Efficient combination immunotherapy for liver cancer using harmonized activation of innate and adaptive immunity

Objective:Immunotherapy that blocks inhibitory pathways in T lymphocytes,such as the PD-L1/PD-1 axis,is undergoing evaluation for various solid tumors.Notably,this emerging therapeutic approach is already in clinical trials for advanced hepatocellular carcinoma(HCC).

An aqueous zinc-ion hybrid super-capacitor for achieving ultrahigh-volumetric energy density

Zinc-ion hybrid super-capacitors are regarded as promising safe energy storage systems,However,the relatively low volumetric energy density has become the main bottlenecks in practical applications of portable electronic devices,In this work,the zinc-ion hybrid super-capacitor with high volumetric energy density and superb cycle stability had been constructed which employing the high-density threedimensional graphene hydrogel as cathode and Zn foil used as anode in 1 mol/L ZnSO4 electrolyte.Benefiting from the abundant ion transport paths and the abundant active sites for graphene hydrogel with high density and porous structure,the zinc-ion hybrid super-capacitor exhibited an extremely high volumetric energy density of 118.42 Wh/L and a superb power density of 24.00 kW/L,as well as an excellent long cycle life(80% retention after 30,000 cycles at 10 A/g),which was superior to the volumetric energy density of the reported zinc-ion hybrid super-capacitors.This device,based on the fast ion adsorption/deso rption on the capacitor-type graphene cathode and reversible Zn^(2+) plating/stripping on the battery-type Zn anode,which will inspire the development of zinc-ion hybrid super-capacitor in miniaturized devices.

Decoding early myelopoiesis from dynamics of core endogenous network

A decade ago mainstream molecular biologists regarded it impossible or biologically ill-motivated to understand the dynamics of complex biological phenomena, such as cancer genesis and progression, from a network perspective. Indeed, there are numerical difficulties even for those who were determined to explore along this direction. Undeterred, seven years ago a group of Chinese scientists started a program aiming to obtain quantitative connections between tumors and network dynamics. Many interesting results have been obtained. In this paper we wish to test such idea from a different angle: the connection between a normal biological process and the network dynamics. We have taken early myelopoiesis as our biological model. A standard roadmap for the cell-fate diversification during hematopoiesis has already been well established experimentally, yet little was known for its underpinning dynamical mechanisms. Compounding this difficulty there were additional experimental challenges, such as the seemingly conflicting hematopoietic roadmaps and the cell-fate inter-conversion events. With early myeloid cell-fate determination in mind, we constructed a core molecular endogenous network from well-documented gene regulation and signal transduction knowledge. Turning the network into a set of dynamical equations, we found computationally several structurally robust states. Those states nicely correspond to known cell phenotypes. We also found the states connecting those stable states.They reveal the developmental routes—how one stable state would most likely turn into another stable state. Such interconnected network among stable states enabled a natural organization of cell-fates into a multi-stable state landscape. Accordingly, both the myeloid cell phenotypes and the standard roadmap were explained mechanistically in a straightforward manner. Furthermore,recent challenging observations were also explained naturally. Moreover, the landscape visually enables a prediction of a pool of additional cell states and developmental routes, including the non-sequential and cross-branch transitions, which are testable by future experiments. In summary, the endogenous network dynamics provide an integrated quantitative framework to understand the heterogeneity and lineage commitment in myeloid progenitors.

From Phage lambda to human cancer： endogenous molecular-cellular network hypothesis

Experimental evidences and theoretical analyses have amply suggested that in cancer genesis and progression genetic information is very important but not the whole. Nevertheless, ＂cancer as a disease of the genome＂ is still currently the dominant doctrine. With such a background and based on the fundamental properties of biological systems, a new endogenous molecular-cellular network theory for cancer was recently proposed by us. Similar proposals were also made by others. The new theory attempts to incorporate both genetic and environmental effects into one single framework, with the possibility to give a quantitative and dynamical description. It is asserted that the complex regulatory machinery behind biological processes may be modeled by a nonlinear stochastic dynamical system similar to a noise perturbed Morse-Smale system. Both qualitative and quantitative descriptions may be obtained. The dynamical variables are specified by a set of endogenous molecular-cellular agents and the structure of the dynamical system by the interactions among those biological agents. Here we review this theory from a pedagogical angle which emphasizes the role of modularization, hierarchy and autonomous regulation. We discuss how the core set of assumptions is exemplified in detail in one of the simple, important and well studied model organisms, Phage lambda. With this concrete and quantitative example in hand, we show that the application of the hypothesized theory in human cancer, such as hepatocellular carcinoma （HCC）, is plausible, and that it may provide a set of new insights on understanding cancer genesis and progression, and on strategies for cancer prevention, cure, and care.

Cobalt-catalyzed cascade hydroalkenylation of 1,6-enynes with chalcones

An efficient stereoselective cobalt-catalyzed hydrovinylative cyclization of 1,6-enynes with chalcones toobtain functionalized pyrrolidines has been developed. The products were furnished in good yields withup to 93% ee. A plausible mechanism through which the transformation was initiated by cyclization of1,6-enynes is proposed.