Manganese-Catalyzed 5--trig Oxygenative Cyclization of α,β-Unsaturated Oximes under Air and Ambient Conditions for the Synthesis of 4,5-Dihydroisoxazoles.

The stereoselective 5--trig oxygenative cyclization of α,β-unsaturated oximes was achieved using molecular oxygen (O) and a manganese catalyst. Several 4-hydroxy-4,5-dihydroisoxazoles were obtained in high yields by directly incorporating O from the atmosphere (eliminating the necessity for a pure oxygen environment) and using an unprecedentedly low loading of Mn(acac) (as little as 0.020 mol %) without additional additives.

Notch activator cyclopiazonic acid induces apoptosis in HL-60 cells through calcineurin activation.

We screened a library of microbial extracts and compounds library using our constructed assay cells and found pulicatins F (1) and G (2), and cyclopiazonic acid (CPA) (3) as Notch activators. Pulicatin F (1) and (±)-pulicatin G were synthesized and their activities were evaluated. Notch activation of CPA (3) was investigated using Western blot and RT-PCR.

Priming treatment with T-cell redirecting bispecific antibody ERY974 reduced cytokine induction without losing cytotoxic activity in vitro by changing the chromatin state in T cells.

CD3 bispecific constructs are anticipated to become an important form of cancer immunotherapy, but they frequently cause cytokine release syndrome (CRS) that is difficult to manage in clinical contexts. A combination of intra-patient dose escalation and immunosuppressive treatment is widely used to mitigate CRS. Studies suggest that CRS after subsequent doses of CD3 bispecific constructs is less severe than after the priming dose, and that step-up dosing reduces cytokine levels in animals and humans.

Self-Sustained Divertor Oscillation Driven by Magnetic Island Dynamics in Torus Plasma.

A new type of self-sustained divertor oscillation is discovered in the Large Helical Device stellarator, where the peripheral plasma is detached from material diverters by means of externally applied perturbation fields. The divertor oscillation is found to be a self-regulation of an isolated magnetic field structure (the magnetic island) width induced by a drastic change in a poloidal inhomogeneity of the plasma radiation across the detachment-attachment transitions. A predator-prey model between the magnetic island width and a self-generated local plasma current (the bootstrap current) is introduced to describe the divertor oscillation, which successfully reproduces the experimental observations.

Immune cell multiomics analysis reveals contribution of oxidative phosphorylation to B-cell functions and organ damage of lupus.

Objective: Systemic lupus erythematosus (SLE) is the prototypical systemic autoimmune disease. While the long-term prognosis has greatly improved, better long-term survival is still necessary. The type I interferon (IFN) signature, a prominent feature of SLE, is not an ideal therapeutic target or outcome predictor.