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The significance of solvent effects in electronic structure calculations has long been noted, and various methods have been developed to consider this effect. The reference interaction site model self-consistent field with constrained spatial electron density (RISM-SCF-cSED) is a hybrid model that combines the integral equation theory of molecular liquids with quantum chemistry. This method can consider the statistically convergent solvent distribution at a significantly lower cost than molecular dynamics simulations. Because the RISM theory explicitly considers the solvent structure, it performs well for systems where hydrogen bonds are formed between the solute and solvent molecules, which is a challenge for continuum solvent models. Taking advantage of being founded on the variational principle, theoretical developments have been made in calculating various properties and incorporating electron correlation effects. In this review, we organize the theoretical aspects of RISM-SCF-cSED and its distinctions from other hybrid methods involving integral equation theories. Furthermore, we carefully present its progress in terms of theoretical developments and recent applications. [ABSTRACT FROM AUTHOR]

In quantum chemical calculations of heterogeneous structures in solids, e.g., when an impurity is located on the surface, the conventional cluster model is insufficient to describe the electronic structure of substrates due to its finite size. The open-boundary cluster model (OCM) overcomes this problem by performing cluster calculations under the outgoing-wave boundary condition. In this method, a complex absorbing potential (CAP) is used to impose the boundary condition, but the CAP used in the previous studies required parameter optimization based on the complex variational principle. This study proposes and applies a parameter-free CAP to OCM calculations. This approach makes it possible to uniquely determine the band-specific CAP based on the surface Green's function theory. Using this CAP, we conducted OCM calculations of the tight-binding model of a one-dimensional semi-infinite chain, and we found that the calculated density of states agreed with the exact one. Surface states of the Newns–Anderson–Grimley model were also computed using the CAP, and the projected density of states on the adsorbed atom was successfully reproduced. [ABSTRACT FROM AUTHOR]

In this study, we analyze mucociliary transport (MCT) by measuring the magnitude and identifying regions of ciliary beats using high-frame-rate microscopic videos. Our methodology, integrating dense optical flow (DOF), connected component labeling (CCL), Butterworth filter, and Fast Fourier Transform (FFT), captures ciliary movement and magnitude. We focus on region extraction, quantification of ciliary activity, and classification of power and recovery strokes in ciliary beat frequency (CBF), which are crucial for evaluating MCT efficiency. Our approach was able to extract the ciliary region semi-automatically, obtain the CBF, and visualize the ciliary movement in each frame. Despite dataset challenges and limited ground truth, our approach shows a promising result for ciliary dynamics research and medical diagnostics. We hope for future open-source datasets with ground-truth ciliary beat patterns to enable developing and evaluating automated ciliary analysis techniques, leading to improved assessment. [ABSTRACT FROM AUTHOR]

We propose a new hybrid approach combining quantum chemistry and statistical mechanics of liquids for calculating the nuclear magnetic resonance (NMR) chemical shifts of solvated molecules. Based on the reference interaction site model self-consistent field with constrained spatial electron density distribution (RISM–SCF–cSED) method, the electronic structure of molecules in solution is obtained, and the expression for the nuclear magnetic shielding tensor is derived as the second-order derivative of the Helmholtz energy of the solution system. We implemented a method for calculating chemical shifts and applied it to an adenine molecule in water, where hydrogen bonding plays a crucial role in electronic and solvation structures. We also performed the calculations of 17O chemical shifts, which showed remarkable solvent dependence. While converged results could not be sometimes obtained using the conventional method, in the present framework with RISM–SCF–cSED, an adequate representation of electron density is guaranteed, making it possible to obtain an NMR shielding constant stably. This introduction of cSED is key to extending the method's applicability to obtain the chemical shift of various chemical species. The present demonstration illustrates our approach's superiority in terms of numerical robustness and accuracy. [ABSTRACT FROM AUTHOR]

Simple Summary: Gut microbiota is a key regulators of the efficacy of immune checkpoint inhibitor (ICIs). Thus, manipulating microbiota may enhance cancer treatment outcomes. Clostridium butyricum MIYAIRI 588 strain (CBM588) enhances the effects of ICI monotherapy in patients with advanced lung cancer. However, its effect on the outcomes of chemoimmunotherapy combinations in lung cancer remains unknown. We retrospectively analyzed 106 patients with stage IV or recurrent metastatic non-small cell lung cancer (NSCLC) consecutively treated with chemoimmunotherapy combination. CBM588 significantly extended the overall survival in patients with NSCLC receiving chemoimmunotherapy combinations and was associated with overall survival in patients using proton pump inhibitors and/or antibiotics. CBM588-induced manipulation of commensal microbiota has the potential to enhance the efficacy of chemoimmunotherapy combinations. The survival benefit of CBM588 in the tumor-programmed cell death ligand 1 (PD-L1) < 1% cohort was higher than that in the PD-L1 1–49% and PD-L1 ≥ 50% cohorts. Further exploration of the synergy between CBM588 and immunotherapy is warranted. The gut microbiota has emerged as a key regulator of immune checkpoint inhibitor (ICI) efficacy. Therapeutic approaches aimed at manipulating the microbiota through targeted reconstitution to enhance cancer treatment outcomes have garnered considerable attention. A single live microbial biotherapeutic bacterium, Clostridium butyricum MIYAIRI 588 strain (CBM588), has been shown to enhance the effects of ICI monotherapy in patients with advanced lung cancer. However, whether CBM588 affects the outcomes of chemoimmunotherapy combinations in lung cancer remains unknown. We hypothesized that CBM588 augments the effect of chemoimmunotherapy combinations and restores diminished effectiveness in patients with non-small cell lung cancer (NSCLC) receiving dysbiosis-inducing drugs. To validate this hypothesis, we retrospectively analyzed 106 patients with stage IV or recurrent metastatic NSCLC consecutively treated with chemoimmunotherapy combinations. A survival analysis was performed employing univariate and multivariate Cox proportional hazard models with inverse probability of treatment weighting (IPTW) using propensity scores. Forty-five percent of patients received Clostridium butyricum therapy. CBM588 significantly extended overall survival in patients with NSCLC receiving chemoimmunotherapy. The favorable impact of CBM588 on the efficacy of chemoimmunotherapy combinations varied based on tumor-programmed cell death ligand 1 (PD-L1) expression. The survival benefit of CBM588 in the PD-L1 <1% cohort was higher than that in the PD-L1 1–49% and PD-L1 ≥ 50% cohorts. Furthermore, CBM588 was associated with improved overall survival in patients receiving proton pump inhibitors and/or antibiotics. CBM588-induced manipulation of the commensal microbiota holds the potential to enhance the efficacy of chemoimmunotherapy combinations, warranting further exploration of the synergy between CBM588 and immunotherapy. [ABSTRACT FROM AUTHOR]

A new method for calculating nuclear magnetic shielding in solutions is developed based on the reference interaction site model self-consistent field (RISM-SCF) with spatial electron density distribution (SEDD). In RISM-SCF-SEDD, the electrostatic interaction between the solute and the solvent is described by considering the spread of electron to obtain more realistic electronic structure in solutions. It is thus expected to allow us to predict more quantitative chemical shifts of a wide variety of chemical species in solutions. In this study, the method is applied to a water molecule in water and is validated by examining the dependence of the solvent temperature and density on chemical shifts. The dependence of solvent species is also investigated, and more accurate results are obtained for polar solvents compared to the previous RISM-SCF study. Another application example of this method is the 15N chemical shifts of two azines in water, which is difficult to predict with the polarizable continuum model (PCM). Our results are in good agreement with the previous quantum mechanical/molecular mechanics study and experimental results. It is also shown that our method gives more realistic results for methanol and acetone than the PCM. [ABSTRACT FROM AUTHOR]

A Mn4N thin film is prepared on MgO(001) single-crystal substrate by introducing VN underlayer and caplayer which are respectively expected to inhibit the oxidation from substrate and surface. The thin film is prepared by ultra-high vacuum radio-frequency magnetron sputtering. The growth, the structure, and the magnetic properties are investigated. A fully epitaxial VN/Mn4N/VN film with sharp interfaces is formed on the substrate. The Mn4N film has low out-of-plane and in-plane orientation dispersions of about 1° and high N site order degree of 0.88. The lattice of Mn4N film is slightly deformed along the perpendicular direction (c/a = 0.9872) possibly due to accommodation of the lattice mismatch at Mn4N/VN interfaces. The film shows a low saturation magnetization of 85 kA/m (85 emu/cm3) and a strong perpendicular magnetic anisotropy. The present study has shown that introduction of VN underlayer and caplayer is useful for preparation of well-defined Mn4N thin films with perpendicular magnetic anisotropy. [ABSTRACT FROM AUTHOR]

A pulmonary carcinoid tumor is a rare tumor that lacks a validated therapeutic approach for unresectable disease. Understanding the intersite tumor‐immune heterogeneity is essential to harness the immune system for cancer therapy. However, little is known about the tumor‐immune microenvironment (TIME). Here, we describe a patient who had heterogeneous TIME between primary and metastatic carcinoid tumors which differentially responded to chemoimmunotherapy. A 72‐year‐old man was diagnosed with an advanced pulmonary carcinoid tumor. CT‐guided biopsies of lung and scapular tumors confirmed typical carcinoid (PD‐L1, 1%–24%) and atypical carcinoid tumors (PD‐L1, negative), respectively. Although the primary lung carcinoid tumor showed a partial response, the scapular tumor was significantly enlarged after two cycles of anti‐PD‐L1 antibody therapy in combination with carboplatin plus etoposide. We performed quantitative pathology imaging analysis with fluorescent multiplex immunohistochemistry. CD8+ T cell infiltration was detected in the PD‐L1‐positive primary lung tumor nest; however, it was mostly restrained in the stroma in a PD‐L1‐negative metastatic scapular tumor. Treg infiltrations into both tumor nests and stroma were detected in the lung tumor, which were not detected in the metastatic scapular tumor. This study provides the first evidence of coexistence of heterogeneous TIME within a single individual with a pulmonary carcinoid tumor. This study may provide new insights into the mechanism of primary resistance to chemoimmunotherapy in pulmonary carcinoid tumors. [ABSTRACT FROM AUTHOR]