Substrate-Controlled Regioselective Cascade Reactions of Deconjugated Butenolides and Cinnamaldehydes: Access to Structurally Diverse Spirobutenolides.

Two different cascade pathways to access spirobutenolides were achieved based on the substrate-controlled regioselectivity of deconjugated butenolides. A new class of functional deconjugated butenolides was designed and exhibited superior γ-regioselectivity in the vinylogous Michael/Michael cascade reactions with cinnamaldehydes. The aryl-substituted deconjugated butenolides and cinnamaldehydes underwent a Michael/Michael/aldol/dehydration cascade process induced by double α-regioselectivities. Both conjugated and deconjugated spirobutenolides could be obtained in good yields with excellent enantioselectivities.

Single-cluster Functionalized TiO2 Nanotube Array for Boosting Water Oxidation and CO2 Photoreduction to CH3OH.

Solar-driven CO2 reduction and water oxidation to liquid fuels represents a promising solution to alleviate energy crisis and climate issue, but it remains a great challenge for generating CH3OH and CH3CH2OH dominated by multi-electron transfer. Single-cluster catalysts with super electron acceptance, accurate molecular structure, customizable electronic structure and multiple adsorption sites, have led to greater potential in catalyzing various challenging reactions. However, accurately controlling the number and arrangement of clusters on functional supports still faces great challenge. Herein, we develop a facile electrosynthesis method to uniformly disperse Wells-Dawson- and Keggin-type polyoxometalates on TiO2 nanotube arrays, resulting in a series of single-cluster functionalized catalysts P2M18O62@TiO2 and PM12O40@TiO2 (M=Mo or W). The single polyoxometalate cluster can be distinctly identified and serves as electronic sponge to accept electrons from excited TiO2 for enhancing surface-hole concentration and promote water oxidation. Among these samples, P2Mo18O62@TiO2-1 exhibits the highest electron consumption rate of 1260 µmol g-1 for CO2-to-CH3OH conversion with H2O as the electron source, which is 11 times higher than that of isolated TiO2 nanotube arrays. This work supplied a simple synthesis method to realize the single-dispersion of molecular cluster to enrich surface-reaching holes on TiO2, thereby facilitating water oxidation and CO2 reduction.

Higher cortical excitability to negative emotions involved in musculoskeletal pain in Parkinson's disease.

OBJECTIVE: Changes in brain structure and neurotransmitter systems are involved in pain in Parkinson's disease (PD), and emotional factors are closely related to pain. Our study applied electroencephalography (EEG) to investigate the role of emotion in PD patients with chronic musculoskeletal pain. METHODS: Forty-two PD patients with chronic musculoskeletal pain and 38 without were enrolled. EEG data were recorded under resting conditions, and while viewing pictures with neutral, positive, and negative content. We compared spectrum power, functional connectivity, and late positive potential (LPP), an event-related potential (ERP), between the groups. RESULTS: PD patients with pain tended to have higher scores for the Hamilton Rating Scale for Depression (HRSD). In the resting EEG, mean ß-band amplitude was significantly higher in patients with pain than in those without. Logistic regression analysis showed that higher HRSD scores and higher mean ß-band amplitude were associated with pain. ERP analysis revealed that the amplitudes of LPP difference waves (the absolute difference between positive and negative condition LPP and neutral condition LPP) at the central-parietal region were significantly reduced in patients with pain (P = 0.029). Spearman correlation analysis showed that the amplitudes of late (700-1000 ms) negative versus neutral condition LPP difference waves were negatively correlated with pain intensity, assessed by visual analogue scale, (r = -0.393, P = 0.010) and HRSD scores (r = -0.366, P = 0.017). CONCLUSION: Dopaminergic and non-dopaminergic systems may be involved in musculoskeletal pain in PD by increasing ß-band activity and weakening the connection of the θ-band at the central-parietal region. PD patients with musculoskeletal pain have higher cortical excitability to negative emotions. The changes in pain-related EEG may be used as electrophysiological markers and therapeutic targets in PD patients with chronic pain.

Water-Mediated Selectivity Control of CH3 OH versus CO/CH4 in CO2 Photoreduction on Single-Atom Implanted Nanotube Arrays.

Controllable methanol production in artificial photosynthesis is highly desirable due to its high energy density and ease of storage. Herein, single atom Fe is implanted into TiO2 /SrTiO3 (TSr) nanotube arrays by two-step anodization and Sr-induced crystallization. The resulting Fe-TSr with both single Fe reduction centers and dominant oxidation facets (001) contributes to efficient CO2 photoreduction and water oxidation for controlled production of CH3 OH and CO/CH4 . The methanol yield can reach to 154.20 µmol gcat -1 h-1 with 98.90% selectivity by immersing all the catalyst in pure water, and the yield of CO/CH4 is 147.48 µmol gcat -1 h-1 with >99.99% selectivity when the catalyst completely outside water. This CH3 OH yield is 50 and 3 times higher than that of TiO2 and TSr and stands among all the state-of-the-art catalysts. The facile gas-solid and gas-liquid-solid phase switch can selectively control CH3 OH production from ≈0% (above H2 O) to 98.90% (in H2 O) via slowly immersing the catalyst into water, where abundant •OH and H2 O around Fe sites play important role in selective CH3 OH production. This work highlights a new insight for water-mediated CO2 photoreduction to controllably produce CH3 OH.

CircUBE2Q2 promotes differentiation of cattle muscle stem cells and is a potential regulatory molecule of skeletal muscle development.

BACKGROUND: The growth and development of muscle stem cells (MuSCs) are significant events known to affect muscle plasticity, disease, meat production, and meat quality, which involves the types and functions of mRNA and non-coding RNA. Here, MuSCs were cultured from Guangxi fetal cattle. RNA sequencing was used to analyze the RNA expression of mRNA and non-coding RNAs during the cell proliferation and differentiation phases. RESULTS: Two thousand one hundred forty-eight mRNAs and 888 non-coding RNAs were differentially expressed between cell proliferation and differentiation phases, including 113 miRNAs, 662 lncRNAs, and 113 circRNAs. RT-qPCR verified the differential expression levels of mRNAs and non-coding RNAs, and the differentially expressed circUBE2Q2 was subsequently characterized. Expression profile analysis revealed that circUBE2Q2 was abundant in muscle tissues and intramuscular fat. The expression of cricUBE2Q2 was also significantly upregulated during MuSCs myogenic differentiation and SVFs adipogenic differentiation and decreased with age in cattle muscle tissue. Finally, the molecular mechanism of circUBE2Q2 regulating MuSCs function that affects skeletal muscle development was investigated. The results showed that circUBE2Q2 could serve as a sponge for miR-133a, significantly promoting differentiation and apoptosis of cultured MuSCs, and inhibiting proliferation of MuSCs. CONCLUSIONS: CircUBE2Q2 is associated with muscle growth and development and induces MuSCs myogenic differentiation through sponging miR-133a. This study will provide new clues for the mechanisms by which mRNAs and non-coding RNAs regulate skeletal muscle growth and development, affecting muscle quality and diseases.

Puerariae Lobatae radix flavonoids and puerarin alleviate alcoholic liver injury in zebrafish by regulating alcohol and lipid metabolism.

Exessive drinking is commonly associated with a wide spectrum of liver injuries. The term alcoholic liver disease (ALD) is generally used to refer to this spectrum of hepatic abnormalities, and the term hepatic steatosis denotes early lesions. Puerariae Lobatae Radix (PLR) is a common traditional Chinese medicine and has been widely used as an efficient treatment for alcohol-induced damage. Flavonoids are the principal components of PLR that could potentially be responsible for the activation of alcohol metabolism and lipid-lowering effects. However, little is known about the mechanisms underlying their activity against alcoholic injury. In this study, PLR flavonoids (PLF) were obtained by microwave extraction. A 2% ethanol solution was used to establish a model of alcoholic fatty liver disease by exposure of zebrafish larvae for 32 h, and then the zebrafish were administered PLF and puerarin. The results showed that PLF and puerarin significantly decreased lipid accumulation and the levels of total cholesterol and triglycerides in zebrafish larvae. Moreover, PLF and puerarin downregulated the expression of genes related to alcohol and lipid metabolism (CYP2y3, CYP3a65, ADH8a, ADH8b, HMGCRB, and FASN), endoplasmic reticulum stress, and DNA damage (CHOP, EDEM1, GADD45αa, and ATF6) and reduced levels of inflammatory factors (IL-1ß, TNF-α) in zebrafish larvae. PLF and puerarin increased the phosphorylation of AMP-activated protein kinase-α (AMPKα) and decreased the total protein level of ACC1. The findings suggested that PLF and puerarin alleviated alcohol-induced hepatic steatosis in zebrafish larvae by regulating alcohol and lipid metabolism, which was closely related to the regulation of the AMPKα-ACC signaling pathway. In conclusion, the study provided a possible therapeutic drug for ALD treatment.

Hydrogen Sulfide Reverses Aging-Associated Amygdalar Synaptic Plasticity and Fear Memory Deficits in Rats.

As an endogenous neuromodulator, hydrogen sulfide (H2S) exerts multiple biological effects in the brain. Previous studies have shown that H2S is involved in the regulation of neural synaptic plasticity and cognition in healthy rodents. It is well known that there is a progressive decline of cognitive function that occurs with increased age. The purpose of this study was to investigate the role of H2S in aging-associated amygdalar synaptic plasticity and cued fear memory deficits as well as to explore the underlying mechanisms. We found that H2S levels in the amygdala were significantly lower in aged rats when compared with healthy adult rates, which displayed significant deficits in long-term potentiation (LTP) in the thalamo-lateral amygdala (LA) pathway and amygdala-dependent cued fear memory. Bath application of an H2S donor, sodium hydrogen sulfide (NaHS), significantly reversed the impaired LTP in brain slices from aged rats, and intra-LA infusion of NaHS restored the cued fear memory in aged rats. Mechanismly, we found that H2S treatment significantly enhanced NMDAR-mediated synaptic responses in the thalamo-LA pathway of aged rats. Notably, GluN2B-containing NMDARs, but not GluN2A-containing NMDARs, contributed to the effects of H2S on aging-associated impairments of amygdalar LTP and fear memory, because applying GluN2B antagonist could abolish the beneficial effects of NaHS treatment on amygdalar LTP and cognitive performance in aged rats. Collectively, these results show that H2S can reverse aging-associated amygdalar synaptic plasticity and fear memory deficits by restoring the function of GluN2B-containing NMDARs, suggesting that supplement of H2S might be a therapeutic approach for aging-related cognitive disorders.

Decreased expression of ALDH1L1 is associated with a poor prognosis in hepatocellular carcinoma.

Microarray data suggested that the expression of aldehyde dehydrogenase 1 family member L1 (ALDH1L1) is reduced in hepatocellular carcinoma (HCC). However, the role of ALDH1L1 in HCC carcinogenesis has not been elucidated. In the present study, we investigated the expression of ALDH1L1 in HCC and evaluated its relationship with clinical features and prognosis of HCC patients. Total 112 tumor samples were collected from patients with HCC, who underwent radical hepatectomy. Out of the 112 samples, 16 paired HCC tumorous and corresponding adjacent nontumor tissues were analyzed by real-time quantitative RT-PCR (qRT-PCR) and Western blotting, and the other 96 HCC samples were detected by immunohistochemical method. The qRT-PCR assay showed that the mRNA level of ALDH1L1 was significantly reduced in tumorous tissues compared with the adjacent nontumorous tissues (P = 0.0007), and Western blotting indicated that protein level of ALDH1L1 also notably down-regulated in tumor tissues. Immunohistochemistry detection revealed that decreased ALDH1L1 expression was present in 56.3% (54/96) of HCC patients. Correlation analysis showed that ALDH1L1 expression was significantly correlated with histological differentiation (P = 0.001), HBsAg status (P = 0.024) and serum AFP (P = 0.001). Patients with low expression of ALDH1L1 had poorer prognosis than those with high expression (P = 0.008). Multivariate analysis showed that ALDH1L1 expression was an independent predictor of overall survival (HR, 0.349; 95% CI, 0.157-0.774; P = 0.01). The results in this study, for the first time, reveal that the mRNA and protein expressions of ALDH1L1 are significantly reduced in HCC tissues and its low protein expression is a new and potential prognostic marker for the survival of HCC patients.

Maternal methyl supplements increase offspring DNA methylation at Axin Fused.

Transient environmental exposures during mammalian development can permanently alter gene expression and metabolism by influencing the establishment of epigenetic gene regulatory mechanisms. The genomic characteristics that confer such epigenetic plasticity upon specific loci, however, have not been characterized. Methyl donor supplementation of female mice before and during pregnancy permanently increases DNA methylation at the viable yellow agouti (A(vy)) metastable epiallele in the offspring. The current study tested whether another murine metastable epiallele, axin fused (Axin(Fu)), similarly exhibits epigenetic plasticity to maternal diet. We found that methyl donor supplementation of female mice before and during pregnancy increased DNA methylation at Axin(Fu) and thereby reduced by half the incidence of tail kinking in Axin(Fu)/+ offspring. The hypermethylation was tail-specific, suggesting a mid-gestation effect. Our results indicate that stochastic establishment of epigenotype at metastable epialleles is, in general, labile to methyl donor nutrition, and such influences are not limited to early embryonic development.

Post-weaning diet affects genomic imprinting at the insulin-like growth factor 2 (Igf2) locus.

IGF2 loss of imprinting (LOI) is fairly prevalent and implicated in the pathogenesis of human cancer and developmental disease; however, the causes of this phenomenon are largely unknown. We determined whether the post-weaning diet of mice affects allelic expression and CpG methylation of Igf2. C57BL/6JxCast/EiJ F1 hybrid mice were weaned onto (1) a standard natural ingredient control diet, (2) a synthetic control diet or (3) a synthetic methyl-donor-deficient diet lacking folic acid, vitamin B(12), methionine and choline. Maternal Igf2 expression in kidney was negligible at birth, but increased to approximately 10% of total expression after 60 days on the natural control diet. By 60 days post-weaning, both synthetic diets caused significant LOI of Igf2 relative to animals weaned onto the natural control diet. Total Igf2 expression was significantly reduced in these groups, however, indicating that the increase in relative maternal Igf2 expression was caused by specific down-regulation of the paternal allele. The LOI induced by the synthetic-deficient diet persisted during a subsequent 100-day 'recuperation' period on natural ingredient diet. There were no group differences in overall or allele-specific CpG methylation in the H19 differentially methylated region (DMR), Igf2 DMR0 or Igf2 DMR1. At 30 and 60 days post-weaning, however, the paternal allele of Igf2 DMR2 was hypermethylated in the kidneys of mice on the control synthetic diet. These results indicate that post-weaning diet can permanently affect expression of Igf2, suggesting that childhood diet could contribute to IGF2 LOI in humans.