BackgroundDendrobium officinale Kimura et Migo (D. officinale) is parasitic on rocks or plants with very few mineral elements that can be absorbed directly, so its growth and development are affected ...by nutritional deficiencies. Previous studies found that phosphorus deficiency promotes polysaccharides accumulation in D. officinale, the expression of DoCSLA6 (glucomannan synthase gene) was positively correlated with polysaccharide synthesis. However, the molecular mechanism by which the low phosphorus environment affects polysaccharide accumulation remains unclear.ResultsWe found that DoSPX1 can reduce phosphate accumulation in plants and promote the expression of PSIs genes, thereby enhancing plant tolerance to low phosphorus environments.Y1H and EMSA experimental show that DoMYB37 can bind the promoter of DoCSLA6. DoSPX1 interact with DoMYB37 transiently overexpressed DoSPX1 and DoMYB37 in D. officinale protocorm-like bodies, decreased the Pi content, while increased the expression of DoCSLA6.ConclusionsThe signaling pathway of DoSPX1-DoMYB37-DoCSLA6 was revealed. This provides a theoretical basis for the accumulation of polysaccharide content in D. officinale under phosphorus starvation.
The orange fluorescence of scapolite has been confirmed to be caused by (S2)−, but the frequent blue fluorescence in gem-quality scapolite has not been well explained. An energy dispersive X-ray ...fluorescence spectrometer (XRF), electron probe microanalyzer (EPMA), X-ray powder diffractometer (XRD), Fourier transform infrared spectrometer (FTIR), Raman spectrometer, ultraviolet-visible spectrophotometer, fluorescence spectrometer, and conventional gemological test methods were used to study the gemological characteristics, chemical composition, coloration mechanism, spectral characteristics, and luminescence of colorless and yellow scapolite. The results show that both yellow and colorless scapolites are mizzonite and that they share the same gemological and spectroscopic characteristics. The results of XRD, FIRT, and Raman spectra show that the yellow scapolite has the same structure as the colorless scapolite. The yellow color of scapolite is caused by Fe3+ and when the Fe content is low it is colorless. Yellow scapolite has about three times the Fe content of colorless scapolite. Under the excitation of long-wave and short-wave ultraviolet light, scapolite forms a strong and wide excitation peak in the blue-violet region centered at approximately 410 nm, which is due to the 4f1 → 5d1 of Ce3+, resulting in blue fluorescence.
Purple scapolite is a precious gemstone. In this paper, we compared the crystal structure and spectral characteristics of purple scapolite before and after heat treatment with conventional ...gemological tests, EPMA, XRF, LA-ICP-MS, infrared spectroscopy, Raman spectroscopy, UV–vis spectrophotometer, EPR, and other tests. The XRD results showed that the structure of purple scapolite fits perfectly with that of marialite. Compositional analyses indicate that purple scapolite has an average Me value of 16.85 and belongs to the subspecies marialite, and thus its specific gravity and refractive index are low. The absorption peak at 1045 cm−1 in the infrared spectra has a direct relationship with the Me value, which is blue-shifted with increasing Me value. After heating at 400 °C for 2 h, the purple scapolite changed to colorless, and no phase transformation or significant structural changes occurred during this process. But this process is accompanied by the disappearance of the signal at g = 2.011 in the EPR spectra, which indicates the presence of oxygen hole centers, thus proving that the color of purple scapolite is caused by oxygen hole centers rather than Fe3+. The chlorine in the marialite structure occupies the structural center, which provides for the appearance of oxygen hole centers, and thus purple scapolite always has a high marialite content. This further leads to the refractive index and specific gravity always being lower. That is a new explanation for the relationship between scapolite coloration mechanism, specific gravity, and refractive index.
Drawing on social cognitive career theory (SCCT) and trait activation theory, this study investigated how and when career exploration affects career outcomes in early adulthood with an integrated ...conceptual framework. Data came from a two-wave survey of young Chinese adults (N = 239). This study examined a serial mediation model in which career exploration related to career satisfaction and person-job fit via career success criteria clarity (CSCC) and career decision making self-efficacy (CDSE) sequentially. Results showed, as expected, that more career exploration was related to higher career satisfaction and better person-job fit via higher career success criteria clarity and CDSE. In addition, results indicated that the indirect effect of career exploration on career outcomes becomes stronger when family socioeconomic status is lower. The current research provided insights into the underlying mechanisms between career exploration and career outcomes and the findings offered practical implications for both career educators and consultants.
Opioid Receptors have long been targeted for analgesic and substance abuse treatment. However, current drugs targeting opioid receptors, e.g., morphine, have side effects such as tolerance, ...dependence and respiratory depression that put the public health at high risk. Thus, there is an unmet need for the discovery of new opioid receptor ligands that have improved profiles than the current marketed drugs. We previously identified that dual action ligands of mu opioid receptor agonist/delta opioid receptor antagonist could exert analgesic activity with mitigated side effects, and thus may have an advantage over the current drugs. Subsequently, we have explored the structure‐activity relationship of a 5′‐aryl‐14‐alkoxypyridomorphinan scaffold that exhibits such a dual action profile. In addition to evaluating the pharmacokinetic properties of this scaffold, we also have performed computational docking studies of mu, delta, and kappa opioid receptors in their agonist and antagonist bound states. Docking results and structural analysis have unveiled key residues that may explain the agonist/antagonist mechanism as well as variant residues among different opioid receptor isoforms that can be targeted for selectivity. Encouragingly, the results from in vivo animal studies showed analgesic activity and less side effects versus morphine, such as tolerance, rewarding effect, and respiratory depression. These results suggest that this chemical series possessing the pyridomorphinan scaffold is worthy for further exploration for either novel analgesic agents or substance abuse treatment.
Seed germination is susceptible to external environmental factors, especially salt stress. Suaeda liaotungensis is a halophyte with strong salt tolerance, and the germination rate of brown seeds ...under 1000 mM NaCl treatment still reached 28.9%. To explore the mechanism of salt stress response during brown seed germination in Suaeda liaotungensis, we conducted transcriptomic analysis on the dry seeds (SlD), germinated seeds under the control condition (SlG_C), and salt treatment (SlG_N). Transcriptome analysis revealed that 13314 and 755 differentially expressed genes (DEGs) from SlD vs. SlG_C and SlG_C vs. SlG_N were detected, respectively. Most DEGs were enriched in pathways related to transcription regulation and hormone signal transduction, ROS metabolism, cell wall organization or biogenesis, and carbohydrate metabolic process in two contrasting groups. Compared with the control condition, POD and CAT activity, H2O2, soluble sugar, and proline contents were increased during germinated seeds under salt stress. Furthermore, functional analysis demonstrated that overexpression of SlNAC2 significantly enhanced salt tolerance during the germination stage in Arabidopsis. These results not only revealed the tolerant mechanism of brown seed germination in response to salinity stress but also promoted the exploration and application of salt-tolerant gene resources of Suaeda liaotungensis.
The macrodomain of nsP3 (nsP3MD) is highly conserved among the alphaviruses and ADP-ribosylhydrolase activity of Chikungunya Virus (CHIKV) nsP3MD is critical for CHIKV viral replication and ...virulence. No small molecule drugs targeting CHIKV nsP3 have been identified to date. Here we report small fragments that bind to nsP3MD which were discovered by virtually screening a fragment library and X-ray crystallography. These identified fragments share a similar scaffold, 2-pyrimidone-4-carboxylic acid, and are specifically bound to the ADP-ribose binding site of nsP3MD. Among the fragments, 2-oxo-5,6-benzopyrimidine-4-carboxylic acid showed anti-CHIKV activity with an IC50 of 23 μM. Our fragment-based drug discovery approach provides valuable information to further develop a specific and potent nsP3 inhibitor of CHIKV viral replication based on the 2-pyrimidone-4-carboxylic acid scaffold. In silico studies suggest this pyrimidone scaffold could also bind to the macrodomains of other alphaviruses and coronaviruses and thus, have potential pan-antiviral activity.
The glmS ribozyme catalyzes a self-cleavage reaction at the phosphodiester bond between residues A-1 and G1. This reaction is thought to occur by an acid–base mechanism involving the ...glucosamine-6-phosphate cofactor and G40 residue. Herein quantum mechanical/molecular mechanical free energy simulations and pK a calculations, as well as experimental measurements of the rate constant for self-cleavage, are utilized to elucidate the mechanism, particularly the role of G40. Our calculations suggest that an external base deprotonates either G40(N1) or possibly A-1(O2′), which would be followed by proton transfer from G40(N1) to A-1(O2′). After this initial deprotonation, A-1(O2′) starts attacking the phosphate as a hydroxyl group, which is hydrogen-bonded to deprotonated G40, concurrent with G40(N1) moving closer to the hydroxyl group and directing the in-line attack. Proton transfer from A-1(O2′) to G40 is concomitant with attack of the scissile phosphate, followed by the remainder of the cleavage reaction. A mechanism in which an external base does not participate, but rather the proton transfers from A-1(O2′) to a nonbridging oxygen during nucleophilic attack, was also considered but deemed to be less likely due to its higher effective free energy barrier. The calculated rate constant for the favored mechanism is in agreement with the experimental rate constant measured at biological Mg2+ ion concentration. According to these calculations, catalysis is optimal when G40 has an elevated pK a rather than a pK a shifted toward neutrality, although a balance among the pK a’s of A-1, G40, and the nonbridging oxygen is essential. These results have general implications, as the hammerhead, hairpin, and twister ribozymes have guanines at a similar position as G40.
The delta opioid receptor (DOR) is a crucial receptor system that regulates pain, mood, anxiety, and similar mental states. DOR agonists, such as SNC80, and DOR-neutral antagonists, such as ...naltrindole, were developed to investigate the DOR in vivo and as potential therapeutics for pain and depression. However, few inverse agonists and non-competitive/irreversible antagonists have been developed, and none are widely available. This leaves a gap in our pharmacological toolbox and limits our ability to investigate the biology of this receptor. Thus, we designed and synthesized the novel compounds SRI-9342 as an irreversible antagonist and SRI-45128 as an inverse agonist. These compounds were then evaluated in vitro for their binding affinity by radioligand binding, their functional activity by
S-GTPγS coupling, and their cAMP accumulation in cells expressing the human DOR. Both compounds demonstrated high binding affinity and selectivity at the DOR, and both displayed their hypothesized molecular pharmacology of irreversible antagonism (SRI-9342) or inverse agonism (SRI-45128). Together, these results demonstrate that we have successfully designed new inverse agonists and irreversible antagonists of the DOR based on a novel chemical scaffold. These new compounds will provide new tools to investigate the biology of the DOR or even new potential therapeutics.