Immunomodulatory Function of Pien Tze Huang in T Cell-Mediated Anti-tumor Activity against B16-F10, MC38 and Hep1-6 Tumor Models.

OBJECTIVE: To investigate the anti-tumor effects of Pien Tze Huang (PZH) in mouse models of B16-F10 melanoma, MC38 colorectal cancer, Hep1-6 hepatocellular carcinoma and chemically induced hepatocellular carcinoma model. METHODS: Various tumor models, including B16-F10, MC38 and Hep1-6 tumor hypodermic inoculation models, B16-F10 and Hep1-6 pulmonary metastasis models, Hep1-6 orthotopic implantation model, and chemically induced hepatocellular carcinoma model, were utilized to evaluate the anti-tumor function of PZH. Tumor growth was assessed by measuring tumor size and weight of solid tumors isolated from C57BL/6 mice. For cell proliferation and death of tumor cells in vitro, as well as T cell activation markers, cytokine production and immune checkpoints analysis, single-cell suspensions were prepared from mouse spleen, lymph nodes, and tumors after PZH treatment. RESULTS: PZH demonstrated significant therapeutic efficacy in inhibiting tumor growth (P<0.01). Treatment with PZH resulted in a reduction in tumor size in subcutaneous MC38 colon adenocarcinoma and B16-F10 melanoma models, and decreased pulmonary metastasis of B16-F10 melanoma and Hep1-6 hepatoma (P<0.01). However, in vitro experiments showed that PZH only had slight impact on the cell proliferation and survival of tumor cells (P>0.05). Nevertheless, PZH exhibited a remarkable ability to enhance T cell activation and the production of interferon gamma, tumor necrosis factor alpha, and interleukin 2 in CD4+ T cells in vitro (P<0.01 or P<0.05). Importantly, PZH substantially inhibited T cell exhaustion and boosted cytokine production by tumor-infiltrating CD8+ T cells (P<0.01 or P<0.05). CONCLUSION: This study has confirmed a novel immunomodulatory function of PZH in T cell-mediated anti-tumor immunity, indicating that PZH holds promise as a potential therapeutic agent for cancer treatment.

Molecular Dissection Unveiling Dwarfing Effects of Plant Growth Retardants on Pomegranate.

Dwarfed stature is a desired trait for modern orchard production systems. One effective strategy for dwarfing cultivation is exogenously applying plant growth retardants (PGRs) to plants. However, for many economic fruit trees, the current knowledge on the regulatory mechanisms underlying the dwarfing effect of PGRs is limited, which largely restricts the agricultural application of PGRs. In this study, we exogenously applied three kinds of PGRs [paclobutrazol, daminozide (B9), and mannitol] to the seedlings of pomegranate (Punica granatum L.) and performed comparative transcriptome analysis to elucidate the molecular features of PGR-induced dwarfing in pomegranates. Our results showed that all the three PGRs could significantly suppress plant growth of pomegranate. The inhibition of auxin biosynthetic processes, as well as auxin-mediated shoot development, may be considered as the main reason for the dwarfing. Besides that, different PGRs were also found to induce dwarfing via specific mechanisms, for example, cellular response to strigolactone was particularly suppressed by the application of paclobutrazol, while the level of carbohydrate homeostasis and metabolism were downregulated in conditions of either B9 or mannitol treatments. Furthermore, exogenous PGR application was supposed to cause adverse impacts on the normal physiological process of pomegranate seedlings, which may bring extra burden to pomegranate plants. These novel findings unveiled the genetic basis underlying the dwarfing in pomegranates, which provides deeper insights into PGR-mediated dwarfing cultivation of pomegranates.

V5/MT+ modulates spatio-temporal integration differently across and within hemifields: Causal evidence from TMS.

It is unclear how the brain reaches the correct balance between temporal and spatial processing necessary to perceive motion across space. Here, we tested whether visual motion area V5/MT + plays a causal role in Ternus illusion. Ternus displays can be perceived as showing either group motion or element motion and are empirically useful for dissociating temporal and spatial grouping across visual fields. Online single-pulse TMS was applied to observers during the presentation of Ternus displays, either within or across hemifields, over left V5/MT + or, respectively, a control site in the left somatosensory cortex, or an additional 'Sham' control condition. In the cross-hemifields condition, observers perceived more element motion with TMS over left V5/MT + than in either control condition. By contrast, in the within-hemifield condition, observers reported more group motion after left V5/MT + TMS. Our findings demonstrate a causal role of left V5/MT+ in the spatio-temporal grouping of Ternus apparent motion, and in maintaining the balance of spatio-temporal processing both within and across individual hemifields.

Rhodium-Catalyzed Highly Regioselective and Stereoselective Intermolecular Hydrosilylation of Internal Ynamides under Mild Conditions.

A rhodium-catalyzed highly regio- and stereoselective intermolecular hydrosilylation of internal ynamides has been developed. With the neutral rhodium complex [Rh(CO)2Cl]2 as a catalyst and the bulky silanes as reactants, various ynamides underwent hydrosilylation smoothly at room temperature with an excellent ß-regioselectivity and anti-stereoselectivity. The synthetically versatile ß-silyl ( Z)-enamide products could be further transformed to diverse useful building blocks. Several possible mechanisms are proposed to rationalize this unique formal trans-addition-type selectivity.