Probing the Molecular and Macroscopic Structure of Solid Solutions by Dynamic Nuclear Polarization (DNP) Enhanced 13C and 15N Solid-State NMR Spectroscopy.

Crystallization is a widely used purification technique in the manufacture of active pharmaceutical ingredients (APIs) and precursor molecules. However, when impurities and desired compounds have similar molecular structures, separation by crystallization may become challenging. In such cases, some impurities may form crystalline solid solutions with the desired product during recrystallization. Understanding the molecular structure of these recrystallized solid solutions is crucial to devise methods for effective purification. Unfortunately, there are limited analytical techniques that provide insights into the molecular structure or spatial distribution of impurities that are incorporated within recrystallized products. In this study, we investigated model solid solutions formed by recrystallizing salicylic acid (SA) in the presence of anthranilic acid (AA). These two molecules are known to form crystalline solid solutions due to their similar molecular structures. To overcome challenges associated with the long 1H longitudinal relaxation times (T1(1H)) of SA and AA, we employed dynamic nuclear polarization (DNP) and 15N isotope enrichment to enable solid-state NMR experiments. Results of solid-state NMR experiments and DFT calculations revealed that SA and AA are homogeneously alloyed as a solid solution. Heteronuclear correlation (HETCOR) experiments and plane-wave DFT structural models provide further evidence of the molecular-level interactions between SA and AA. This research provides valuable insights into the molecular structure of recrystallized solid solutions, contributing to the development of effective purification strategies and an understanding of the physicochemical properties of solid solutions.

Electrochemically Stable Ligands of ZnO Electron-Transporting Layers for Quantum-Dot Light-Emitting Diodes.

Thin films of ZnO nanocrystals are actively pursued as electron-transporting layers (ETLs) in quantum-dot light-emitting diodes (QLEDs). However, the developments of ZnO-based ETLs are highly engineering oriented and the design of ZnO-based ETLs remains empirical. Here, we identified a previously overlooked efficiency-loss channel associated with the ZnO-based ETLs: i.e., interfacial exciton quenching induced by surface-bound ethanol. Accordingly, we developed a general surface-treatment procedure to replace the redox-active surface-bound ethanol with electrochemically inert alkali carboxylates. Characterization results show that the surface treatment procedure does not change other key properties of the ETLs, such as the conductance and work function. Our single-variable experimental design unambiguously demonstrates that improving the electrochemical stabilities of the ZnO ETLs leads to QLEDs with a higher efficiency and longer operational lifetime. Our work provides a crucial guideline to design ZnO-based ETLs for optoelectronic devices.

Composition-Defined Optical Properties and the Direct-to-Indirect Transition in Core-Shell In1-xGaxP/ZnS Colloidal Quantum Dots.

Semiconductors are commonly divided into materials with direct or indirect band gaps based on the relative positions of the top of the valence band and the bottom of the conduction band in crystal momentum (k) space. It has, however, been debated if k is a useful quantum number to describe the band structure in quantum-confined nanocrystalline systems, which blur the distinction between direct and indirect gap semiconductors. In bulk III-V semiconductor alloys like In1-xGaxP, the band structure can be tuned continuously from the direct- to indirect-gap by changing the value of x. The effect of strong quantum confinement on the direct-to-indirect transition in this system has yet to be established because high-quality colloidal nanocrystal samples have remained inaccessible. Herein, we report one of the first systematic studies of ternary III-V nanocrystals by utilizing an optimized molten-salt In-to-Ga cation exchange protocol to yield bright In1-xGaxP/ZnS core-shell particles with photoluminescence quantum yields exceeding 80%. We performed two-dimensional solid-state NMR studies to assess the alloy homogeneity and the extent of surface oxidation in In1-xGaxP cores. The radiative decay lifetime for In1-xGaxP/ZnS monotonically increases with higher gallium content. Transient absorption studies on In1-xGaxP/ZnS nanocrystals demonstrate signatures of direct- and indirect-like behavior based on the presence or absence, respectively, of excitonic bleach features. Atomistic electronic structure calculations based on the semi-empirical pseudopotential model are used to calculate absorption spectra and radiative lifetimes and evaluate band-edge degeneracy; the resulting calculated electronic properties are consistent with experimental observations. By studying photoluminescence characteristics at elevated temperatures, we demonstrate that a reduced lattice mismatch at the III-V/II-VI core-shell interface can enhance the thermal stability of emission. These insights establish cation exchange in molten inorganic salts as a viable synthetic route to nontoxic, high-quality In1-xGaxP/ZnS QD emitters with desirable optoelectronic properties.

General Strategy for Incorporation of Functional Group Handles into Covalent Organic Frameworks via the Ugi Reaction.

The library of imine-linked covalent organic frameworks (COFs) has grown significantly over the last two decades, featuring a variety of morphologies, pore sizes, and applications. An array of synthetic methods has been developed to expand the scope of the COF functionalities; however, most of these methods were designed to introduce functional scaffolds tailored to a specific application. Having a general approach to diversify COFs via late-stage incorporation of functional group handles would greatly facilitate the transformation of these materials into platforms for a variety of useful applications. Herein, we report a general strategy to introduce functional group handles in COFs via the Ugi multicomponent reaction. To demonstrate the versatility of this approach, we have synthesized two COFs with hexagonal and kagome morphologies. We then introduced azide, alkyne, and vinyl functional groups, which could be readily utilized for a variety of post-synthetic modifications. This facile approach enables the functionalization of any COFs containing imine linkages.

Search for Light Dark Matter with Ionization Signals in the PandaX-4T Experiment.

We report the search results of light dark matter through its interactions with shell electrons and nuclei, using the commissioning data from the PandaX-4T liquid xenon detector. Low energy events are selected to have an ionization-only signal between 60 to 200 photoelectrons, corresponding to a mean nuclear recoil energy from 0.77 to 2.54 keV and electronic recoil energy from 0.07 to 0.23 keV. With an effective exposure of 0.55 tonne·year, we set the most stringent limits within a mass range from 40 MeV/c^{2} to 10 GeV/c^{2} for pointlike dark matter-electron interaction, 100 MeV/c^{2} to 10 GeV/c^{2} for dark matter-electron interaction via a light mediator, and 3.2 to 4 GeV/c^{2} for dark matter-nucleon spin-independent interaction. For DM interaction with electrons, our limits are closing in on the parameter space predicted by the freeze-in and freeze-out mechanisms in the early Universe.

Search for Solar

A search for interactions from solar ^{8}B neutrinos elastically scattering off xenon nuclei using PandaX-4T commissioning data is reported. The energy threshold of this search is further lowered compared with the previous search for dark matter, with various techniques utilized to suppress the background that emerges from data with the lowered threshold. A blind analysis is performed on the data with an effective exposure of 0.48 tonne year, and no significant excess of events is observed. Among the results obtained using the neutrino-nucleus coherent scattering, our results give the best constraint on the solar ^{8}B neutrino flux. We further provide a more stringent limit on the cross section between dark matter and nucleon in the mass range from 3 to 9 GeV/c^{2}.

Visible light driven multicomponent synthesis of difluoroamidosulfonyl quinoline derivatives.

A visible-light-induced photocatalyst-free three-component radical tandem cyclization of N-propargylamine and N-allylbromodifluoroacetamides with the insertion of sulfur dioxide has been developed. Diverse difluoroamidosulfonylated quinolines are obtained in moderate to good yields. This protocol features broad functional group tolerance and high regioselectivity. Moreover, mechanistic studies reveal the involvement of the radical pathway and the formation of an electron donor-acceptor (EDA) complex in this reaction.

Trimethylamine N-oxide Promotes Atherosclerosis by Regulating Low-Density Lipoprotein-Induced Autophagy in Vascular Smooth Muscle Cells Through PI3K/AKT/mTOR Pathway.

The research aimed to study the mechanism of how trimethylamine N-oxide (TMAO) regulates autophagy to promote atherosclerosis (AS). The AS in vitro model was constructed with vascular smooth muscle cells (VSMCs) treated with ox-LDL. The Cell Counting Kit-8 (CCK-8) trial was chosen to examine VSMCs' absorbance (OD) value. A transmission electron microscope (TEM) was selected for monitoring autophagosomes. Western blotting (WB) was adopted for examining the expression of Beclin-1, p62, LC3, α-SMA, SM22-α, OPN, PI3K, AKT, mTOR, p-PI3K, p-AKT, and p-mTOR proteins. Real-time fluorescent quantitative PCR (RT-qPCR) was accepted for testing the expression of α-SMA, SM22-α, OPN, PI3K, AKT, mTOR, Beclin-1, p62, and LC3 genes. The transwell assay was employed to examine the ability of migration in VSMCs. Oil red O staining assay was accepted to stain lipid droplets in VSMCs. TMAO noticeably promoted autophagy inhibition and the phenotypic transformation of AS. Protein expressions of p-PI3K/PI3K, p-AKT/AKT, p-mTOR/mTOR, and p62 of the TMAO+ox-LDL group were higher than the ox-LDL group, while Beclin-1 and LC3 were lower than the ox-LDL group. Gene expressions of PI3K, AKT, mTOR, and p62 of the TMAO+ox-LDL group were higher than the ox-LDL group, while Beclin-1 and LC3 were lower than the ox-LDL group. The intervention of LY294002 reversed the regulation of the corresponding proteins and genes. The study proved that TMAO could promote autophagy inhibition of AS via activating the PI3K/AKT/mTOR pathway. It supplied a reliable basis for improving clinical diagnostic methods and developing targeted AS drugs.

Effects of arginine vasopressin on the transcriptome of prefrontal cortex in autistic rat model.

Our previous studies have also demonstrated that AVP can significantly improve social interaction disorders and stereotypical behaviours in rats with VPA-induced autism model. To further explore the mechanisms of action of AVP, we compared the PFC transcriptome changes before and after AVP treatment in VPA-induced autism rat model. The autism model was induced by intraperitoneally injected with VPA at embryonic day 12.5 and randomly assigned to two groups: the VPA-induced autism model group and the AVP treatment group. The AVP treatment group were treated with intranasal AVP at postnatal day 21 and for 3 weeks. The gene expression levels and function changes on the prefrontal cortex were measured by RNA-seq and bioinformatics analysis at PND42 and the mRNA expression levels of synaptic and myelin development related genes were validated by qPCR. Our results confirmed that AVP could significantly improve synaptic and axon dysplasia and promote oligodendrocyte development in the prefrontal cortex in VPA-induced autism models by regulating multiple signalling pathways.

Upper Critical Solution Temperature Polyvalent Scaffolds Aggregate and Exterminate Bacteria.

Specific recognition and strong affinities of bacteria receptors with the host cell glycoconjugates pave the way to control the bacteria aggregation and kill bacteria. Herein, using aggregation-induced emission (AIE) molecules decorated upper critical solution temperature (UCST) polyvalent scaffold (PATC-GlcN), an approach toward visualizing bacteria aggregation and controlling bacteria-polyvalent scaffolds affinities under temperature stimulus is described. Polyvalent scaffolds with diblocks, one UCST block PATC of polyacrylamides showing a sharp UCST transition and typical AIE behavior, the second bacteria recognition block GlcN of hydrophilic glucosamine modified polyacrylamide, are prepared through a reversible addition and fragmentation chain transfer polymerization. Aggregated chain conformation of polyvalent scaffolds at temperature below UCST induces the aggregation of E. coli ATCC8739, because of the high density of glucosamine moieties, whereas beyond UCST, the hydrophilic state of the scaffolds dissociates the bacteria aggregation. The sweet-talking of bacteria toward the polyvalent scaffolds can be visualized by the fluorescent imaging technique, simultaneously. Due to the specific recognition of polyvalent scaffolds with bacteria, the photothermal agent IR780 loaded PATC-GlcN shows the targeted killing ability toward E. coli ATCC8739 in vitro and in vivo under NIR radiation.

The Surface Chemistry and Structure of Colloidal Lead Halide Perovskite Nanocrystals.

ConspectusSince the initial discovery of colloidal lead halide perovskite nanocrystals, there has been significant interest placed on these semiconductors because of their remarkable optoelectronic properties, including very high photoluminescence quantum yields, narrow size- and composition-tunable emission over a wide color gamut, defect tolerance, and suppressed blinking. These material attributes have made them attractive components for next-generation solar cells, light emitting diodes, low-threshold lasers, single photon emitters, and X-ray scintillators. While a great deal of research has gone into the various applications of colloidal lead halide perovskite nanocrystals, comparatively little work has focused on the fundamental surface chemistry of these materials. While the surface chemistry of colloidal semiconductor nanocrystals is generally affected by their particle morphology, surface stoichiometry, and organic ligands that contribute to the first coordination sphere of their surface atoms, these attributes are markedly different in lead halide perovskite nanocrystals because of their ionicity.In this Account, emerging work on the surface chemistry of lead halide perovskite nanocrystals is highlighted, with a particular focus placed on the most-studied composition of CsPbBr3. We begin with an in-depth exploration of the native surface chemistry of as-prepared, 0-D cuboidal CsPbBr3 nanocrystals, including an atomistic description of their surface termini, vacancies, and ionic bonding with ligands. We then proceed to discuss various post-synthetic surface treatments that have been developed to increase the photoluminescence quantum yields and stability of CsPbBr3 nanocrystals, including the use of tetraalkylammonium bromides, metal bromides, zwitterions, and phosphonic acids, and how these various ligands are known to bind to the nanocrystal surface. To underscore the effect of post-synthetic surface treatments on the application of these materials, we focus on lead halide perovskite nanocrystal-based light emitting diodes, and the positive effect of various surface treatments on external quantum efficiencies. We also discuss the current state-of-the-art in the surface chemistry of 1-D nanowires and 2-D nanoplatelets of CsPbBr3, which are more quantum confined than the corresponding cuboidal nanocrystals but also generally possess a higher defect density because of their increased surface area-to-volume ratios.

Search for Cosmic-Ray Boosted Sub-GeV Dark Matter at the PandaX-II Experiment.

We report a novel search for the cosmic-ray boosted dark matter using the 100 tonne·day full dataset of the PandaX-II detector located at the China Jinping Underground Laboratory. With the extra energy gained from the cosmic rays, sub-GeV dark matter particles can produce visible recoil signals in the detector. The diurnal modulations in rate and energy spectrum are utilized to further enhance the signal sensitivity. Our result excludes the dark matter-nucleon elastic scattering cross section between 10^{-31} and 10^{-28} cm^{2} for dark matter masses from 0.1 MeV/c^{2} to 0.1 GeV/c^{2}, with a large parameter space previously unexplored by experimental collaborations.

First Search for the Absorption of Fermionic Dark Matter with the PandaX-4T Experiment.

Compared with the signature of dark matter elastic scattering off nuclei, the absorption of fermionic dark matter by nuclei opens up a new searching channel for light dark matter with a characteristic monoenergetic signal. In this Letter, we explore the 95.0-day data from the PandaX-4T commissioning run and report the first dedicated searching results of the fermionic dark matter absorption signal through a neutral current process. No significant signal was found, and the lowest limit on the dark matter-nucleon interaction cross section is set to be 1.5×10^{-50} cm^{2} for a fermionic dark matter mass of 40 MeV/c^{2} with 90% confidence level.

Search for Light Fermionic Dark Matter Absorption on Electrons in PandaX-4T.

We report a search on sub-MeV fermionic dark matter absorbed by electrons with an outgoing active neutrino using the 0.63 tonne year exposure collected by the PandaX-4T liquid xenon experiment. No significant signals are observed over the expected background. The data are interpreted into limits to the effective couplings between such dark matter and the electron. For axial-vector or vector interactions, our sensitivity is competitive in comparison to existing astrophysical bounds on the decay of such a dark matter candidate into photon final states. In particular, we present the first direct detection limits for a vector (axial-vector) interaction which are the strongest in the mass range from 35 to 55 (25 to 45) keV/c^{2} in comparison to other astrophysical and cosmological constraints.

Ba6(CuxZy)Sn4S16 (Z = Mg, Mn, Zn, Cd, In, Bi, Sn): High Chemical Flexibility Resulting in Good Nonlinear-Optical Properties.

Seven acentric sulfides Ba6(CuxZy)Sn4S16 (Z = Mg, Mn, Zn, Cd, In, Bi, Sn) were grown by a high-temperature salt flux method. The crystal structures of the Ba6(CuxZy)Sn4S16 (Z = Mg, Mn, Zn, Cd, In, Bi, Sn) compounds were determined by single-crystal X-ray diffraction with the aid of solid-state NMR spectroscopy. The Ba6(CuxZy)Sn4S16 (Z = Mg, Mn, Zn, Cd, In, Bi) compounds are isostructural and crystallize in the Ba6Ag4Sn4S16 structure type. The Sn-containing compound exhibits high structural similarity to Ba6(CuxZy)Sn4S16 (Z = Mg, Mn, Zn, Cd, In, Bi) with the presence of an interstitial atomic position partially occupied by Sn atoms. The chemical bonding characteristics of Ba6(Cu2.9Sn0.4)Sn4S16 were understood with electron localization function calculations coupled with crystal orbital Hamilton population calculations. The Ba-S and Cu-S interactions are dominantly ionic, but the Sn-S interactions consist of strong covalent bonding characteristics in Ba6(Cu2.9Sn0.4)Sn4S16. The monovalent Cu atoms, mixed with certain metals with various oxidation states, significantly shift the optical properties of the Ba6(CuxZy)Sn4S16 (Z = Mg, Mn, Zn, Cd, In, Bi) compounds. This results in a good balance between the second-harmonic-generation (SHG) response and laser damage threshold (LDT). Ba6(Cu1.9Zn1.1)Sn4S16 possesses a high SHG response and a high LDT of 2.8 × AGS and 3 × AGS, respectively. A density functional theory calculation revealed that CuS4 and SnS4 tetrahedra significantly contribute to the SHG response in Ba6(Cu2Mg)Sn4S16, which also confirmed that CuS4 tetrahedra are crucial for the stability and optical properties of the Ba6(CuxZy)Sn4S16 (Z = Mg, Mn, Zn, Cd, In, Bi, Sn) compounds revealed by electronic structure analysis.

Magic angle spinning dynamic nuclear polarization solid-state NMR spectroscopy of γ-irradiated molecular organic solids.

In the past 15 years, magic angle spinning (MAS) dynamic nuclear polarization (DNP) has emerged as a method to increase the sensitivity of high-resolution solid-state NMR spectroscopy experiments. Recently, γ-irradiation has been used to generate significant concentrations of homogeneously distributed free radicals in a variety of solids, including quartz, glucose, and cellulose. Both γ-irradiated quartz and glucose previously showed significant MAS DNP enhancements. Here, γ-irradiation is applied to twelve small organic molecules to test the applicability of γ-irradiation as a general method of creating stable free radicals for MAS DNP experiments on organic solids and pharmaceuticals. Radical concentrations in the range of 0.25 â€‹mM-10 â€‹mM were observed in irradiated glucose, histidine, malic acid, and malonic acid, and significant 1H DNP enhancements of 32, 130, 19, and 11 were obtained, respectively, as measured by 1H→13C CPMAS experiments. However, concentrations of free radicals below 0.05 â€‹mM were generally observed in organic molecules containing aromatic rings, preventing sizeable DNP enhancements. DNP sensitivity gains for several of the irradiated compounds exceed that which can be obtained with the relayed DNP approach that uses exogeneous polarizing agent solutions and impregnation procedures. In several cases, significant 1H DNP enhancements were realized at room temperature. This study demonstrates that in many cases γ-irradiation is a viable alternative to addition of stable exogenous radicals for DNP experiments on organic solids.

Revealing the Surface Structure of CdSe Nanocrystals by Dynamic Nuclear Polarization-Enhanced 77Se and 113Cd Solid-State NMR Spectroscopy.

Dynamic nuclear polarization (DNP) solid-state NMR (SSNMR) spectroscopy was used to obtain detailed surface structures of zinc blende CdSe nanocrystals (NCs) with plate or spheroidal morphologies which are capped by carboxylic acid ligands. 1D 113Cd and 77Se cross-polarization magic angle spinning (CPMAS) NMR spectra revealed distinct signals from Cd and Se atoms on the surface of the NCs, and those residing in bulk-like environments, below the surface. 113Cd cross-polarization magic-angle-turning (CP-MAT) experiments identified CdSe3O, CdSe2O2, and CdSeO3 Cd coordination environments on the surface of the NCs, where the oxygen atoms are presumably from coordinated carboxylate ligands. The sensitivity gain from DNP enabled natural isotopic abundance 2D homonuclear 113Cd-113Cd and 77Se-77Se and heteronuclear 113Cd-77Se scalar correlation solid-state NMR experiments which revealed the connectivity of the Cd and Se atoms. Importantly, 77Se{113Cd} scalar heteronuclear multiple quantum coherence (J-HMQC) experiments were used to selectively measure one-bond 77Se-113Cd scalar coupling constants (1J(77Se, 113Cd)). With knowledge of 1J(77Se, 113Cd), heteronuclear 77Se{113Cd} spin echo (J-resolved) NMR experiments were used to determine the number of Cd atoms bonded to Se atoms and vice versa. The J-resolved experiments directly confirmed that major Cd and Se surface species have CdSe2O2 and SeCd4 stoichiometries, respectively. Considering the crystal structure of zinc blende CdSe and the similarity of the solid-state NMR data for the platelets and spheroids, we conclude that the surface of the spheroidal CdSe NCs is primarily composed of {100} facets. The methods outlined here will generally be applicable to obtain detailed surface structures of various main group semiconductor nanoparticles.

Mechanisms of vasculogenic mimicry in hypoxic tumor microenvironments.

BACKGROUND: Vasculogenic mimicry (VM) is a recently discovered angiogenetic process found in many malignant tumors, and is different from the traditional angiogenetic process involving vascular endothelium. It involves the formation of microvascular channels composed of tumor cells; therefore, VM is considered a new model for the formation of new blood vessels in aggressive tumors, and can provide blood supply for tumor growth. Many studies have pointed out that in recent years, some clinical treatments against angiogenesis have not been satisfactory possibly due to the activation of VM. Although the mechanisms underlying VM have not been fully elucidated, increasing research on the soil "microenvironment" for tumor growth suggests that the initial hypoxic environment in solid tumors is inseparable from VM. MAIN BODY: In this review, we describe that the stemness and differentiation potential of cancer stem cells are enhanced under hypoxic microenvironments, through hypoxia-induced epithelial-endothelial transition (EET) and extracellular matrix (ECM) remodeling to form the specific mechanism of vasculogenic mimicry; we also summarized some of the current drugs targeting VM through these processes, suggesting a new reference for the clinical treatment of tumor angiogenesis. CONCLUSION: Overall, the use of VM inhibitors in combination with conventional anti-angiogenesis treatments is a promising strategy for improving the effectiveness of targeted angiogenesis treatments; further, considering the importance of hypoxia in tumor invasion and metastasis, drugs targeting the hypoxia signaling pathway seem to achieve good results.

Search for Light Dark Matter-Electron Scattering in the PandaX-II Experiment.

We report constraints on light dark matter through its interactions with shell electrons in the PandaX-II liquid xenon detector with a total 46.9 tonnes/day exposure. To effectively search for these very low energy electron recoils, ionization-only signals are selected from the data. 1821 candidates are identified within an ionization signal range between 50 and 75 photoelectrons, corresponding to a mean electronic recoil energy from 0.08 to 0.15 keV. The 90% C.L. exclusion limit on the scattering cross section between the dark matter and electron is calculated with systematic uncertainties properly taken into account. Under the assumption of point interaction, we provide the world's most stringent limit within the dark matter mass range from 15 to 30 MeV/c^{2}, with the corresponding cross section from 2.5×10^{-37} to 3.1×10^{-38} cm^{2}.

Dark Matter Search Results from the PandaX-4T Commissioning Run.

We report the first dark matter search results using the commissioning data from PandaX-4T. Using a time projection chamber with 3.7 tonne of liquid xenon target and an exposure of 0.63 tonne·year, 1058 candidate events are identified within an approximate nuclear recoil energy window between 5 and 100 keV. No significant excess over background is observed. Our data set a stringent limit to the dark matter-nucleon spin-independent interactions, with a lowest excluded cross section (90% C.L.) of 3.8×10^{-47} cm^{2} at a dark matter mass of 40 GeV/c^{2}.