Photodynamic therapy is an effective alternative to traditional treatments due to its minimally invasive nature, negligible systemic toxicity, fewer side effects, and avoidance of drug resistance. However, it is still challenging to design photosensitizers with high singlet oxygen (1O2) quantum yields (QY) due to severe aggregation of the hydrophobic photosensitizers. Herein, we developed a discrete organoplatinum(II) metallacage using therapeutic cis-(PEt3)2Pt(OTf)2 as the building block to improve the 1O2 QY, thus achieving synergistic anticancer efficacy. The metallacage-loaded nanoparticles (MNPs) with tri-modality imaging capability allow precise diagnosis of tumor and real-time monitoring the delivery, biodistribution, and excretion of the MNPs. MNPs exhibited excellent anti-metastatic effect and superior anti-tumor performance against U87MG, drug resistant A2780CIS, and orthotopic tumor models, ablating the tumors without recurrence after a single treatment. Gene chip analyses confirmed the contribution of different therapeutic modalities to the tumor abrogation. This supramolecular platform holds potential in precise cancer theranostics.

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Dielectric-barrier-discharge ionization is an ambient-ionization technique. Since its first description in 2007, it has attracted much attention in such fields as biological analysis, food safety, mass-spectrometry imaging, forensic identification, and reaction monitoring for its advantages, e.g., low energy consumption, solvent-free method, and easy miniaturization. In this review a brief introduction to dielectric barrier discharge is provided, and then a detailed introduction to the dielectric-barrier-discharge-ionization technique is given, including instrumentation, applications, and mechanistic studies. Based on the summary of reported work, possible future uses of this type of ionization source are discussed at the end.

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Inhibition of γ-secretase activity represents a potential therapeutic strategy for Alzheimer’s disease (AD). MRK-560 is a selective inhibitor with higher potency for Presenilin 1 (PS1) than for PS2, the two isoforms of the catalytic subunit of γ-secretase, although the underlying mechanism remains elusive. Here we report the cryo-electron microscopy (cryo-EM) structures of PS1 and PS2-containing γ-secretase complexes with and without MRK-560 at overall resolutions of 2.9-3.4 Å. MRK-560 occupies the substrate binding site of PS1, but is invisible in PS2. Structural comparison identifies Thr281 and Leu282 in PS1 to be the determinant for isoform-dependent sensitivity to MRK-560, which is confirmed by swapping experiment between PS1 and PS2. By revealing the mechanism for isoform-selective inhibition of presenilin, our work may facilitate future drug discovery targeting γ-secretase.

Compactifications of 6d N = (1, 0) SCFTs give rise to new 4d N = 1 SCFTs and shed light on interesting dualities between such theories. In this paper we continue exploring this line of research by extending the class of compactified 6d theories to the Dtype case. The simplest such 6d theory arises from D5 branes probing D-type singularities. Equivalently, this theory can be obtained from an F-theory compactification using −2curves intersecting according to a D-type quiver. Our approach is twofold. We start by compactifying the 6d SCFT on a Riemann surface and compute the central charges of the resulting 4d theory by integrating the 6d anomaly polynomial over the Riemann surface. As a second step, in order to find candidate 4d UV Lagrangians, there is an intermediate 5d theory that serves to construct 4d domain walls. These can be used as building blocks to obtain torus compactifications. In contrast to the A-type case, the vanishing of anomalies in the 4d theory turns out to be very restrictive and constraints the choices of gauge nodes and matter content severely. As a consequence, in this paper one has to resort to nonmaximal boundary conditions for the 4d domain walls. However, the comparison to the 6d theory compactified on the Riemann surface becomes less tractable.