Ferromagnetic single-atom spin catalyst for boosting water splitting.

Heterogeneous single-atom spin catalysts combined with magnetic fields provide a powerful means for accelerating chemical reactions with enhanced metal utilization and reaction efficiency. However, designing these catalysts remains challenging due to the need for a high density of atomically dispersed active sites with a short-range quantum spin exchange interaction and long-range ferromagnetic ordering. Here, we devised a scalable hydrothermal approach involving an operando acidic environment for synthesizing various single-atom spin catalysts with widely tunable substitutional magnetic atoms (M1) in a MoS2 host. Among all the M1/MoS2 species, Ni1/MoS2 adopts a distorted tetragonal structure that prompts both ferromagnetic coupling to nearby S atoms as well as adjacent Ni1 sites, resulting in global room-temperature ferromagnetism. Such coupling benefits spin-selective charge transfer in oxygen evolution reactions to produce triplet O2. Furthermore, a mild magnetic field of ~0.5 T enhances the oxygen evolution reaction magnetocurrent by ~2,880% over Ni1/MoS2, leading to excellent activity and stability in both seawater and pure water splitting cells. As supported by operando characterizations and theoretical calculations, a great magnetic-field-enhanced oxygen evolution reaction performance over Ni1/MoS2 is attributed to a field-induced spin alignment and spin density optimization over S active sites arising from field-regulated S(p)-Ni(d) hybridization, which in turn optimizes the adsorption energies for radical intermediates to reduce overall reaction barriers.

Catalytically active atomically thin cuprate with periodic Cu single sites.

Rational design and synthesis of catalytically active two-dimensional (2D) materials with an abundance of atomically precise active sites in their basal planes remains a great challenge. Here, we report a ligand exchange strategy to exfoliate bulk [Cu4(OH)6][O3S(CH2)4SO3] cuprate crystals into atomically thin 2D cuprate layers ([Cu2(OH)3]+). The basal plane of 2D cuprate layers contains periodic arrays of accessible unsaturated Cu(II) single sites (2D-CuSSs), which are found to promote efficient oxidative Chan-Lam coupling. Our mechanistic studies reveal that the reactions proceed via coordinatively unsaturated CuO4(II) single sites with the formation of Cu(I) species in the rate-limiting step, as corroborated by both operando experimental and theoretical studies. The robust stability of 2D-CuSSs in both batch and continuous flow reactions, coupled with their recyclability and good performance in complex molecule derivatization, render 2D-CuSSs attractive catalyst candidates for broad utility in fine chemical synthesis.

[Effect of continuous renal replacement therapy on plasma concentration, clinical efficacy and safety of colistin sulfate].

OBJECTIVE: To investigate the effects of continuous renal replacement therapy (CRRT) on plasma concentration, clinical efficacy and safety of colistin sulfate. METHODS: Clinical data of patients received with colistin sulfate were retrospectively analyzed from our group's previous clinical registration study, which was a prospective, multicenter observation study on the efficacy and pharmacokinetic characteristics of colistin sulfate in patients with severe infection in intensive care unit (ICU). According to whether patients received blood purification treatment, they were divided into CRRT group and non-CRRT group. Baseline data (gender, age, whether complicated with diabetes, chronic nervous system disease, etc), general data (infection of pathogens and sites, steady-state trough concentration, steady-state peak concentration, clinical efficacy, 28-day all-cause mortality, etc) and adverse event (renal injury, nervous system, skin pigmentation, etc) were collected from the two groups. RESULTS: A total of 90 patients were enrolled, including 22 patients in the CRRT group and 68 patients in the non-CRRT group. (1) There was no significant difference in gender, age, basic diseases, liver function, infection of pathogens and sites, colistin sulfate dose between the two groups. Compared with the non-CRRT group, the acute physiology and chronic health evaluation II (APACHE II) and sequential organ failure assessment (SOFA) were higher in the CRRT group [APACHE II: 21.77±8.26 vs. 18.01±6.34, P < 0.05; SOFA: 8.5 (7.8, 11.0) vs. 6.0 (4.0, 9.0), P < 0.01], serum creatinine level was higher [µmol/L: 162.0 (119.5, 210.5) vs. 72.0 (52.0, 117.0), P < 0.01]. (2) Plasma concentration: there was no significant difference in steady-state trough concentration between CRRT group and non-CRRT group (mg/L: 0.58±0.30 vs. 0.64±0.25, P = 0.328), nor was there significant difference in steady-state peak concentration (mg/L: 1.02±0.37 vs. 1.18±0.45, P = 0.133). (3) Clinical efficacy: there was no significant difference in clinical response rate between CRRT group and non-CRRT group [68.2% (15/22) vs. 80.9% (55/68), P = 0.213]. (4) Safety: acute kidney injury occurred in 2 patients (2.9%) in the non-CRRT group. No obvious neurological symptoms and skin pigmentation were found in the two groups. CONCLUSIONS: CRRT had little effect on the elimination of colistin sulfate. Routine blood concentration monitoring (TDM) is warranted in patients received with CRRT.

Experimental and Thermodynamic Viewpoints on Claims of a Spontaneous H2O2 Formation at the Air-Water Interface.

Recent claims of the spontaneous H2O2 formation at the air-water interface of water microdroplets have sparked debates on its feasibility. New results from different research groups have provided more insight into these claims, but conclusive proofs are still far from realized. In this Perspective, thermodynamic viewpoints, potential experiments, and theoretical approaches are presented as references for future studies. We suggest that future work should seek for H2 byproduct as indirect evidence to confirm the feasibility of this phenomenon. Examining potential energy surfaces for H2O2 formation reaction when moving from the bulk to the interface under the influence of the local electric fields is also critical to establish this phenomenon.

Periodic Distributions and Ultrafast Dynamics of Hot Electrons in Plasmonic Resonators.

Understanding and managing hot electrons in metals are of fundamental and practical interest in plasmonic studies and applications. A major challenge for the development of hot electron devices requires the efficient and controllable generation of long-lived hot electrons so that they can be harnessed effectively before relaxation. Here, we report the ultrafast spatiotemporal evolution of hot electrons in plasmonic resonators. Using femtosecond-resolution interferometric imaging, we show the unique periodic distributions of hot electrons due to standing plasmonic waves. In particular, this distribution can be flexibly tuned by the size, shape, and dimension of the resonator. We also demonstrate that the hot electron lifetimes are substantially prolonged at hot spots. This appealing effect is interpreted as a result of the locally concentrated energy density at the antinodes in standing hot electron waves. These results could be useful to control the distributions and lifetimes of hot electrons in plasmonic devices for targeted optoelectronic applications.

URINARY METABOLOMICS OF CENTRAL SEROUS CHORIORETINOPATHY.

PURPOSE: To analyze the urinary metabolomic profile of central serous chorioretinopathy cases. METHODS: In a cross-sectional study, 80 participants with central serous chorioretinopathy were compared with 80 age-matched and sex-matched controls. Urinary metabolites were measured using Metabolon's Discovery HD4 platform. RESULTS: Of 1,031 metabolites total that were measured in urine samples, 53 were upregulated and 27 downregulated in central serous chorioretinopathy participants compared with controls. After exclusion of potentially confounding xenobiotics and bile compounds that could represent digestive processes, 14 metabolites were significantly higher and 12 metabolites were significantly lower in cases compared with controls. One upregulated metabolite (tetrahydrocortisol sulfate) is involved in the corticosteroid subpathway. The downregulated metabolites are unrelated to the identified corticosteroid subpathway. CONCLUSION: The upregulation of urinary tetrahydrocortisol sulfate in central serous chorioretinopathy cases provides a precise molecular basis to further study the role of corticosteroids in producing choroidal venous congestion.

IReNA: Integrated regulatory network analysis of single-cell transcriptomes and chromatin accessibility profiles.

Recently, single-cell RNA sequencing (scRNA-seq) and single-cell assay for transposase-accessible chromatin using sequencing (scATAC-seq) have been developed to separately measure transcriptomes and chromatin accessibility profiles at the single-cell resolution. However, few methods can reliably integrate these data to perform regulatory network analysis. Here, we developed integrated regulatory network analysis (IReNA) for network inference through the integrated analysis of scRNA-seq and scATAC-seq data, network modularization, transcription factor enrichment, and construction of simplified intermodular regulatory networks. Using public datasets, we showed that integrated network analysis of scRNA-seq data with scATAC-seq data is more precise to identify known regulators than scRNA-seq data analysis alone. Moreover, IReNA outperformed currently available methods in identifying known regulators. IReNA facilitates the systems-level understanding of biological regulatory mechanisms and is available at https://github.com/jiang-junyao/IReNA.

Improving performance of deep learning models using 3.5D U-Net via majority voting for tooth segmentation on cone beam computed tomography.

Deep learning allows automatic segmentation of teeth on cone beam computed tomography (CBCT). However, the segmentation performance of deep learning varies among different training strategies. Our aim was to propose a 3.5D U-Net to improve the performance of the U-Net in segmenting teeth on CBCT. This study retrospectively enrolled 24 patients who received CBCT. Five U-Nets, including 2Da U-Net, 2Dc U-Net, 2Ds U-Net, 2.5Da U-Net, 3D U-Net, were trained to segment the teeth. Four additional U-Nets, including 2.5Dv U-Net, 3.5Dv5 U-Net, 3.5Dv4 U-Net, and 3.5Dv3 U-Net, were obtained using majority voting. Mathematical morphology operations including erosion and dilation (E&D) were applied to remove diminutive noise speckles. Segmentation performance was evaluated by fourfold cross validation using Dice similarity coefficient (DSC), accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV). Kruskal-Wallis test with post hoc analysis using Bonferroni correction was used for group comparison. P < 0.05 was considered statistically significant. Performance of U-Nets significantly varies among different training strategies for teeth segmentation on CBCT (P < 0.05). The 3.5Dv5 U-Net and 2.5Dv U-Net showed DSC and PPV significantly higher than any of five originally trained U-Nets (all P < 0.05). E&D significantly improved the DSC, accuracy, specificity, and PPV (all P < 0.005). The 3.5Dv5 U-Net achieved highest DSC and accuracy among all U-Nets. The segmentation performance of the U-Net can be improved by majority voting and E&D. Overall speaking, the 3.5Dv5 U-Net achieved the best segmentation performance among all U-Nets.

Gate-Tunable Resonance State and Screening Effects for Proton-Like Atomic Charge in Graphene.

The ability to create a robust and well-defined artificial atomic charge in graphene and understand its carrier-dependent electronic properties represents an important goal toward the development of graphene-based quantum devices. Herein, we devise a new pathway toward the atomically precise embodiment of point charges into a graphene lattice by posterior (N) ion implantation into a back-gated graphene device. The N dopant behaves as an in-plane proton-like charge manifested by formation of the characteristic resonance state in the conduction band. Scanning tunneling spectroscopy measurements at varied charge carrier densities reveal a giant energetic renormalization of the resonance state up to 220 meV with respect to the Dirac point, accompanied by the observation of gate-tunable long-range screening effects close to individual N dopants. Joint density functional theory and tight-binding calculations with modified perturbation potential corroborate experimental findings and highlight the short-range character of N-induced perturbation.

Structural basis of ion uptake in copper-transporting P1B-type ATPases.

Copper is essential for living cells, yet toxic at elevated concentrations. Class 1B P-type (P1B-) ATPases are present in all kingdoms of life, facilitating cellular export of transition metals including copper. P-type ATPases follow an alternating access mechanism, with inward-facing E1 and outward-facing E2 conformations. Nevertheless, no structural information on E1 states is available for P1B-ATPases, hampering mechanistic understanding. Here, we present structures that reach 2.7 Å resolution of a copper-specific P1B-ATPase in an E1 conformation, with complementing data and analyses. Our efforts reveal a domain arrangement that generates space for interaction with ion donating chaperones, and suggest a direct Cu+ transfer to the transmembrane core. A methionine serves a key role by assisting the release of the chaperone-bound ion and forming a cargo entry site together with the cysteines of the CPC signature motif. Collectively, the findings provide insights into P1B-mediated transport, likely applicable also to human P1B-members.

New Advances in Using Virus-like Particles and Related Technologies for Eukaryotic Genome Editing Delivery.

The designer nucleases, including Zinc Finger Nuclease (ZFN), Transcription Activator-Like Effector Nuclease (TALEN), and Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR-associated (CRISPR/Cas), have been widely used for mechanistic studies, animal model generation, and gene therapy development. Clinical trials using designer nucleases to treat genetic diseases or cancers are showing promising results. Despite rapid progress, potential off-targets and host immune responses are challenges to be addressed for in vivo uses, especially in clinical applications. Short-term expression of the designer nucleases is necessary to reduce both risks. Currently, delivery methods enabling transient expression of designer nucleases are being pursued. Among these, virus-like particles as delivery vehicles for short-term designer nuclease expression have received much attention. This review will summarize recent developments in using virus-like particles (VLPs) for safe delivery of gene editing effectors to complement our last review on the same topic. First, we introduce some background information on how VLPs can be used for safe and efficient CRISPR/Cas9 delivery. Then, we summarize recently developed virus-like particles as genome editing vehicles. Finally, we discuss applications and future directions.

Decrypting Material Performance by Wide-field Femtosecond Interferometric Imaging of Energy Carrier Evolution.

Energy carrier evolution is crucial for material performance. Ultrafast microscopy has been widely applied to visualize the spatiotemporal evolution of energy carriers. However, direct imaging of a small amount of energy carriers on the nanoscale remains difficult due to extremely weak transient signals. Here, we present a method for ultrasensitive and high-throughput imaging of energy carrier evolution in space and time. This method combines femtosecond pump-probe techniques with interferometric scattering microscopy (iSCAT), named Femto-iSCAT. The interferometric principle and unique spatially modulated contrast enhancement enable the exploration of new science. We address three important and challenging problems: transport of different energy carriers at various interfaces, heterogeneous hot-electron distribution and relaxation in single plasmonic resonators, and distinct structure-dependent edge-state dynamics of carriers and excitons in optoelectronic semiconductors. Femto-iSCAT holds great potential as a universal tool for ultrasensitive imaging of energy carrier evolution in space and time.

Continuous Authentication against Collusion Attacks.

As mobile devices become more and more popular, users gain many conveniences. It has also made smartphone makers install new software and prebuilt hardware on their products, including many kinds of sensors. With improved storage and computing power, users also become accustomed to storing and interacting with personally sensitive information. Due to convenience and efficiency, mobile devices use gait authentication widely. In recent years, protecting the information security of mobile devices has become increasingly important. It has become a hot research area because smartphones are vulnerable to theft or unauthorized access. This paper proposes a novel attack model called a collusion attack. Firstly, we study the imitation attack in the general state and its results and propose and verify the feasibility of our attack. We propose a collusion attack model and train participants with quantified action specifications. The results demonstrate that our attack increases the attacker's false match rate only using an acceleration sensor in some systems sensor. Furthermore, we propose a multi-cycle defense model based on acceleration direction changes to improve the robustness of smartphone-based gait authentication methods against such attacks. Experimental results show that our defense model can significantly reduce the attacker's success rate.

LRLoop: a method to predict feedback loops in cell-cell communication.

MOTIVATION: Intercellular communication (i.e. cell-cell communication) plays an essential role in multicellular organisms coordinating various biological processes. Previous studies discovered that feedback loops between two cell types are a widespread and vital signaling motif regulating development, regeneration and cancer progression. While many computational methods have been developed to predict cell-cell communication based on gene expression datasets, these methods often predict one-directional ligand-receptor interactions from sender to receiver cells and are not suitable to identify feedback loops. RESULTS: Here, we describe ligand-receptor loop (LRLoop), a new method for analyzing cell-cell communication based on bi-directional ligand-receptor interactions, where two pairs of ligand-receptor interactions are identified that are responsive to each other and thereby form a closed feedback loop. We first assessed LRLoop using bulk datasets and found our method significantly reduces the false positive rate seen with existing methods. Furthermore, we developed a new strategy to assess the performance of these methods in single-cell datasets. We used the between-tissue interactions as an indicator of potential false-positive prediction and found that LRLoop produced a lower fraction of between-tissue interactions than traditional methods. Finally, we applied LRLoop to the single-cell datasets obtained from retinal development. We discovered many new bi-directional ligand-receptor interactions among individual cell types that potentially control proliferation, neurogenesis and/or cell fate specification. AVAILABILITY AND IMPLEMENTATION: An R package is available at https://github.com/Pinlyu3/LRLoop. The source code can be found at figshare (https://doi.org/10.6084/m9.figshare.20126138.v1). The datasets can be found at figshare (https://doi.org/10.6084/m9.figshare.20126021.v1). SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Electronic Self-Passivation of Single Vacancy in Black Phosphorus via Ionization.

We report that monoelemental black phosphorus presents a new electronic self-passivation scheme of single vacancy (SV). By means of low-temperature scanning tunneling microscopy and noncontact atomic force microscopy, we demonstrate that the local reconstruction and ionization of SV into negatively charged SV^{-} leads to the passivation of dangling bonds and, thus, the quenching of in-gap states, which can be achieved by mild thermal annealing or STM tip manipulation. SV exhibits a strong and symmetric Friedel oscillation (FO) pattern, while SV^{-} shows an asymmetric FO pattern with local perturbation amplitude reduced by one order of magnitude and a faster decay rate. The enhanced passivation by forming SV^{-} can be attributed to its weak dipolelike perturbation, consistent with density-functional theory numerical calculations. Therefore, self-passivated SV^{-} is electrically benign and acts as a much weaker scattering center, which may hold the key to further enhance the charge mobility of black phosphorus and its analogs.

Cell-specific cis-regulatory elements and mechanisms of non-coding genetic disease in human retina and retinal organoids.

Cis-regulatory elements (CREs) play a critical role in the development and disease-states of all human cell types. In the retina, CREs have been implicated in several inherited disorders. To better characterize human retinal CREs, we performed single-nucleus assay for transposase-accessible chromatin sequencing (snATAC-seq) and single-nucleus RNA sequencing (snRNA-seq) on the developing and adult human retina and on induced pluripotent stem cell (iPSC)-derived retinal organoids. These analyses identified developmentally dynamic, cell-class-specific CREs, enriched transcription-factor-binding motifs, and putative target genes. CREs in the retina and organoids are highly correlated at the single-cell level, and this supports the use of organoids as a model for studying disease-associated CREs. As a proof of concept, we disrupted a disease-associated CRE at 5q14.3, confirming its principal target gene as the miR-9-2 primary transcript and demonstrating its role in neurogenesis and gene regulation in mature glia. This study provides a resource for characterizing human retinal CREs and showcases organoids as a model to study the function of CREs that influence development and disease.

Mechanistic insight into deep holes from interband transitions in Palladium nanoparticle photocatalysts.

Utilizing hot electrons generated from localized surface plasmon resonance is of widespread interest in the photocatalysis of metallic nanoparticles. However, hot holes, especially generated from interband transitions, have not been fully explored for photocatalysis yet. In this study, a photocatalyzed Suzuki-Miyaura reaction using mesoporous Pd nanoparticle photocatalyst served as a model to study the role of hot holes. Quantum yields of the photocatalysts increase under shorter wavelength excitations and correlate to "deeper" energy of the holes from the Fermi level. This work suggests that deeper holes in the d-band catalyze the oxidative addition of aryl halide R-X onto Pd0 at the nanoparticles' surface to form R-PdII-X complex, thus accelerating the rate-determining step of the catalytic cycle. The hot electrons do not play a decisive role. In the future, catalytic mechanisms induced by deep holes should deserve as much attention as the well-known hot electron transfer mechanism.

Etanercept Reduces Neuron Injury and Neuroinflammation via Inactivating c-Jun N-terminal Kinase and Nuclear Factor-κB Pathways in Alzheimer's Disease: An In Vitro and In Vivo Investigation.

Inflammation contributes to amyloid beta (Aß) aggregation and neuron loss in Alzheimer's disease (AD). Meanwhile, tumor necrosis factor-α (TNF-α) inhibitors present strong effect on suppressing inflammation. Thus, this study aimed to investigated the effect and molecular mechanism of etanercept (ETN) (a commonly used TNF-α inhibitor) on neuron injury and neuroinflammation in AD. AD cellular model was constructed by co-culture of primary embryonic neuron cells and microglial cells, followed by Aß treatment. Subsequently, ETN was used to treat AD cellular model. Besides, APPswe/PS1M146V/tauP301L transgenic (AD) mice were respectively treated with saline or ETN by intravenous injection once per 3 days for 10 times. In vitro data revealed that cell viability and neurite outgrowth were increased, but apoptosis and levels of pro-inflammatory cytokines (including TNF-α, interleukin-1ß, Interleukin-6 and C-C motif chemokine ligand 2 (CCL2)) were decreased by ETN treatment in AD cellular model. In vivo experiments found that ETN treatment improved spatial, long-term memory (reflected by Morrison water maze) and working memory (reflected by Y maze) in AD mice. Besides, ETN treatment reduced neuron injury (reflected by Hematoxylin-Eosin (HE) and terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) assays) and levels of pro-inflammatory cytokines (including TNF-α, interleukin-1ß, Interleukin-6 and CCL2) in AD mice. Moreover, ETN repressed the activation of c-Jun N-terminal kinase (JNK) and nuclear factor-κB (NF-κB) pathways in AD both in vitro and in vivo. In conclusion, ETN exerts neuroprotective function via inactivating JNK and NF-κB pathways in AD, indicating the potential of ETN for improving AD management.

Structure and ion-release mechanism of PIB-4-type ATPases.

Transition metals, such as zinc, are essential micronutrients in all organisms, but also highly toxic in excessive amounts. Heavy-metal transporting P-type (PIB) ATPases are crucial for homeostasis, conferring cellular detoxification and redistribution through transport of these ions across cellular membranes. No structural information is available for the PIB-4-ATPases, the subclass with the broadest cargo scope, and hence even their topology remains elusive. Here, we present structures and complementary functional analyses of an archetypal PIB-4-ATPase, sCoaT from Sulfitobacter sp. NAS14-1. The data disclose the architecture, devoid of classical so-called heavy-metal-binding domains (HMBDs), and provide fundamentally new insights into the mechanism and diversity of heavy-metal transporters. We reveal several novel P-type ATPase features, including a dual role in heavy-metal release and as an internal counter ion of an invariant histidine. We also establish that the turnover of PIB-ATPases is potassium independent, contrasting to many other P-type ATPases. Combined with new inhibitory compounds, our results open up for efforts in for example drug discovery, since PIB-4-ATPases function as virulence factors in many pathogens.

Heavy metals such as zinc and cobalt are toxic at high levels, yet most organisms need tiny amounts for their cells to work properly. As a result, proteins studded through the cell membrane act as gatekeepers to finetune import and export. These proteins are central to health and disease; their defect can lead to fatal illnesses in humans, and they also help bacteria infect other organisms. Despite their importance, little is known about some of these metal-export proteins. This is particularly the case for P_IB-4-ATPases, a subclass found in plants and bacteria and which includes, for example, a metal transporter required for bacteria to cause tuberculosis. Intricate knowledge of the three-dimensional structure of these proteins would help to understand how they select metals, shuttle the compounds in and out of cells, and are controlled by other cellular processes. To reveal this three-dimensional organisation, Grønberg et al. used X-ray diffraction, where high-energy radiation is passed through crystals of protein to reveal the positions of atoms. They focused on a type of PIB-4-ATPases found in bacteria as an example. The work showed that the protein does not contain the metal-binding regions seen in other classes of metal exporters; however, it sports unique features that are crucial for metal transport such as an adapted pathway for the transport of zinc and cobalt across the membrane. In addition, Grønberg et al. tested thousands of compounds to see if they could block the activity of the protein, identifying two that could kill bacteria. This better understanding of how PIB-4-ATPases work could help to engineer plants capable of removing heavy metals from contaminated soils, as well as uncover new compounds to be used as antibiotics.

Effect of Photocharging on Catalysis of Metallic Nanoparticles.

The photocharging effect is widely known across different research fields, has rarely been quantified as a background contribution in photocatalysis, and has often been overlooked in mechanistic interpretation of nanoparticle photocatalysts. To address these issues, this work presents a two-step experiment: charging colloidal Pd nanoparticles with light and hole scavengers and using the charged particles to catalyze the reduction of 4-nitrophenol by NaBH4 under non-irradiation conditions. Experimental kinetics demonstrated a proportional correlation between accumulated electrons and catalytic improvement of Pd nanoparticles. This work reminds us that photocharged nanoparticles may still catalyze chemical reactions as a background phenomenon even when they are not undergoing photoexcitation.