First-principles method of propagation of tightly bound excitons: verifying the exciton band structure of LiF with inelastic x-ray scattering.

We propose a simple first-principles method to describe the propagation of tightly bound excitons. By viewing the exciton as a composite object (an effective Frenkel exciton in Wannier orbitals), we define an exciton kinetic kernel to encapsulate the exciton propagation and decay for all binding energies. Applied to prototypical LiF, our approach produces three exciton bands, which we verified quantitatively via inelastic x-ray scattering. The proposed real-space picture is computationally inexpensive and thus enables study of the full exciton dynamics, even in the presence of surfaces and impurity scattering. It also provides an intuitive understanding to facilitate practical exciton engineering in semiconductors, strongly correlated oxides, and their nanostructures.

Dynamical reconstruction of the exciton in LiF with inelastic x-ray scattering.

The absorption of light by materials proceeds through the formation of excitons, which are states in which an excited electron is bound to the valence hole it vacated. Understanding the structure and dynamics of excitons is important, for example, for developing technologies for light-emitting diodes or solar energy conversion. However, there has never been an experimental means to study the time-dependent structure of excitons directly. Here, we use causality-inverted inelastic x-ray scattering (IXS) to image the charge-transfer exciton in the prototype insulator LiF, with resolutions Delta t = 20.67 as (2.067 x 10(-17) s) in time and Delta x = 0.533 A (5.33 x 10(-11) m) in space. Our results show that the exciton has a modulated internal structure and is coherently delocalized over two unit cells of the LiF crystal (approximately 8 A). This structure changes only modestly during the course of its life, which establishes it unambiguously as a Frenkel exciton and thus amenable to a simplified theoretical description. Our results resolve an old controversy about excitons in the alkali halides and demonstrate the utility of IXS for imaging attosecond electron dynamics in condensed matter.

Antimetabolite pemetrexed primes a favorable tumor microenvironment for immune checkpoint blockade therapy.

BACKGROUND: The immune checkpoint blockade (ICB) targeting programmed cell death-1 (PD-1) and its ligand (PD-L1) has been proved beneficial for numerous types of cancers, including non-small-cell lung cancer (NSCLC). However, a significant number of patients with NSCLC still fail to respond to ICB due to unfavorable tumor microenvironment. To improve the efficacy, the immune-chemotherapy combination with pemetrexed, cis/carboplatin and pembrolizumab (anti-PD-1) has been recently approved as first-line treatment in advanced NSCLCs. While chemotherapeutic agents exert beneficial effects, the underlying antitumor mechanism(s) remains unclear. METHODS: Pemetrexed, cisplatin and other chemotherapeutic agents were tested for the potential to induce PD-L1 expression in NSCLC cells by immunoblotting and flow cytometry. The ability to prime the tumor immune microenvironment was then determined by NSCLC/T cell coculture systems and syngeneic mouse models. Subpopulations of NSCLC cells responding differently to pemetrexed were selected and subjected to RNA-sequencing analysis. The key signaling pathways were identified and validated in vitro and in vivo. RESULTS: Pemetrexed induced the transcriptional activation of PD-L1 (encoded by CD274) by inactivating thymidylate synthase (TS) in NSCLC cells and, in turn, activating T-lymphocytes when combined with the anti-PD-1/PD-L1 therapy. Nuclear factor κB (NF-κB) signaling was activated by intracellular reactive oxygen species (ROSs) that were elevated by pemetrexed-mediated TS inactivation. The TS-ROS-NF-κB regulatory axis actively involves in pemetrexed-induced PD-L1 upregulation, whereas when pemetrexed fails to induce PD-L1 expression in NSCLC cells, NF-κB signaling is unregulated. In syngeneic mouse models, the combinatory treatment of pemetrexed with anti-PD-L1 antibody created a more favorable tumor microenvironment for the inhibition of tumor growth. CONCLUSIONS: Our findings reveal novel mechanisms showing that pemetrexed upregulates PD-L1 expression and primes a favorable microenvironment for ICB, which provides a mechanistic basis for the combinatory chemoimmunotherapy in NSCLC treatment.

Utilization of well-baby care visits provided by Taiwan's National Health Insurance Program.

In April of 1995, Taiwan's National Health Insurance Program started providing each eligible child a total of six well-baby care visits. The first four are for infancy, the fifth is for the second and the third years of life, and the sixth is for the fourth year. These services are in addition to neonatal screening and a series of primary immunizations that have been publicly financed and utilized conventionally for years. The purposes of this study were to investigate the utilization level of these well-baby care visits, and explore relevant factors. The results reveal that 36% of eligible children did not use any of the first four visits, 58% did not utilize the fifth, and 82% did not use the sixth in the late 1990s. It appears that the take-up of these services is much less than satisfactory. Maternal awareness of and attitudes toward the services appeared to be the most important factors influencing utilization. These two factors not only were most influential, but also significantly contributed to disparities in utilization among different regions and types of residential districts. As a result, they should be the focus of interventions for advancing well-baby care. While these two factors are at the individual level, they are not independent from the health care system because the health care system has impacts on individual factors. Since physicians can serve as a good vehicle for teaching parents about relevant information and correct attitudes, and most physicians in Taiwan complained about the payment scheme, offering stronger incentives for physicians to promote such services might be helpful for achieving a high utilization level of well-baby care.