Programming inactive RNA-binding small molecules into bioactive degraders.

Target occupancy is often insufficient to elicit biological activity, particularly for RNA, compounded by the longstanding challenges surrounding the molecular recognition of RNA structures by small molecules. Here we studied molecular recognition patterns between a natural-product-inspired small-molecule collection and three-dimensionally folded RNA structures. Mapping these interaction landscapes across the human transcriptome defined structure-activity relationships. Although RNA-binding compounds that bind to functional sites were expected to elicit a biological response, most identified interactions were predicted to be biologically inert as they bind elsewhere. We reasoned that, for such cases, an alternative strategy to modulate RNA biology is to cleave the target through a ribonuclease-targeting chimera, where an RNA-binding molecule is appended to a heterocycle that binds to and locally activates RNase L1. Overlay of the substrate specificity for RNase L with the binding landscape of small molecules revealed many favourable candidate binders that might be bioactive when converted into degraders. We provide a proof of concept, designing selective degraders for the precursor to the disease-associated microRNA-155 (pre-miR-155), JUN mRNA and MYC mRNA. Thus, small-molecule RNA-targeted degradation can be leveraged to convert strong, yet inactive, binding interactions into potent and specific modulators of RNA function.

Transcriptome-Wide, Unbiased Profiling of Ribonuclease Targeting Chimeras.

Various approaches have been developed to target RNA and modulate its function with modes of action including binding and cleavage. Herein, we explored how small molecule binding is correlated with cleavage induced by heterobifunctional ribonuclease targeting chimeras (RiboTACs), where RNase L is recruited to cleave the bound RNA target, in a transcriptome-wide, unbiased fashion. Only a fraction of bound targets was cleaved by RNase L, induced by RiboTAC binding. Global analysis suggested that (i) cleaved targets generally form a region of stable structure that encompasses the small molecule binding site; (ii) cleaved targets have preferred RNase L cleavage sites nearby small molecule binding sites; (iii) RiboTACs facilitate a cellular interaction between cleaved targets and RNase L; and (iv) the expression level of the target influences the extent of cleavage observed. In one example, we converted a binder of LGALS1 (galectin-1) mRNA into a RiboTAC. In MDA-MB-231 cells, the binder had no effect on galectin-1 protein levels, while the RiboTAC cleaved LGALS1 mRNA, reduced galectin-1 protein abundance, and affected galectin-1-associated oncogenic cellular phenotypes. Using LGALS1, we further assessed additional factors including the length of the linker that tethers the two components of the RiboTAC, cellular uptake, and the RNase L-recruiting module on RiboTAC potency. Collectively, these studies may facilitate triangulation of factors to enable the design of RiboTACs.

Efficient Initialization of Fluxonium Qubits based on Auxiliary Energy Levels.

Fast and high-fidelity qubit initialization is crucial for low-frequency qubits such as fluxonium, and in applications of many quantum algorithms and quantum error correction codes. In a circuit quantum electrodynamics system, the initialization is typically achieved by transferring the state between the qubit and a short-lived cavity through microwave driving, also known as the sideband cooling process in atomic system. Constrained by the selection rules from the parity symmetry of the wave functions, the sideband transitions are only enabled by multiphoton processes which require multitone or strong driving. Leveraging the flux tunability of fluxonium, we circumvent this limitation by breaking flux symmetry to enable an interaction between a noncomputational qubit transition and the cavity excitation. With single-tone sideband driving, we realize qubit initialization with a fidelity exceeding 99% within a duration of 300 ns, robust against the variation of control parameters. Furthermore, we show that our initialization scheme has a built-in benefit in simultaneously removing the second-excited state population of the qubit, and can be easily incorporated into a large-scale fluxonium processor.

Native Approach to Controlled-Z Gates in Inductively Coupled Fluxonium Qubits.

The fluxonium qubits have emerged as a promising platform for gate-based quantum information processing. However, their extraordinary protection against charge fluctuations comes at a cost: when coupled capacitively, the qubit-qubit interactions are restricted to XX interactions. Consequently, effective ZZ or XZ interactions are only constructed either by temporarily populating higher-energy states, or by exploiting perturbative effects under microwave driving. Instead, we propose and demonstrate an inductive coupling scheme, which offers a wide selection of native qubit-qubit interactions for fluxonium. In particular, we leverage a built-in, flux-controlled ZZ interaction to perform qubit entanglement. To combat the increased flux-noise-induced dephasing away from the flux-insensitive position, we use a continuous version of the dynamical decoupling scheme to perform noise filtering. Combining these, we demonstrate a 20 ns controlled-z gate with a mean fidelity of 99.53%. More than confirming the efficacy of our gate scheme, this high-fidelity result also reveals a promising but rarely explored parameter space uniquely suitable for gate operations between fluxonium qubits.

Shedding light on cellular dynamics: the progress in developing photoactivated fluorophores.

Photoactivated fluorophores (PAFs) are highly effective imaging tools that exhibit a removal of caging groups upon light excitation, resulting in the restoration of their bright fluorescence. This unique property allows for precise control over the spatiotemporal aspects of small molecule substances, making them indispensable for studying protein labeling and small molecule signaling within live cells. In this comprehensive review, we explore the historical background of this field and emphasize recent advancements based on various reaction mechanisms. Additionally, we discuss the structures and applications of the PAFs. We firmly believe that the development of more novel PAFs will provide powerful tools to dynamically investigate cells and expand the applications of these techniques into new domains.

Build a High-Performance All-Solid-State Lithium Battery through Introducing Competitive Coordination Induction Effect in Polymer-Based Electrolyte.

Polymer-inorganic composite electrolytes (PICE) have attracted tremendous attention in all-solid-state lithium batteries (ASSLBs) due to facile processability. However, the poor Li+ conductivity at room temperature (RT) and interfacial instability severely hamper the practical application. Herein, we propose a concept of competitive coordination induction effects (CCIE) and reveal the essential correlation between the local coordination structure and the interfacial chemistry in PEO-based PICE. CCIE introduction greatly enhances the ionic conductivity and electrochemical performances of ASSLBs at 30 °C. Owing to the competitive coordination (Cs+…TFSI-…Li+, Cs+…C-O-C…Li+ and 2,4,6-TFA…Li…TFSI-) from the competitive cation (Cs+ from CsPF6) and molecule (2,4,6-TFA: 2,4,6-trifluoroaniline), a multimodal weak coordination environment of Li+ is constructed enabling a high efficient Li+ migration at 30 °C (Li+ conductivity: 6.25×10-4 S cm-1; tLi +=0.61). Since Cs+ tends to be enriched at the interface, TFSI- and PF6 - in situ form LiF-Li3N-Li2O-Li2S enriched solid electrolyte interface with electrostatic shielding effects. The assembled ASSLBs without adding interfacial wetting agent exhibit outstanding rate capability (LiFePO4: 147.44 mAh g-1@1 C and 107.41mAhg-1@2 C) and cycling stability at 30 °C (LiFePO4:94.65 %@200cycles@0.5 C; LiNi0.5Co0.2Mn0.3O2: 94.31 %@200 cycles@0.3 C). This work proposes a concept of CCIE and reveals its mechanism in designing PICE with high ionic conductivity as well as high interfacial compatibility at near RT for high-performance ASSLBs.

Achieving the High Capacity and High Stability of Li-Rich Oxide Cathode in Garnet-Based Solid-State Battery.

Solid-state batteries (SSBs) based on Li-rich Mn-based oxide (LRMO) cathodes attract much attention because of their high energy density as well as high safety. But their development was seriously hindered by the interfacial instability and inferior electrochemical performance. Herein, we design a three-dimensional foam-structured GaN-Li composite anode and successfully construct a high-performance SSB based on Co-free Li1.2 Ni0.2 Mn0.6 O2 cathode and Li6.5 La3 Zr1.5 Ta0.5 O12 (LLZTO) solid electrolyte. The interfacial resistance is considerably reduced to only 1.53â€…Ω cm2 and the assembled Li symmetric cell is stably cycled more than 10,000 h at 0.1-0.2 mA cm-2 . The full battery shows a high initial capacity of 245 mAh g-1 at 0.1 C and does not show any capacity degradation after 200 cycles at 0.2 C (≈100 %). The voltage decay is well suppressed and it is significantly decreased from 2.96 mV/cycle to only 0.66 mV/cycle. The SSB also shows a very high rate capability (≈170 mAh g-1 at 1 C) comparable to a liquid electrolyte-based battery. Moreover, the oxygen anion redox (OAR) reversibility of LRMO in SSB is much higher than that in liquid electrolyte-based cells. This study offers a distinct strategy for constructing high-performance LRMO-based SSBs and sheds light on the development and application of high-energy density SSBs.

Quantum Instruction Set Design for Performance.

A quantum instruction set is where quantum hardware and software meet. We develop characterization and compilation techniques for non-Clifford gates to accurately evaluate its designs. Applying these techniques to our fluxonium processor, we show that replacing the iSWAP gate by its square root SQiSW leads to a significant performance boost at almost no cost. More precisely, on SQiSW we measure a gate fidelity of up to 99.72% and averaging at 99.31%, and realize Haar random two-qubit gates with an average fidelity of 96.38%. This is an average error reduction of 41% for the former and a 50% reduction for the latter compared to using iSWAP on the same processor.

Fluxonium: An Alternative Qubit Platform for High-Fidelity Operations.

Superconducting qubits provide a promising path toward building large-scale quantum computers. The simple and robust transmon qubit has been the leading platform, achieving multiple milestones. However, fault-tolerant quantum computing calls for qubit operations at error rates significantly lower than those exhibited in the state of the art. Consequently, alternative superconducting qubits with better error protection have attracted increasing interest. Among them, fluxonium is a particularly promising candidate, featuring large anharmonicity and long coherence times. Here, we engineer a fluxonium-based quantum processor that integrates high qubit coherence, fast frequency tunability, and individual-qubit addressability for reset, readout, and gates. With simple and fast gate schemes, we achieve an average single-qubit gate fidelity of 99.97% and a two-qubit gate fidelity of up to 99.72%. This performance is comparable to the highest values reported in the literature of superconducting circuits. Thus our work, within the realm of superconducting qubits, reveals an alternative qubit platform that is competitive with the transmon system.

Structural Reorganization of Imidazolium Ionic Liquids Induced by Pressure-Enhanced Ionic Liquid-Polyethylene Oxide Interactions.

Mixtures of polyethylene oxide (PEO, M.W.~900,000) and imidazolium ionic liquids (ILs) are studied using high-pressure Fourier-transform infrared spectroscopy. At ambient pressure, the spectral features in the C-H stretching region reveal that PEO can disturb the local structures of the imidazolium rings of [BMIM]+ and [HMIM]+. The pressure-induced phase transition of pure 1-butyl-3-methylimidazolium bromide ([BMIM]Br) is observed at a pressure of 0.4 GPa. Pressure-enhanced [BMIM]Br-PEO interactions may assist PEO in dividing [BMIM]Br clusters to hinder the aggregation of [BMIM]Br under high pressures. The C-H absorptions of pure 1-hexyl-3-methylimidazolium bromide [HMIM]Br do not show band narrowing under high pressures, as observed for pure [BMIM]Br. The band narrowing of C-H peaks is observed at 1.5 GPa for the [HMIM]Br-PEO mixture containing 80 wt% of [HMIM]Br. The presence of PEO may reorganize [HMIM]Br clusters into a semi-crystalline network under high pressures. The differences in aggregation states for ambient-pressure phase and high-pressure phase may suggest the potential of [HMIM]Br-PEO (M.W.~900,000) for serving as optical or electronic switches.

Sulfidated nanoscale zero-valent iron derived from iron sludge for tetracycline removal: Role of sulfur and iron in reactivity and mechanisms.

Iron sludge, produced during the drinking water treatment process, can be recycled as potential iron resource to create environmental functional material. In this study, sulfur-iron composites derived from iron sludge (S-Fe composites) was synthesized through sulfidation and carbonization, and used for the tetracycline (TC) removal under aerobic and anoxic conditions. The reactivities of these as-prepared products were strongly depended on pyrolysis temperatures. In particular, sulfidated nanoscale zero-valent iron loaded on carbon (S-nFe0@CIS) carbonized at 800 °C exhibited the highest TC removal efficiency with 86.6% within 30 min at circumneutral pH compared with other S-Fe composites. The crystalline structure of α-Fe0, FeSx and S0 as main active sites in S-nFe0@CIS promoted the degradation of TC. Moreover, the Fe/S molar ratios significantly affected the TC removal rates, which reached the best value as the optimal S/Fe of 0.27. The results illustrated that the optimized extent of sulfidation could facilitate electron transfer from nFe0 towards contaminants and accelerate Fe(III)/Fe(II) cycle in reaction system compared to bared nFe0@CIS. We revealed that removal of TC by S-nFe0@CIS in the presence of dissolved oxygen (DO) is mainly attributed to oxidation, adsorption and reduction pathways. Their contribution to TC removal were 31.6%, 25.2% and 28.8%, respectively. Furthermore, this adsorption-oxygenation with the formation of S-nFe0@CIS-TC* complexes was a surface-mediated process, in which DO was transformed by the structural FeSx on complex surface to •OH with the generation of H2O2 intermediate. The intermediates of TC and toxicity analysis indicate that less toxicity products generated through degradation process. This study provides a new reclamation of iron sludge and offers a new insight into the TC removal by S-nFe0@CIS under aerobic conditions.

Salt tolerance in Brassicaceae crops: physiological responses and molecular mechanisms.

Soil salinisation is a growing threat to global agriculture, reducing crop yields. Brassicaceae crops are vital vegetables and cash crops. Salt stress significantly affects the growth and development of Brassicaceae crops. A better understanding of the molecular and physiological mechanisms of salt tolerance is of theoretical and practical importance to improve Brassicaceae crop's salt tolerance and crop quality. Combined with previous research results, we discuss recent advances in research on salt stress response and salt tolerance in Brassicaceae crops. We summarised recent research progress on the physiological and molecular mechanisms of ionic homeostasis, antioxidant regulation, hormonal regulation and accumulation of osmotic-adjustment substances. We also discussed the molecular mechanism of Brassicaceae crop salt tolerant varieties from the perspective of differentially expressed genes, differentially expressed proteins and metabolites through transcriptome, proteome and metabonomic analysis methods. This paper summarises the molecular mechanisms in the perspective of differentially expressed genes, differentially expressed proteins, and metabolites through transcriptomic, proteome and metabolomics analysis. The review provides abundant data for accelerating the breeding of salt-tolerant Brassicaceae and laid a foundation for understanding the mechanism of salt tolerance of Brassicaceae crops and breeding salt-tolerance varieties.

Corrigendum to: Salt tolerance in Brassicaceae crops: physiological responses and molecular mechanisms.

Soil salinisation is a growing threat to global agriculture, reducing crop yields. Brassicaceae crops are vital vegetables and cash crops. Salt stress significantly affects the growth and development of Brassicaceae crops. A better understanding of the molecular and physiological mechanisms of salt tolerance is of theoretical and practical importance to improve Brassicaceae crop's salt tolerance and crop quality. Combined with previous research results, we discuss recent advances in research on salt stress response and salt tolerance in Brassicaceae crops. We summarised recent research progress on the physiological and molecular mechanisms of ionic homeostasis, antioxidant regulation, hormonal regulation and accumulation of osmotic-adjustment substances. We also discussed the molecular mechanism of Brassicaceae crop salt tolerant varieties from the perspective of differentially expressed genes, differentially expressed proteins and metabolites through transcriptome, proteome and metabonomic analysis methods. This paper summarises the molecular mechanisms in the perspective of differentially expressed genes, differentially expressed proteins, and metabolites through transcriptomic, proteome and metabolomics analysis. The review provides abundant data for accelerating the breeding of salt-tolerant Brassicaceae and laid a foundation for understanding the mechanism of salt tolerance of Brassicaceae crops and breeding salt-tolerance varieties.

Case report: Double filtration plasmapheresis (DFPP) for severe rhesus-D alloimmunization in two pregnant patients.

Maternal erythrocyte alloimmunization is one of the most important causes of fetal anemia. The standard treatment for anemic fetuses is intrauterine blood transfusion (IUT). However, IUT may have adverse effects, particularly before 20 weeks of gestation. In this report, two women who had previously had severely affected alloimmunized pregnancy developed high titers of anti-D antibodies before 20 weeks of gestation. Ultrasound Doppler showed severe fetal anemia, and intrauterine transfusion was expected to be unavoidable. To prolong pregnancy to a gestation in which intravascular IUT was possible, we used repeated double filtration plasmapheresis (DFPP) as a rescue therapy. The titers of IgG-D, IgG-A, and IgG-B decreased after DFPP treatment. One woman successfully prolonged pregnancy until 20 weeks of gestation. Subsequently, she underwent four cycles of IUTs and delivered at 30 weeks of gestation by emergency cesarean section due to fetal bradycardia during the fifth intrauterine transfusion. The other woman successfully delayed intrauterine transfusion until 26 weeks of gestation. The favorable results of the two patients indicate that DFPP may be an effective and safe treatment modality for RhD immunity in pregnant women. Moreover, DFPP is potentially helpful for reducing the occurrence of ABO hemolytic disease in neonates due to the clearance of IgG-A and IgG-B antibodies (e.g., O pregnant women harbored A/B/AB neonates). However, more clinical trials are needed to verify the results.

Pressure-Dependent Clustering in Ionic-Liquid-Poly (Vinylidene Fluoride) Mixtures: An Infrared Spectroscopic Study.

The nanostructures of ionic liquids (ILs) have been the focus of considerable research attention in recent years. Nevertheless, the nanoscale structures of ILs in the presence of polymers have not been described in detail at present. In this study, nanostructures of ILs disturbed by poly(vinylidene fluoride) (PVdF) were investigated via high-pressure infrared spectra. For 1-(2-hydroxyethyl)-3-methylimidazolium bis(trifluoromethanesulfonyl)imide ([HEMIm][TFSI])-PVdF mixtures, non-monotonic frequency shifts of the C4,5-H vibrations upon dilution were observed under ambient pressure. The experimental results suggest the presence of microheterogeneity in the [HEMIm][TFSI] systems. Upon compression, PVdF further influenced the local structure of C4,5-H via pressure-enhanced IL-PVdF interactions; however, the local structures of C2-H and hydrogen-bonded O-H were not affected by PVdF under high pressures. For choline [TFSI]-PVdF mixtures, PVdF may disturb the local structures of hydrogen-bonded O-H. In the absence of the C4,5-H⋯anion and C2-H⋯anion in choline [TFSI]-PVdF mixtures, the O-H group becomes a favorable moiety for pressure-enhanced IL-PVdF interactions. Our results indicate the potential of high-pressure application for designing pressure-dependent electronic switches based on the possible changes in the microheterogeneity and electrical conductivity in IL-PVdF systems under various pressures.

The emission quenching of upconversion nanoparticles coated with amorphous silica by fluorescence resonance energy transfer: A mercury-sensing nanosensor excited by near-infrared radiation.

In this paper, a rhodamine derivative was synthesized as a probe for Hg(II) detection. Its spectral response and sensing mechanism towards Hg(II) were discussed carefully. It was found that its absorption and emission were increased by Hg(II), via a direct bonding stoichiometry of 1:1. Its association constant was determined with absorption titration as 2.59 × 105 M-1, which suggested a coordination procedure between Hg(II) and this rhodamine probe. It showed good selectivity towards Hg(II) over competing metal cations, no increased emission or absorption was observed in the presence of interfering metal cations. It was then covalently grafted onto silica (SiO2)-encapsulated upconversion nanoparticles (UCNPs). Upon near-infrared (NIR) excitation (980 nm), RHO accepted energy from these UCNPs through a FRET (fluorescence resonance energy transfer) procedure, quenching their upconversion emission. A sensing response towards Hg(II) was thus constructed. Good linearity and selectivity were still preserved in this composite sample. On the other hand, this work found a different phenomenon from literature cases, which was the emission absence of rhodamine emission in this composite structure. Detailed analysis suggested that rhodamine emission absence was caused by its self-quenching effect.

Efficient parallelization of tensor network contraction for simulating quantum computation.

We develop an algorithmic framework for contracting tensor networks and demonstrate its power by classically simulating quantum computation of sizes previously deemed out of reach. Our main contribution, index slicing, is a method that efficiently parallelizes the contraction by breaking it down into much smaller and identically structured subtasks, which can then be executed in parallel without dependencies. We benchmark our algorithm on a class of random quantum circuits, achieving greater than 105 times acceleration over the original estimate of the simulation cost. We then demonstrate applications of the simulation framework for aiding the development of quantum algorithms and quantum error correction. As tensor networks are widely used in computational science, our simulation framework may find further applications.

Characterization of Local Structures of Confined Imidazolium Ionic Liquids in PVdF-co-HFP Matrices by High Pressure Infrared Spectroscopy.

The nanoscale ion ordering of ionic liquids at confined interfaces under high pressures was investigated in this study. 1-Hexyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ([HMIM][NTf2])/poly(vinylidene fluoride-co-hexafluoropropylene) (PVdF-co-HFP) and 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ([EMIM][NTf2])/PVdF-co-HFP were prepared and characterized by using high-pressure infrared spectroscopy. Under ambient pressure, imidazolium C2-H and C4,5-H absorptions were blue-shifted in frequency due to the presence of PVdF-co-HFP. However, the absorption of anionic νa SO2 did not reveal any significant shifts in frequency upon dilution by PVdF-co-HFP. The experimental results suggest that PVdF-co-HFP disturbs the local structures of the imidazolium C-H groups instead of the anionic SO2 groups. The frequency shifts of C4,5-H became dramatic for the mixtures at high pressures. These results suggest that pressure-enhanced ionic liquid-polymer interactions may play an appreciable role in IL-PVdF-co-HFP systems under high pressures. The pressure-induced blue-shifts due to the PVdF-co-HFP additions were more obvious for the [HMIM][NTf2] mixtures than for [EMIM][NTf2] mixtures.

Functional Results after Intramuscular Ulnar Nerve Anterior Transposition for Young Adults Patients.

Background: This study investigated the functional outcomes of intramuscular ulnar nerve transposition (IMUNT) in young adults with cubital tunnel syndrome (CuTS). Methods: This retrospective study enrolled 37 military soldiers on active duty diagnosed with and treated for CuTS to determine the compression sites, complication rate, and postoperative results. Patient outcomes were analyzed using the Disability of the Arm, Shoulder, and Hand (DASH) questionnaire and the Bishop-Kleinman rating scales. Results: Patient outcomes were analyzed after a mean follow-up duration of 26.1 (22-29) months for 37 extremities. DASH scores improved from 38.7 (range, 13-63 points) preoperatively to 5.8 (range, 0-18 points) postoperatively. Patient improvement was statistically significant (p < 0.05). Based on the 12-point Bishop-Kleinman rating system, 30 (82.1%) patients were graded as excellent; five (13.5%) as good, and two (5.4%) as failed outcomes. Statistically significant improvements in both key pinch and grip strength were noted. Complications included one case of transient neuroparaxias of the medial antebrachial cutaneous nerve and one case of hematoma formation. Conclusions: We consider intramuscular ulnar nerve transposition to be a satisfactory procedure for CuTS. The procedure enhances upper limb function, thus allowing the patients to resume their physically demanding work with minimal complications.

Pressure-Dependent Confinement Effect of Ionic Liquids in Porous Silica.

The effect of confining ionic liquids (ILs) such as 1-ethyl-3-methylimidazolium tetrafluoroborate [C2C1Im][BF4] or 1-butyl-3-methylimidazolium tetrafluoroborate [C4C1Im][BF4] in silica matrices was investigated by high-pressure IR spectroscopy. The samples were prepared via the sol-gel method, and the pressure-dependent changes in the C-H absorption bands were investigated. No appreciable changes were observed in the spectral features when the ILs were confined in silica matrices under ambient pressure. That is, the infrared measurements obtained under ambient pressure were not sufficient to detect the interfacial interactions between the ILs and the porous silica. However, dramatic differences were observed in the spectral features of [C2C1Im][BF4] and [C4C1Im][BF4] in silica matrices under the conditions of high pressures. The surfaces of porous silica appeared to weaken the cation-anion interactions caused by pressure-enhanced interfacial IL-silica interactions. This confinement effect under high pressures was less obvious for [C4C1Im][BF4]. The size of the cations appeared to play a prominent role in the IL-silica systems.