Mated-Atom Nanozymes with Efficient Assisted NAD+ Replenishment for Skin Regeneration.

Excessive accumulation of reduced nicotinamide adenine dinucleotide (NADH) within biological organisms is closely associated with many diseases. It remains a challenge to efficiently convert superfluous and detrimental NADH to NAD+. NADH oxidase (NOX) is a crucial oxidoreductase that catalyzes the oxidation of NADH to NAD+. Herein, M1M2 (Mi=V/Mn/Fe/Co/Cu/Mo/Rh/Ru/Pd, i = 1 or 2) mated-atom nanozymes (MANs) are designed by mimicking natural enzymes with polymetallic active centers. Excitingly, RhCo MAN possesses excellent and sustainable NOX-like activity, with Km-NADH (16.11 µM) being lower than that of NOX-mimics reported so far. Thus, RhCo MAN can significantly promote the regeneration of NAD+ and regulate macrophage polarization toward the M2 phenotype through down-regulation of TLR4 expression, which may help to recover skin regeneration. However, RhRu MAN with peroxidase-like activity and RhMn MAN with superoxide dismutase-like activity exhibit little modulating effects on eczema. This work provides a new strategy to inhibit skin inflammation and promote skin regeneration.

Bioactive NIR-II gold clusters for three-dimensional imaging and acute inflammation inhibition.

Strong fluorescence and high catalytic activities cannot be achieved simultaneously due to conflicts in free electron utilization, resulting in a lack of bioactivity of most near-infrared-II (NIR-II) fluorophores. To circumvent this challenge, we developed atomically precise Au22 clusters with strong NIR-II fluorescence ranging from 950 to 1300 nm exhibiting potent enzyme-mimetic activities through atomic engineering to create active Cu single-atom sites. The developed Au21Cu1 clusters show 18-fold higher antioxidant, 90-fold higher catalase-like, and 3-fold higher superoxide dismutase-like activities than Au22 clusters, with negligible fluorescence loss. Doping with single Cu atoms decreases the bandgap from 1.33 to 1.28 eV by predominant contributions from Cu d states, and Cu with lost electron states effectuates high catalytic activities. The renal clearable clusters can monitor cisplatin-induced renal injury in the 20- to 120-minute window and visualize it in three dimensions using NIR-II light-sheet microscopy. Furthermore, the clusters inhibit oxidative stress and inflammation in the cisplatin-treated mouse model, particularly in the kidneys and brain.

Esophageal papillomatosis: an exceedingly rare disease.

If esophageal papilloma (EP) is a rare condition, esophageal papillomatosis (EPS) is a distinct rarity. To date, only 53 well documented cases have been described in English literature. However, the number of reports on EPS significantly increased to over 40 cases during the past 20 years. Perhaps, this is due to the broad use of endoscopy and related research achievements. Most of the cases are individual and it seems that there are no associations between them. And up to now no guidelines can be followed. To further understand this exceedingly rare disease, we had a comprehensive review of the epidemiology, etiology, clinical manifestations, pathogenesis, treatment, and clinical course of EPS.

Ratiometric fluorescent detection of sulfide ions in Radix Codonopsis and living cells based on PVP-supported gold/copper nanoclusters with tunable dual emission.

Herein, a novel fluorometric-sensor with dual-emission system was constructed on the basis of polyvinylpyrrolidone (PVP) and 2-mercaptobenzothiazole (MBT) co-functionalized gold/copper nanoclusters (PVP/MBT-Au@CuNCs) by a facile and eco-friendly one-pot approach. The sensor exhibited ratiometric fluorescence emission (F590 nm/F422 nm) for visual and selective detection of S2- with a sensitive detection limit of 11.9 nM. Besides, fluorescence quenched sensing of S2- was chalked up by a quickly selectivity monitoring time of 30 s, owing to the strongly binding of Cu2S and Au2S by hard-soft-acid-base theory and the destruction of the aggregated structure of PVP/MBT-Au@CuNCs. Furthermore, the platform also provided the portable analysis for visual detection of S2- by capturing the change in fluorescence color with a single dual-emissive ratiometric paper strip. It is worth mentioning that the fluorescent gold-copper nanoclusters showed excellent application activities in the selective detection of S2- in Radix Codonopsis or Tremella samples and recognition of S2- in HeLa cells or macrophages by confocal microscopy fluorescent imaging. Overall, the sensing system paved a new avenue for effectively developing a convenient ratiometric fluorescent sensor platform for evaluating the safety of food with S2- pollution in environment and biological system.

An electrochemical modification strategy to fabricate NiFeCuPt polymetallic carbon matrices on nickel foam as stable electrocatalysts for water splitting.

Electrochemical modification is a mild and economical way to prepare electrocatalytic materials with abundant active sites and high atom efficiency. In this work, a stable NiFeCuPt carbon matrix deposited on nickel foam (NFFeCuPt) was fabricated with an extremely low Pt load (∼28 µg cm-2) using one-step electrochemical co-deposition modification, and it serves as a bifunctional catalyst for overall water splitting and achieves 100 mA cm-2 current density at a low cell voltage of 1.54 V in acidic solution and 1.63 V in alkaline solution, respectively. In addition, a novel electrolyte was developed to stabilize the catalyst under acidic conditions, which provides inspiration for the development of highly efficient, highly stable, and cost-effective ways to synthesize electrocatalysts.

Contactless Haptic Display Through Magnetic Field Control.

Haptic rendering enables people to touch, perceive, and manipulate virtual objects in a virtual environment. Using six cascaded identical hollow disk electromagnets and a small permanent magnet attached to an operator's finger, this paper proposes and develops an untethered haptic interface through magnetic field control. The concentric hole inside the six cascaded electromagnets provides the workspace, where the 3D position of the permanent magnet is tracked with a Microsoft Kinect sensor. The driving currents of six cascaded electromagnets are calculated in real-time for generating the desired magnetic force. Offline data from an FEA (finite element analysis) based simulation, determines the relationship between the magnetic force, the driving currents, and the position of the permanent magnet. A set of experiments including the virtual object recognition experiment, the virtual surface identification experiment, and the user perception evaluation experiment were conducted to demonstrate the proposed system, where Microsoft HoloLens holographic glasses are used for visual rendering. The proposed magnetic haptic display leads to an untethered and non-contact interface for natural haptic rendering applications, which overcomes the constraints of mechanical linkages in tool-based traditional haptic devices.

MST1-knockdown protects against impairment of working memory via regulating neural activity in depression-like mice.

We reported that over-expression of MST1 induced the impairment of spatial memory via disturbing neural oscillation patterns in mice. Meanwhile, the P-MST1 is increased in the hippocampus after chronic unpredictable mild stress (CUMS). However, it is unclear if MST1 knockdown protects against stress-induced memory deficits via modulating neural activities. In the study, a CUMS mouse model was established and an intrahippocampal injection of AAV-shMST1 was used to knockdown MST1 in the hippocampus. The data showed that there were memory deficits with over-expressed P-MST1 level in CUMS mice. However, MST1 knockdown can significantly prevent the damages of CUMS-induced working memory and synaptic plasticity via regulating neural oscillation patterns. It suggests that MST1 down-regulation effectively protected against stress-induced behavioral dysfunctions. Moreover, as a more convenient way, neural oscillation analysis could provide some assistance for the auxiliary diagnosis and treatment of depression.

Using the Newcomb-Benford law to study the association between a country's COVID-19 reporting accuracy and its development.

The COVID-19 pandemic has spurred controversies related to whether countries manipulate reported data for political gains. We study the association between accuracy of reported COVID-19 data and developmental indicators. We use the Newcomb-Benford law (NBL) to gauge data accuracy. We run an OLS regression of an index constructed from developmental indicators (democracy level, gross domestic product per capita, healthcare expenditures, and universal healthcare coverage) on goodness-of-fit measures to the NBL. We find that countries with higher values of the developmental index are less likely to deviate from the Newcomb-Benford law. The relationship holds for the cumulative number of reported deaths and total cases but is more pronounced for the death toll. The findings are robust for second-digit tests and for a sub-sample of countries with regional data. The NBL provides a first screening for potential data manipulation during pandemics. Our study indicates that data from autocratic regimes and less developed countries should be treated with more caution. The paper further highlights the importance of independent surveillance data verification projects.

Experiment Study for Wrist-Wearable Electro-Tactile Display.

Tactile sensation is a promising information display channel for human beings that involves supplementing or replacing degraded visual or auditory channels. In this paper, a wrist-wearable tactile rendering system based on electro-tactile stimulation is designed for information expression, where a square array with 8 × 8 spherical electrodes is used as the touch panel. To verify and improve this touch-based information display method, the optimal mode for stimulus signals was firstly investigated through comparison experiments, which show that sequential stimuli with consecutive-electrode-in-active mode have a better performance than those with single-electrode-in-active mode. Then, simple Chinese and English characters and 26 English characters' recognition experiments were carried out and the proposed method was verified with an average recognition rate of 95% and 82%, respectively. This wrist-wearable tactile display system would be a new and promising medium for communication and could be of great value for visually impaired people.

Activation of liver X receptors prevents emotional and cognitive dysfunction by suppressing microglial M1-polarization and restoring synaptic plasticity in the hippocampus of mice.

Depression is a long-lasting and persistent mood disorder in which the regulatory mechanisms of neuroinflammation are thought to play a contributing role to the physiopathology of the condition. Previous studies have shown that liver X receptors (LXRs) can regulate the activation of microglia and neuroinflammation. However, the role of LXRs in depression remains to be fully understood. In this study, we hypothesized that stress impairs the function of LXRs and that the LXRs agonist GW3965 plays a potential anti-depressive role by inhibiting neuroinflammation. The anti-depressive effects of GW3965 were evaluated in both chronic unpredictable mild stress (CUMS) and lipopolysaccharide (LPS) models. The LXRs antagonist GSK2033 was also employed to block LXRs. Behavioural tests were performed to measure depression-like phenotypes and learning abilities. Electrophysiological recordings and Golgi staining were used to measure the plasticity of the dentate gyrus synapse. The expression of synapse and neuroinflammation related proteins were evaluated by Western blotting and immunofluorescence. The activation of LXRs by GW3965 prevented emotional and cognitive deficits induced by either CUMS or LPS. GW3965 prevented the decreased level of LXR-ß induced by CUMS. The activation of LXRs significantly improved the impairment of synaptic plasticity, prevented the up-regulation of inflammatory factors and inhibited NF-κB phosphorylation and microglial M1-polarization in both models. The antidepressive-like effects of GW3965 were blocked by GSK2033 in the CUMS and LPS models. Our data suggest that inhibition of the LXRs signalling pathway may be a key driver in the pathogenesis of neuroinflammation during depression and that LXRs agonists have a high potential in the treatment of depression.

Down-regulation of MST1 in hippocampus protects against stress-induced depression-like behaviours and synaptic plasticity impairments.

Depression is a common mental disorder, and its main environmental risk factor is chronic stress. The activation of mammalian STE20-like kinase 1 (MST1), a key factor involved in the underlying pathophysiology of stress, can trigger synaptic plasticity impairment, neuronal dysfunction and neuroinflammation. However, it is unclear whether down-regulation of MST1 in the hippocampus protects against stress-induced behavioural dysfunctions. In this study, three mouse models were used to assess the role of MST1 in stress. Various behavioural tests, in vivo electrophysiological recordings, Western blotting, Golgi staining and immunofluorescence assay were used. The data showed that the level of phospho-MST1 (T183) was significantly increased in the hippocampus of mice subjected to chronic unpredictable mild stress (CUMS) and that mice with MST1 overexpression showed depression-like behaviours. Importantly, the impairment of cognitive functions and the hippocampal synaptic plasticity induced by CUMS were significantly improved by MST1 knockdown, suggesting that MST1 down-regulation effectively protected against stress-induced behavioural dysfunctions. Moreover, MST1 knockdown suppressed CUMS-induced microglial activation, reduced the abnormal expression of inflammatory cytokines and impeded the activation of p38, implying that the antidepressant-like effects of MST1 knockdown were associated with inhibiting the p38 pathway. These findings suggest that hippocampal MST1 is an essential regulator of stress, which can be an ideal target for the development of antidepressants in the future.

Recognition and Removal of Amyloid-ß by a Heteromultivalent Macrocyclic Coassembly: A Potential Strategy for the Treatment of Alzheimer's Disease.

The imbalance of amyloid-ß (Aß) production and clearance causes aggregation of Aß1-42 monomers to form fibrils and amyloid plaques, which is an indispensable process in the pathogenesis of Alzheimer's disease (AD), and eventually leads to pathological changes and cognitive impairment. Consequently, Aß1-42 is the most important target for the treatment of AD. However, developing a single treatment method that can recognize Aß1-42 , inhibit Aß1-42 fibrillation, eliminate amyloid plaques, improve cognitive impairments, and alleviate AD-like pathology is challenging. Here, a coassembly composed of cyclodextrin (CD) and calixarene (CA) is designed, and it is used as an anti-Aß therapy agent. The CD-CA coassembly is based on the previously reported heteromultivalent recognition strategy and is able to successfully eliminate amyloid plaques and degrade Aß1-42 monomers in 5xFAD mice. More importantly, the coassembly improves recognition and spatial cognition deficits, and synaptic plasticity impairment in the 5xFAD mice. In addition, the coassembly ameliorates AD-like pathology including prevention of neuronal apoptosis and oxidant stress, and alteration of M1/M2 microglial polarization states. This supramolecular approach makes full use of both molecular recognition and self-assembly of macrocyclic amphiphiles, and is a promising novel strategy for AD treatment.

Legumain Knockout Protects Against Aß1-42-Induced AD-like Cognitive Deficits and Synaptic Plasticity Dysfunction Via Inhibiting Neuroinflammation Without Cleaving APP.

Neuroinflammation is the important pathological feature of Alzheimer's disease (AD). Legumain, a lysosomal cysteine protease, plays an important role in neuroinflammation during ischemic stroke and depressive disorder. Legumain is involved in AD process through cleaving APP; however, it is unclear if legumain can possibly modulate neuroinflammation without cleaving APP in AD. Thus, we established a mouse model of AD by single intracerebroventricular injections of Aß1-42 in legumain knockout (KO) mice. The behavioral tests showed that legumain-KO effectively ameliorated cognitive impairment induced by Aß1-42. Moreover, legumain deprivation significantly improves the synaptic plasticity damages in Aß1-42-treated mice. Moreover, legumain-KO considerably inhibited the activation of microglia and reduced the expression of inflammatory cytokines in the hippocampus of Aß1-42-treated mice. Interestingly, we found that legumain-KO inhibited TLR4/MyD88/NF-κB pathway, which was activated by Aß1-42 in the hippocampus. In conclusion, our results suggested that legumain-KO reduced the level of neuroinflammation that was associated with inhibiting TLR4/MyD88/NF-κB pathways, thereby improving the hippocampal synaptic plasticity and reducing the cognitive impairments in Aß1-42-treated mice. Legumain knockout blocked microglia activation by inhibiting TLR4/MyD88/NF-κB signaling pathways, and further reduced inflammatory cytokine expression. As a result, legumain knockout alleviated synaptic damage and cognitive impairment induced by Aß1--42.

Mesoporous Nanoarchitectures for Electrochemical Energy Conversion and Storage.

Mesoporous materials have attracted considerable attention because of their distinctive properties, including high surface areas, large pore sizes, tunable pore structures, controllable chemical compositions, and abundant forms of composite materials. During the last decade, there has been increasing research interest in constructing advanced mesoporous nanomaterials possessing short and open channels with efficient mass diffusion capability and rich accessible active sites for electrochemical energy conversion and storage. Here, the synthesis, structures, and energy-related applications of mesoporous nanomaterials are the main focus. After a brief summary of synthetic methods of mesoporous nanostructures, the delicate design and construction of mesoporous nanomaterials are described in detail through precise tailoring of the particle sizes, pore sizes, and nanostructures. Afterward, their applications as electrode materials for lithium-ion batteries, supercapacitors, water-splitting electrolyzers, and fuel cells are discussed. Finally, the possible development directions and challenges of mesoporous nanomaterials for electrochemical energy conversion and storage are proposed.

General Formation of Macro-/Mesoporous Nanoshells from Interfacial Assembly of Irregular Mesostructured Nanounits.

Mesoporous core-shell nanostructures with controllable ultra-large open channels in their nanoshells are of great interest. However, soft template-directed cooperative assembly to mesoporous nanoshells with highly accessible pores larger than 30 nm, or even above 50 nm into macroporous range, remains a significant challenge. Herein we report a general approach for precisely tailored coating of hierarchically macro-/mesoporous polymer and carbon shells, possessing highly accessible radial channels with extremely wide pore size distribution from ca. 10 nm to ca. 200 nm, on diverse functional materials. This strategy creates opportunities to tailor the interfacial assembly of irregular mesostructured nanounits on core materials and generate various core-shell nanomaterials with controllable pore architectures. The obtained Fe,N-doped macro-/mesoporous carbon nanoshells show enhanced electrochemical performance for the oxygen reduction reaction in alkaline condition.

Over-expressed MST1 impaired spatial memory via disturbing neural oscillation patterns in mice.

The activated mammalian Ste20-like serine/threonine kinases 1 (MST1) was found in the central nervous system diseases, such as cerebral ischemia, stroke and ALS, which were related with cognitions. The aim of this study was to examine the effect of elevated MST1 on memory functions in C57BL/6J mice. We also explored the underlying mechanism about the pattern alteration of neural oscillations, closely associated with cognitive dysfunctions, at different physiological rhythms, which were related to a wide range of basic and higher-level cognitive activities. A mouse model of the adeno-associated virus (AAV)-mediated overexpression of MST1 was established. The behavioral experiments showed that spatial memory was significantly damaged in MST1 mice. The distribution of either theta or gamma power was clearly disturbed in MST1 animals. Moreover, the synchronization in both theta and gamma rhythms, and theta-gamma cross-frequency coupling were significantly weakened in MST1 mice. In addition, the expressions of GABAA receptor, GAD67 and parvalbumin (PV) were obviously increased in MST1 mice. Meanwhile, blocking MST1 activity could inhibit the activation of FOXO3a and YAP. The above data suggest that MST1-overexpression may induce memory impairments via disturbing the patterns of neural activities, which is possibly associated with the abnormal GABAergic expression level.

Repetitive transcranial magnetic stimulation ameliorates recognition memory impairment induced by hindlimb unloading in mice associated with BDNF/TrkB signaling.

Repetitive transcranial magnetic stimulation (rTMS), which could improve learning and memory, is widely used in psychiatry and neurology as a therapeutic approach. There are few studies reporting effective countermeasures to cognition decline in astronauts during space flight. Accordingly, we examined whether rTMS was able to significantly alleviate the learning and memory deficits induced by hindlimb unloading (HU), a general accepted rodent model to simulate microgravity, in mice. Male C57BL/6 J mice were randomly divided into four groups: Sham, rTMS, HU, and HU + rTMS groups. The hindlimb unloading procedure continued for consecutive 14 days. Meanwhile, high frequency rTMS (15 Hz) was applied for 14 days from the 1st day of HU procedure. The novel object recognition test showed that the recognition memory was evidently impaired in the HU group compared to that in the Sham group, however, rTMS significantly attenuated the impairment of the memory. Furthermore, rTMS significantly improved the HU-induced LTP impairment and increased spine density in the hippocampal dentate gyrus region. Additionally, rTMS enhanced the expressions of postsynaptic function-associated proteins N-methyl-d-aspartic acid receptors (NR2B and NR2 A) and postsynaptic density protein (PSD95), upregulated BDNF/TrkB signaling and increased phosphorylation of protein kinase B (Akt) in the HU + rTMS group. In conclusion, the data suggest that high frequency rTMS may be an effective countermeasure against the learning and memory deficiency, induced by simulated microgravity.

Firefly-Inspired Approach to Develop New Chemiluminescence Materials.

Bioluminescence, wherein marine and terrestrial organisms chemically produce light for communication, is a burgeoning area of research. Herein, we demonstrate a new series of artificial chemiluminescent compounds inspired by the enol-degradation reaction of natural bioluminescent molecules, luciferins. Based on systematic optical experiments, isotope labeling, and theoretical calculations, the chemiluminescent mechanism of these new materials and the relationship of enol-degradation reaction and chemiluminescence are fully discussed. The color and efficiency of the artificial chemiluminescent materials can be easily adjusted, and blue (486 nm), yellow (565 nm), and near-infrared (756 nm) luminescence can thus be obtained. The findings and in-depth understanding herein may accelerate the development of bio/chemiluminescent materials for analytical applications and non-invasive bioluminescence imaging.