The interferon-stimulated gene RIPK1 regulates cancer cell intrinsic and extrinsic resistance to immune checkpoint blockade.

Interferon-gamma (IFN-γ) has pleiotropic effects on cancer immune checkpoint blockade (ICB), including roles in ICB resistance. We analyzed gene expression in ICB-sensitive versus ICB-resistant tumor cells and identified a strong association between interferon-mediated resistance and expression of Ripk1, a regulator of tumor necrosis factor (TNF) superfamily receptors. Genetic interaction screening revealed that in cancer cells, RIPK1 diverted TNF signaling through NF-κB and away from its role in cell death. This promoted an immunosuppressive chemokine program by cancer cells, enhanced cancer cell survival, and decreased infiltration of T and NK cells expressing TNF superfamily ligands. Deletion of RIPK1 in cancer cells compromised chemokine secretion, decreased ARG1+ suppressive myeloid cells linked to ICB failure in mice and humans, and improved ICB response driven by CASP8-killing and dependent on T and NK cells. RIPK1-mediated resistance required its ubiquitin scaffolding but not kinase function. Thus, cancer cells co-opt RIPK1 to promote cell-intrinsic and cell-extrinsic resistance to immunotherapy.

Proteomic Profiling of Colorectal Adenomas Identifies a Predictive Risk Signature for Development of Metachronous Advanced Colorectal Neoplasia.

BACKGROUND & AIMS: Colonic adenomatous polyps, or adenomas, are frequent precancerous lesions and the origin of most cases of colorectal adenocarcinoma. However, we know from epidemiologic studies that although most colorectal cancers (CRCs) originate from adenomas, only a small fraction of adenomas (3%-5%) ever progress to cancer. At present, there are no molecular markers to guide follow-up surveillance programs. METHODS: We profiled, by mass spectrometry-based proteomics combined with machine learning analysis, a selected cohort of formalin-fixed, paraffin-embedded high-grade (HG) adenomas with long clinical follow-up, collected as part of the Danish national screening program. We grouped subjects in the cohort according to their subsequent history of findings: a nonmetachronous advanced neoplasia group (G0), with no new HG adenomas or CRCs up to 10 years after polypectomy, and a metachronous advanced neoplasia group (G1) where individuals developed a new HG adenoma or CRC within 5 years of diagnosis. RESULTS: We generated a proteome dataset from 98 selected HG adenoma samples, including 20 technical replicates, of which 45 samples belonged to the nonmetachronous advanced neoplasia group and 53 to the metachronous advanced neoplasia group. The clear distinction of these 2 groups seen in a uniform manifold approximation and projection plot indicated that the information contained within the abundance of the ∼5000 proteins was sufficient to predict the future occurrence of HG adenomas or development of CRC. CONCLUSIONS: We performed an in-depth analysis of quantitative proteomic data from 98 resected adenoma samples using various novel algorithms and statistical packages and found that their proteome can predict development of metachronous advanced lesions and progression several years in advance.

Isotope Effect and Heavy-Light-Heavy Reactivity Oscillation in the Cl + CHD3/CHT3 Reaction.

Previous experiments and theories have shown the existence of heavy-light-heavy (HLH) reactivity oscillation in the Cl + CH4 reaction and anticipated that similar oscillations should exist in many HLH reactions involving polyatomic reagents. However, the total reaction probabilities for the Cl + CHD3 → HCl + CD3 reaction exhibit only a step-like feature, and the total reaction probabilities for Cl + CHT3 → HCl + CT3 do not show any structure at all. Here, we report seven-dimensional state-to-state quantum dynamics studies for this reaction on the FI-NN PES, and we demonstrate that HLH reactivity oscillations also exist in these two reactions, manifesting as peaks in the reaction probabilities for low product rotational states. These oscillations, however, are obscured in the total reaction probability because of the higher excitation of j ≥ 2 product rotational states. Furthermore, the isotope replacement of nonreactive hydrogen with deuterium and tritium significantly enhances reactivity at collision energies above 0.112 eV, indicating an inverse secondary isotope effect on the probabilities, which is proved to be also caused by HLH mass combination. We also demonstrate that the highly rotational excitation of CHD3 substantially enhances reactivity and the HLH oscillations, similar to HLH triatomic reactions. These observations are completely different from those in the H + CHD3 reaction, which is also a late-barrier reaction. Therefore, the HLH mass combination is very important, which affects not only the reactivity oscillation but also the amplitude and product rotational state distribution and makes the initial rotation excitation play a pivotal role in the reaction.

An efficient and universal parallel algorithm for high-dimensional quantum dynamics in poly-atomic reactions.

This study presents a parallel algorithm for high-dimensional quantum dynamics simulations in poly atomic reactions, integrating distributed- and shared-memory models. The distributions of the wave function and potential energy matrix across message passing interface processes are based on bundled radial and angular dimensions, with implementations featuring either two- or one-sided communication schemes. Using realistic parameters for the H + NH3 reaction, performance assessment reveals linear scalability, exceeding 90% efficiency with up to 600 processors. In addition, owing to the universal and concise structure, the algorithm demonstrates remarkable extensibility to diverse reaction systems, as demonstrated by successes with six-atom and four-atom reactions. This work establishes a robust foundation for high-dimensional dynamics studies, showcasing the algorithm's efficiency, scalability, and adaptability. The algorithm's potential as a valuable tool for unraveling quantum dynamics complexities is underscored, paving the way for future advancements in the field.

Beyond ray optics absorption of light in CsPbBr3perovskite nanowire arrays studied experimentally and with wave optics modelling.

We study experimentally and with wave optics modelling the absorption of light in CsPbBr3perovskite nanowire arrays fabricated into periodic pores of an anodized aluminum oxide matrix, for nanowire diameters from 30 to 360 nm. First, we find that all the light that couples into the array can be absorbed by the nanowires at sufficient nanowire length. This behavior is in strong contrast to the expectation from a ray-optics description of light where, for normally incident light, only the rays that hit the cross-section of the nanowires can be absorbed. In that case, the absorption in the sample would be limited to the area fill factor of nanowires in the hexagonal array, which ranges from 13% to 58% for the samples that we study. Second, we find that the absorption saturates already at a nanowire length of 1000-2000 nm, making these perovskite nanowires promising for absorption-based applications such as solar cells and photodetectors. The absorption shows a strong diameter dependence, but for all diameters the transmission is less than 24% already at a nanowire length of 500 nm. For some diameters, the absorption exceeds that of a calculated thin film with 100% coverage. Our analysis indicates that the strong absorption in these nanowires originates from light-trapping induced by the out-of-plane disorder due to random axial position of each nanowire within its pore in the matrix.

Free-Standing Metal Halide Perovskite Nanowire Arrays with Blue-Green Heterostructures.

Vertically aligned metal halide perovskite (MHP) nanowires are promising for various optoelectronic applications, which can be further enhanced by heterostructures. However, present methods to obtain free-standing vertically aligned MHP nanowire arrays and heterostructures lack the scalability needed for applications. We use a low-temperature solution process to prepare free-standing vertically aligned green-emitting CsPbBr3 nanowires from anodized aluminum oxide templates. The length is controlled from 1 to 20 µm by the precursor amount. The nanowires are single-crystalline and exhibit excellent photoluminescence, clear light guiding and high photoconductivity with a responsivity of 1.9 A/W. We demonstrate blue-green heterostructured nanowire arrays by converting the free-standing part of the nanowires to CsPbCl1.1Br1.9 in an anion exchange process. Our results demonstrate a scalable, self-aligned, and lithography-free approach to achieve high quality free-standing MHP nanowires arrays and heterostructures, offering new possibilities for optoelectronic applications.

Methane activation on single-atom Ir-doped metal nanoparticles from first principles.

The breaking of the C-H bond of CH4 is of great importance, and one of the most efficient strategies in heterogeneous catalysis is to alter the electronic structure of a surface by doping it with different metal elements or controlling the stoichiometry. We present an in-depth study on methane activation on pure metal and single-atom Ir-doped alloy nanoparticles, which are constructed based on (100), (110), (111) surfaces using density functional theory (DFT) calculations. DFT results show that the dissociation barriers of CH4 on the Ir-doped alloy surfaces are about 0.3-0.4 eV, much lower than those on the pure metal surfaces (i.e., 0.6-0.8 eV). DFT-based transition state theory further reveals the rates of the first C-H activation on single-atom Ir-doped alloy nanoparticles at the early stages. Importantly, a strong temperature dependence is mainly contributed by the proportion of the exposed (110) surface. The Ir-doped Pt nanoparticle is found to be an efficient catalyst for methane activation in potential industrial applications. These important results are helpful for further designing new metal catalysts for methane activation at the atomic/molecular level.

A full-dimensional ab initio potential energy and dipole moment surfaces for (NH3)2.

A full-dimensional ab initio potential energy surface (PES) and dipole moment surface (DMS) for the ammonia dimer (NH3)2 are reported. The database of the PES consists of 27 736 ab initio energy points and all of these points were calculated at the UCCSD(T)-F12a/AVTZ level. The PES was fitted by using the fundamental invariant neural network (FI-NN) method that satisfies the permutational symmetry of identical atoms, and the root mean square fitting error for the PES is very small as low as 0.562 meV. The geometries for the (NH3)2 DMS are the same as those used for the PES and are calculated at the XYG3/AVTZ level. This PES can describe a variety of internal floppy motions, including all kinds of vibrational modes no matter intermolecular or intramolecular. The CCSD(T)-PES can dissociate correctly to two NH3 monomers, with De = 1135.55 cm-1 (13.58 kJ/mol) which agrees accurately with the 13.5 ± 0.3 kJ/mol predicted by previous work.

Full-dimensional quantum dynamics study of isotope effects for the H2 + NH2/ND2/NHD and H2/D2/HD + NH2 reactions.

A full-dimensional quantum dynamical study for the bimolecular reactions of hydrogen molecules with amino radicals for different isotopologues is reported. The nonreactive amino radical is described by two Radau vectors that are very close to the valence bond coordinates. Potential-optimized discrete variable representation basis is used for the vibrational coordinates of the amino radical. Starting from the reaction H2 + NH2, we study the isotope effects for the two reagents separately, i.e., H2 + NH2/ND2/NHD and H2/D2/HD + NH2. The effects of different vibrational mode excitations of the reagents on the reactivities are studied. Physical explanations about the isotope effects are also provided thoroughly including the influence of vibrational energy differences between the different isotopologues and the impact of the tunneling effect.

Dissociative chemisorption of O2 on Agn and Agn-1Ir (n = 3-26) clusters: a first-principle study.

Understanding the interactions between O2 and small metal clusters is of great importance in exploring heterogeneous catalysis particularly involving an oxidation reaction. We herein present the dissociative chemisorption of O2 on Agn and Agn-1Ir clusters (n = 3-26) by using density functional theory calculations. Combining a particle swarm optimization algorithm and a minima hopping method, we have optimized and obtained stable geometric structures of Agn and Agn-1Ir clusters without and with O2 adsorption. Some important physical parameters, including bond length, adsorption energy, dissociation barriers and bader charge, have been systematically calculated for appraising the stability and reactivity of Agn and Agn-1Ir clusters. It is found that the dopant Ir atom can largely enhance the stability and promote the O2 dissociation, especially on small Agn-1Ir clusters (n = 3-10). It is mainly attributed to the dopant Ir atom being completely exposed outside the Ag atoms. For O2 adsorption and dissociation on large Agn-1Ir clusters (n = 11-26), the dissociation barriers are much higher due to the dopant Ir emerging into the core of Agn-1Ir clusters, which is very similar to those on large Agn (n = 11-26). Microkinetic simulation results provide direct evidence for high reaction temperature and pressure effects on improving O2 dissociation on Agn and Agn-1Ir clusters especially for small clusters (n < 10). It is found that the Ag5Ir cluster is the most suitable nanocluster for promoting O2 dissociation at the given reaction temperatures and pressures. Our theoretical work is helpful for the rational design of doped silver nanocluster catalysts in future experiments.

Full-dimensional quantum mechanical calculations of the reaction probability of the H + CH4 reaction based on a mixed Jacobi and Radau description.

A full-dimensional time-dependent wave packet study using mixed polyspherical Jacobi and Radau coordinates for the title reaction has been reported. The non-reactive moiety CH3 has been described using three Radau vectors, whereas two Jacobi vectors have been used for the bond breaking/formation process. A potential-optimized discrete variable representation basis has been employed to describe the vibrational coordinates of the reagent CH4. About one hundred billion basis functions have been necessary to achieve converged results. The reaction probabilities for some initial vibrational states are given. A comparison between the present approach and other methods, including reduced and full-dimensional ones, is also presented.

Full dimensional quantum mechanical calculations of the reaction probability of the H + NH3 collision based on a mixed Jacobi and Radau description.

The collision between hydrogen and ammonia is a benchmark system to study chemical elementary reactions with five atoms. In this work, we present a description of the system based on mixed Jacobi and Radau coordinates combined with the time-dependent wave packet method to study the H + NH3 reaction. The Radau coordinates are used to describe the reactive moiety NH2. A salient feature of this approach is that the present coordinates have a great advantage that a very small number of basis set functions can be used to describe the NH2 group. Potential-optimized discrete variable representation basis is applied for the vibrational coordinates of the reagent NH3. The reaction probabilities for several initial vibrational states are presented in this paper. The role of the different vibrational excitations on the reactivity is thoroughly described.

Well converged quantum rate constants for the H2 + OH → H2O + H reaction via transition state wave packet.

Transition state wave packet calculations have been carried out to compute cumulative reaction probabilities for the H2 + OH reaction on the NN1 potential energy surface, as given in the work of Chen et al., from which well converged thermal rate constants for the reaction up to a temperature of 1000 K were obtained. It was found that both the centrifugal sudden approximation and the "J-K-shifting" approximation slightly underestimated the thermal rate constants, while the ring-polymer molecular dynamics overestimated the rates in the low temperature region. After considering the correction of the barrier height by spin-orbit coupling effect and the more accurate level of theory, the calculated rate constants were in good consistency with experimental measurements in the entire temperature region for this benchmark reaction.

Water dissociating on rigid Ni(100): A quantum dynamics study on a full-dimensional potential energy surface.

We constructed a nine-dimensional (9D) potential energy surface (PES) for the dissociative chemisorption of H2O on a rigid Ni(100) surface using the neural network method based on roughly 110 000 energies obtained from extensive density functional theory (DFT) calculations. The resulting PES is accurate and smooth, based on the small fitting errors and the good agreement between the fitted PES and the direct DFT calculations. Time dependent wave packet calculations also showed that the PES is very well converged with respect to the fitting procedure. The dissociation probabilities of H2O initially in the ground rovibrational state from 9D quantum dynamics calculations are quite different from the site-specific results from the seven-dimensional (7D) calculations, indicating the importance of full-dimensional quantum dynamics to quantitatively characterize this gas-surface reaction. It is found that the validity of the site-averaging approximation with exact potential holds well, where the site-averaging dissociation probability over 15 fixed impact sites obtained from 7D quantum dynamics calculations can accurately approximate the 9D dissociation probability for H2O in the ground rovibrational state.

Computing energy levels of CH4, CHD3, CH3D, and CH3F with a direct product basis and coordinates based on the methyl subsystem.

Quantum mechanical calculations of ro-vibrational energies of CH4, CHD3, CH3D, and CH3F were made with two different numerical approaches. Both use polyspherical coordinates. The computed energy levels agree, confirming the accuracy of the methods. In the first approach, for all the molecules, the coordinates are defined using three Radau vectors for the CH3 subsystem and a Jacobi vector between the remaining atom and the centre of mass of CH3. Euler angles specifying the orientation of a frame attached to CH3 with respect to a frame attached to the Jacobi vector are used as vibrational coordinates. A direct product potential-optimized discrete variable vibrational basis is used to build a Hamiltonian matrix. Ro-vibrational energies are computed using a re-started Arnoldi eigensolver. In the second approach, the coordinates are the spherical coordinates associated with four Radau vectors or three Radau vectors and a Jacobi vector, and the frame is an Eckart frame. Vibrational basis functions are products of contracted stretch and bend functions, and eigenvalues are computed with the Lanczos algorithm. For CH4, CHD3, and CH3D, we report the first J > 0 energy levels computed on the Wang-Carrington potential energy surface [X.-G. Wang and T. Carrington, J. Chem. Phys. 141(15), 154106 (2014)]. For CH3F, the potential energy surface of Zhao et al. [J. Chem. Phys. 144, 204302 (2016)] was used. All the results are in good agreement with experimental data.

MicroRNA 200a inhibits erythroid differentiation by targeting PDCD4 and THRB.

Previous studies on erythropoiesis revealed that microRNAs (miRNAs) play a critical role in erythroid differentiation. Given the abundance of identified miRNAs and the limited understanding of erythroid miRNAs, additional examination is required. Here, two sets of erythroid differentiation miRNome data were analysed to screen for novel erythroid-inhibiting miRNAs. MIR200A was selected based on its pattern of downregulated expression in the miRNome datasets during induction of erythroid differentiation. Overexpression of MIR200A in K562 and TF-1 cells confirmed its inhibitory role in erythroid differentiation. Further in vivo study indicated that overexpression of mir200a inhibited primitive erythropoiesis of zebrafish. Transcriptome analyses after MIR200A overexpression in TF-1 cells indicated a significant role in regulating erythroid function and revealed potential regulation networks. Additionally, bioinformatics and experimental analyses confirmed that PDCD4 (programmed cell death 4) and THRB (thyroid hormone receptor, beta) are both targets of MIR200A-3p. Gain- and loss-of-function studies of PDCD4 and THRB revealed that the two targets were capable of promoting erythroid gene expression. Overall, our results revealed that microRNA 200a inhibits erythroid differentiation by targeting PDCD4 and THRB.

Methane dissociation on Ni(111): A seven-dimensional to nine-dimensional quantum dynamics study.

As one benchmark system of CH4 dissociation on the Ni(111) surface, it is of great significance to explore the role of each degree of freedom (DOF) of reactant CH4 in its first C-H bond dissociation from quantum dynamics simulations. Here, the influence of the CH stretching DOF of methyl limited in C3v symmetry is quantitatively investigated as well as the important role of azimuth. We calculated the sticking probabilities, S0, of ground state (GS) CH4 dissociation on a rigid Ni(111) surface by performing some seven-dimensional to nine-dimensional (9D) quantum dynamics simulations based on one highly accurate and fifteen-dimensional (15D) ab initio potential energy surface which we recently developed. Our direct quantum dynamics results show that S0 of GS CH4 on four given surface impact sites are weakly enhanced by adding the CH stretching DOF of methyl but strongly weakened by the DOF of azimuth. Furthermore, using a 9D quantum dynamics model, we improve the post-treatment model for treating the influence of surface impact sites through a linear relationship between the effective potential barriers and the distances relative to that on the transition state site. These developed high-dimensional quantum dynamics models and improved post-treatments can be usefully extended for studying some complex polyatomic gas-surface reactions by other theoretical groups.

Mode specificity for the dissociative chemisorption of H2O on Cu(111): a quantum dynamics study on an accurately fitted potential energy surface.

The mode-specific dynamics for the dissociative chemisorption of H2O on Cu(111) is first investigated by seven-dimensional quantum dynamics calculations, based on an accurately fitted potential energy surface (PES) recently developed by neural network fitting to DFT energy points. It is indicated that excitations in all three vibrational modes have a significant impact on reactivity, which are more efficacious than increasing the translational energy in promoting the reaction, with the largest enhancement for the excitation in the asymmetric stretching mode. There is large discrepancy between the six-dimensional reactivities with fixed azimuthal angles and seven-dimensional results, revealing that the 6D "flat surface" model cannot accurately characterize the reaction dynamics. The azimuthal angle-averaging approach is validated for vibrational excited states of the reactant, where the 7D mode-specific probability can be well reproduced by averaging the 6D azimuthal angle-fixed probabilities over 18 angles.

Mode specificity of the dissociative chemisorption of HOD on rigid Cu(111): an approximate full-dimensional quantum dynamics study.

The validity of the site averaging approximation with exact potential (SAEP) has been confirmed in a recent work on the H2O/Cu(111) system [Z. Zhang, T. Liu, B. Fu, X. Yang, D. H. Zhang, Nat. Commun. 2016, 7, 11953]. Here, the mode specificity of the dissociative chemisorption of HOD on a rigid Cu(111) surface is investigated by carrying out the seven-dimensional (7D) quantum dynamics calculations on an accurate nine-dimensional (9D) potential energy surface together with the implementation of the SAEP. The approximate 9D dissociation probabilities for HOD initially in various vibrational states are obtained by averaging the site-specific 7D results over 9 impact sites. A strong bond-selective effect for the title reaction is observed, where vibrational excitation of a particular bond leads to a large enhancement only in the reaction in which the excited bond is broken. The product branching ratios strongly depend on which bond is excited, and the product from the cleavage of the excited bond is much more favored than the other product. The implementation of the SAEP allows us to investigate the mode-specific dynamics at a level of accuracy that can only be achieved in full-dimensional quantum dynamics calculations.

Communication: Methane dissociation on Ni(111) surface: Importance of azimuth and surface impact site.

Understanding the role of reactant ro-vibrational degrees of freedom (DOFs) in reaction dynamics of polyatomic molecular dissociation on metal surfaces is of great importance to explore the complex chemical reaction mechanism. Here, we present an expensive quantum dynamics study of the dissociative chemisorption of CH4 on a rigid Ni(111) surface by developing an accurate nine-dimensional quantum dynamical model including the DOF of azimuth. Based on a highly accurate fifteen-dimensional potential energy surface built from first principles, our simulations elucidate that the dissociation probability of CH4 has the strong dependence on azimuth and surface impact site. Some improvements are suggested to obtain the accurate dissociation probability from quantum dynamics simulations.