarbothioamide, X = F or Cl, x = 0 to 1), in which the adjacent layers are adhered via hydrogen bonding. Notably, the Tc of this system can be fine-tuned across 90 K (227-316 K) in a linear manner by modulating the fraction x of the LF ligand. Elevating x results in strengthened hydrogen bonding between adjacent layers, which leads to enhanced intermolecular interactions between adjacent SCO molecules. Single-crystal diffraction analysis and periodic density functional theory calculations revealed that such a special kind of alteration in interlayer interactions strengthens the FeIIIN2O2S2 ligand field and corresponding SCO energy barrier, consequently resulting in increased Tc. This work provides a new pathway for tuning the Tc of SCO materials through delicate manipulation of molecular interactions, which could expand the application of bistable molecular solids to a much wider temperature regime.

Vascular smooth muscle-specific LRRC8A knockout ameliorates angiotensin II-induced cerebrovascular remodeling by inhibiting the WNK1/FOXO3a/MMP signaling pathway.

Hypertensive cerebrovascular remodeling involves the enlargement of vascular smooth muscle cells (VSMCs), which activates volume-regulated Cl- channels (VRCCs). The leucine-rich repeat-containing family 8 A (LRRC8A) has been shown to be the molecular identity of VRCCs. However, its role in vascular remodeling during hypertension is unclear. In this study, we used vascular smooth muscle-specific LRRC8A knockout (CKO) mice and an angiotensin II (Ang II)-induced hypertension model. The results showed that cerebrovascular remodeling during hypertension was ameliorated in CKO mice, and extracellular matrix (ECM) deposition was reduced. Based on the RNA-sequencing analysis of aortic tissues, the level of matrix metalloproteinases (MMPs), such as MMP-9 and MMP-14, were reduced in CKO mice with hypertension, which was further verified in vivo by qPCR and immunofluorescence analysis. Knockdown of LRRC8A in VSMCs inhibited the Ang II-induced upregulation of collagen I, fibronectin, and matrix metalloproteinases (MMPs), and overexpression of LRRC8A had the opposite effect. Further experiments revealed an interaction between with-no-lysine (K)-1 (WNK1), which is a "Cl--sensitive kinase", and Forkhead transcription factor O3a (FOXO3a), which is a transcription factor that regulates MMP expression. Ang II induced the phosphorylation of WNK1 and downstream FOXO3a, which then increased the expression of MMP-2 and MMP-9. This process was inhibited or potentiated when LRRC8A was knocked down or overexpressed, respectively. Overall, these results demonstrate that LRRC8A knockout in vascular smooth muscle protects against cerebrovascular remodeling during hypertension by reducing ECM deposition and inhibiting the WNK1/FOXO3a/MMP signaling pathway, demonstrating that LRRC8A is a potential therapeutic target for vascular remodeling-associated diseases such as stroke.

Enhanced production of health-promoting phenolic compounds using a novel endophytic fungus Talaromyces neorugulosus R-209 isolated from pigeon pea in a natural habitat by l-phenylalanine feeding.

In this study, nine endophytic fungi capable of producing multiple phenolic compounds were screened and identified from 152 fungi isolated from pigeon pea in a natural habitat (Honghe, Yunnan Province, China). Talaromyces neorugulosus R-209 exhibited the highest potential for phenolic compound production. L-phenylalanine feeding was used to enhance phenolic compound production in T. neorugulosus R-209 cultures. Under the optimal feeding conditions (l-phenylalanine dose of 0.16 g/L and feeding phase of 6 days), the yields of genistein, apigenin, biochanin A, and cajaninstilbene acid increased by 15.59-fold, 7.20-fold, 25.93-fold, and 10.30-fold over control, respectively. T. neorugulosus R-209 fed with l-phenylalanine was found to be stable in the production of phenolic compounds during ten successive subcultures. Moreover, bioactivities of extracts of T. neorugulosus R-209 cultures were significantly increased by l-phenylalanine feeding. Overall, l-phenylalanine feeding strategy made T. neorugulosus R-209 more attractive as a promising alternative source for the production of health-beneficial phenolic compounds in the nutraceutical/medicinal industries.

Machine learning applications in breast cancer survival and therapeutic outcome prediction based on multi-omic analysis.

The high heterogeneity within and between breast cancer patients complicates treatment determination and prognosis assessment. Treatment decision-making is influenced by various factors, such as tumor subtype, histological grade, and genotype, necessitating personalized treatment strategies. Prognostic outcomes vary significantly depending on patient-specific conditions. As a critical branch of artificial intelligence, machine learning efficiently handles large datasets and automates decision-making processes. The introduction of machine learning offers new solutions for breast cancer treatment selection and prognosis assessment. In the field of cancer therapy, traditional methods for predicting treatment and survival outcomes often rely on single or few biomarkers, limiting their ability to capture the complexity of biological processes comprehensively. Machine learning analyzes patients' multi-omic data and the intricate patterns of variations during cancer initiation and progression to predict patients' survival and treatment outcomes. Consequently, it facilitates the selection of appropriate therapeutic interventions to implement early intervention and improve treatment efficacy for patients. Here, we first introduce common machine learning methods, and then elaborate on the application of machine learning in the field of survival prediction and prognosis from two aspects: evaluating survival and predicting treatment outcomes for breast cancer patients. The aim is to provide breast cancer patients with precise treatment strategies to improve therapeutic outcomes and quality of life.

Neuronal MeCP2 in the dentate gyrus regulates mossy fiber sprouting of mice with temporal lobe epilepsy.

Sprouting of mossy fibers, one of the most consistent findings in tissue from patients with mesial temporal lobe epilepsy, exhibits several uncommon axonal growth features and has been considered a paradigmatic example of circuit plasticity that occurs in the adult brain. Clarifying the mechanisms responsible may provide new insight into epileptogenesis as well as axon misguidance in the central nervous system. Methyl-CpG-binding protein 2 (MeCP2) binds to methylated genomic DNA to regulate a range of physiological functions implicated in neuronal development and adult synaptic plasticity. However, exploring the potential role of MeCP2 in the documented misguidance of axons in the dentate gyrus has not yet been attempted. In this study, a status epilepticus-induced decrease of neuronal MeCP2 was observed in the dentate gyrus (DG). An essential regulatory role of MeCP2 in the development of functional mossy fiber sprouting (MFS) was confirmed through stereotaxic injection of a recombinant adeno-associated virus (AAV) to up- or down-regulate MeCP2 in the dentate neurons. Chromatin immunoprecipitation sequencing (ChIP-seq) was performed to identify the binding profile of native MeCP2 using micro-dissected dentate tissues. In both dentate tissues and HT22 cell lines, we demonstrated that MeCP2 could act as a transcription repressor on miR-682 with the involvement of the DNA methylation mechanism. Further, we found that miR-682 could bind to mRNA of phosphatase and tensin homolog (PTEN) in a sequence specific manner, thus leading to the suppression of PTEN and excessive activation of mTOR. This study therefore presents a novel epigenetic mechanism by identifying MeCP2/miR-682/PTEN/mTOR as an essential signal pathway in regulating the formation of MFS in the temporal lobe epileptic (TLE) mice. SIGNIFICANCE STATEMENT: Understanding the mechanisms that regulate axon guidance is important for a better comprehension of neural disorders. Sprouting of mossy fibers, one of the most consistent findings in patients with mesial temporal lobe epilepsy, has been considered a paradigmatic example of circuit plasticity in the adult brain. Although abnormal regulation of DNA methylation has been observed in both experimental rodents and humans with epilepsy, the potential role of DNA methylation in this well-documented example of sprouting of dentate axon remains elusive. This study demonstrates an essential role of methyl-CpG-binding protein 2 in the formation of mossy fiber sprouting. The underlying signal pathway has been also identified. The data hence provide new insight into epileptogenesis as well as axon misguidance in the central nervous system.

[Physical growth and neurodevelopment of preterm infants at the corrected age of 18-24 months]. / æ—©äº§å„¿æ ¡æ­£18~24æœˆé¾„ä½“æ ¼ç”Ÿé•¿å’Œç¥žç»å‘è‚²æ°´å¹³ç ”ç©¶.

OBJECTIVES: To investigate the levels of physical growth and neurodevelopment in preterm infants at the corrected age of 18-24 months. METHODS: The physical growth data and neurodevelopment data of 484 preterm infants at corrected age of 18-24 months were prospectively collected by a post-discharge follow-up system for preterm infants. The infants were regularly followed up in Shenzhen Bao'an Maternal and Child Health Hospital Affiliated to Jinan University from April 2018 to December 2021. The neurodevelopment was evaluated by the Children Neuropsychological and Behavioral Scale-Revision 2016. A total of 219 full-term infants served as controls. The infants were divided into groups (extremely preterm, very preterm, moderate late preterm, and full-term) based on gestational age, and the groups were compared in the levels of physical growth and neurodevelopment. RESULTS: Except that the moderate preterm group had a higher length-for-age Z-score than the full-term group (P=0.038), there was no significant difference in physical growth indicators between the preterm groups and the full-term group (P>0.05). Each preterm group had a significantly lower total developmental quotient (DQ) than the full-term group (P<0.05). Except for the social behavior domain, the DQ of other domains in the extremely preterm and very preterm groups was significantly lower than that in the full-term group (P<0.05). The <32 weeks preterm group had a significantly higher incidence rate of global developmental delay than the full-term group (16.7% vs 6.4%, P=0.012), and the incidence rate of global developmental delay tended to increase with the reduction in gestational age (P=0.026). CONCLUSIONS: Preterm infants can catch up with full-term infants in terms of physical growth at the corrected age of 18-24 months, but with a lower neurodevelopmental level than full-term infants. Neurodevelopment monitoring and early intervention should be taken seriously for preterm infants with a gestational age of <32 weeks.

Selenium Status Affects Hypertrophic Growth of Skeletal Muscle in Growing Zebrafish by Mediating Protein Turnover.

BACKGROUND: Selenium (Se) status is closely related to skeletal muscle physiological status. However, its influence on skeletal muscle growth has not been well studied. OBJECTIVES: This study aimed to analyze the impacts of overall Se status (deficient, adequate, and high) on skeletal muscle growth using a growing zebrafish model. METHODS: Zebrafish (1.5-mo-old) were fed graded levels of Se (deficient: 0.10 mg Se/kg; marginally deficient: 0.22 mg Se/kg; adequate: 0.34 mg Se/kg; high: 0.44, 0.57, and 0.69 mg Se/kg) as Se-enriched yeast for 30 d. Zebrafish growth, and Se accumulation, selenoenzyme activity, selenotranscriptome profiles, and oxidative status in the whole body, and selenotranscriptome profiles, histological characteristics, biochemicals, and gene and protein expression profiles related to muscle growth in the skeletal muscle were analyzed by model fitting and/or 1-factor ANOVA. RESULTS: Se status biomarkers within the whole body and skeletal muscle indicated that 0.34 mg Se/kg was adequate for growing zebrafish. For biomarkers related to skeletal muscle growth, compared with 0.34 mg Se/kg, 0.10 mg Se/kg decreased the white muscle cross-sectional area (WMCSA) and the mean diameter of white muscle fibers (MDWMF) by 14.4%-15.1%, inhibited protein kinase B-target of rapamycin complex 1 signaling by 63.7%-68.5%, and stimulated the autophagy-lysosome pathway by 1.07 times and the ubiquitin-proteasome pathway (UPP) by 96.0% (P < 0.05), whereas 0.22 mg Se/kg only decreased the WMCSA by 7.8% (P < 0.05); furthermore, 0.44 mg Se/kg had no clear effects on skeletal muscle biomarkers, whereas 0.57-0.69 mg Se/kg decreased the WMCSA and MDWMF by 6.3%-25.9% and 5.1%-21.3%, respectively, and stimulated the UPP by 2.23 times (P < 0.05). CONCLUSIONS: A level of 0.34 mg Se/kg is adequate for the growth of zebrafish skeletal muscle, whereas ≤0.10 and ≥0.57 mg Se/kg are too low or too high, respectively, for maintaining efficient protein accretion and normal hypertrophic growth.

Exploration of the core genes in ulcerative interstitial cystitis/bladder pain syndrome.

OBJECTIVE: Interstitial cystitis (IC)/bladder pain syndrome (BPS) is a chronic inflammatory disease that can cause bladder pain and accompanying symptoms, such as long-term urinary frequency and urgency. IC/BPS can be ulcerative or non-ulcerative. The aim of this study was to explore the core genes involved in the pathogenesis of ulcerative IC, and thus the potential biomarkers for clinical treatment. MATERIALS AND METHODS: First, the gene expression dataset GSE11783 was downloaded using the Gene Expression Omnibus (GEO) database and analyzed using the limma package in R to identify differentially expressed genes (DEGs). Then, the Database for Annotation, Visualization and Integrated Discovery (DAVID) was used for Gene Ontology (GO) functional analysis, and the Kyoto Encyclopedia of Genes and Genomes (KEGG) was used for pathway enrichment analysis. Finally, the protein-protein interaction (PPI) network was constructed, and key modules and hub genes were determined using the STRING and Cytoscape software. The resulting key modules were then analyzed for tissue-specific gene expression using BioGPS. RESULTS: A total of 216 up-regulated DEGs and 267 down-regulated genes were identified, and three key modules and nine hub genes were obtained. CONCLUSION: The core genes (CXCL8, CXCL1, IL6) obtained in this study may be potential biomarkers of interstitial cystitis with guiding significance for clinical treatment.

Cholesterol-lowering potentials of lactic acid bacteria based on bile-salt hydrolase activity and effect of potent strains on cholesterol metabolism in vitro and in vivo.

This study collected different probiotic isolates from animal and plant sources to evaluate the bile-salt hydrolase activity of probiotics in vitro. The deconjugation potential of bile acid was determined using high-performance liquid chromatography. HepG2 cells were cultured with probiotic strains with high BSH activity. The triglyceride (TG) and apolipoprotein B (apo B) secretion by HepG2 cells were evaluated. Our results show that the BSH activity and bile-acid deconjugation abilities of Pediococcus acidilactici NBHK002, Bifidobacterium adolescentis NBHK006, Lactobacillus rhamnosus NBHK007, and Lactobacillus acidophilus NBHK008 were higher than those of the other probiotic strains. The cholesterol concentration in cholesterol micelles was reduced within 24 h. NBHK007 reduced the TG secretion by 100% after 48 h of incubation. NBHK002, NBHK006, and NBHK007 could reduce apo B secretion by 33%, 38%, and 39%, respectively, after 24 h of incubation. The product PROBIO S-23 produced a greater decrease in the total concentration of cholesterol, low-density lipoprotein, TG, and thiobarbituric acid reactive substance in the serum or livers of hamsters with hypercholesterolemia compared with that of hamsters fed with a high-fat and high-cholesterol diet. These results show that the three probiotic strains of lactic acid bacteria are better candidates for reducing the risk of cardiovascular disease.

[Clinical effect of Yisui decoction plus western medicine in treating multiple system atrophy].

To observe the clinical effect of Yisui decoction plus western medicine in treating multiple system atrophy patients, totally 65 patients from China-Japan Friendship hospital during 2008-2012 with complete clinical data and received consecutive traditional Chinese medicine and western medicine treatment for more than 3 months were observed changes of traditional Chinese medicine symptom score, part 1 of unified multiple system atrophy rating scale, orthostatic hypotension before treatment and after 3 months treatment. After 3 months treatment, total effective rate of traditional Chinese medicine symptom was 70.8%. Compared with before treatment, score of part 1 of unified multiple system atrophy rating scale was obviously reduced after 3 month treatment (P < 0.001). Ex- cept swallow function without significant improvement, the remaining projects of unified multiple system atrophy rating scale were im- proved obviously (P < 0.05), of which the most obvious differences were orthostatic symptoms, falls and intestinal function (P < 0.001). Orthostatic hypotension after 1 month treatment and 3 month treatment was obviously better than before treatment (P < 0.001). There was no significant difference in orthostatic hypotension between 1 month treatment and 3 month treatment. The research results show that Yisui decoction plus western medicine has a certain effect on improving clinical symptoms of multiple system atrophy patients, especially has a significant effect on orthostatic hypotension, and can maintain a stable clinical effect in a certain period of time.

[Exercise and health: from evaluation of health-promoting effects of exercise to exploration of exercise mimetics].

Regular endurance exercise promotes favorable structure and metabolism adaptations in contracting organ (skeletal muscle) and "far-sited" organ (heart, brain, liver, adipose tissue). Exercise induced skeletal muscle remodeling by activating a series of signaling and transcriptional circuitry (e. g., PPARδ, AMPK, SIRT1 and PGC-1α). In addition, contracting skeletal muscle is an endocrine organ producing and releasing myokines (e. g. IL-6, BDNF and Irisin), which work in a hormone-like fashion, exerting specific endocrine effects on " far-sited" organ. It has been suggested that myokines may contribute to exercise-induced protection against several chronic disease. In this review, we discuss recent discoveries that raise the possibility of synthetically mimicking exercise with pathway-specific drugs to improve health.

Effects of different exercise regimens on prognosis of patients with chronic obstructive pulmonary disease: a systematic reviews and meta-analysis.

INTRODUCTION: Skeletal muscle dysfunction is a significant factor contributing to exercise limitation in patients with chronic obstructive pulmonary disease (COPD). Although exercise training is often recommended to enhance patient outcomes, there continues to be ongoing debate regarding its exact effects. OBJECTIVE: The aim of this study is to evaluate the effectiveness of endurance exercise, strength training and combined exercise on cardiorespiratory fitness (including maximal oxygen uptake, maximal minute ventilation, and the 6-minute walk test), strength of lower limbs (measured by leg press), and quality of life (using the COPD Assessment Test) in patients with COPD. By conducting a systematic review and meta-analysis of randomized controlled trials (RCTs), our objective is to provide tailored training methods and intensity recommendations for patients with COPD in order to improve their quality of life. METHODS: The meta-analysis included 10 randomized controlled trials (RCTs) of exercise rehabilitation programs involving 180 patients with COPD that were retrieved from electronic databases (PubMed, Cochrane Library, and Embase). Two reviewers independently assessed the topical relevance, trial quality, and extracted data for the meta-analysis. RESULTS: Meta-analysis showed that primary outcomes representing exercise endurance were elevated under different exercise interventions compared to pre-test, such as maximal oxygen uptake (VO2max (ml/kg/min)) [SMD = 0.40, 95% CI (0.15, 0.64)] and the 6-min walk test (6MWT) [MD = 33.90, 95% CI (25.25, 42.55)], and primary outcomes representing strength also increased, such as leg press (1RM) [MD = 24.59, 95% CI (16.08, 33.11)], while secondary outcomes such as assessments of life such as the COPD Assessment Test (CAT) recovered [MD = 2.51, 95% CI (2.01, 3.00)], with all differences being statistically significant (p < 0.05). However, Maximum minute ventilation (VEmax (L)) [MD = 0.91, 95%CI (3.61, 5.43)] was not statistically significant (p > 0.05) when compared with the post-test data. The sensitivity test data were stable, and the results were reliable. We subgrouped the data from different types of exercise interventions and found that different types of exercise affected the experimental results. CONCLUSION: Exercise interventions have a positive effect on the treatment of patients with COPD, significantly improving functional capacity, aerobic capacity, and exercise tolerance, but they should be individualized and developed according to the patient's condition to achieve the best therapeutic effect.

Synergism between two BLA-to-BNST pathways for appropriate expression of anxiety-like behaviors in male mice.

Understanding how distinct functional circuits are coordinated to fine-tune mood and behavior is of fundamental importance. Here, we observe that within the dense projections from basolateral amygdala (BLA) to bed nucleus of stria terminalis (BNST), there are two functionally opposing pathways orchestrated to enable contextually appropriate expression of anxiety-like behaviors in male mice. Specifically, the anterior BLA neurons predominantly innervate the anterodorsal BNST (adBNST), while their posterior counterparts send massive fibers to oval BNST (ovBNST) with moderate to adBNST. Optogenetic activation of the anterior and posterior BLA inputs oppositely regulated the activity of adBNST neurons and anxiety-like behaviors, via disengaging and engaging the inhibitory ovBNST-to-adBNST microcircuit, respectively. Importantly, the two pathways exhibited synchronized but opposite responses to both anxiolytic and anxiogenic stimuli, partially due to their mutual inhibition within BLA and the different inputs they receive. These findings reveal synergistic interactions between two BLA-to-BNST pathways for appropriate anxiety expression with ongoing environmental demands.

Exserolide J ameliorates lipid accumulation in vitro by regulating liver X receptor alpha and peroxisome proliferator-activated receptor alpha proteins.

Exserolides are isocoumarin derivatives containing lactone moiety. Recently, some isocoumarins have been demonstrated to ameliorate hyperlipidemia, a major factor for inducing cardiovascular diseases. However, the effects and mechanisms of action of exserolides on hyperlipidemia are not known. The aim of this study is to investigate whether the marine fungus Setosphaeria sp.-derived exserolides (compounds I, J, E, and F) exert lipid-lowering effects via improving reverse cholesterol transport (RCT) in vitro. RAW264.7 macrophages and HepG2 cells were used to establish lipid-laden models, and the levels of intracellular lipids and RCT-related proteins were determined by assay kits and Western blotting, respectively. We observed that exserolides (at a 5 µM concentration) significantly decreased intracellular cholesterol and triglyceride levels in oxidized low-density lipoprotein-laden RAW264.7 cells and markedly improved [3H]-cholesterol efflux. Among the four tested compounds, exserolide J increased the protein levels of ATP-binding cassette transporter A1, peroxisome proliferator-activated receptor α (PPARα), and liver X receptor α (LXRα). Furthermore, treatment with exserolides significantly decreased oleic acid-laden lipid accumulation in HepG2 hepatocytes. Mechanistically, exserolides enhance PPARα protein levels; furthermore, compound J increases cholesterol 7 alpha-hydroxylase A1 and LXRα protein levels. Molecular docking revealed that exserolides, particularly compound J, can interact with PPARα and LXRα proteins. These data suggest that the terminal carboxyl group of compound J plays a key role in lowering lipid levels by stimulating LXRα and PPARα proteins. In conclusion, compound J exhibits powerful lipid-lowering effects in vitro. However, its hypolipidemic effects in vivo should be investigated in the future.

A novel surface molecularly imprinted polymer based on the natural biological macromolecule sporopollenin for the specific and efficient adsorption of resveratrol from Polygonum cuspidatum extracts.

Sporopollenin is a natural biological macromolecule consisting of highly cross-linked carbon, hydrogen, and oxygen atoms, with a highly porous structure and multifunctional groups. In this work, a novel surface molecularly imprinted polymer based on magnetically aminated cattail sporopollenin (MACSp-SMIP) was prepared for the specific and efficient adsorption of resveratrol, with the aim of purifying resveratrol from Polygonum cuspidatum extracts. MACSp-SMIP was found to have a porous structure covered with the multi-layered sponge-like imprinted polymers. MACSp-SMIP had a high adsorption capacity for resveratrol (65.77 mg·g-1) and excellent selectivity (imprinting factor 5.64). The adsorption of resveratrol by MACSp-SMIP was a homogeneous diffusion dominated by chemical adsorption with three stages of external diffusion, internal diffusion, and micropore diffusion. MACSp-SMIP was used as an adsorbent in molecularly imprinted solid-phase extraction for the purification of resveratrol from P. cuspidatum extracts, achieving a resveratrol recovery of 94.33 % and a purity of 76.67 % in the final products. MACSp-SMIP maintained a satisfactory recovery of resveratrol (88.18 %) after six cycles. Overall, this work developed a promising biological macromolecule-based adsorbent MACSp-SMIP for the specific and efficient adsorption of resveratrol, and also provided an efficient and simple approach for the selective purification of resveratrol from P. cuspidatum extracts for food/nutraceutical applications.

Enhanced Accumulation of Health-Promoting Cajaninstilbene Acid in Pigeon Pea Hairy Root Cultures Cocultured with an Endophytic Fungus during Early Stages of Colonization.

Endophytic fungi can effectively regulate the biosynthesis of health-beneficial metabolites in plants. However, few studies have revealed how the accumulation of host metabolites varies during interactions with endophytic fungi. Here, pigeon pea hairy root cultures (PPHRCs) were cocultured with an endophytic fungus Penicillium rubens to explore the impact on the biosynthesis and accumulation of cajaninstilbene acid (CSA). The results showed that CSA accumulation in PPHRCs increased significantly (15.29-fold) during the early stages of P. rubens colonization (fungal attachment and invasion phases). Once P. rubens successfully colonized the intercellular gap of hairy roots to form a symbiotic relationship, the CSA levels in PPHRCs decreased drastically. Moreover, P. rubens could be recognized by plant pattern recognition receptors that regulate immunity/symbiosis, triggering the expression of genes related to pathogenesis, CSA biosynthesis, and ABC transporter. Overall, P. rubens could enhance the accumulation of health-promoting CSA in PPHRCs during the early stages of colonization.

Dual action of macrophage miR-204 confines cyclosporine A-induced atherosclerosis.

BACKGROUND AND PURPOSE: Atherosclerosis induced by cyclosporine A (CsA), an inhibitor of the calcineurin/nuclear factor of activated T cells (NFAT) pathway, is a major concern after organ transplantation. However, the atherosclerotic mechanisms of CsA remain obscure. We previously demonstrated that calcineurin/NFAT signalling inhibition contributes to atherogenesis via suppressing microRNA-204 (miR-204) transcription. We therefore hypothesised that miR-204 is involved in the development of CsA-induced atherosclerosis. EXPERIMENTAL APPROACH: ApoE-/- mice with macrophage-miR-204 overexpression were generated to determine the effects of miR-204 on CsA-induced atherosclerosis. Luciferase reporter assays and chromatin immunoprecipitation sequencing were performed to explore the targets mediating miR-204 effects. KEY RESULTS: CsA alone did not significantly affect atherosclerotic lesions or serum lipid levels. However, it exacerbated high-fat diet-induced atherosclerosis and hyperlipidemia in C57BL/6J and ApoE-/- mice, respectively. miR-204 levels decreased in circulating monocytes and plaque lesions during CsA-induced atherosclerosis. The upregulation of miR-204 in macrophages inhibited CsA-induced atherosclerotic plaque formation but did not affect serum lipid levels. miR-204 limited the CsA-induced foam cell formation by reducing the expression of the scavenger receptors SR-BII and CD36. SR-BII was post-transcriptionally regulated by mature miR-204-5p via 3'-UTR targeting. Additionally, nuclear-localised miR-204-3p prevented the CsA-induced binding of Ago2 to the CD36 promoter, suppressing CD36 transcription. SR-BII or CD36 expression restoration dampened the beneficial effects of miR-204 on CsA-induced atherosclerosis. CONCLUSION AND IMPLICATIONS: Macrophage miR-204 ameliorates CsA-induced atherosclerosis, suggesting that miR-204 may be a potential target for the prevention and treatment of CsA-related atherosclerotic side effects.

Rapid determination of total flavonoid content, xanthine oxidase inhibitory activities, and antioxidant activity in Prunus mume by near-infrared spectroscopy.

Evaluating the quality of herbal medicine based on the content and activity of its main components is highly beneficial. Developing an eco-friendly determination method has significant application potential. In this study, we propose a new method to simultaneously predict the total flavonoid content (TFC), xanthine oxidase inhibitory (XO) activity, and antioxidant activity (AA) of Prunus mume using near-infrared spectroscopy (NIR). Using the sodium nitrite-aluminum nitrate-sodium hydroxide colorimetric method, uric acid colorimetric method, and 2,2-diphenyl-1-picrylhydrazyl radical (DPPH) free radical scavenging activity as reference methods, we analyzed TFC, XO, and AA in 90 P. mume samples collected from different locations in China. The solid samples were subjected to NIR. By employing spectral preprocessing and optimizing spectral bands, we established a rapid prediction model for TFC, XO, and AA using partial least squares regression (PLS). To improve the model's performance and eliminate irrelevant variables, competitive adaptive reweighted sampling (CARS) was used to calculate the pretreated full spectrum. Evaluation model indicators included the root mean square error of cross-validation (RMSECV) and determination coefficient (R2) values. The TFC, XO, and AA model, combining optimal spectral preprocessing and spectral bands, had RMSECV values of 0.139, 0.117, and 0.121, with RCV2 values exceeding 0.92. The root mean square error of prediction (RMSEP) for the TFC, XO, and AA model on the prediction set was 0.301, 0.213, and 0.149, with determination coefficient (RP2) values of 0.915, 0.933, and 0.926. The results showed a strong correlation between NIR with TFC, XO, and AA in P. mume. Therefore, the established model was effective, suitable for the rapid quantification of TFC, XO, and AA. The prediction method is simple and rapid, and can be extended to the study of medicinal plant content and activity.

Crocetin protects cardiomyocytes against hypoxia/reoxygenation injury by attenuating Drp1-mediated mitochondrial fission via PGC-1α.

BACKGROUND: Saffron (Crocus sativus L.) has been traditionally used as food, spice, and medicine. Crocetin (CRT), as main bioactive component of saffron, has accumulated pieces of beneficial evidence on myocardial ischemia/reperfusion (I/R) injury. However, the mechanisms are poorly explored. This study aims to investigate the effects of CRT on H9c2 cells under hypoxia/reoxygenation (H/R) and elucidated the possible underlying mechanism. METHODS: H/R attack was performed on H9c2 cells. Cell counting kit-8 was used to detect the cell viability. Cell samples and culture supernatants were evaluated via commercial kits to measure the superoxide dismutase (SOD) activity, malondialdehyde (MDA) content, and cellular adenosine triphosphate (ATP) content. Various fluorescent probes were used to detect cell apoptosis, intracellular and mitochondrial reactive oxygen species (ROS) content, mitochondrial morphology, mitochondrial membrane potential (MMP), and mitochondrial permeability transition pore (mPTP) opening. Proteins were evaluated via Western Blot. RESULTS: H/R exposure severely reduced cell viability and increased LDH leakage. Peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) suppression and dynamin-related protein 1 (Drp1) activation were coincided with excessive mitochondrial fission, mitochondrial permeability transition pore (mPTP) opening and mitochondrial membrane potential (MMP) collapse in H9c2 cells treated with H/R. Mitochondria fragmentation under H/R injury induced ROS over-production, oxidative stress, and cell apoptosis. Notably, CRT treatment significantly prevented mitochondrial fission, mPTP opening, MMP loss, and cell apoptosis. Moreover, CRT sufficiently activated PGC-1α and inactivated Drp1. Interestingly, mitochondrial fission inhibition with mdivi-1 similarly suppressed mitochondrial dysfunction, oxidative stress and cell apoptosis. However, silencing PGC-1α with small interfering RNA (siRNA) abolished the beneficial effects of CRT on H9c2 cells under H/R injury, accompanied with increased Drp1 and p-Drp1ser616 levels. Furthermore, over-expression of PGC-1α with adenovirus transfection replicated the beneficial effects of CRT on H9c2 cells. CONCLUSIONS: Our study identified PGC-1α as a master regulator in H/R-injured H9c2 cells via Drp1-mediated mitochondrial fission. We also presented the evidence that PGC-1α might be a novel target against cardiomyocyte H/R injury. Our data revealed the role of CRT in regulating PGC-1α/Drp1/mitochondrial fission process in H9c2 cells under the burden of H/R attack, and we suggested that modulation of PGC-1α level may provide a therapeutic target for treating cardiac I/R injury.

Research advance in the distribution and ecotoxicological effects of microcystins in aquatic ecosystem.

Cyanotoxins produced by the toxic cyanobacteria is a great threat to global freshwater ecosystems, with hepatotoxic microcystins (MCs) as the most widely distributed and harmful ones. MCs have negative impacts on the structure, function and stability of aquatic ecosystems, posing threats to human health. In this study, we reviewed the distribution of MCs in waterbody, sediments, and different groups of aquatic animals. The toxicity mechanisms of MCs were also reviewed. The ecotoxicological effects of MCs on aquatic animals, aquatic and terrestrial plants, human health risk were summarized. Several biological methods about the prevention and control of MCs were mentioned. Many aspects about MCs that need to be further studied were proposed, aiming to provide a scientific basis for risk assessment and management of MCs.