Sono-Driven STING Activation using Semiconducting Polymeric Nanoagonists for Precision Sono-Immunotherapy of Head and Neck Squamous Cell Carcinoma.

Immunotherapy has offered new opportunities to treat head and neck squamous cell carcinoma (HNSCC); however, its clinical applications are hindered by modest therapeutic outcomes and the "always-on" pharmacological activity of immunomodulatory agents. Strategies for precise spatiotemporal activation of antitumor immunity can tackle these issues but remain challenging. Herein, a semiconducting polymeric nanoagonist (SPNM) with in situ sono-activatable immunotherapeutic effects for precision sono-immunotherapy of HNSCC is reported. SPNM is self-assembled from a sonodynamic semiconducting polymer core conjugated with a stimulator of interferon genes (STING) agonist (MSA-2) via a singlet oxygen cleavable linker. Under sono-irradiation, SPNM produces singlet oxygen not only to eradicate tumor cells to trigger immunogenic cell death but also to unleash caged STING agonists via the cleavage of diphenoxyethene bonds for in situ activation of the STING pathway in the tumor region. Such sono-driven STING activation mediated by SPNM promotes effector T cell infiltration and potentiates systemic antitumor immunity, eventually leading to tumor growth inhibition and long-term immunological memory. This study thus presents a promising strategy for the precise spatiotemporal activation of cancer immunotherapy.

Biomimetic control of charge transfer in MOFs by solvent coordination for boosting photocatalysis.

The role of the coordination solvent in MOFs with photocatalysis can't be ignored. Novel [Ni(PTCA)·sol]-MOFs with a 3D open wavy-layered structure are selected for in-depth study by imitating the internal environment of a chameleon. The results confirm that the coordination solvent can modulate the band structure and the polarity is the key to accelerate the formation of intermediate H*.

Effects of semi-deep water irrigation on hybrid indica rice lodging resistance.

Recently, rice-aquatic animal integrated farming (RAAIF) has grown rapidly in China due to its favorable benefits and the lower application of pesticides and fertilizers. However, rice lodging occurs frequently under RAAIF, which restricts rice yield. We assumed that semi-deep water irrigation may cause weaker rice-lodging resistance since it is the most significant environmental factor for RAAIF that distinguishes it from rice monoculture. To investigate the response of rice stem lodging resistance to semi-deep water irrigation and its mechanism, three irrigation management modes, namely the typical high-yield irrigation model that is mainly based on swallow and wetting (CK), semi-deep water irrigation from the late tillering stage to the jointing stage (SDI1), and semi-deep water irrigation from the jointing stage to the middle grain-filling stage (SDI2), were conducted using three hybrid indica rice varieties: Shenliangyou136 (SLY136), Huiliangyousimiao (HLYSM), and Wanxiangyou982 (WXY982). Mechanics analysis indicated that the bending moment by the whole plant (WP) and the breaking strength (M) were both decreased by semi-deep water irrigation when compared with CK, while M presented a larger decreasing amplitude than WP, which induced the increased lodging index (LI) of rice, for all the tested varieties. SLY136 and HLYSM were affected more strongly by SDI1, whereas WXY982 was affected more strongly by SDI2. Significant weaker breaking force under two semi-deep water irrigation modes contributed to the decreased M relative to CK. Morphology results showed that semi-deep water irrigation reduced the thickness of mechanical tissues, sclerenchyma cells, and parenchyma cells; reduced the number of vascular bundles; and caused a looser arrangement, inducing the lower fullness of the rice basal internode. Decreased accumulation of lignin and cellulose was also linked to the weaker breaking force of the basal internode under semi-deep water irrigation, which was verified by correlation analysis. WXY982 had obvious lower structural carbohydrates content under semi-deep water irrigation than the other two varieties and thus showed worse breaking force and LI. In conclusion, the worse mechanical strength of the rice basal internode under semi-deep water irrigation was closely associated with weaker vascular bundle development and suppressed structural carbohydrate accumulation, and the decreasing degree of lodging resistance varied between rice varieties and semi-deep water irrigation periods.

Palladium catalyzed reductive Heck coupling and its application in total synthesis of (-)-17-nor-excelsinidine.

Monoterpene indole alkaloids, bearing a highly substituted piperidine ring, are a structurally diverse class of bioactive natural products, found in various parts of the world. Herein, we reported the construction of the key piperidine ring via palladium catalyzed reductive Heck coupling with a good syn selective manner, avoiding the usage of stoichiometric, highly toxic, air sensitive and moisture sensitive Ni(COD)2. To further showcase the value of this methodology, we realized the total synthesis of the structurally unique zwitterionic monoterpene indole alkaloid (-)-17-nor-excelsinidine in 9 steps, in which the key ammonium-acetate connection (N4-C16) of (-)-17-nor-excelsinidine was constructed via oxidative coupling in excellent yield and high regioselectivity under NBS/pyridine from the enolate of geissoschizine.

Discovery of A031 as effective proteolysis targeting chimera (PROTAC) androgen receptor (AR) degrader for the treatment of prostate cancer.

Androgen receptor (AR) is an effective therapeutic target for the treatment of prostate cancer. We report herein the design, synthesis, and biological evaluation of highly effective proteolysis targeting chimeras (PROTAC) androgen receptor (AR) degraders, such as compound A031. It could induce the degradation of AR protein in VCaP cell lines in a time-dependent manner, achieving the IC 50 value of less than 0.25 µM. The A031 is 5 times less toxic than EZLA and works with an appropriate half-life (t 1/2) or clearance rate (Cl). Also, it has a significant inhibitory effect on tumor growth in zebrafish transplanted with human prostate cancer (VCaP). Therefore, A031 provides a further idea of developing novel drugs for prostate cancer.