A two-step quadrature-based variational calculation of ro-vibrational levels and wavefunctions of CO2 using a bisector-x molecule-fixed frame.

In this paper, we propose a new two-step strategy for computing ro-vibrational energy levels and wavefunctions of a triatomic molecule and apply it to CO2. A two-step method [J. Tennyson and B. T. Sutcliffe, Mol. Phys., 1986, 58, 1067] uses a basis whose functions are products of K-dependent "vibrational" functions and symmetric top functions. K is the quantum number for the molecule-fixed z component of the angular momentum. For a linear molecule, a two-step method is efficient because the Hamiltonian used to compute the basis functions includes the largest coupling term. The most important distinguishing feature of the two-step method we propose is that it uses an associated Legendre basis and quadrature rather than a K-dependent discrete variable representation. This reduces the cost of the calculation and simplifies the method. We have computed ro-vibrational energy levels with J up to 100 for CO2, on an accurate available potential energy surface which is known as the AMES-2 PES and present a subset of those levels. We have converged most levels up to 20 000 cm-1 to 0.0001 cm-1.

[Advances in molecular mechanisms and therapeutic strategies of white matter injury after intracerebral hemorrhage].

Intracerebral hemorrhage (ICH) is the most common subtype of stroke with high disability and high mortality rates. Due to the hypertension with arteriosclerosis, hemopathy and cerebrovascular amyloidosis, the influx of blood from ruptured vessels into the brain destroys the cerebral parenchyma and results in dysfunction of central nervous system because of hematoma compression and a series of toxic metabolites. The cerebral parenchyma consists of gray and white matter. The white matter consists of myelinated axons and oligodendrocytes, whereas the gray matter consists of neuronal cell bodies and dendrites. Currently, most of studies have explored the mechanisms of gray matter injury. But researches of white matter injury (WMI) are still in their infancy, which may be partially responsible for the failure of treatments with neuroprotectants targeting degenerating neuronal cells. In recent years, researchers have progressively identified pathophysiological mechanisms of WMI after ICH including mass effect, neuroinflammation and oxidative stress, but information on the molecular mechanisms of WMI and its effective treatment remains limited. In this paper, we will describe the structure and function of white matter, summarize pathology of WMI and focus on the research advances in the molecular mechanisms and therapeutic strategies of WMI after ICH.

Computing excited OH stretch states of water dimer in 12D using contracted intermolecular and intramolecular basis functions.

Due to the ubiquity and importance of water, water dimer has been intensively studied. Computing the (ro-)vibrational spectrum of water dimer is challenging. The potential has eight wells separated by low barriers, which makes harmonic approximations of limited utility. A variational approach is imperative, but difficult because there are 12 coupled vibrational coordinates. In this paper, we use a product contracted basis whose functions are products of intramolecular and intermolecular functions computed using an iterative eigensolver. An intermediate matrix F facilitates calculating matrix elements. Using F, it is possible to do calculations on a general potential without storing the potential on the full quadrature grid. We find that surprisingly many intermolecular functions are required. This is due to the importance of coupling between inter- and intra-molecular coordinates. The full G16 symmetry of water dimer is exploited. We calculate, for the first time, monomer excited stretch states and compare P(1) transition frequencies with their experimental counterparts. We also compare with experimental vibrational shifts and tunneling splittings. Surprisingly, we find that the largest tunneling splitting, which does not involve the interchange of the two monomers, is smaller in the asymmetric stretch excited state than in the ground state. Differences between levels we compute and those obtained with a [6+6]D adiabatic approximation [Leforestier et al. J. Chem. Phys. 137 014305 (2012)] are ∼0.6 cm-1 for states without monomer excitation, ∼4 cm-1 for monomer excited bend states, and as large as ∼10 cm-1 for monomer excited stretch states.

Using nondirect product Wigner D basis functions and the symmetry-adapted Lanczos algorithm to compute the ro-vibrational spectrum of CH4-H2O.

By doing calculations on the methane-water van der Waals complex, we demonstrate that highly converged energy levels and wavefunctions can be obtained using Wigner D basis functions and the Symmetry-Adapted Lanczos (SAL) method. The Wigner D basis is a nondirect product basis and, therefore, efficient when the kinetic energy operator has accessible singularities. The SAL method makes it possible to exploit symmetry to label energy levels and reduce the cost of the calculation, without explicitly using symmetry-adapted basis functions. Line strengths are computed, and new bands are identified. In particular, we find unusually strong transitions between states associated with the isomers of the global minimum and the secondary minimum.

Transcriptional regulation of the bovine FGFR1 gene facilitates myoblast proliferation under hypomethylation of the promoter.

DNA methylation, which can affect the expression level of genes, is one of the most vital epigenetic modifications in mammals. Fibroblast growth factor receptor 1 (FGFR1) plays an important role in muscle development; however, DNA methylation of the FGFR1 promoter has not been studied to date in cattle. Our study focused on methylation of the FGFR1 promoter and its effect on bovine myoblast proliferation and differentiation. We identified the FGFR1 core promoter by using luciferase reporter assays; we then studied FGFR1 expression by reverse transcription quantitative polymerase chain reaction, and the methylation pattern in the FGFR1 core promoter by bisulfite sequencing polymerase chain reaction in bovine muscle tissue at three different developmental stages. We used RNAi strategy to investigate the function of FGFR1 in myoblast proliferation and differentiation. Results showed that the FGFR1 core promoters were located at the R2 (-509 to ~-202 bp) and R4 (-1295 to ~-794 bp) regions upstream of the FGFR1 gene. FGFR1 expression level was negatively associated with the degree of methylation of the FGFR1 core promoter during the developmental process. In addition, we found that FGFR1 can promote myoblast proliferation, but had no effect on myoblast differentiation. In conclusion, our results suggest that FGFR1 can promote myoblast proliferation and its transcription can be regulated by the methylation level of the core promoter. Our findings provide a mechanistic basis for the improvement of animal breeding.

Computational study of the rovibrational spectrum of CO2-N2.

The CO2-N2 complex is formed from two key components of Earth's atmosphere, and as such, has received some attention from both experimental and theoretical studies. On the theory side, a potential energy surface (PES) based on high level ab initio data was reported [Nasri et al., J. Chem. Phys., 2015, 142, 174301] and then used in more recently reported rovibrational calculations [Lara-Moreno et al., Phys. Chem. Chem. Phys., 2019, 21, 3550]. Accuracy of about 1 percent was achieved for calculated rotational transitions of the ground vibrational state of the complex, compared with previously reported microwave spectra. However, a very recent measurement of the geared bending mode frequency [Barclay et al., J. Chem. Phys., 2020, 153, 014303] recorded a value of 21.4 cm-1, which is wildly different from the corresponding calculated value of 45.9 cm-1. To provide some insight into this discrepancy, we have constructed a new more accurate PES, and used it to perform highly converged variational rovibrational calculations. Our new results yield a value of 21.1 cm-1 for that bending frequency, in close agreement with the experiment. We also obtain significantly improved predicted rotational transitions. Finally, we note that a very shallow well, previously reported as a distinct second isomer, is not found on our new PES, but rather a transition structure is seen in that location.

A variational calculation of vibrational levels of vinyl radical.

We report the vibrational energy levels of vinyl radical (VR) that are computed with a Lanczos eigensolver and a contracted basis. Many of the levels of the two previous VR variational calculations differ significantly and differ also from those reported in this paper. We identify the source of and correct symmetry errors on the potential energy surfaces used in the previous calculations. VR has two equivalent equilibrium structures. By plotting wavefunction cuts, we show that two tunneling paths play an important role. Using the computed wavefunctions, it is possible to assign many states and thereby to determine tunneling splittings that are compared with their experimental counterparts. Our computed red shift of the hot band at 2897.23 cm-1, observed by Dong et al. [J Chem. Phys. 128, 044305 (2008)], is 4.47 cm-1, which is close to the experimental value of 4.63 cm-1.

Construction of Flexible-on-Rigid Hybrid-Phase Metal-Organic Frameworks for Controllable Multi-Drug Delivery.

Multi-component MOFs contain multiple sets of unique and hierarchical pores, with different functions for different applications, distributed in their inter-linked domains. Herein, we report the construction of a class of precisely aligned flexible-on-rigid hybrid-phase MOFs with a unique rods-on-octahedron morphology. We demonstrated that hybrid-phase MOFs can be constructed based on two prerequisites: the partially matched topology at the interface of the two frameworks, and the structural flexibility of MOFs with acs topology, which can compensate for the differences in lattice parameters. Furthermore, we achieved domain selective loading of multiple guest molecules into the hybrid-phase MOF, as observed by scanning transmission electron microscopy-energy-dispersive X-ray spectrometry elemental mapping. Most importantly, we successfully applied the constructed hybrid-phase MOF to develop a dual-drug delivery system with controllable loading ratio and release kinetics.

Insights into the Self-Assembly of a Heterocluster Janus Molecule into Colloidal Onions.

Diverse nanostructures and nano-objects for advanced applications are created by the self-assembly of lipids, surfactants, and block copolymers. Understanding this process is critical for improving their functions and expanding their applications. Accordingly, we pioneered the synthesis and application of heterocluster Janus molecules (HCJMs), which resemble conventional amphiphiles. Their self-assembly into nanostructures and nano-objects can be directly characterized by transmission electron microscopy (TEM), allowing the process to be unraveled through the monitoring of the intermediates. In this study, we focused on the TEM characterization of HCJM-based colloidal onions, which have an onion-like inner structure, to gain insight into the self-assembly process from molecules to perfect onions. Multiple mechanisms, including molecular aggregation, structural ordering within aggregates into colloidal onions, and layer-by-layer growth caused by particle coarsening, contributed to the overall self-assembly process. The analysis also indicated that the reduction in the Gibbs free energy and bending free energy of curved layers are the driving forces for structural ordering and onion growth. Finally, this work provided a useful method for preparing colloidal onions for attractive applications in nanomedicine and other areas.

Computing vibration-rotation-tunnelling levels of HOD dimer.

Using an accurate 6D water dimer potential energy surface, we compute vibration-rotation-tunnelling levels of HOD dimer, by assuming that the two monomers are rigid. HOD dimer has two isomers, a D-bonded isomer and an H-bonded isomer, and the wavefunctions of both isomers have amplitude in four wells. HOD dimer is important because, unlike the case of H2O dimer or D2O dimer, it is possible to measure the largest tunnelling splitting. Results for HOD dimer, therefore facilitate the testing of H2O dimer potentials. In J. Chem. Phys., 1995, 102, 1114, experimental results were interpreted in terms of 1D models. Experimental splittings of both isomers, obtained by fitting an energy level equation to spectra, are in good agreement with those we compute.

Vibronic interaction in CO3- photo-detachment: Jahn-Teller effects beyond structural distortion and general formalisms for vibronic Hamiltonians in trigonal symmetries.

Recently, the negative ion photoelectron spectrum of CO3- was reported and the second lowest energy band is assigned to the close-lying 3E'' and 3E' states that undergo Jahn-Teller distortions (Chem. Sci., 2016, 7, 1142). This assignment is based on the Born-Oppenheimer approximation and the assumption of a static Jahn-Teller effect that distorts the CO3 structure from D3h to C2v symmetry. In this work, we employ a 4 states 6 modes vibronic coupling model to investigate the triplet band and uncover the dynamic and non-adiabatic nature of the Jahn-Teller and pseudo-Jahn-Teller interactions in the triplet states. The apparent four peaks progression in the band is studied in depth, and is found to consist of more than four transitions. By comparing the simulated spectra using the full model and the reduced-dimension 2 states 2 modes models, we characterize those transitions. The origin of the complexities of the spectrum is traced to the C-O nonbonding character of the orbitals that lose electron in the photo-detachment process. Methodology-wise, we derive and present the formalisms for arbitrary order expansions of all bimodal trigonal Jahn-Teller and pseudo-Jahn-Teller Hamiltonians in vibrational coordinates.

Computational Study of the Rovibrational Spectra of CH2D+ and CHD2.

In this paper, we present rovibrational energy levels of CH2D+ and CHD2+. They are computed with a large basis and the Lanczos algorithm. CH2D+ and CHD2+ are believed to play an important role in interstellar space, but so far, there are no definitive observations. The predictions of this paper should facilitate detection. For CH2D+, two CH stretch bands have been studied at high resolution. Compared to our calculated energies, the root-mean-square error is 0.08 cm-1. For CHD2+, one CH stretch band has been studied at high resolution. Compared to our calculated energies, the root-mean-square error is 0.5 cm-1. Errors are larger, for both isotopologues, for bend states. We attribute these errors to the potential energy surface. Wave function and probability distribution plots are used to make assignments. The ν1 band of CHD2+ is significantly perturbed, and according to our calculations, the 3ν3 state is closest and might be the most important perturber.

Computational study of the ro-vibrational spectrum of CO-CO2.

An accurate ab initio ground-state intermolecular potential energy surface (PES) was determined for the CO-CO2 van der Waals dimer. The Lanczos algorithm was used to compute rovibrational energies on this PES. For both the C-in and O-in T-shaped isomers, the fundamental transition frequencies agree well with previous experimental results. We confirm that the in-plane states previously observed are geared states. In addition, we have computed and assigned many other vibrational states. The rotational constants we determine from J = 1 energy levels agree well with their experimental counterparts. Planar and out-of-plane cuts of some of the wavefunctions we compute are quite different, indicating strong coupling between the bend and torsional modes. Because the stable isomers are T-shaped, vibration along the out-of-plane coordinates is very floppy. In CO-CO2, when the molecule is out-of-plane, interconversion of the isomers is possible, but the barrier height is higher than the in-plane geared barrier height.

Double-Targeting Explosible Nanofirework for Tumor Ignition to Guide Tumor-Depth Photothermal Therapy.

This study reports a double-targeting "nanofirework" for tumor-ignited imaging to guide effective tumor-depth photothermal therapy (PTT). Typically, ≈30 nm upconversion nanoparticles (UCNP) are enveloped with a hybrid corona composed of ≈4 nm CuS tethered hyaluronic acid (CuS-HA). The HA corona provides active tumor-targeted functionality together with excellent stability and improved biocompatibility. The dimension of UCNP@CuS-HA is specifically set within the optimal size window for passive tumor-targeting effect, demonstrating significant contributions to both the in vivo prolonged circulation duration and the enhanced size-dependent tumor accumulation compared with ultrasmall CuS nanoparticles. The tumors featuring hyaluronidase (HAase) overexpression could induce the escape of CuS away from UCNP@CuS-HA due to HAase-catalyzed HA degradation, in turn activating the recovery of initially CuS-quenched luminescence of UCNP and also driving the tumor-depth infiltration of ultrasmall CuS for effective PTT. This in vivo transition has proven to be highly dependent on tumor occurrence like a tumor-ignited explosible firework. Together with the double-targeting functionality, the pathology-selective tumor ignition permits precise tumor detection and imaging-guided spatiotemporal control over PTT operation, leading to complete tumor ablation under near infrared (NIR) irradiation. This study offers a new paradigm of utilizing pathological characteristics to design nanotheranostics for precise detection and personalized therapy of tumors.

Infrared spectrum and intermolecular potential energy surface of the CO-O2 dimer.

Only a few weakly-bound complexes containing the O2 molecule have been characterized by high resolution spectroscopy, no doubt due to the complications added by the oxygen molecule's unpaired electron spin. Here we report an extensive infrared spectrum of CO-O2, observed in the CO fundamental band region using a tunable quantum cascade laser to probe a pulsed supersonic jet expansion. The rotational energy level pattern derived from the spectrum consists of stacks of levels characterized by the total angular momentum, J, and its projection on the intermolecular axis, K. Five such stacks are observed in the ground vibrational state, and ten in the excited state (ν(CO) = 1). They are divided into two groups, with no observed transitions between groups. The groups correspond to different projections of the O2 electron spin, and correlate with the two lowest fine structure states of O2, (N, J) = (1, 0) and (1, 2). The rotational constant of the lowest K = 0 stack implies an effective intermolecular separation of 3.82 Å, but this should be interpreted with caution since it ignores possible effects of electron spin. A new high-level 4-dimensional potential energy surface is developed for CO-O2, and rotational energy levels are calculated for this surface, ignoring electron spin. By comparing calculated and observed levels, it is possible to assign detailed quantum labels to the observed level stacks.

Ab initio study of the CO-N2 complex: a new highly accurate intermolecular potential energy surface and rovibrational spectrum.

A new, highly accurate ab initio ground-state intermolecular potential-energy surface (IPES) for the CO-N2 complex is presented. Thousands of interaction energies calculated with the CCSD(T) method and Dunning's aug-cc-pVQZ basis set extended with midbond functions were fitted to an analytical function. The global minimum of the potential is characterized by an almost T-shaped structure and has an energy of -118.2 cm-1. The symmetry-adapted Lanczos algorithm was used to compute rovibrational energies (up to J = 20) on the new IPES. The RMSE with respect to experiment was found to be on the order of 0.038 cm-1 which confirms the very high accuracy of the potential. This level of agreement is among the best reported in the literature for weakly bound systems and considerably improves on those of previously published potentials.

Using monomer vibrational wavefunctions to compute numerically exact (12D) rovibrational levels of water dimer.

We compute numerically exact rovibrational levels of water dimer, with 12 vibrational coordinates, on the accurate CCpol-8sf ab initio flexible monomer potential energy surface [C. Leforestier et al., J. Chem. Phys. 137, 014305 (2012)]. It does not have a sum-of-products or multimode form and therefore quadrature in some form must be used. To do the calculation, it is necessary to use an efficient basis set and to develop computational tools, for evaluating the matrix-vector products required to calculate the spectrum, that obviate the need to store the potential on a 12D quadrature grid. The basis functions we use are products of monomer vibrational wavefunctions and standard rigid-monomer basis functions (which involve products of three Wigner functions). Potential matrix-vector products are evaluated using the F matrix idea previously used to compute rovibrational levels of 5-atom and 6-atom molecules. When the coupling between inter- and intra-monomer coordinates is weak, this crude adiabatic type basis is efficient (only a few monomer vibrational wavefunctions are necessary), although the calculation of matrix elements is straightforward. It is much easier to use than an adiabatic basis. The product structure of the basis is compatible with the product structure of the kinetic energy operator and this facilitates computation of matrix-vector products. Compared with the results obtained using a [6 + 6]D adiabatic approach, we find good agreement for the inter-molecular levels and larger differences for the intra-molecular water bend levels.

Vibrational spectra of halide-water dimers: Insights on ion hydration from full-dimensional quantum calculations on many-body potential energy surfaces.

Full-dimensional vibrational spectra are calculated for both X-(H2O) and X-(D2O) dimers (X = F, Cl, Br, I) at the quantum-mechanical level. The calculations are carried out on two sets of recently developed potential energy functions (PEFs), namely, Thole-type model energy (TTM-nrg) and many-body energy (MB-nrg), using the symmetry-adapted Lanczos algorithm with a product basis set including all six vibrational coordinates. Although both TTM-nrg and MB-nrg PEFs are derived from coupled-cluster single double triple-F12 data obtained in the complete basis set limit, they differ in how many-body effects are represented at short range. Specifically, while both models describe long-range interactions through the combination of two-body dispersion and many-body classical electrostatics, the relatively simple Born-Mayer functions employed in the TTM-nrg PEFs to represent short-range interactions are replaced in the MB-nrg PEFs by permutationally invariant polynomials to achieve chemical accuracy. For all dimers, the MB-nrg vibrational spectra are in close agreement with the available experimental data, correctly reproducing anharmonic and nuclear quantum effects. In contrast, the vibrational frequencies calculated with the TTM-nrg PEFs exhibit significant deviations from the experimental values. The comparison between the TTM-nrg and MB-nrg results thus reinforces the notion that an accurate representation of both short-range interactions associated with electron density overlap and long-range many-body electrostatic interactions is necessary for a correct description of hydration phenomena at the molecular level.

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.

Efficacy and safety of sodium-glucose cotransporter 2 inhibitors as add-on to metformin and sulfonylurea treatment for the management of type 2 diabetes: a meta-analysis.

This study evaluates the efficacy and safety of sodium-glucose cotransporter 2 (SGLT2) inhibitors as add-on to metformin and sulfonylurea treatment for type 2 diabetes management. The literature search was conducted in electronic databases and meta-analyses of mean differences in the changes from baseline in selected disease endpoints (efficacy endpoints) or odds ratios (for safety endpoints) were performed to compare outcomes between SGLT2 inhibitor- and placebo-/comparator-treatments. Seven studies (5,143 patients; age 56.75 years [95% CI: 56.19, 57.37]; body mass index 29.53 kg/m2 [28.23, 30.83]; and 51.87% [50.46, 53.57] males) were included. Compared to placebo, SGLT2 inhibitors significantly (p < 0.00001) reduced glycated hemoglobin (HbA1c; -0.79% [95% CI: -0.90, -0.68]), fasting plasma glucose (FPG; -1.73 mmol/L [-1.86, -1.60]) and body weight (-1.85 kg [-2.11, -1.59]) after 52-78 weeks of treatment. There were no significant differences in reduction of either HbA1c, FPG or body weight between 18-24 weeks and after 52-76 weeks of treatment. Treatment with SGLT2 inhibitors as add-on to metformin and sulfonylurea was also associated with significant reductions in blood pressure and triglycerides and increase in high-density lipoprotein-cholesterol. Incidence of hypoglycemia was significantly higher, but incidence of hyperglycemia was significantly lower in SGLT2 inhibitor group. Overall, drug-related adverse events were more common in SGLT2 group mainly due to higher incidence of genital tract infections.