Solid-State NMR Dipolar and Chemical Shift Anisotropy Recoupling Techniques for Structural and Dynamical Studies in Biological Systems.

With the development of NMR methodology and technology during the past decades, solid-state NMR (ssNMR) has become a particularly important tool for investigating structure and dynamics at atomic scale in biological systems, where the recoupling techniques play pivotal roles in modern high-resolution MAS NMR. In this review, following a brief introduction on the basic theory of recoupling in ssNMR, we highlight the recent advances in dipolar and chemical shift anisotropy recoupling methods, as well as their applications in structural determination and dynamical characterization at multiple time scales (i.e., fast-, intermediate-, and slow-motion). The performances of these prevalent recoupling techniques are compared and discussed in multiple aspects, together with the representative applications in biomolecules. Given the recent emerging advances in NMR technology, new challenges for recoupling methodology development and potential opportunities for biological systems are also discussed.

Gene expression variability across cells and species shapes the relationship between renal resident macrophages and infiltrated macrophages.

BACKGROUND: Two main subclasses of macrophages are found in almost all solid tissues: embryo-derived resident tissue macrophages and bone marrow-derived infiltrated macrophages. These macrophage subtypes show transcriptional and functional divergence, and the programs that have shaped the evolution of renal macrophages and related signaling pathways remain poorly understood. To clarify these processes, we performed data analysis based on single-cell transcriptional profiling of renal tissue-resident and infiltrated macrophages in human, mouse and rat. RESULTS: In this study, we (i) characterized the transcriptional divergence among species and (ii) illustrated variability in expression among cells of each subtype and (iii) compared the gene regulation network and (iv) ligand-receptor pairs in human and mouse. Using single-cell transcriptomics, we mapped the promoter architecture during homeostasis. CONCLUSIONS: Transcriptionally divergent genes, such as the differentially TF-encoding genes expressed in resident and infiltrated macrophages across the three species, vary among cells and include distinct promoter structures. The gene regulatory network in infiltrated macrophages shows comparatively better species-wide consistency than resident macrophages. The conserved transcriptional gene regulatory network in infiltrated macrophages among species is uniquely enriched in pathways related to kinases, and TFs associated with largely conserved regulons among species are uniquely enriched in kinase-related pathways.

Achmatowicz Rearrangement-Inspired Development of Green Chemistry, Organic Methodology, and Total Synthesis of Natural Products.

The six-membered heterocycles containing oxygen and nitrogen (tetrahydropyrans, pyrans, piperidines) are among the most common heterocyclic structures ubiquitously present in bioactive molecules such as carbohydrates, small-molecule drugs, and natural products. Chemical synthesis of fully functionalized pyrans and piperidines is a research theme of practical importance and scientific significance and, thus, has attracted continuous interest from synthetic chemists. Among the numerous synthetic approaches, Achmatowicz rearrangement (AchR) represents a general and unique strategy that uses biomass-derived furfuryl alcohols as the renewable starting material to obtain fully functionalized six-membered oxygen/nitrogen heterocycles, which provides golden opportunities for organic chemists to address various synthetic challenges.This Account summarizes our 10 years of work on exploiting AchR to address some challenges in organic synthesis ranging from green chemistry and organic methodology to the total synthesis of natural products. We enabled the sustainable and safe use of AchR in a small (academia) or large (industrial) scale by developing two generations of green approaches for AchR (oxone-halide and Fenton-halide), which largely eliminate the use of the most popular, but more toxic and expansive, NBS and m-CPBA. This triggered our intensive interest in developing new green chemistry for important organic reactions, in particular, halogenation/oxidation reactions involving reactive halogenating species with the aim of eliminating the use of commonly used toxic halogen agents such as elemental bromine, chlorine gas, and various N-haloamide reagents (NBS, NCS, and NIS). We successfully employed oxone-halide and Fenton-halide as green alternatives to several mechanistically related organic reactions including arene/alkene halogenation, oxidation or oxidative rearrangement of indoles, oxidation of alcohols/thioacetals, and oxidative halogenation of aldoximes for the in situ generation of nitrile oxide. These green reactions are expected to have a solid impact on the future of organic synthesis in academia and industries.We expanded the synthetic utility of AchR by exploring several new transformations of AchR products and developed a cascade reductive ring expansion, reductive deoxygenation/Heck-Matsuda arylation, palladium-catalyzed C-arylation, and regiodivergent [3 + 2] cycloaddition with 1,3-dicarbonyls. These methodologies offer a new avenue to fully functionalized six-membered heterocycles.The synthetic utility of AchR was demonstrated in our total synthesis of 28 natural products with a pyran/piperidine moiety. The AchR-based strategy endows the total synthesis with scalability, sustainability, and flexibility. The green and scalable approaches developed in our lab for AchR allow us to easily obtain decagrams of synthetically valuable pyrans and/or piperidines with low risk and low cost from biomass-derived furfuryl alcohol/aldehyde.

Bistable Optoelectronic Properties Originated from the Scissoring Motion of the TEMPO Skeleton in Supramolecular Radical Ferroelectrics.

Bistable materials with multiphysical channels, such as optical, electrical, and magnetic properties, have been paid dramatic attention due to their alternativity of the signal status in electronic devices. Herein, three stable supramolecular radicals ([(NH3-TEMPO)(18-crown-6)][XF6] (1, X = P; 2, X = As; 3, X = Sb)) were synthesized and characterized. The former two molecules present ferroelectric phase transitions around 381.7 and 382.7 K, respectively, with bistability in dielectric property and second-harmonic generation (SHG) effect, which are first found in supramolecular radicals. Their ferroelectric transition and bistable properties are generated from a net polar crystal structure owing to the static ordered packing of NH3-TEMPO radical cations in the low-temperature phase (LTP) to a nonpolar structure owing to a distinctive symmetric scissoring motion of NH3-TEMPO radical cations between two 18-crown-6 molecules in the high-temperature phase (HTP). Both of them exhibit paramagnetic properties in HTP and LTP states since no intermolecular spin-spin interaction occurs due to the long distances among the radicals in their crystals. These results make us possible to design bistable optoelectronic radical materials with bistability in magnetic property in the future.

Direct Detection of Reactive Gallium-Hydride Species on the Ga2O3 Surface via Solid-State NMR Spectroscopy.

Surface metal hydrides (M-H) are ubiquitous in heterogeneous catalytic reactions, while the detailed characterizations are frequently hindered by their high reactivity/low concentration, and the complicated surface structures of the host solids, especially in terms of practical solid catalysts. Herein, combining instant quenching capture and advanced solid-state NMR methodology, we report the first direct and unambiguous NMR evidence on the highly reactive surface gallium hydrides (Ga-H) over a practical Ga2O3 catalyst during direct H2 activation. The spectroscopic effects of 69Ga and 71Ga isotopes on the 1H NMR signal are clearly differentiated and clarified, allowing a concrete discrimination of the Ga-H signal from the hydroxyl crowd. Accompanied with quantitative and two-dimensional NMR spectroscopical methods, as well as density functional theory calculations, information on the site specification, structural configuration, and formation mechanism of the Ga-H species has been revealed, along with the H2 dissociation mechanism. More importantly, the successful spectroscopic identification and isolation of the surface Ga-H allow us to clearly reveal the critical but ubiquitous intermediate role of this species in catalytic reactions, such as propane dehydrogenation and CO2 hydrogenation reactions. The analytic approach presented in this work can be extended to other M-H analysis, and the insights will benefit the design of more efficient Ga-based catalysts.

[Outcome indicators in randomized controlled trials on traditional Chinese medicine intervention of sepsis-induced myocardial injury in recent five years].

This study aims to analyze the outcome indicators of randomized controlled trial(RCT) on traditional Chinese medicine(TCM) intervention of sepsis-induced myocardial injury(SIMI) in recent five years, which is expected to lay a basis for the construction of core outcome set(COS) for this disease treated by TCM. To be specific, RCT on the treatment of SIMI with TCM was retrieved from 4 Chinese databases, 3 English databases, and 2 clinical trial protocol registries. The quality of the included studies was evaluated with Cochrane risk-of-bias(ROB) tool, and the outcome indicators were analyzed. Finally, 42 RCTs were included, of which 2 were clinical trial registration schemes. The study found that 42 RCTs had a high risk of bias, and reported a total of 86 indicators in "clinical effective rate, disease severity, TCM syndrome score, inflammation, myocardium, cardiac structure and hemodynamics, electrocardiogram, immunology, metabolism and liver and kidney function, and safety". Outcome indicators on myocardium had the highest emergence frequency, followed by indicators on the cardiac structure and hemodynamics. A total of 8 RCTs reported TCM syndrome scores. Further analysis suggested the following problems in the selection of outcome indicators in the RCTs on TCM intervention of SIMI: no classification of primary and secondary indicators, disregard of endpoint indicators, irrational selection of alternative indicators, neglection of TCM characteristics, no assessment of patients' immune status, and no emphasis on economic indicators and safety indicators. Therefore, according to the recommendations of the core outcome measures in effectiveness trials(COMET) working group, a COS for TCM intervention of TCM for SIMI should be developed, so as to facilitate clinical researchers to select appropriate outcome indicators, the combination of conclusions of similar clinical studies, and the promotion of TCM interventions.

Unraveling the Surface Hydroxyl Network on In2O3 Nanoparticles with High-Field Ultrafast Magic Angle Spinning Nuclear Magnetic Resonance Spectroscopy.

Hydroxyl groups are among the major active surface sites over metal oxides. However, their spectroscopic characterizations have been challenging due to limited resolutions, especially on hydroxyl-rich surfaces where strong hydroxyl networks are present. Here, using nanostructured In2O3 as an example, we show significantly enhanced discrimination of the surface hydroxyl groups, owing to the high-resolution 1H NMR spectra performed at a high magnetic field (18.8 T) and a fast magic angle spinning (MAS) of up to 60 kHz. A total of nine kinds of hydroxyl groups were distinguished and their assignments (µ1, µ2, and µ3) were further identified with the assistance of 17O NMR. The spatial distribution of these hydroxyl groups was further explored via two-dimensional (2D) 1H-1H homonuclear correlation experiments with which the complex surface hydroxyl network was unraveled at the atomic level. Moreover, the quantitative analysis of these hydroxyl groups with such high resolution enables further investigations into the physicochemical property and catalytic performance characterizations (in CO2 reduction) of these hydroxyl groups. This work provides insightful understanding on the surface structure/property of the In2O3 nanoparticles and, importantly, may prompt general applications of high-field ultrafast MAS NMR techniques in the study of hydroxyl-rich surfaces on other metal oxide materials.

Enhanced Fluoride Uptake by Layered Double Hydroxides under Alkaline Conditions: Solid-State NMR Evidence of the Role of Surface >MgOH Sites.

Layered double hydroxides (LDHs) are potential low-cost filter materials for use in fluoride removal from drinking water, but molecular-scale defluoridation mechanisms are lacking. In this research, we employed 19F solid-state NMR spectroscopy to identify fluoride sorption products on 2:1 MgAl LDH and to reveal the relationship between fluoride sorption and the LDH structure. A set of six 19F NMR peaks centered at -140, -148, -156, -163, -176, and -183 ppm was resolved. Combining quantum chemical calculations based on density function theory (DFT) and 19F{27Al} transfer of populations in double resonance (TRAPDOR) analysis, we could assign the peaks at -140, -148, -156, and -163 ppm to Al-F (F coordinated to surface Al) and those at -176 and -183 ppm to Mg-F (F coordinated to surface Mg only). Interestingly, the spectroscopic data reveal that the formation of Al-F is the predominant mode of F- sorption at low pH, whereas the formation of Mg-F is predominant at high pH (or a higher Mg/Al ratio). This finding supports the fact that the F- uptake of 2:1 MgAl LDH was nearly six times that of activated alumina at pH 9. Overall, we explicitly revealed the different roles of the surface >MgOH and >AlOH sites of LDHs in defluoridation, which explained why the use of classic activated alumina for defluoridation is limited at high pH. The findings from this research may also provide new insights into material screening for potential filters for F- removal under alkaline conditions.

89Y chemical shift anisotropy: a sensitive structural probe of layered yttrium hydroxides revealed by solid-state NMR spectroscopy and DFT calculations.

Anion-exchangeable Y2(OH)5X·nH2O (LYH-X, X = monovalent anions, n ≈ 1.5) materials are an ideal platform for incorporating the unique properties of layered metal hydroxides and rare-earth (RE) ions, and thus have exhibited promising prospects for various applications. To further improve the performance of LYH-X and related functional materials, their structure-property relationships must be explored. However, due to the intrinsic felxibility, extracting the local structural details of these materials is particularly challenging. In this work, we utilized a combined approach of 89Y solid-state NMR (ssNMR) spectroscopy and density functional theory (DFT) calculations to reveal the response of 89Y chemical shift anisotropy (CSA) in LYH-X to the structural changes including a small displacement of cationic yttrium hydroxide layers and intercalated anions. Such subtle structural changes are often associated with dehydration/rehydration, anion-exchange, exfoliation, and the self-assembly process of LYH-X and related functional materials, which are exceedingly difficult to detect using other techniques. The principal components of 89Y CSA show a larger variation range than isotropic chemical shifts, making CSA a more sensitive probe. In addition, it is found that the response of 89Y CSA to structural changes is distinct for Y sites with different local coordination environments, opening great opportunities to analyze each Y site within these materials. All these observations suggest that the strategy involving both experimental (89Y ssNMR) and theoretical (DFT) approaches can be utilized to extract previously unavailable ultrafine structural information of LYH-X and related materials, and provide fruitful insights into their thorough structure-property relationships.

Recent progress in dipolar recoupling techniques under fast MAS in solid-state NMR spectroscopy.

With the recent advances in NMR hardware and probe design technology, magic-angle spinning (MAS) rates over 100 â€‹kHz are accessible now, even on commercial solid NMR probes. Under such fast MAS conditions, excellent spectral resolution has been achieved by efficient suppression of anisotropic interactions, which also opens an avenue to the proton-detected NMR experiments in solids. Numerous methods have been developed to take full advantage of fast MAS during the last decades. Among them, dipolar recoupling techniques under fast MAS play vital roles in the determination of the molecular structure and dynamics, and are also key elements in multi-dimensional correlation NMR experiments. Herein, we review the dipolar recoupling techniques, especially those developed in the past two decades for fast-to-ultrafast MAS conditions. A major focus for our discussion is the ratio of RF field strength (in frequency) to MAS frequency, ν1/νr, in different pulse sequences, which determines whether these dipolar recoupling techniques are suitable for NMR experiments under fast MAS conditions. Systematic comparisons are made among both heteronuclear and homonuclear dipolar recoupling schemes. In addition, the schemes developed specially for proton-detection NMR experiments under ultrafast MAS conditions are highlighted as well.

Catalytic Asymmetric Alkynylation of 3,4-Dihydro-ß-carbolinium Ions Enables Collective Total Syntheses of Indole Alkaloids.

Chiral tetrahydro-ß-carboline (THßC) is not only a prevailing structural feature of many natural alkaloids but also a versatile synthetic precursor for a vast array of monoterpenoid indole alkaloids. Asymmetric synthesis of C1-alkynyl THßCs remains rarely explored and challenging. Herein, we describe the development of two complementary approaches for the catalytic asymmetric alkynylation of 3,4-dihydro-ß-carbolinium ions with up to 96 % yield and 99 % ee. The utility of chiral C1-alkynyl THßCs was demonstrated by the collective total syntheses of seven indole alkaloids: harmicine, eburnamonine, desethyleburnamonine, larutensine, geissoschizol, geissochizine, and akuammicine.

Self-Assembly of a Purely Covalent Cage with Homochirality by Imine Formation in Water.

Self-assembly of host molecules in aqueous media via metal-ligand coordination is well developed. However, the preparation of purely covalent counterparts in water has remained a formidable task. An anionic tetrahedron cage was successfully self-assembled in a [4+4] manner by condensing a trisamine and a trisformyl in water. Even although each individual imine bond is rather labile and apt to hydrolyze in water, the tetrahedron is remarkably stable or inert due to multivalence. The tetrahedral cages, as well as its neutral counterparts dissolved in organic solvent, have homochirality, namely that their four propeller-shaped trisformyl residues adopt the same rotational conformation. The cage is able to take advantage of hydrophobic effect to accommodate a variety of guest molecules in water. When a chiral guest was recognized, the formation of one enantiomer of the cage became more favored relative to the other. As a consequence, the cage could be produced in an enantioselective manner. The tetrahedron is able to maintain its chirality after removal of the chiral guest-probably on account of the cooperative occurrence of intramolecular forces that restrict the intramolecular flipping of phenyl units in the cage framework.

Comprehensive Understanding of Polyester Stereocomplexation.

We report a comprehensive understanding of the stereoselective interaction between two opposite enantiomeric polyesters prepared from the regioselective copolymerization of chiral terminal epoxides and cyclic anhydrides. For many of the resultant polyesters, the interactions between polymer chains of opposite chirality are stronger than those of polymer chains with the same chirality, resulting in the formation of a stereocomplex with an enhanced melting point (Tm) and crystallinity. The backbone, tacticity, steric hindrance of the pendant group, and molecular weight of the polyesters have significant effects on stereocomplex formation. Bulky substituent groups favor stereocomplexation, resulting in a greater rise in Tm in comparison to the component enantiomeric polymers. The stereocomplex assembly of discrete (R)- and (S)-poly(phenyl glycidyl ether-alt-phthalic anhydride)s oligomers revealed that the minimum degree of polymerization required for stereocomplex formation is five. Raman spectroscopy and solid-state NMR studies indicate that stereocomplex formation significantly restricts the local mobilities of C═O and C-H groups along the backbone of chains. The reduced mobility results in the enhanced spin-lattice relaxation time and both 1H and 13C downfield shifts due to the strong intermolecular interactions between R- and S-chains.

Measurement of proton chemical shift anisotropy in solid-state NMR spectroscopy.

Proton chemical shift anisotropy (CSA) is significantly important as it provides the information of the dynamics and local environmental structure of the proton. The measurement of proton CSA keeps drawing the attention of NMR researchers, and great efforts have been expended. In the early years, measuring proton CSA in solid-state NMR, especially with the strong 1H-1H dipolar network, was hampered by ineffective decoupling or selectively recoupling techniques, and the applications were only limited to those with sparse proton sites or single crystals. Till the latest decades, the dramatic progress on NMR methodology and magic-angle spinning (MAS) technology enable accurate detection of proton CSA in complicated powder samples even proteins. In this review, following a brief description of the measurement of proton CSA in solution and LCs NMR, a retrospect of the experimental development of proton CSA measurement in solid state NMR is presented, from the continuous wave (CW) and multiple pulse sequences for static solid samples, to combined rotation and multiple pulse spectroscopy (CRAMPS), then to the latest methods including rotary resonance, CSA amplification and R-symmetry pulse sequences under MAS conditions.

Administration of SB203580, a p38 MAPK Inhibitor, Reduced the Expression of MMP9, and Relieved Neurologic Severity in the Experimental Autoimmune Neuritis (EAN) in Rats.

Dysfunctional expression of matrix metalloproteinase-9 (MMP-9) has been found to be closely associated with the experimental autoimmune neuritis (EAN). In this study, we explored the role of p38 mitogen-activated protein kinases (p38 MAPK) in the regulation of MMP-9 in sciatic nerves of EAN rats. We analyzed the expression changes of MMP-2, MMP-3, MMP-9, and mitogen-activated protein kinases (MAP kinases) in sciatic nerves of EAN rats and investigated the effect of p38 MAPK inhibitor (SB203580) on MMP-9 expression and pathological changes in EAN. Real-time PCR and western blot analyses showed that the expression of MMP-2 exhibited no significant changes throughout the course of EAN, while MMP-3 and MMP-9 presented the relatively increased expression compared with that in control group. MAP kinases, including p38 MAPK, ERK1/2, and JNK1/2, were activated in the sciatic nerve of EAN rats, and phosphorylated p38 MAPK showed similar patterns of expression to MMP-9. The expression of MMP-9 and phosphorylated p38 MAPK in sciatic nerves were in positive correlation with disease severity. In addition, SB203580 treatment significantly reduced the mRNA and protein level of MMP-9 in sciatic nerves on the peak phase of EAN. Inhibition of p38 MAPK also relieved neurologic severity and ameliorated pathological changes in EAN. In conclusion, SB203580 may ameliorate clinical deficit and pathological changes in EAN by reducing the MMP-9 expression in sciatic nerves, which suggest that p38 MAPK inhibitor such as SB203580 could be considered as a therapeutic candidate in autoimmune neuropathies.

Brain-inspired modular echo state network for EEG-based emotion recognition.

Previous studies have successfully applied a lightweight recurrent neural network (RNN) called Echo State Network (ESN) for EEG-based emotion recognition. These studies use intrinsic plasticity (IP) and synaptic plasticity (SP) to tune the hidden reservoir layer of ESN, yet they require extra training procedures and are often computationally complex. Recent neuroscientific research reveals that the brain is modular, consisting of internally dense and externally sparse subnetworks. Furthermore, it has been proved that this modular topology facilitates information processing efficiency in both biological and artificial neural networks (ANNs). Motivated by these findings, we propose Modular Echo State Network (M-ESN), where the hidden layer of ESN is directly initialized to a more efficient modular structure. In this paper, we first describe our novel implementation method, which enables us to find the optimal module numbers, local and global connectivity. Then, the M-ESN is benchmarked on the DEAP dataset. Lastly, we explain why network modularity improves model performance. We demonstrate that modular organization leads to a more diverse distribution of node degrees, which increases network heterogeneity and subsequently improves classification accuracy. On the emotion arousal, valence, and stress/calm classification tasks, our M-ESN outperforms regular ESN by 5.44, 5.90, and 5.42%, respectively, while this difference when comparing with adaptation rules tuned ESNs are 0.77, 5.49, and 0.95%. Notably, our results are obtained using M-ESN with a much smaller reservoir size and simpler training process.

Significant enhancement of proton conductivity in solid acid at the monolayer limit.

Proton transport in nanofluidic channels is not only fundamentally important but also essential for energy applications. Although various strategies have been developed to improve the concentration of active protons in the nanochannels, it remains challenging to achieve a proton conductivity higher than that of Nafion, the benchmark for proton conductors. Here, taking H3Sb3P2O14 and HSbP2O8 as examples, we show that the interactions between protons and the layer frameworks in layered solid acid HnMnZ2O3n+5 are substantially reduced at the monolayer limit, which significantly increases the number of active protons and consequently improves the proton conductivities by ∼8 ‒ 66 times depending on the humidity. The membranes assembled by monolayer H3Sb3P2O14 and HSbP2O8 nanosheets exhibit in-plane proton conductivities of ~ 1.02 and 1.18 S cm-1 at 100% relative humidity and 90 °C, respectively, which are over 5 times higher than the conductivity of Nafion. This work provides a general strategy for facilitating proton transport, which will have broad implications in advancing both nanofluidic research and device applications from energy storage and conversion to neuromorphic computing.

A Robust Brain Tumor Detector Using BiLSTM and Mayfly Optimization and Multi-Level Thresholding.

A brain tumor refers to an abnormal growth of cells in the brain that can be either benign or malignant. Oncologists typically use various methods such as blood or visual tests to detect brain tumors, but these approaches can be time-consuming, require additional human effort, and may not be effective in detecting small tumors. This work proposes an effective approach to brain tumor detection that combines segmentation and feature fusion. Segmentation is performed using the mayfly optimization algorithm with multilevel Kapur's threshold technique to locate brain tumors in MRI scans. Key features are achieved from tumors employing Histogram of Oriented Gradients (HOG) and ResNet-V2, and a bidirectional long short-term memory (BiLSTM) network is used to classify tumors into three categories: pituitary, glioma, and meningioma. The suggested methodology is trained and tested on two datasets, Figshare and Harvard, achieving high accuracy, precision, recall, F1 score, and area under the curve (AUC). The results of a comparative analysis with existing DL and ML methods demonstrate that the proposed approach offers superior outcomes. This approach has the potential to improve brain tumor detection, particularly for small tumors, but further validation and testing are needed before clinical use.

Marine Alkaloid Lepadins E and H Induce Ferroptosis for Cancer Chemotherapy.

Induction of ferroptosis emerges as an effective method for cancer treatment. With massive efforts to elucidate the ferroptosis mechanism, the development of new ferroptosis inducers proceeds rather slowly, with only a few small molecules identified. Herein, we report our discovery of marine alkaloid lepadins E and H as a new class of ferroptosis inducers. Our in vitro studies show that lepadins E and H exhibit significant cytotoxicity, promote p53 expression, increase ROS production and lipid peroxides, reduce SLC7A11 and GPX4 levels, and upregulate ACSL4 expression, all of which consistently support induction of ferroptosis through the classical p53-SLC7A11-GPX4 pathway. Our animal model study of lepadin H confirms its in vivo antitumor efficacy with negligible toxicity to normal organs. This work elucidates the mode of action of lepadins (E and H) and verifies their in vivo efficacy as a new class of ferroptosis inducers for anticancer therapy with translational potential.

Supercycled R-symmetry sequences for robust heteronuclear polarization transfer in solid-state NMR.

Herein, we introduce supercycle of R-symmetry sequences (SR-sequences) and incomplete supercycle schemes of R-symmetry sequences (iSR-I- and iSR-II-sequences) to improve the robustness of PRESTO for heteronuclear polarization transfer in MAS NMR. The constructions of SR- and iSR-I/II- sequences are based on the different phase-inverted supercycles of R-symmetry sequences, and such supercycles can suppress the influence of CSA, resonance offset and RF mismatch when incorporated into the PRESTO method. Moreover, the SR- and iSR-II-sequences are more efficient in suppressing the interference of homonuclear dipolar coupling. The improved robustness of SR-, iSR-I- and iSR-II-PRESTO over the original R-PRESTO has been verified by numerical simulations and NMR experiments on NH4H2PO4 and gamma-alumina at fast MAS conditions. It is also important to note that the SR- and iSR-II-PRESTO can greatly lengthen the transverse relaxation times and lead to much higher polarization transfer efficiency compared to R-PRESTO, thanks to their superior tolerance to RF inhomogeneity and homonuclear dipolar coupling.