Therapeutic Effects and Metabolic Spectrum of Traditional Chinese Medicine Hengqing II Prescription on Alzheimer's Disease.

Alzheimer's disease (AD) seriously damages elders' social and daily abilities around the world. Traditional Chinese medicine (TCM), a rich drug resource bank, could help research AD. In order to explore the role of TCM in AD treatment, 86 AD patients were recruited from the hospital, then treated with Hengqing II prescription and donepezil hydrochloride. The cognitive and serum lipid levels were investigated before and after treatment. The patient's urine was collected after three months of treatment. Metabolites in the urine samples were extracted with methanol and detected on the UHPLC-MS platform. Results proved that Hengqing II can improve cognitive levels and reduce the levels of Hcy, D-D, FIB, Apo B, TC, and LDL-C compared with donepezil hydrochloride (P < 0.05). The results of multivariate statistical analysis revealed that the metabolism of HQII was significantly different compared with Control groups. A total of 66 differential metabolites were found in this comparison (50 were down-regulated and 16 were up-regulated). Four amino acid pathways and one linoleic acid pathway were found through these metabolites. After receiver operating characteristic analysis, it was suggested that palmitic acid, palmitoleic acid, linoleic acid, oleic acid, SAH, and methionine can be used as biomarkers for treating AD, while the effects of daidzein, genistein, and naringenin on the treatment of AD need to be further studied.

Cognitive, psychological and social factors associated with older adults' mobility: a scoping review of self-report and performance-based measures.

Although many factors have been associated with mobility among older adults, there is paucity of research that explores the complexity of factors that influence mobility. This review aims to synthesise the available evidence for factors comprising the cognitive, psychological, and social mobility determinants and their associations with mobility self-reported and performance-based outcomes in older adults (60 years). We followed Arksey and O'Malley's five stages of a scoping review and searched PubMed, EMBASE, PsychINFO, Web of Science, AgeLine, Allied and Complementary Medicine Database, Cumulative Index to Nursing and Allied Health Literature and Sociological Abstract databases. Reviewers in pairs independently conducted title, abstract, full-text screening and data extraction. We reported associations by analyses rather than articles because articles reported multiple associations for factors and several mobility outcomes. Associations were categorised as significantly positive, negative, or not significant. We included 183 peer-reviewed articles published in 27 countries, most of which were cross-sectional studies and conducted among community-dwelling older adults. The 183 articles reported 630 analyses, of which 381 (60.5%) were significantly associated with mobility outcomes in the expected direction. For example, older adults with higher cognitive functioning such as better executive functioning had better mobility outcomes (e.g., faster gait speed), and those with poor psychological outcomes, such as depressive symptoms, or social outcomes such as reduced social network, had poorer mobility outcomes (e.g., slower gait speed) compared to their counterparts. Studies exploring the association between cognitive factors, personality (a psychological factor) and self-reported mobility outcomes (e.g., walking for transportation or driving), and social factors and performance-based mobility outcomes in older adults are limited. Understanding the additive relationships between cognitive, psychological, and social factors highlights the complexity of older adults' mobility across different forms of mobility, including independence, use of assistive devices, transportation, and driving.

Metabolomics Deciphering the Potential Biomarkers of Hengqing I Prescription against Vascular Dementia.

With the aging of population, vascular dementia (VaD) seriously threatens people's health and quality of life. It is of great significance to explore biomarkers of VaD from the perspective of metabolomics and traditional Chinese medicine (TCM). Therefore, VaD was divided into kidney deficiency and blood stasis syndrome (KDBS) and non-KDBS according to TCM. Then, some patients received the treatment of Hengqing I (HQI) prescription. The urine of six groups (VaD group, normal group, KDBS group, non-KDBS group, HQI group, and control group) was detected on LC-MS/MS. Multivariate statistical analysis showed that the metabolic profiles of the three comparisons were significantly different. The top analysis-ready molecules of downregulated histamine and upregulated biotin, methionine, pantothenic acid, SAH, histidine, and kaempferol may be the most related metabolites. These putative biomarkers play an important role in the regulation of key metabolic processes linked to VaD. Additionally, pathway analysis showed aminoacyl-tRNA biosynthesis, and amino acids metabolic pathways were highly correlated with the occurrence of VaD. In this present paper, vitamins, amino acids, and their derivatives were selected as the basis for VaD diagnosis and treatment monitoring, and the significance of TCM classification and Hengqing I prescription in the treatment of VaD was discussed.

Metal ion implantation into transparent dielectric slab: an effective route to high-stability localized surface plasmon resonance sensors.

Ag/SiO2and Au/SiO2samples were prepared by separately implanting 30 keV Ag and Au ions into 0.5-mm-thick SiO2slabs at a fluence of 6 × 1016ion·cm-2, and their optical and structural properties were studied in detail by using a fiber spectrometer and a transmission electron microscope, respectively. Our results showed that the two samples featured by their respective nanocomposite surface layers were asymmetrical in structure, and hence, their characteristic signals in the reflectance spectra excited by the lights incident from the rear surfaces were able to exhibit corresponding blueshifts when the overlays on the implanted surfaces were increased in refractive index with respect to air. Our results also showed that each of characteristic signals was strongly dependent on the localized surface plasmon resonance (LSPR) behavior of the involved Ag or Au nanoparticles (NPs), and it could not appear at a wavelength position smaller than or equal to that of the LSPR absorption peak since the involved Ag or Au NPs were quite small in size. These results meant that the two samples could be regarded as the LSPR sensors with a negative refractive index sensitivity (RIS), although their sensing abilities would lose when the overlays were very large in refractive index. Especially, the two samples were demonstrated to be relatively high in stability because the involved Ag and Au NPs were closely hugged and chemically protected by the matrices of SiO2, and consequently, they could have a chance to become prospective sensing devices in some special fields as long as their RISs and linearities could be improved in the future. The above findings substantially confirmed that the metal ion implantation into transparent dielectric slab was an effective route to the high-stability LSPR sensors.

A new sawfly of Megalodontesidae (Insecta, Hymenoptera, Pamphilioidea) with pectinate antennae from the Early Cretaceous of China.

A new sawfly of Megalodontesidae, Jibaissodes peichenae sp. nov., is described from the Lower Cretaceous Yixian Formation of Northeastern China. It is established mainly based on the pectinate antenna comprising 42 flagellomeres and the proximal 28 bearing apical rami, which gradually shorten in length toward the apex of the flagellum. The pterostigma of the forewing is infuscated apically and on the hind wing, vein 1-Rs is nearly equal to 1r-m and slightly shorter than 1-M. The first tergum is widely excised posteriorly and roundly protruding laterally alike in Megalodontes. This find supports that pectinate antennae in extant sawflies of Megalodontesidae originated at least during or before the Early Cretaceous.

Thioether-functionalized trifluoromethyl-alkynes, 1,3-dienes and allenes: divergent synthesis from reaction of 2-trifluoromethyl-1,3-conjugated enynes with sulfur nucleophiles.

A divergent synthesis of thioether-functionalized trifluoromethyl-alkynes, 1,3-dienes and allenes via regioselective nucleophilic addition of sulfur nucleophiles to 2-trifluoromethyl-1,3-conjugated enynes was developed. The addition patterns depend on the type of enyne, sulfur nucleophile and reaction conditions used. 1,4-Addition leading to thioether-functionalized trifluoromethyl-allenes was realized when enynes possessing electron-withdrawing aryl groups on the alkyne moiety were used as reaction partners and alkanethiols were used as nucleophiles, whereas solvent-controlled construction of thioether-functionalized 1,3-dienes and alkynes was realized, respectively, via a 3,4-addition pattern or 1,2-addition pattern if thiophenols were applied as nucleophiles. The three types of compounds containing both sulfur and fluorine elements are valuable building blocks for synthesis of multifunctional fluorinated vinyl sulfides and thiophene derivatives.

DNA methyltransferase activity detection based on fluorescent silver nanocluster hairpin-shaped DNA probe with 5'-C-rich/G-rich-3' tails.

DNA methylation has received a large amount of attention due to its close relationship to a wide range of biological phenomena, such as gene activation, gene imprinting, and chromatin stability. Herein, we have designed a hairpin-shaped DNA probe with 5'-C-rich/G-rich-3' tails and developed a simple and reliable fluorescence turn-off assay for DNA adenine methylation (Dam) methyltransferase (MTase) detection combining site recognition and the fluorescence enhancement of DNA-templated silver nanoclusters (DNA-AgNCs) by guanine-rich DNA sequences. A designed hairpin probe with 5' CCCTTACCCC and 3' GGGTGGGGTGGGGTGGGG displays a bright red emission after reacting with AgNO3 and NaBH4. In the presence of Dam MTase, the methylation-sensitive restriction endonuclease Dpn I which has the same recognition site with the Dam MTase can split the probe, freeing the G-rich sequence from the C-rich sequence, thus quenching the fluorescence of DNA-AgNCs. Compared to traditional fluorescent-based methods, this strategy is simple and inexpensive. A linear response to concentrations of Dam MTase which range from 1 U/mL to 100 U/mL and a detection limit of 1 U/mL are obtained without any amplification steps. In addition, we also demonstrate the method can be used for evaluation and screening of inhibitors for Dam MTase.

The bed nucleus of the stria terminalis is critical for anxiety-related behavior evoked by CO2 and acidosis.

Carbon dioxide (CO2) inhalation lowers brain pH and induces anxiety, fear, and panic responses in humans. In mice, CO2 produces freezing and avoidance behavior that has been suggested to depend on the amygdala. However, a recent study in humans with bilateral amygdala lesions revealed that CO2 can trigger fear and panic even in the absence of amygdalae, suggesting the importance of extra-amygdalar brain structures. Because the bed nucleus of the stria terminalis (BNST) contributes to fear- and anxiety-related behaviors and expresses acid-sensing ion channel-1A (ASIC1A), we hypothesized that the BNST plays an important role in CO2-evoked fear-related behaviors in mice. We found that BNST lesions decreased both CO2-evoked freezing and CO2-conditioned place avoidance. In addition, we found that CO2 inhalation caused BNST acidosis and that acidosis was sufficient to depolarize BNST neurons and induce freezing behavior; both responses depended on ASIC1A. Finally, disrupting Asic1a specifically in the BNST reduced CO2-evoked freezing, whereas virus-vector-mediated expression of ASIC1A in the BNST of Asic1a(-/-) and Asic1a(+/+) mice increased CO2-evoked freezing. Together, these findings identify the BNST as an extra-amygdalar fear circuit structure important in CO2-evoked fear-related behavior.

Acid-sensing ion channels contribute to synaptic transmission and inhibit cocaine-evoked plasticity.

Acid-sensing ion channel 1A (ASIC1A) is abundant in the nucleus accumbens (NAc), a region known for its role in addiction. Because ASIC1A has been suggested to promote associative learning, we hypothesized that disrupting ASIC1A in the NAc would reduce drug-associated learning and memory. However, contrary to this hypothesis, we found that disrupting ASIC1A in the mouse NAc increased cocaine-conditioned place preference, suggesting an unexpected role for ASIC1A in addiction-related behavior. Moreover, overexpressing ASIC1A in rat NAc reduced cocaine self-administration. Investigating the underlying mechanisms, we identified a previously unknown postsynaptic current during neurotransmission that was mediated by ASIC1A and ASIC2 and thus well positioned to regulate synapse structure and function. Consistent with this possibility, disrupting ASIC1A altered dendritic spine density and glutamate receptor function, and increased cocaine-evoked plasticity, which resemble changes previously associated with cocaine-induced behavior. Together, these data suggest that ASIC1A inhibits the plasticity underlying addiction-related behavior and raise the possibility of developing therapies for drug addiction by targeting ASIC-dependent neurotransmission.