Role of Polarization Interactions in the Formation of Dipole-Bound States.

Even though there is a critical dipole moment required to support a dipole-bound state (DBS), how molecular polarizability may influence the formation of DBSs is not well understood. Pyrrolide, indolide, and carbazolide provide an ideal set of anions to systematically examine the role of polarization interactions in the formation of DBSs. Here, we report an investigation of carbazolide using cryogenic photodetachment spectroscopy and high-resolution photoelectron spectroscopy (PES). A polarization-assisted DBS is observed at 20 cm-1 below the detachment threshold for carbazolide, even though the carbazolyl neutral core has a dipole moment (2.2 D) smaller than the empirical critical value (2.5 D) to support a dipole-bound state. Photodetachment spectroscopy reveals nine vibrational Feshbach resonances of the DBS, as well as three intense and broad shape resonances. The electron affinity of carbazolyl is measured accurately to be 2.5653 ± 0.0004 eV (20,691 ± 3 cm-1). The combination of photodetachment spectroscopy and resonant PES allows fundamental frequencies for 14 vibrational modes of carbazolyl to be measured. The three shape resonances are due to above-threshold excitation to the three low-lying electronic states (S1-S3) of carbazolide. Resonant PES of the shape resonances is dominated by autodetachment processes. Ultrafast relaxation from the S2 and S3 states to S1 is observed, resulting in constant kinetic energy features in the resonant PES. The current study provides decisive information about the role that polarization plays in the formation of DBSs, as well as rich spectroscopic information about the carbazolide anion and the carbazolyl radical.

Clinical validation of a 90-gene expression test for tumor tissue of origin diagnosis: a large-scale multicenter study of 1417 patients.

BACKGROUND: Once malignancy tumors were diagnosed, the determination of tissue origin and tumor type is critical for clinical management. Although the significant advance in imaging techniques and histopathological approaches, the diagnosis remains challenging in patients with metastatic and poorly differentiated or undifferentiated tumors. Gene expression profiling has been demonstrated the ability to classify multiple tumor types. The present study aims to assess the performance of a 90-gene expression test for tumor classification (i.e. the determination of tumor tissue of origin) in real clinical settings. METHODS: Formalin-fixed paraffin-embedded samples and associated clinicopathologic information were collected from three cancer centers between January 2016 and January 2021. A total of 1417 specimens that met quality control criteria (RNA quality, tumor cell content ≥ 60% and so on) were analyzed by the 90-gene expression test to identify the tumor tissue of origin. The performance was evaluated by comparing the test results with histopathological diagnosis. RESULTS: The 1417 samples represent 21 main tumor types classified by common tissue origins and anatomic sites. Overall, the 90-gene expression test reached an accuracy of 94.4% (1338/1417, 95% CI: 0.93 to 0.96). Among different tumor types, sensitivities were ranged from 74.2% (head&neck tumor) to 100% (adrenal carcinoma, mesothelioma, and prostate cancer). Sensitivities for the most prevalent cancers of lung, breast, colorectum, and gastroesophagus are 95.0%, 98.4%, 93.9%, and 90.6%, respectively. Moreover, specificities for all 21 tumor types are greater than 99%. CONCLUSIONS: These findings showed robust performance of the 90-gene expression test for identifying the tumor tissue of origin and support the use of molecular testing as an adjunct to tumor classification, especially to those poorly differentiated or undifferentiated tumors in clinical practice.

Resonant two-photon photoelectron imaging and adiabatic detachment processes from bound vibrational levels of dipole-bound states.

Anions cannot have Rydberg states, but anions with polar neutral cores can support highly diffuse dipole-bound states (DBSs) as a class of interesting electronically excited states below the electron detachment threshold. The binding energies of DBSs are extremely small, ranging from a few to few hundred wavenumbers and generally cannot support bound vibrational levels below the detachment threshold. Thus, vibrational excitations in the DBS are usually above the electron detachment threshold and they have been used to conduct resonant photoelectron spectroscopy, which is dominated by state-specific autodetachment. Here we report an investigation of a cryogenically-cooled complex anion, the enantiopure (R)-(-)-1-(9-anthryl)-2,2,2-trifluoroethanolate (R-TFAE-). The neutral R-TFAE radical is relatively complex and highly polar with a non-planar structure (C1 symmetry). Photodetachment spectroscopy reveals a DBS 209 cm-1 below the detachment threshold of R-TFAE- and seven bound and eight above-threshold vibrational levels of the DBS. Resonant two-photon detachment (R2PD) via the bound vibrational levels of the DBS exhibits strictly adiabatic photodetachment behaviors by the second photon, in which the vibrational energies in the DBS are carried to the neutral final states, because of the parallel potential energy surfaces of the DBS and the corresponding neutral ground electronic state. Relaxation processes from the bound DBS levels to the ground and low-lying electronically excited states of R-TFAE- are also observed in the R2PD photoelectron spectra. The combination of photodetachment and resonant photoelectron spectroscopy yields frequencies for eight vibrational modes of the R-TFAE radical.

Observation of a dipole-bound excited state in 4-ethynylphenoxide and comparison with the quadrupole-bound excited state in the isoelectronic 4-cyanophenoxide.

Negative ions do not possess Rydberg states but can have Rydberg-like nonvalence excited states near the electron detachment threshold, including dipole-bound states (DBSs) and quadrupole-bound states (QBSs). While DBSs have been studied extensively, quadrupole-bound excited states have been more rarely observed. 4-cyanophenoxide (4CP-) was the first anion observed to possess a quadrupole-bound exited state 20 cm-1 below its detachment threshold. Here, we report the observation of a DBS in the isoelectronic 4-ethynylphenoxide anion (4EP-), providing a rare opportunity to compare the behaviors of a dipole-bound and a quadrupole-bound excited state in a pair of very similar anions. Photodetachment spectroscopy (PDS) of cryogenically cooled 4EP- reveals a DBS 76 cm-1 below its detachment threshold. Photoelectron spectroscopy (PES) at 266 nm shows that the electronic structure of 4EP- and 4CP- is nearly identical. The observed vibrational features in both the PDS and PES, as well as autodetachment from the nonvalence excited states, are also found to be similar for both anions. However, resonant two-photon detachment (R2PD) from the bound vibrational ground state is observed to be very different for the DBS in 4EP- and the QBS in 4CP-. The R2PD spectra reveal that decays take place from both the DBS and QBS to the respective anion ground electronic states within the 5 ns detachment laser pulse due to internal conversion followed by intramolecular vibrational redistribution and relaxation, but the decay mechanisms appear to be very different. In the R2PD spectrum of 4EP-, we observe strong threshold electron signals, which are due to detachment, by the second photon, of highly rotationally excited anions resulted from the decay of the DBS. On the other hand, in the R2PD spectrum of 4CP-, we observe well-resolved vibrational peaks due to the three lowest-frequency vibrational modes of 4CP-, which are populated from the decay of the QBS. The different behaviors of the R2PD spectra suggest unexpected differences between the relaxation mechanisms of the dipole-bound and quadrupole-bound excited states.

Probing the Dipole-Bound State in the 9-Phenanthrolate Anion by Photodetachment Spectroscopy, Resonant Two-Photon Photoelectron Imaging, and Resonant Photoelectron Spectroscopy.

Valence-bound anions with a dipolar core can support dipole-bound states (DBSs) below the electron detachment threshold. The highly diffuse DBS observed is usually of σ symmetry with an s-like orbital. Recently, a π-type DBS was observed experimentally in the 9-anthrolate anion (9AT-) and it was shown to be stabilized due to the large anisotropic polarizability of the 9AT core. To confirm the general existence of π-DBS and its structural dependence, here we report an investigation of the 9-phenanthrolate anion (9PT-), which has a different structure and lower symmetry than 9AT-. Photodetachment spectroscopy revealed a DBS 257 cm-1 below the detachment threshold of 9PT- at 19 627 cm-1 (2.4334 eV). Resonant two-photon photoelectron imaging indeed showed a π symmetry for the DBS. Similar to that observed in 9AT-, the π-DBS in 9PT- is also stabilized by the anisotropic polarizability of the 9PT core and accessed via nonadiabatic population transfer from the initially populated σ-DBS. Photodetachment spectroscopy unveiled nine above-threshold vibrational resonances of the DBS, resulting in nine highly non-Franck-Condon resonant photoelectron spectra by tuning the detachment laser to the vibrational resonances. The combination of photodetachment spectroscopy and resonant photoelectron spectroscopy allowed frequencies for nine vibrational modes of the 9-phenathroxy radical to be measured, including the six lowest frequency bending modes.

Photodetachment spectroscopy and resonant photoelectron imaging of cryogenically cooled 1-pyrenolate.

We report an investigation of the 1-pyrenolate anion (PyO-) and the 1-pyrenoxy radical (PyO) using photodetachment spectroscopy and resonant photoelectron imaging of cryogenically cooled anions. The electron affinity of PyO is measured to be 2.4772(4) eV (19 980 ± 3 cm-1) from high-resolution photoelectron spectroscopy. Photodetachment spectroscopy reveals a dipole-bound state (DBS) for PyO- 280 cm-1 below the detachment threshold as well as a broad and intense valence excited state (shape resonance) 1077 cm-1 above the detachment threshold. The shape resonance with an excitation energy of 21 055 cm-1 is due to excitation of an electron from the highest occupied molecular orbital of PyO- to its lowest unoccupied molecular orbital in the continuum. Twenty-nine vibrational levels of the DBS are observed, including 27 above-threshold vibrational levels (vibrational Feshbach resonances). Twenty-seven resonant photoelectron spectra are obtained by tuning the detachment laser to the vibrational Feshbach resonances, resulting in highly non-Franck-Condon photoelectron spectra and rich vibrational information. In total, the frequencies of 21 vibrational modes are obtained for the PyO radical by the combination of the photodetachment and resonant photoelectron spectroscopy, including 13 out-of-plane bending modes.

Observation of a Symmetry-Forbidden Excited Quadrupole-Bound State.

We report the observation of a symmetry-forbidden excited quadrupole-bound state (QBS) in the tetracyanobenzene anion (TCNB-) using both photoelectron and photodetachment spectroscopies of cryogenically-cooled anions. The electron affinity of TCNB is accurately measured as 2.4695 eV. Photodetachment spectroscopy of TCNB- reveals selected symmetry-allowed vibronic transitions to the QBS, but the ground vibrational state was not observed because the transition from the ground state of TCNB- (Au symmetry) to the QBS (Ag symmetry) is triply forbidden by the electric and magnetic dipoles and the electric quadrupole. The binding energy of the QBS is found to be 0.2206 eV, which is unusually large due to strong correlation and polarization effects. A centrifugal barrier is observed for near-threshold autodetachment, as well as relaxations from the QBS vibronic levels to the ground and a valence excited state of TCNB-. The current study shows a rare example where symmetry selection rules, rather than the Franck-Condon principle, govern vibronic transitions to a nonvalence state in an anion.

Polarization of Valence Orbitals by the Intramolecular Electric Field from a Diffuse Dipole-Bound Electron.

The diffuse electron in a dipole-bound state is spatially well separated from the valence electrons and is known to have negligible effects on the dipole-bound state's molecular structure. Here, we show that a dipole-bound state is observed in deprotonated 4-(2-phenylethynyl)-phenoxide anions, 348 cm-1 below the anion's detachment threshold. The photodetachment of the dipole-bound electron is observed to accompany a simultaneous shakeup process in valence orbitals in this aromatic molecular anion. This shakeup process is due to configuration mixing as a result of valence orbital polarization by the intramolecular electric field of the dipole-bound electron. This observation suggests that dipole-bound anions can serve as a new platform to probe how oriented electric fields influence the valence electronic structure of polyatomic molecules.

Observation of a π-Type Dipole-Bound State in Molecular Anions.

We report the observation of a π-type dipole-bound state (π-DBS) in cryogenically cooled deprotonated 9-anthrol molecular anions (9AT^{-}) by resonant two-photon photoelectron imaging. A DBS is observed 191 cm^{-1} (0.0237 eV) below the detachment threshold, and the existence of the π-DBS is revealed by a distinct (s+d)-wave photoelectron angular distribution. The π-DBS is stabilized by the large anisotropic in-plane polarizability of 9AT. The population of the dipole-forbidden π-DBS is proposed to be via a nonadiabatic coupling with the dipole-allowed σ-type DBS mediated by molecular rotations.

Photodetachment spectroscopy and resonant photoelectron imaging of the 2-naphthoxide anion via dipole-bound excited states.

We report a photodetachment spectroscopy and high-resolution resonant photoelectron imaging study of cryogenically cooled 2-naphthoxide anions (C10H7O-). The photodetachment spectrum revealed a dipole-bound state (DBS) 202(4) cm-1 below the detachment threshold and 38 resonances corresponding to the vibrational levels of the DBS. By tuning the detachment laser to these above-threshold resonances, we obtained 38 resonantly enhanced photoelectron spectra, which were highly non-Franck-Condon as a result of mode-selective vibrational autodetachment from the DBS. The resonances were assigned by comparing the resonant and non-resonant photoelectron spectra, assisted by the computed vibrational frequencies. Specifically, vibrational features with low Franck-Condon factors or from Franck-Condon-forbidden vibrational modes were significantly enhanced in the resonant photoelectron spectra, resulting in much richer spectroscopic information. The electron affinity of the 2-naphthoxy radical was measured accurately to be 19 387(4) cm-1 or 2.4037(5) eV. In addition, a total of 17 vibrational frequencies were obtained for the 2-naphthoxy radical. In particular, seven Franck-Condon-forbidden out-of-plane bending modes, including the two lowest frequency modes (ν48 at 102 cm-1 and ν47 at 171 cm-1), were observed, demonstrating the advantages of combining photodetachment spectroscopy and resonant photoelectron spectroscopy in obtaining vibrational information for polar radical species via DBS.

Probing the Critical Dipole Moment To Support Excited Dipole-Bound States in Valence-Bound Anions.

We report photodetachment spectroscopy and high-resolution photoelectron imaging of para-halogen substituted phenoxide anions, p-XC6H4O- (X = F, Cl, Br, I). The dipole moments of the p-XC6H4O neutral radicals increase from 2.56 to 3.19 D for X = F to I, providing a series of similar molecules to allow the examination of charge-dipole interactions by minimizing molecule-dependent effects. Excited DBSs ([XC6H4O]*-) are observed for the four anions with binding energies of 8, 11, 24, and 53 cm-1, respectively, for X = F to I, below their respective detachment thresholds. The binding energies exhibit a linear correlation with the dipole moments of the neutral radicals, extrapolating to a critical dipole moment of 2.5 D for zero binding energy. Because of the small binding energy of the excited DBS of [FC6H4O]*-, rotational autodetachment is observed to compete with vibrational autodetachment in the resonant photoelectron spectra, resulting in electrons with near zero kinetic energies.

Resonant Two-Photon Photoelectron Imaging and Intersystem Crossing from Excited Dipole-Bound States of Cold Anions.

We report the observation of a dipole-bound state (DBS) 659 cm-1 below the electron detachment threshold of cryogenically cooled deprotonated 4,4'-biphenol anion (bPh-) and 19 of its lowest vibrational levels. Resonant two-photon photoelectron imaging (R2P-PEI) via the vibrational levels of the DBS displays a sharp peak with a constant binding energy. This observation indicates vertical detachment from the vibrational levels of the DBS to the corresponding neutral levels with the conservation of the vibrational energy, suggesting that the highly diffuse electron in the DBS has little effect on the neutral core. The R2P-PEI spectra also exhibit two features at lower binding energies, which come from intersystem crossings from the DBS to two lower-lying valence-bound triplet excited states of bPh-. The current study discloses the first R2P-PEI spectra from vibrational excited states of a DBS and direct spectroscopic evidence of transitions from a DBS to valence-bound states of anions.

Sulfur in Mesoporous Tungsten Nitride Foam Blocks: A Rational Lithium Polysulfide Confinement Experimental Design Strategy Augmented by Theoretical Predictions.

To enhance the utilization of sulfur in lithium-sulfur batteries, three-dimensional tungsten nitride (WN) mesoporous foam blocks are designed to spatially localize the soluble Li2S6 and Li2S4 within the pore spaces. Meanwhile, the chemisorption behaviors of polysulfides and the capability of WN as an effective confiner are systematically investigated through density functional theory calculations and experimental studies. The theoretical calculations reveal a decrease in chemisorption strength between WN and the soluble polysulfides (Li2S8 > Li2S6 > Li2S4), while the interactions between WN and the insoluble Li2S2/Li2S show a high chemisorption strength of ca. 3 eV. Validating theoretical insights through electrochemical measurements further manifest that the assembled battery configurations with sulfur cathode confined in the thickest WN blocks exhibit the best rate capabilities (1090 and 510 mAh g-1 at 0.5C and 5C, respectively) with the highest initial Coulombic efficiency of 90.5%. Moreover, a reversible capacity of 358 mAh g-1 is maintained with a high Coulombic efficiency approaching to 100%, even after 500 cycles at 2C. As guided by in silico design, this work not only provides an effective strategy to improve the retentivity of polysulfides but also underpins that properly architectured WN can be effective retainers of polysulfides.

Gene Expression Profiling for Diagnosis of Triple-Negative Breast Cancer: A Multicenter, Retrospective Cohort Study.

Background: Triple-negative breast cancer (TNBC) accounts for 12-20% of all breast cancers. Diagnosis of TNBC is sometimes quite difficult based on morphological assessment and immunohistochemistry alone, particularly in the metastatic setting with no prior history of breast cancer. Methods: Molecular profiling is a promising diagnostic approach that has the potential to provide an objective classification of metastatic tumors with unknown primary. In this study, performance of a novel 90-gene expression signature for determination of the site of tumor origin was evaluated in 115 TNBC samples. For each specimen, expression profiles of the 90 tumor-specific genes were analyzed, and similarity scores were obtained for each of the 21 tumor types on the test panel. Predicted tumor type was compared to the reference diagnosis to calculate accuracy. Furthermore, rank product analysis was performed to identify genes that were differentially expressed between TNBC and other tumor types. Results: Analysis of the 90-gene expression signature resulted in an overall 97.4% (112/115, 95% CI: 0.92-0.99) agreement with the reference diagnosis. Among all specimens, the signature correctly classified 97.6% of TNBC from the primary site (41/42) and lymph node metastasis (41/42) and 96.8% of distant metastatic tumors (30/31). Furthermore, a list of genes, including AZGP1, KRT19, and PIGR, was identified as differentially expressed between TNBC and other tumor types, suggesting their potential use as discriminatory markers. Conclusion: Our results demonstrate excellent performance of a 90-gene expression signature for identification of tumor origin in a cohort of both primary and metastatic TNBC samples. These findings show promise for use of this novel molecular assay to aid in differential diagnosis of TNBC, particularly in the metastatic setting.

Tautomer-Specific Resonant Photoelectron Imaging of Deprotonated Cytosine Anions.

Tautomers of the nucleobases play fundamental roles in spontaneous mutations of DNA. Tautomers of neutral cytosine have been studied in the gas phase, but much less is known about charged species. Here, we report the observation and characterization of three tautomers of deprotonated cytosine anions, [trans-keto-amino-N3H-H8b] (tKAN3H8b- ), [cis-keto-amino-N3H-H8a] (cKAN3H8a- ) and [keto-amino-H] (KAN1- ), produced by electrospray ionization. Excited dipole-bound states (DBSs) are uncovered for the three anions by photodetachment spectroscopy. Excitations to selected DBS vibrational levels of cKAN3H8a- and tKAN3H8b- yield tautomer-specific resonant photoelectron spectra. The current study provides further insight into tautomerism of cytosine and suggests a new method to study the tautomers of nucleobases using electrospray ionization and anion spectroscopy.

Dipole-bound excited states and resonant photoelectron imaging of phenoxide and thiophenoxide anions.

We report photodetachment and resonant photoelectron-imaging studies of cryogenically cooled phenoxide (C6H5O-) and thiophenoxide (C6H5S-) anions. In a previous study [H. T. Liu et al. Angew. Chem., Int. Ed. 52, 8976 (2013)], a dipole-bound excited state was observed for C6H5O- at 97 cm-1 below the detachment threshold. Eight resonant photoelectron spectra were obtained via excitations to eight vibrational levels of the dipole-bound state (DBS) followed by autodetachment. Here we present a complete photodetachment spectrum of C6H5O- covering a spectral range 2600 cm-1 above the detachment threshold and revealing nine additional vibrational resonances of the DBS. We also report the first observation of a dipole-bound excited state for C6H5S-, 39 cm-1 below its detachment threshold of 18 982 cm-1. Photodetachment spectroscopy covering a spectral range 1500 cm-1 above the threshold reveals twelve vibrational resonances for the DBS of C6H5S-. By tuning the detachment laser to the vibrational resonances in the DBS of C6H5O- and C6H5S-, we obtain highly non-Franck-Condon resonant photoelectron spectra, as a result of mode-selectivity and the Δv = -1 propensity rule for vibrational autodetachment. Five new fundamental vibrational frequencies are obtained for the ground state of the C6H5O (X 2B1) radical. Intramolecular inelastic scattering is observed in some of the resonant photoelectron spectra, leading to the excitation of the Franck-Condon-inactive lowest-frequency bending mode (ν20) of C6H5O. The first excited state of C6H5O (A 2B2) is observed to be 0.953 eV above the ground state. Twelve resonant photoelectron spectra are obtained for C6H5S-, allowing the measurements of seven fundamental vibrational frequencies of the C6H5S radical, whereas the non-resonant photoelectron spectrum exhibits only a single Franck-Condon active mode. The current study again demonstrates that the combination of photodetachment spectroscopy and resonant photoelectron spectroscopy is a powerful technique to obtain vibrational information about polar radical species.

Construction of pH-Sensitive "Submarine" Based on Gold Nanoparticles with Double Insurance for Intracellular pH Mapping, Quantifying of Whole Cells and in Vivo Applications.

A series of "submarines", which composed of gold nanoparticles and modified with rhodamine and fluorescein derivatives, were presented. With dual sensitive units for both acidic and basic environment, these "gold nano-submarines" not only allow efficient intracellular pH mapping but also provide more accurate quantitative detection of pH alteration under different stimuli with distinct pH quantification range. Moreover, they even have the ability to pass through the blood brain barrier (BBB).