CoCl2-Induced hypoxia promotes hPDLSCs osteogenic differentiation through AKT/mTOR/4EBP-1/HIF-1α signaling and facilitates the repair of alveolar bone defects.

Bone defects are characterized by a hypoxic environment, which affects bone tissue repair. However, the role of hypoxia in the repair of alveolar bone defects remains unclear. Human periodontal ligament stem cells (hPDLSCs) are high-quality seed cells for repairing alveolar bone defects, whose behavior changes under hypoxia. However, their mechanism of action is not known and needs to be elucidated. We hypothesized that hypoxia might be beneficial to alveolar bone defect repair and the osteogenic differentiation of hPDLSCs. To test this hypothesis, cobalt chloride (CoCl2) was used to create a hypoxic environment, both in vitro and in vivo. In vitro study, the best osteogenic effect was observed after 48 h of hypoxia in hPDLSCs, and the AKT/mammalian target of rapamycin/eukaryotic translation initiation factor 4e-binding protein 1 (AKT/mTOR/4EBP-1) signaling pathway was significantly upregulated. Inhibition of the AKT/mTOR/4EBP-1 signaling pathway decreased the osteogenic ability of hPDLSCs under hypoxia and hypoxia-inducible factor 1 alpha (HIF-1α) expression. The inhibition of HIF-1α also decreased the osteogenic capacity of hPDLSCs under hypoxia without significantly affecting the level of phosphorylation of AKT/mTOR/4EBP-1. In vitro study, Micro-CT and tissue staining results show better bone regeneration in hypoxic group than control group. These results suggested that hypoxia promoted alveolar bone defect repair and osteogenic differentiation of hPDLSCs, probably through AKT/mTOR/4EBP-1/HIF-1α signaling. These findings provided important insights into the regulatory mechanism of hypoxia in hPDLSCs and elucidated the effect of hypoxia on the healing of alveolar bone defects. This study highlighted the importance of physiological oxygen conditions for tissue engineering.

Brain potentials reveal how emotion filters native language access when bilinguals read words in their second language.

It is now well established that reading words in a second language (L2) automatically activates native language (L1) translations in bilinguals. Although there is evidence that access to such representations is inhibited when words have a negative emotional valence, the mechanism underlying such inhibition is elusive, and it is unknown whether inhibition arises online as L2 is being processed or whether negative valence affects subsequent L1 processing. Here, we recorded event-related brain potentials in Chinese-English bilinguals engaged in an implicit translation-priming paradigm involving L2 (English) word pairs. Participants performed a semantic relatedness task, unaware that word pairs could conceal a sound repetition if translated into Chinese. When emotional valence was manipulated in prime position (first word), we observed form repetition priming through L1 translations for positive but not for negative words. However, when emotional valence was manipulated in target position (second word), priming occurred for both positive and negative word valences. This result begins to elucidate the mechanism by which emotion regulates language processing in bilinguals: Negative words in L2 induce a refractory period during which cross-language lexical access is blocked. These findings show that despite being neuroanatomically distinct in the human brain, emotional (limbic) regulation systems can penetrate language processing.

Design, synthesis and mechanism study of novel natural-derived isoquinoline derivatives as antifungal agents.

In screening for natural fungicidal leads, two series of novel 3-aryl-isoquinoline derivatives 8 and 9 were designed and synthesized based on sanguinarine, chelerythrine and berberine. Their structures were confirmed by 1D, 2D NMR and HRMS. Most of the title compounds showed medium to excellent antifungal activity in vitro at 50 mg/L, which were much more active than the lead of sanguinarine. Especially, 9f possessed the best effective against Alternaria solani (80.4%), Alternaria alternata (88.2%) and Physalospora piricola (93.8%). Furthermore, the EC50 of 9f (3.651 mg/L) against P. piricola was marginally better than chlorothalonil (3.869 mg/L). In vivo antifungal activity of 9f against P. piricola was studied on apples. The curative and protection results at the dosage of 50 and 100 mg/L showed as 70.45 ~ 81.67% and 64.96 ~ 80.34%, respectively, which were equal to that of chlorothalonil (80.30 ~ 86.67%, 73.08 ~ 76.92%). Molecular electrostatic potential and molecular docking analysis revealed that 9f was fully covered by positive potential contour, which was easier to interact with the negative amino acid resides of succinate dehydrogenase than 8f. 9f could be used as a novel antifungal lead compound for further study. Two series of novel isoquinoline derivatives 8, 9 containing 3-aryl were rational designed and synthesized based on quaternary isoquinoline alkaloids. The bioassay and interaction mechanism studies indicated that 9f should be considered as potential antifungal lead.

Naringenin modulates the NO­cGMP­PKG signaling pathway by binding to AKT to enhance osteogenic differentiation in hPDLSCs.

Naringenin (NAR) is a prominent flavanone that has been recognized for its capacity to promote the osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs). The present study aimed to explore how NAR promotes the osteogenic differentiation of hPDLSCs and to assess its efficacy in repairing alveolar bone defects. For this purpose, a protein­protein interaction network of NAR action was established by mRNA sequencing and network pharmacological analysis. Gene and protein expression levels were evaluated by reverse transcription­quantitative and western blotting. Alizarin red and alkaline phosphatase staining were also employed to observe the osteogenic capacity of hPDLSCs, and immunofluorescence was used to examine the co­localization of NAR molecular probes and AKT in cells. The repair of mandibular defects was assessed by micro­computed tomography (micro­CT), Masson staining and immunofluorescence. Additionally, computer simulation docking software was utilized to determine the binding affinity of NAR to the target protein, AKT. The results demonstrated that activation of the nitric oxide (NO)­cyclic guanosine monophosphate (cGMP)­protein kinase G (PKG) signaling pathway could promote the osteogenic differentiation of hPDLSCs. Inhibition of AKT, endothelial nitric oxide synthase and soluble guanylate cyclase individually attenuated the ability of NAR to promote the osteogenic differentiation of hPDLSCs. Micro­CT and Masson staining revealed that the NAR gavage group exhibited more new bone formation at the defect site. Immunofluorescence assays confirmed the upregulated expression of Runt­related transcription factor 2 and osteopontin in the NAR gavage group. In conclusion, the results of the present study suggested that NAR promotes the osteogenic differentiation of hPDLSCs by activating the NO­cGMP­PKG signaling pathway through its binding to AKT.

{Mo4}-directed structural evolution of highly reduced molybdenum red clusters for efficient proton conduction.

A series of highly reduced Mo red clusters {Mo28} (1), {Mo30} (2), and {Mo40} (3) are synthesized from the rational assembly of planar {MoV4} building blocks and employed for proton conduction. 3 exhibits the best conductivity of 7.56 × 10-3 S cm-1 under optimal conditions due to the most efficient hydrogen-bonding network.

Personality Counts More Than Appearance for Men Making Affective Judgments of Verbal Comments.

Previous research has shown that that evaluative verbal information (praise and criticism) conveys different affective values: criticism is perceived as unpleasant while praise is generally considered pleasant. Here, using praise and criticism in Chinese, we investigated how affective value is modulated in men and women, depending on the particular attribute (personality vs. appearance) targeted by social comments. Results showed that whereas praise was rated as pleasant and criticism as unpleasant overall, criticizing personality reduced pleasantness more than criticizing appearance. In men, moreover, criticism of personality was deemed more unpleasant than criticism of appearance while personality-targeted praise was rated more pleasant than appearance-targeted praise. This effect was absent in women and consistent with men's higher arousal ratings for personality- relative to appearance-targeted comments. Our findings suggest that men are more concerned about external perception of their personality than that of their appearance whereas women's affective judgment is more balanced. These gender-specific results may have implications for topic selection in evaluative social communication.

Utilization of washed MSWI fly ash as partial cement substitute with the addition of dithiocarbamic chelate.

The management of the big amount of fly ash as hazardous waste from the municipal solid waste incinerator (MSWI) has encountered many problems in China. In this study, a feasibility research on MSWI fly ash utilization as partial cement substitute in cement mortars was therefore carried out. MSWI fly ash was subjected to washing process to reduce its chlorine content (from 10.16% to 1.28%). Consequently, it was used in cement mortars. Ten percent and 20% replacement of cement by washed ash showed acceptable strength properties. In TCLP and 180-day monolithic tests, the mortars with washed ash presented a little stronger heavy metal leachability, but this fell to the blank level (mortar without washed ash) with the addition of 0.25% chelate. Therefore, this method is proposed as an environment-friendly technology to achieve a satisfactory solution for MSWI fly ash management.

[Distribution and characters of heavy metals from municipal solid waste incinerator fly ash].

The distribution and characters of heavy metals from municipal solid waste incinerator fly ash was studied in East China. The result indicate that heavy metals in fly ash were mainly distributed in fine particles. The heavy metals including Cd, Pb, Mg, and Cu could migrate easily from fly ash while Ag and Sn would be more stable. The metal mobility changed with the pH level. For environmentally important metals such as Cd, Co, Cu, Mn, Ni, Pb, and Zn, the increase in mobility due to the decrease in pH was more pronounced and significant than for other elements, while Cr and As with the opposite condition.