A Thermostable mRNA Vaccine against COVID-19.

There is an urgent need for vaccines against coronavirus disease 2019 (COVID-19) because of the ongoing SARS-CoV-2 pandemic. Among all approaches, a messenger RNA (mRNA)-based vaccine has emerged as a rapid and versatile platform to quickly respond to this challenge. Here, we developed a lipid nanoparticle-encapsulated mRNA (mRNA-LNP) encoding the receptor binding domain (RBD) of SARS-CoV-2 as a vaccine candidate (called ARCoV). Intramuscular immunization of ARCoV mRNA-LNP elicited robust neutralizing antibodies against SARS-CoV-2 as well as a Th1-biased cellular response in mice and non-human primates. Two doses of ARCoV immunization in mice conferred complete protection against the challenge of a SARS-CoV-2 mouse-adapted strain. Additionally, ARCoV is manufactured as a liquid formulation and can be stored at room temperature for at least 1 week. ARCoV is currently being evaluated in phase 1 clinical trials.

Interior Exciton Extraction by Spatial-Controlled Iodine Doping in BiOBr Photocatalysts.

Extracting interior photoinduced species to the surface before their recombination is of great importance in pursuing high-efficiency semiconductor-based photocatalysis. Traditional strategies toward charge-carrier extraction, mostly relying on the construction of an electric field gradient, would be invalid toward the neutral-exciton counterpart in low-dimensional systems. In this work, by taking bismuth oxybromide (BiOBr) as an example, we manipulate interior exciton extraction to the surface by implementing iodine doping at the edges of BiOBr plates. Spatial- and time-resolved spectroscopic analyses verified the accumulation of excitons and charge carriers at the edges of iodine-doped BiOBr (BiOBr-I) plates. This phenomenon could be associated with interior exciton extraction, driven by an energy-level gradient between interior and edge exciton states, and the following exciton dissociation processes. As such, BiOBr-I shows remarkable performance in photocatalytic C-H fluorination, mediated by both energy- and charge-transfer processes. This work uncovers the importance of spatial regulation of excitonic properties in low-dimensional semiconductor-based photocatalysis.

Metal-Semiconductor Heterojunction with Ohmic Contact Realizes Efficient Infrared-Light-Driven Photocatalysis.

Efficient utilization of solar energy for photocatalytic applications, particularly in the infrared spectrum, is crucial for addressing environmental challenges and energy scarcity. Herein we present a general strategy for constructing efficient infrared-driven photocatalysts in a metal/semiconductor heterojunction with Ohmic contact, where metals with low work function as the infrared-light absorber and semiconductors with electron storage ability can overcome the unfavorable electron flowback. Taking the NixB/MO2 (M = Ce, Ti, Sn, Ge, Zr, etc.) heterojunction as an example, both experimental and theoretical investigations reveal that the formation of an Ohmic contact facilitates the transfer of hot electrons from NixB to MO2, which are stored by the ion redox pairs for the variable valence character of M. As expected, the heterojunction exhibits remarkable photocatalytic activity under infrared light (λ ≥ 800 nm), as evidenced by the efficient photofixation of CO2 to high-value-added cyclic carbonates. This study offers a general platform for designing infrared-light-driven photocatalysts.

Spatially and Temporally Resolved Dynamic Response of Co-Based Composite Interface during the Oxygen Evolution Reaction.

Interfacial interaction dictates the overall catalytic performance and catalytic behavior rules of the composite catalyst. However, understanding of interfacial active sites at the microscopic scale is still limited. Importantly, identifying the dynamic action mechanism of the "real" active site at the interface necessitates nanoscale, high spatial-time-resolved complementary-operando techniques. In this work, a Co3O4 homojunction with a well-defined interface effect is developed as a model system to explore the spatial-correlation dynamic response of the interface toward oxygen evolution reaction. Quasi in situ scanning transmission electron microscopy-electron energy-loss spectroscopy with high spatial resolution visually confirms the size characteristics of the interface effect in the spatial dimension, showing that the activation of active sites originates from strong interfacial electron interactions at a scale of 3 nm. Multiple time-resolved operando spectroscopy techniques explicitly capture dynamic changes in the adsorption behavior for key reaction intermediates. Combined with density functional theory calculations, we reveal that the dynamic adjustment of multiple adsorption configurations of intermediates by highly activated active sites at the interface facilitates the O-O coupling and *OOH deprotonation processes. The dual dynamic regulation mechanism accelerates the kinetics of oxygen evolution and serves as a pivotal factor in promoting the oxygen evolution activity of the composite structure. The resulting composite catalyst (Co-B@Co3O4/Co3O4 NSs) exhibits an approximately 70-fold turnover frequency and 20-fold mass activity than the monomer structure (Co3O4 NSs) and leads to significant activity (η10 ∼257 mV). The visual complementary analysis of multimodal operando/in situ techniques provides us with a powerful platform to advance our fundamental understanding of interfacial structure-activity relationships in composite structured catalysts.

Nanoconfined Silver Nanoclusters Combined with X-Shaped DNA Recognizer-Triggered Cascade Amplification for Electrochemiluminescence Detection of APE1.

Apurinic/apyrimidinic endonuclease 1 (APE1), as a vital base excision repair enzyme, is essential for maintaining genomic integrity and stability, and its abnormal expression is closely associated with malignant tumors. Herein, we constructed an electrochemiluminescence (ECL) biosensor for detecting APE1 activity by combining nanoconfined ECL silver nanoclusters (Ag NCs) with X-shaped DNA recognizer-triggered cascade amplification. Specifically, the Ag NCs were prepared and confined in the glutaraldehyde-cross-linked chitosan hydrogel network using the one-pot method, resulting in a strong ECL response and exceptional stability in comparison with discrete Ag NCs. Furthermore, the self-assembled X-shaped DNA recognizers were designed for APE1 detection, which not only improved reaction kinetics due to the ordered arrangement of recognition sites but also achieved high sensitivity by utilizing the recognizer-triggered cascade amplification of strand displacement amplification (SDA) and DNAzyme catalysis. As expected, this biosensor achieved sensitive ECL detection of APE1 in the range of 1.0 × 10-3 U·µL-1 to 1.0 × 10-10 U·µL-1 with the detection limit of 2.21 × 10-11 U·µL-1, rendering it a desirable approach for biomarker detection.

Logic Signal Amplification System for Sensitive Electrochemiluminescence Detection and Subtype Identification of Cancer Cells.

Achieving sensitive detection and accurate identification of cancer cells is vital for diagnosing and treating the disease. Here, we developed a logic signal amplification system using DNA tetrahedron-mediated three-dimensional (3D) DNA nanonetworks for sensitive electrochemiluminescence (ECL) detection and subtype identification of cancer cells. Specially designed hairpins were integrated into DNA tetrahedral nanostructures (DTNs) to perform a catalytic hairpin assembly (CHA) reaction in the presence of target microRNA, forming hyperbranched 3D nanonetworks. Benefiting from the "spatial confinement effect," the DNA tetrahedron-mediated catalytic hairpin assembly (DTCHA) reaction displayed significantly faster kinetics and greater cycle conversion efficiency than traditional CHA. The resulting 3D nanonetworks could load a large amount of Ru(phen)32+, significantly enhancing its ECL signal, and exhibit detection limits for both miR-21 and miR-141 at the femtomolar level. The biosensor based on modular logic gates facilitated the distinction and quantification of cancer cells and normal cells based on miR-21 levels, combined with miR-141 levels, to further identify different subtypes of breast cancer cells. Overall, this study provides potential applications in miRNA-related clinical diagnostics.

Interfacial Hydrogen-Bond Interactions Driven Assembly toward Polychromatic Copper Nanoclusters.

Constructing versatile metal nanoclusters (NCs) assemblies through noncovalent weak interactions between inter-ligands is a long-standing challenge in interfacial chemistry, while compelling interfacial hydrogen-bond-driven metal NCs assemblies remain unexplored so far. Here, the study reports an amination-ligand o-phenylenediamine-coordinated copper NCs (CuNCs), demonstrating the impact of interfacial hydrogen-bonds (IHBs) motifs on the luminescent behaviors of metal NCs as the alteration of protic solvent. Experimental results supported by theoretical calculation unveil that the flexibility of interfacial ligand and the distance of cuprophilic CuI···CuI interaction between intra-/inter-NCs can be tailored by manipulating the cooperation between the diverse IHBs motifs reconstruction, therewith the IHBs-modulated fundamental structure-property relationships are established. Importantly, by utilizing the IHBs-mediated optical polychromatism of aminated CuNCs, portable visualization of humidity sensing test-strips with fast response is successfully manufactured. This work not only provides further insights into exploring the interfacial chemistry of NCs based on inter-ligands hydrogen-bond interactions, but also offers a new opportunity to expand the practical application for optical sensing of metal NCs.

Rh(III)-Catalyzed C-H Allylation of Aromatic Ketoximes with Vinylaziridines.

The Rh(III)-catalyzed reaction of aromatic ketoximes with 2-vinylaziridines affords ortho-allylation products of the phenyl rings of aromatic ketoximes in moderate to excellent yields. The reaction requires 0.5 equiv of NaOAc as a base and occurs under mild conditions. The protocol exhibits ortho-monoallylation selectivity, wide scope of substrates, and good compatibility of functional groups.

Palladium-Catalyzed Reaction of Indolines with Dihydropyrroles: Access to N-Alkylated Indoles.

Palladium-catalyzed reaction of indolines with 1-acyl-2,3-dihydro-1H-pyrroles or 1-acyl-2,5-dihydro-1H-pyrroles in air produces N-alkylated indoles. A combination of Pd(CH3CN)2Cl2 and dppf effectively catalyzes the reaction of 1-acyl-2,3-dihydro-1H-pyrroles, and the combination of Pd(CH3CN)2Cl2 and dcypf is more effective for the reaction of 1-acyl-2,5-dihydro-1H-pyrroles. The method has a wide scope of substrates and shows good compatibility of functional groups.

Hypervalent Iodine Promoted Selective [2 + 2 + 1] Cycloaddition of Aromatic Ketones and Methylamines: A One-Pot Access to 1-Pyrrolines.

Herein, a versatile highly regioselective three-component annulation of simple aromatic ketones and methylamines using a hypervalent iodine reagent for polyarylated 1-pyrrolines has been described in good to excellent yields. Meanwhile, unsymmetrical 1-pyrroline isomers could be realized and synthesized. Such an intriguing one-pot two-step tandem assembly strategy with green conditions and high regioselectivity shows predictable inspiration in related annulation reactions.

Preparation and utilization of carbon dots as a nanoprobe for sensitive detection of tartrazine and palladium (II).

We prepared novel green, eco-friendly carbon dots as a dual-channel probe for highly sensitive and selective detection of tartrazine (Trz) and palladium(II) (Pd(II)) involving, respectively, FRET and electron transfer mechanisms. Furthermore, the successful utilization of the carbon dots for detecting Trz and Pd(II) in actual samples implies its potential application prospects in analysis.

Selective identification of p-nitroaniline by bromine-mediated polarization of carbon dots.

A fluorometric method based on boron, bromide-codoped carbon dots (BBCNs) was developed for the first time for the highly selective detection of p-nitroaniline (PNA) in wastewater samples. It should be noted that the introduction of bromine greatly increases the molecular polarizability of the probe, which can regulate the energy level matching between the probe and PNA, resulting in the interaction between BBCNs and PNA. In the presence of PNA, the fluorescence of BBCNs is obviously quenched and accompanied by a red shift of the fluorescence band, which might be attributed to the formation of aggregates caused by the polar adsorption of BBCNs and PNA. It is beneficial for constructing a highly selective sensing platform for PNA determination compared to its isomers (o-nitroaniline and m-nitroaniline) through atomic bromine-mediated polarization of the BBCNs. With the help of this mechanism, an excellent linear range of 0.5-300 µM with a low detection limit of 0.24 µM toward PNA was obtained. This work further confirms that there is a significant relationship between the nature of doping elements and the optical and physicochemical properties of fluorescent materials.

Ruthenium-catalyzed C-H functionalization of indoles and indolines with 7-azabenzonorbornadienes: access to aminodihydronaphthyl indoles and indolines.

Indoles, indolines and hydronaphthylamines are ubiquitous structural motifs in natural products, pharmaceuticals, and biologically active molecules. In this paper, we report the synthesis of aminodihydronaphthyl-substituted indoles and indolines via a Ru-catalyzed carbamoyl-directed C-H functionalization of indoles and indolines with 7-azabenzonorbornadienes. In the presence of Cu(OAc)2 and AgSbF6, [Ru(p-cymene)Cl2]2 catalyzes the reaction of 1-carbamoylindoles with 7-azabenzonorbornadienes to produce 2-(1-amino-1,2-dihydronaphthalen-2-yl)indoles. Under the same conditions, the reaction of 1-carbamoylindolines with 7-azabenzonorbornadienes affords 7-(1-amino-1,2-dihydronaphthalen-2-yl)indolines. In both cases, the reactions yield cis-configured products.

Readiness for return to work and its influencing factors among head and neck cancer patients: a cross-sectional study.

PURPOSE: This study aims to investigate the Readiness for Return-to-Work (RRTW) of patients with head and neck tumours and to analyse the relationships among self-efficacy, disease uncertainty, psychosocial adaptation, and RRTW in head and neck cancer (HNC) patients. METHODS: A cross-sectional study was conducted with 259 HNC patients with a discharge length of ≥1 month at a tertiary hospital in Liaoning Province. The research tools included a self-designed general information questionnaire, the Readiness for Return-to-Work (RRTW) Scale, the General Self-Efficacy Scale (GSES), the Mishel Uncertainty in Illness Scale (MUIS), and the Self-Reporting Psychosocial Adjustment to Illness Scale (PAIS-SR). Descriptive statistical analysis, the rank sum test, Spearman correlation analysis, and ordered multiple and dichotomous logistic regression analyses were used. RESULTS: The overall RRTW among HNC patients was low (41.9%). HNC patients who did not return to work were mainly in the precontemplation stage (38.1%) and contemplation stage (29.9%). HNC patients who returned to work were mainly in the active maintenance stage (64.2%). Children's status (OR = 0.218, 95% CI 0.068-0.703), self-efficacy (OR = 1.213, 95% CI 1.012-1.454), unpredictability (OR = 0.845, 95% CI 0.720-0.990), occupational environment (OR = 0.787, 95% CI 0.625-0.990), and family environment (OR = 0.798, 95% CI 0.643-0.990) influence the RRTW of HNC patients who have not returned to work. Educational level (OR = 62.196, 95% CI 63.307-68.567), children's status (OR = 0.058, 95% CI 1.004-2.547), self-efficacy (OR = 1.544, 95% CI 3.010-8.715), unpredictability (OR = 0.445, 95% CI 1.271-2.280), and psychological status (OR = 0.340, 95% CI 1.141-2.401) influence the RRTW of HNC patients who have returned to work. CONCLUSION: Children's status, education level, self-efficacy, illness uncertainty, and psychosocial adjustment are crucial to RRTW. This study provides a theoretical basis for formulating intervention measures aimed at improving the RRTW of patients.

Health information-seeking experience in people with head and neck neoplasms undergoing treatment: a qualitative study.

PURPOSE: To describe the health information-seeking experience and its influencing factors of people with head and neck neoplasms undergoing treatment. METHODS: This was a descriptive phenomenology study. Participants were recruited by purposive sampling. The semistructured interviews and all observation results were recorded. The data were analysed using Colaizzi's method. RESULTS: Fourteen participants were selected. We identified four themes that illustrate factors that influence the health information-seeking behaviour of participants: patients' awareness of health information needs, patients' competence, doctor-patient communication, and online advertising interference. We also determined the value of different types of information and patients' information needs and sources. CONCLUSION: These findings can help professionals understand patients' behaviours and think about how to deliver practical information support in a network environment to guide patients in continuous information seeking while taking specific factors into account.

Manipulating the Spin State of Spinel Octahedral Sites via a π-π Type Orbital Coupling to Boost Water Oxidation.

Spin state is often regarded as the crucial valve to release the reactivity of energy-related catalysts, yet it is also challenging to precisely manipulate, especially for the active center ions occupied at the specific geometric sites. Herein, a π-π type orbital coupling of 3d (Co)-2p (O)-4f (Ce) was employed to regulate the spin state of octahedral cobalt sites (CoOh) in the composite of Co3O4/CeO2. More specifically, the equivalent high-spin ratio of CoOh can reach to 54.7 % via tuning the CeO2 content, thereby triggering the average eg filling (1.094) close to the theoretical optimum value. The corresponding catalyst exhibits a superior water oxidation performance with an overpotential of 251 mV at 10 mA cm-2, rivaling most cobalt-based oxides state-of-the-art. The π-π type coupling corroborated by the matched energy levels between Ce t1u/t2u-O and CoOh t2g-O π type bond in the calculated crystal orbital Hamilton population and partial density of states profiles, stimulates a π-donation between O 2p and π-symmetric Ce 4fyz 2 orbital, consequently facilitating the electrons hopping from t2g to eg orbital of CoOh. This work offers an in-depth insight into understanding the 4f and 3d orbital coupling for spin state optimization in composite oxides.

Doxycycline Combined With Bortezomib-Cyclophosphamide-Dexamethasone Chemotherapy for Newly Diagnosed Cardiac Light-Chain Amyloidosis: A Multicenter Randomized Controlled Trial.

BACKGROUND: Doxycycline was demonstrated in a retrospective study to be associated with greater survival in patients with light chain amyloidosis. Therefore, we prospectively compared the efficacy of bortezomib-cyclophosphamide-dexamethasone (CyBorD) and CyBorD combined with doxycycline for cardiac light chain amyloidosis. METHODS: This was a multicenter, open-label, randomized controlled trial. Patients with Mayo 2004 stage II to III light chain amyloidosis were included. Patients were randomized to doxycycline 100 mg twice daily along with 9 cycles of CyBorD (doxycycline group) or to 9 cycles of CyBorD alone (control group). The primary outcome was 2-year progression-free survival (PFS). PFS was defined as the time from randomization to death, hematologic progression, or organ progression (heart, kidney or liver). Hematologic progression was defined on the basis of a substantial increase in free light chain. An increase in either NT-proBNP (N-terminal pro B-type natriuretic peptide) or cardiac troponin was the main criterion for defining cardiac progression. Cardiac PFS, defined as the time from randomization to cardiac progression or death, was compared between groups in an exploratory analysis. The corresponding treatment hazard ratio was estimated with a Cox regression model. RESULTS: One hundred forty patients underwent randomization, with 70 in each group. The median age was 61 years (range, 33-78 years) with a male:female ratio of 1.75:1. Stage II disease was present in 34 (48.6%) and 33 (47.1%) patients in the doxycycline and control groups, respectively. After a median follow-up duration of 24.4 months, 32 of 70 (45.7%) patients in the doxycycline group and 30 of 70 (42.9%) patients in the control group experienced progression. PFS was not significantly different between groups (hazard ratio, 0.97 [95% CI, 0.59-1.60]; P=0.91). Cardiac progression occurred in 29 of 70 (41.4%) patients in the doxycycline group and 26 of 70 (37.1%) patients in the control group. The death rates for both groups by the end of follow-up was the same, 25 of 70 (35.7%). No significant differences were observed for either cardiac PFS (hazard ratio, 0.91 [95% CI, 0.54-1.55]; P=0.74) or overall survival (hazard ratio, 1.04 [95% CI, 0.60-1.81]; P=0.89). CONCLUSIONS: Our trial demonstrated that doxycycline combined with CyBorD failed to prolong PFS or cardiac PFS compared with CyBorD alone in cardiac light chain amyloidosis. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03401372.

Large Piezoelectric Response in a Metal-Free Three-Dimensional Perovskite Ferroelectric.

Metal-free perovskites with light weight and eco-friendly processability have received great interest in recent years due to their superior physical features in ferroelectrics, X-ray detection, and optoelectronics. The famous metal-free perovskite ferroelectric MDABCO-NH4-I3 (MDABCO = N-methyl-N'-diazabicyclo[2.2.2]octonium) has been demonstrated to exhibit excellent ferroelectricity comparable to that of inorganic ceramic ferroelectric BaTiO3, such as large spontaneous polarization and high Curie temperature (Ye et al. Science 2018, 361, 151). However, piezoelectricity as a vitally important index is far from enough in the metal-free perovskite family. Here, we report the discovery of large piezoelectric response in a new metal-free three-dimensional perovskite ferroelectric NDABCO-NH4-Br3 (NDABCO = N-amino-N'-diazabicyclo[2.2.2]octonium) by replacing the methyl group of MDABCO with the amino group. Besides the evident ferroelectricity, strikingly, NDABCO-NH4-Br3 shows a large d33 of 63 pC/N more than 4 times that of MDABCO-NH4-I3 (14 pC/N). The d33 value is also strongly supported by the computational study. To the best of our knowledge, such a large d33 value ranks the highest among the documented organic ferroelectric crystals to date and represents a major breakthrough in metal-free perovskite ferroelectrics. Combined with decent mechanical properties, NDABCO-NH4-Br3 is expected to be a competitive candidate for medical, biomechanical, wearable, and body-compatible ferroelectric devices.

Identification and Quantification of 5-Methylcytosine and 5-Hydroxymethylcytosine on Random DNA Sequences by a Nanoconfined Electrochemiluminescence Platform.

5-Methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) are two of the most abundant epigenetic marks in mammalian genomes, and it has been proven that these dual epigenetic marks give a more accurate prediction of recurrence and survival in cancer than the individual mark. However, due to the similar structure and low expression of 5mC and 5hmC, it is challenging to distinguish and quantify the two methylation modifications. Herein, we employed the ten-eleven translocation family dioxygenases (TET) to convert 5mC to 5hmC via a specific labeling process, which realized the identification of the two marks based on a nanoconfined electrochemiluminescence (ECL) platform combined with the amplification strategy of a recombinase polymerase amplification (RPA)-assisted CRISPR/Cas13a system. Benefiting from the TET-mediated conversion strategy, a highly consistent labeling pathway was developed for identifying dual epigenetic marks on random sequence, which reduced the system error effectively. The ECL platform was established via preparing a carbonized polymer dot embedded SiO2 nanonetwork (CPDs@SiO2), which exhibited higher ECL efficiencies and more stable ECL performance compared to those of the scattered emitters due to the nanoconfinement-enhanced ECL effect. The proposed bioanalysis strategy could be employed for the identification and quantification of 5mC and 5hmC in the range from 100 aM to 100 pM, respectively, which provides a promising tool for early diagnosis of diseases associated with abnormal methylation.

Schrödinger-Heisenberg Variational Quantum Algorithms.

Recent breakthroughs have opened the possibility of intermediate-scale quantum computing with tens to hundreds of qubits, and shown the potential for solving classical challenging problems, such as in chemistry and condensed matter physics. However, the high accuracy needed to surpass classical computers poses a critical demand on the circuit depth, which is severely limited by the non-negligible gate infidelity, currently around 0.1%-1%. The limited circuit depth places restrictions on the performance of variational quantum algorithms (VQA) and prevents VQAs from exploring desired nontrivial quantum states. To resolve this problem, we propose a paradigm of Schrödinger-Heisenberg variational quantum algorithms (SHVQA). Using SHVQA, the expectation values of operators on states that require very deep circuits to prepare can now be efficiently measured by rather shallow circuits. The idea is to incorporate a virtual Heisenberg circuit, which acts effectively on the measurement observables, into a real shallow Schrödinger circuit, which is implemented realistically on the quantum hardware. We choose a Clifford virtual circuit, whose effect on the Hamiltonian can be seen as efficient classical processing. Yet, it greatly enlarges the state's expressivity, realizing much larger unitary t designs. Our method enables accurate quantum simulation and computation that otherwise are only achievable with much deeper circuits or more accurate operations conventionally. This has been verified in our numerical experiments for a better approximation of random states, higher-fidelity solutions to the XXZ model, and the electronic structure Hamiltonians of small molecules. Thus, together with effective quantum error mitigation, our work paves the way for realizing accurate quantum computing algorithms with near-term quantum devices.