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Given the malignancy of gastric cancer, developing highly effective and low‐toxic targeted drugs is essential to prolong patient survival and improve patient outcomes. In this study, we conducted structural optimizations based on the benzimidazole scaffold. Notably, compound 8 f presented the most potent antiproliferative activity in MGC803 cells and induced cell cycle arrest at the G0/G1 phase. Further mechanistic studies demonstrated that compound 8 f caused the apoptosis of MGC803 cells by elevating intracellular reactive oxygen species (ROS) levels and activating the mitogen‐activated protein kinase (MAPK) signaling pathway, accompanied by corresponding markers change. In vivo investigations additionally validated the inhibitory effect of compound 8 f on tumor growth in xenograft models bearing MGC803 cells without obvious toxicity. Our studies suggest that compound 8 f holds promise as a potential and safe lead compound for developing anti‐gastric cancer agents. [ABSTRACT FROM AUTHOR]

Cherry Valley ducks (CVDs) and White Kaiya ducks (WKDs) are judged to be fast‐ and slow‐growing lines, respectively. To investigate the carcass traits and nutritional profile at their marketable ages, 12 birds (38 days for CVDs, n = 6; 56 days for WKDs, n = 6) were randomly selected and slaughtered. Indicators such as breast muscle weight, shear force, and proximate composition were comprehensively detected. Although the carcass and breast muscle weight in WKDs were significantly lower, remarkably higher intramuscular fat and tenderness and less moisture content were observed in WKDs. Besides, WKDs contained higher contents of Cu, Zn, and Ca, whereas CVDs contained higher leucine (Leu) and histidine (His) compositions (P < 0.01). Moreover, higher monounsaturated fatty acids (MUFAs) and polyunsaturated fatty acids (PUFAs) along with lower saturated fatty acids (SFAs) were detected in WKDs (P < 0.01). Taken together, despite light carcass and breast muscle weight, WKDs had advantages in nutritional compositions except for amino acid constituents, including intramuscular fat, MUFAs, and PUFAs, as well as Cu, Zn, and Ca. These data would not only provide genetic resources for breeding new duck lines but also offer a useful reference for making decisions on high‐nutrient meat consumption. [ABSTRACT FROM AUTHOR]

The human sensorimotor cortex has multiple subregions showing functional commonalities and differences, likely attributable to their connectivity profiles. However, the molecular substrates underlying such connectivity profiles are unclear. Here, transcriptome‐neuroimaging spatial correlation analyses were performed between transcriptomic data from the Allen human brain atlas and resting‐state functional connectivity (rsFC) of 24 fine‐grained sensorimotor subregions from 793 healthy subjects. Results showed that rsFC of six sensorimotor subregions were associated with expression measures of six gene sets that were specifically expressed in brain tissue. These sensorimotor subregions could be classified into the polygenic‐ and oligogenic‐modulated subregions, whose rsFC were related to gene sets diverging on their numbers (hundreds vs. dozens) and functional characteristics. First, the former were specifically expressed in multiple types of neurons and immune cells, yet the latter were not specifically expressed in any cortical cell types. Second, the former were preferentially expressed during the middle and late stages of cortical development, while the latter showed no preferential expression during any stages. Third, the former were prone to be enriched for general biological functions and pathways, but the latter for specialized biological functions and pathways. Fourth, the former were enriched for neuropsychiatric disorders, whereas this enrichment was absent for the latter. Finally, although the identified genes were commonly associated with sensorimotor behavioral processes, the polygenic‐modulated subregions associated genes were additionally related to vision and dementia. These findings may advance our understanding of the functional homogeneity and heterogeneity of the human sensorimotor cortex from the perspective of underlying genetic architecture. [ABSTRACT FROM AUTHOR]

Zhedong white goose (Anser cygnoides domesticus) is a native Chinese breed with strong broodiness and low egg production, which is related to the physiology of reproduction. However, thus far, the physiology of goose reproduction has not been well elucidated. In the present study, the ovarian morphology and reproductive hormones of Zhedong white geese were investigated during the reproductive cycle (the laying and brooding periods). The results showed that the surface of the ovary was atrophied and follicular atresia appeared to some extent in the brooding period compared with the laying period. The concentrations of follicle‐stimulating hormone, progesterone and luteinizing hormone were significantly higher than those in the brooding period (p < 0.05). In contrast, the concentrations of prolactin (PRL) and anti‐Müllerian hormone (AMH) in the laying period were significantly lower than those in the brooding period (p < 0.05). In addition, the mRNA expression levels of PRL, AMH, dopamine‐β‐hydroxylase (DβH) and cytochrome P450 side‐chain cleavage enzyme (P450scc) were detected in the hypothalamus, pituitary and ovaries by using real‐time polymerase chain reaction. The results showed that AMH mRNA was expressed specifically in ovary tissue. The expression levels of DβH and PRL in the brooding period was significantly higher than those in the laying period in the three tissues, especially in the early and middle stages of the brooding period. Moreover, AMH mRNA expression in the ovaries presented the same trend. In addition, P450scc mRNA was highly expressed in both the ovary and pituitary in the laying period. These results revealed the remarkable features of ovarian morphology and characterized the hormonal pattern and expression profile during the reproductive cycle, all of which contribute to understanding the differences in reproductive physiology between the laying and brooding periods in Zhedong white geese. [ABSTRACT FROM AUTHOR]

Network neuroscience has broadly conceptualized the functions of the brain as complex communication within and between large‐scale neural networks. Nevertheless, whether and how the gut microbiota influence functional network connectivity that in turn impact human behaviors has yet to be determined. We collected fecal samples from 157 healthy young adults and used 16S sequencing to assess gut microbial diversity and enterotypes. Large‐scale inter‐ and intranetwork functional connectivity was measured using a combination of resting‐state functional MRI data and independent component analysis. Sleep quality and core executive functions were also evaluated. Then, we tested for potential associations between gut microbiota, functional network connectivity and behaviors. We found significant associations of gut microbial diversity with internetwork functional connectivity between the executive control, default mode and sensorimotor systems, and intranetwork connectivity of the executive control system. Moreover, some internetwork functional connectivity mediated the relations of microbial diversity with sleep quality, working memory, and attention. In addition, there was a significant effect of enterotypes on intranetwork connectivity of the executive control system, which could mediate the link between enterotypes and executive function. Our findings not only may expand existing biological knowledge of the gut microbiota‐brain‐behavior relationships from the perspective of large‐scale functional network organization, but also may ultimately inform a translational conceptualization of how to improve sleep quality and executive functions through the regulation of gut microbiota. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) regulate gene expression and thereby influence cell development and function. Numerous studies have shown the significant roles of miRNAs in regulating immune cells including natural killer (NK) cells. However, little is known about the role of miRNAs in NK cells with aging. We previously demonstrated that the aged C57BL/6 mice have significantly decreased proportion of mature (CD27−CD11b+) NK cells compared with young mice, indicating impaired maturation of NK cells with aging. Here, we performed deep sequencing of CD27+ NK cells from young and aged mice. Profiling of the miRNome (global miRNA expression levels) revealed that 49 miRNAs displayed a twofold or greater difference in expression between young and aged NK cells. Among these, 30 miRNAs were upregulated and 19 miRNAs were downregulated in the aged NK cells. We found that the expression level of miR‐l8la‐5p was increased with the maturation of NK cells, and significantly decreased in NK cells from the aged mice. Knockdown of miR‐181a‐5p inhibited NK cell development in vitro and in vivo. Furthermore, miR‐181a‐5p is highly conserved in mice and human. MiR‐181a‐5p promoted the production of IFN‐γ and cytotoxicity in stimulated NK cells from both mice and human. Importantly, miR‐181a‐5p level markedly decreased in NK cells from PBMC of elderly people. Thus, our results demonstrated that the miRNAs profiles in NK cells change with aging, the decreased level of miR‐181a‐5p contributes to the defective NK cell development and function with aging. This opens new strategies to preserve or restore NK cell function in the elderly. [ABSTRACT FROM AUTHOR]

Background: Cognitive deterioration and atrophy of the brain gray matter volume (GMV) are the main symptoms of Alzheimer's disease (AD). Accumulated pieces of evidence have shown that plasma concentrations of phosphorylated‐tau (p‐tau) performed better in early diagnosing, differentiating, and monitoring the progression of AD. However, the relationship between plasma p‐tau concentrations, the GMV of brain regions, and cognitive function remains poorly understood. Previous studies indicate that brain GMV may mediate the relationship between biomarkers and cognitive function, and in this study, we aimed to investigate whether GMV plays a mediating role in the association between plasma p‐tau concentrations and cognition. Method: 99 participants in total, including 47 patients with a diagnosis of early AD and 52 cognitively unimpaired (CU) individuals, were enrolled in this study. All participants completed laboratory tests, magnetic resonance imaging scans, and neuropsychological assessments. Plasma p‐tau217 and p‐tau181 concentrations were measured using an enzyme‐linked immunosorbent assay kit. Voxel‐based morphometry was performed to assess brain GMV. Partial correlations and mediation analyses were performed in the AD group. Result: Concentrations of both plasma p‐tau217 and p‐tau181 were significantly higher in the AD group than in the CU group. Patients with AD had significant brain GMV atrophy in the right hippocampus, bilateral middle temporal gyrus, and right inferior temporal gyrus. In the AD group, there were significant correlations between plasma p‐tau217 concentrations, GMV, and Mini‐Mental State Examination (MMSE) scores. Brain GMV of the right hippocampus mediated the association between plasma p‐tau217 concentrations and MMSE scores. We did not find a significant correlation between plasma p‐tau181 concentrations and MMSE scores. Conclusion: The findings indicate that p‐tau217 was a promising biomarker for central processes affecting brain GMV and cognitive function. It may provide potential targets for future intervention and treatment of tau‐targeting therapies at the early stage of AD. [ABSTRACT FROM AUTHOR]

In Arabidopsis, the phytohormone abscisic acid (ABA) plays a vital role in inhibiting seed germination and in postgermination seedling establishment. In the ABA signaling pathway, ABI5, a basic Leu zipper transcription factor, has important functions in the regulation of seed germination. ABI5 protein localizes in nuclear bodies, alongwith AFP, COP1, and SIZ1, and was degraded through the 26S proteasome pathway. However, the mechanisms of ABI5 nuclear body formation and ABI5 protein degradation remain obscure. In this study, we found that the Arabidopsis CROWDED NUCLEI (CRWN) proteins, predicted nuclear matrix proteins essential for maintenance of nuclear morphology, also participate in ABA-controlled seed germination by regulating the degradation ofABI5 protein. During seed germination, the crwn mutants are hypersensitive to ABA and have higher levels of ABI5 protein compared to wild type. Genetic analysis suggested that CRWNs act upstreamof ABI5. The observation that CRWN3 colocalizes with ABI5 in nuclear bodies indicates that CRWNs might participate in ABI5 protein degradation in nuclear bodies. Moreover, we revealed that the extreme C-terminal of CRWN3 protein is necessary for its function in the response to ABA in germination. Our results suggested important roles of CRWNs in ABI5 nuclear body organization and ABI5 protein degradation during seed germination. [ABSTRACT FROM AUTHOR]

Background Information: Substantial evidence indicates the existence of NCSCs (neural crest-derived stem cells) in embryonic mandibular processes; however, they have not been fully investigated or isolated. The aim of the present study was to isolate stem cells from mandibular process during embryonic development by MACS (magnetic-activated cell sorting). The findings show that the cells are multipotent and self-renewing., Results: LNGFR (low-affinity nerve-growth-factor receptor)+ cells were isolated from rat embryonic mandibular processes by MACS. The cells were grown in clonal culture by limiting dilution to assess their developmental potential. Clone analysis indicated that, first, LNGFR+ cells are multipotent, being able to generate at least neurons and Schwann cells, similar to peripheral neural crest stem cells. Secondly, multipotent LNGFR+ cells generate multipotent progenies, indicating that they are capable of self-renewal and therefore are stem cells. Thirdly, manipulation of the medium supplementation alters the fate of the isolated LNGFR+ cells., Conclusions: These results indicate that LNGFR antibodies label NCSCs with high specificity and purity, and suggest that positive selection using these antibodies may become the method of choice for obtaining multipotent cells from rat embryonic mandibular processes for tissue engineering or regenerative therapeutic use.