Synthesis and Antitumor Activity of Panaxadiol Pyrazole and Isooxazole Derivatives.

In this study, we designed and synthesized 19 nitrogen-containing heterocyclic derivatives of panaxadiol (PD). We first reported the antiproliferative activity of these compounds against four different tumor cells. The results of the MTT assay showed that the PD pyrazole derivative (compound 12b) had the best antitumor activity and could significantly inhibit the proliferation of four tested tumor cells. For A549 cells, the IC50 value was as low as 13.44±1.23 µM. Western blot analysis showed that the PD pyrazole derivative was a bifunctional regulator. On the one hand, it can down-regulate the expression of HIF-1α by acting on PI3 K/AKT signaling pathway in A549 cells. On the other hand, it can induce the decrease of CDKs protein family and E2F1 protein expression levels, thus playing a crucial role in cell cycle arrest. According to the results of molecular docking, we found that multiple hydrogen bonds were formed between the PD pyrazole derivative and two related proteins, and the docking score of the derivative was also significantly higher than that of the crude drug. In summary, the study of the PD pyrazole derivative laid a foundation for the development of ginsenoside as an antitumor agent.

Self-Organized Synchronization of Phonon Lasers.

Self-organized synchronization is a ubiquitous collective phenomenon, in which each unit adjusts their rhythms to achieve synchrony through mutual interactions. The optomechanical systems, due to their inherently engineerable nonlinearities, provide an ideal platform to study self-organized synchronization. Here, we demonstrate the self-organized synchronization of phonon lasers in a two-membrane-in-the-middle optomechanical system. The probe of each individual membrane enables us to monitor the real-time transient dynamics of synchronization, which reveals that the system enters into the synchronization regime via a torus birth bifurcation line. The phase-locking phenomenon and the transition between in-phase and antiphase regimes are directly observed. Moreover, such a system greatly facilitates the controllable synchronous states, and consequently a phononic memory is realized by tuning the system parameters. This result is an important step towards the future studies of many-body collective behaviors in multiresonator optomechanics with long distances, and might find potential applications in quantum information processing and complex networks.

Genome-wide identification and characterization of TCP gene family in Dendrobium nobile and their role in perianth development.

TCP is a widely distributed, essential plant transcription factor that regulates plant growth and development. An in-depth study of TCP genes in Dendrobium nobile, a crucial parent in genetic breeding and an excellent model material to explore perianth development in Dendrobium, has not been conducted. We identified 23 DnTCP genes unevenly distributed across 19 chromosomes and classified them as Class I PCF (12 members), Class II: CIN (10 members), and CYC/TB1 (1 member) based on the conserved domain and phylogenetic analysis. Most DnTCPs in the same subclade had similar gene and motif structures. Segmental duplication was the predominant duplication event for TCP genes, and no tandem duplication was observed. Seven genes in the CIN subclade had potential miR319 and -159 target sites. Cis-acting element analysis showed that most DnTCP genes contained many developmental stress-, light-, and phytohormone-responsive elements in their promoter regions. Distinct expression patterns were observed among the 23 DnTCP genes, suggesting that these genes have diverse regulatory roles at different stages of perianth development or in different organs. For instance, DnTCP4 and DnTCP18 play a role in early perianth development, and DnTCP5 and DnTCP10 are significantly expressed during late perianth development. DnTCP17, 20, 21, and 22 are the most likely to be involved in perianth and leaf development. DnTCP11 was significantly expressed in the gynandrium. Specially, MADS-specific binding sites were present in most DnTCP genes putative promoters, and two Class I DnTCPs were in the nucleus and interacted with each other or with the MADS-box. The interactions between TCP and the MADS-box have been described for the first time in orchids, which broadens our understanding of the regulatory network of TCP involved in perianth development in orchids.

Cedrol from ginger alleviates rheumatoid arthritis through dynamic regulation of intestinal microenvironment.

The imbalance of intestinal flora would induce immune inflammation. Cedrol (CE), found from ginger by our group earlier, has been proven to play an excellent role in ameliorating rheumatoid arthritis (RA) via acting on JAK3, MAPK, and NF-κB. However, there have been no studies on CE ameliorating RA through the regulation of the micro-environment. In this study, the adjuvant arthritis model (AIA) is established to evaluate the weight, arthritis score, paw swelling, bone destruction, immune organ index, inflammatory cell infiltration, cartilage erosion, and metabolic enzymes of kidneys in AIA rats after CE intervention. The results indicated CE could alleviate paw swelling, reduce arthritis score, decrease the secretion of TNF-α, IL-6, and IL-1ß in serum in a dose-dependent manner, and inhibit the immune organ index of the spleen while having no significant effect on metabolic enzymes of the kidney. In addition, pathological sections of ankle and knee joints suggested CE might significantly prevent inflammatory cell infiltration, synovial hyperplasia, and joint degeneration and protect articular cartilage. Then, for the first time, 16S rRNA gene was applied to analyze the regulatory effect of CE on intestinal flora. CE could effectively improve the uniformity, diversity, and richness of intestinal flora, reduce the number of pathogenic bacteria, and increase the proportion of beneficial bacteria, and it significantly inhibited the abundance of Prevotella in RA rats, which was 12.43 times smaller than that in methotrexate. The distribution and excretion of CE in vivo were detected by GC-MS. It was found that CE would massively accumulate in the gastrointestinal tract after oral administration, which is then mainly excreted through feces. Interestingly, the research suggested that CE, which plays a role in the dynamic regulation of the intestinal micro-environment, could be used as a potential component to prevent RA.

Cedrol from Ginger Ameliorates Rheumatoid Arthritis via Reducing Inflammation and Selectively Inhibiting JAK3 Phosphorylation.

Ginger, as a food spice, is widely applied due to its extensive effects. Cedrol (CE) found in ginger is a sesquiterpene with anti-inflammatory activity. The objective of this research is to discuss the efficacy of CE on ameliorating rheumatoid arthritis (RA). CE inhibited chronic inflammation and pain in a dose-dependent manner accompanied by rapid onset and long duration. Besides, CE treatment effectively ameliorated the paw edema volume and arthritis score with no significant effect on body weight. Organ index, T-cell and B-cell proliferation, histopathology, and immunohistochemistry demonstrated that CE had immunological enhancement and attenuated RA effects. Remarkably, inhibition of phosphorylated-JAK3 protein, thereby abating the secretion of pro-inflammatory cytokines and inflammation-related mediators, was involved in the potential mechanism of CE efficiency through forming a hydrogen bond with ARG953 and ILE955 in the JAK3 active pocket. At the same time, the pharmacokinetic results showed that the absolute bioavailability of CE at 20, 40, and 80 mg/kg was 30.30, 23.68, and 16.11%, respectively. The current results offered clues for mastering the ameliorated RA of CE and further perfected the effective substance basis on the anti-inflammatory effect of ginger, which was beneficial for further applications.

Phonon heat transport in cavity-mediated optomechanical nanoresonators.

The understanding of heat transport in nonequilibrium thermodynamics is an important research frontier, which is crucial for implementing novel thermodynamic devices, such as heat engines and refrigerators. The convection, conduction, and radiation are the well-known basic ways to transfer thermal energy. Here, we demonstrate a different mechanism of phonon heat transport between two spatially separated nanomechanical resonators coupled by the cavity-enhanced long-range interactions. The single trajectory for thermalization and non-equilibrium dynamics is monitored in real-time. In the strong coupling regime, the instant heat flux spontaneously oscillates back and forth in the nonequilibrium steady states. The universal bound on the precision of nonequilibrium steady-state heat flux, i.e. the thermodynamic uncertainty relation, is verified in such a temperature gradient driven far-off equilibrium system. Our results give more insight into the heat transfer with nanomechanical oscillators, and provide a playground for testing fundamental theories in non-equilibrium thermodynamics.