Bionic Potassium Ion Channel in Live Cells Repairs Cardiomyocyte Function.

The disturbance of potassium current in cardiac myocytes caused by potassium channel dysfunction can lead to cardiac electrophysiological disorders, resulting in associated cardiovascular diseases. The emergence of artificial potassium ion channels opens up a way to replace dysfunctional natural ion channels and cure related diseases. However, bionic potassium ion channels have not been introduced into living cells to regulate cell function. One of the biggest challenges is that when the bionic channel fuses with the cell, it is difficult to control the inserting angle of the bionic potassium channel to ensure its penetration of the entire cell membrane. In nature, the extracellular vesicles can fuse with living cells with a completely preserved structure of vesicle protein. Inspired by this, we developed a vesicle fusion-based bionic porin (VFBP), which integrates bionic potassium ion channels into cardiomyocytes to replace damaged potassium ion channels. Theoretical and experimental results show that the inserted bionic ion channels have a potassium ion transport rate comparable to that of natural ion channels, which can restore the potassium ion outflow in cardiomyocytes and repair the abnormal action potential and excitation-contraction coupling of cardiomyocytes. Therefore, the bionic potassium ion channel system based on membrane fusion is expected to become the research object in many fields such as ultrafast ion transport, transmembrane delivery, and channelopathies treatment.

A Radical Activation Strategy for Versatile and Stereoselective N-Glycosylation.

Previous N-glycosylation approaches have predominately involved acidic conditions, facing challenges of low stereoselectivity and limited scope. Herein, we introduce a radical activation strategy that enables versatile and stereoselective N-glycosylation using readily accessible glycosyl sulfinate donors under basic conditions and exhibits exceptional tolerance towards various N-aglycones containing alkyl, aryl, heteroaryl and nucleobase functionalities. Preliminary mechanistic studies indicate a pivotal role of iodide, which orchestrates the formation of a glycosyl radical from the glycosyl sulfinate and subsequent generation of the key intermediate, a configurationally well-defined glycosyl iodide, which is subsequently attacked by an N-aglycone in a stereospecific SN2 manner to give the desired N-glycosides. An alternative route involving the coupling of a glycosyl radical and a nitrogen-centered radical is also proposed, affording the exclusive 1,2-trans product. This novel approach promises to broaden the synthetic landscape of N-glycosides, offering a powerful tool for the construction of complex glycosidic structures under mild conditions.

A radiomics feature-based machine learning models to detect brainstem infarction (RMEBI) may enable early diagnosis in non-contrast enhanced CT.

OBJECTIVES: Magnetic resonance imaging has high sensitivity in detecting early brainstem infarction (EBI). However, MRI is not practical for all patients who present with possible stroke and would lead to delayed treatment. The detection rate of EBI on non-contrast computed tomography (NCCT) is currently very low. Thus, we aimed to develop and validate the radiomics feature-based machine learning models to detect EBI (RMEBIs) on NCCT. METHODS: In this retrospective observational study, 355 participants from a multicentre multimodal database established by Huashan Hospital were randomly divided into two data sets: a training cohort (70%) and an internal validation cohort (30%). Fifty-seven participants from the Second Affiliated Hospital of Xuzhou Medical University were included as the external validation cohort. Brainstems were segmented by a radiologist committee on NCCT and 1781 radiomics features were automatically computed. After selecting the relevant features, 7 machine learning models were assessed in the training cohort to predict early brainstem infarction. Accuracy, sensitivity, specificity, positive predictive value, negative predictive value, F1-score, and the area under the receiver operating characteristic curve (AUC) were used to evaluate the performance of the prediction models. RESULTS: The multilayer perceptron (MLP) RMEBI showed the best performance (AUC: 0.99 [95% CI: 0.96-1.00]) in the internal validation cohort. The AUC value in external validation cohort was 0.91 (95% CI: 0.82-0.98). CONCLUSIONS: RMEBIs have the potential in routine clinical practice to enable accurate computer-assisted diagnoses of early brainstem infarction in patients with NCCT, which may have important clinical value in reducing therapeutic decision-making time. KEY POINTS: • RMEBIs have the potential to enable accurate diagnoses of early brainstem infarction in patients with NCCT. • RMEBIs are suitable for various multidetector CT scanners. • The patient treatment decision-making time is shortened.

Contralesional macrostructural plasticity in patients with frontal low-grade glioma: a voxel-based morphometry study.

PURPOSE: Neuroplasticity can partially compensate for the neurological deficits caused by brain tumors. However, the structural plasticity of the brain caused by brain tumors is not fully understood. This study aimed to assess the structural plasticity of the contralesional hemisphere in patients with frontal low-grade gliomas (LGGs). METHODS: A total of 25 patients with left frontal LGGs (LFLGGs), 19 patients with right frontal LGGs (RFLGGs), and 25 healthy controls (HCs) were enrolled in this study. High-resolution structural T1-weighted imaging and fluid attenuation inversion recovery were performed on all participants. Voxel-based morphometry (VBM) analysis was used to detect differences in the brain structural plasticity between patients with unilateral LGGs and HCs. RESULTS: VBM analysis revealed that compared with HCs, the gray matter volume (GMV) of the contralesional putamen and amygdala was significantly smaller and larger in the patients with RFLGGs and LFLGGs, respectively, while the GMVs of the contralesional cuneus and superior temporal gyrus (STG) were significantly larger in the patients with LFLGGs. The surviving clusters of the right hemisphere included 1357 voxels in the amygdala, 1680 voxels in the cuneus, 384 voxels in the STG, and 410 voxels in the putamen. The surviving clusters of the left hemisphere were 522 voxels in the amygdala and 320 voxels in the putamen. CONCLUSION: The unilateral frontal LGGs are accompanied by structural plasticity in the contralesional cortex and vary with tumor laterality. Contralesional structural reorganization may be one of the physiological basis for functional reorganization or compensation in the frontal LGGs.

Bioaugmentation of intertidal sludge enhancing the development of salt-tolerant aerobic granular sludge.

Three parallel bioreactors were operated with different inoculation of activated sludge (R1), intertidal sludge (ItS) (R2), and ItS-added AS (R3), respectively, to explore the effects of ItS bioaugmentation on the formation of salt-tolerant aerobic granular sludge (SAGS) and the enhancement of COD removal performance. The results showed that compared to the control (R1-2), R3 promoted a more rapid development of SAGS with a cultivation time of 25 d. Following 110-day cultivation, R3 exhibited a higher granular diameter of 1.3 mm and a higher hydrophobic aromatic protein content than that in control. Compared to the control, the salt-tolerant performance in R3 was also enhanced with the COD removal efficiency of 96.4% due to the higher sludge specific activity of 14.4 g·gVSS-1·d-1 and the salinity inhibition constant of 49.3 gL-1. Read- and genome-resolved metagenomics together indicated that a higher level of tryptophan/tyrosine synthase gene (trpBD, tyrBC) and enrichment of the key gene hosts Rhodobacteraceae, Marinicella in R3, which was about 5.4-fold and 1.4-fold of that in control, could be the driving factors of rapid development of SAGS. Furthermore, the augmented salt-tolerant potential in R3 could result from that R1 was dominated by Rhodospirillaceae, Bacteroidales, which carried more trehalose synthase gene (otsB, treS), while the dominant members Rhodobacteraceae, Marinicella in R3 were main contributors to the glycine betaine synthase gene (ectC, betB, gbsA). This study could provide deeper insights into the rapid development and improved salt-tolerant potential of SAGS via bioaugmentation of intertidal sludge, which could promote the application of hypersaline wastewater treatment.

Dynamic changes of IgM and IgG antibodies in asymptomatic patients as an effective way to detect SARS-CoV-2 infection.

BACKGROUND: COVID-19 has become a global pandemic, and close contacts and asymptomatic patients are worthy of attention. METHODS: A total of 1844 people in close contacts with 76 COVID-19 patients were investigated, and nasopharyngeal swabs and venous blood were collected for centralized medical quarantine observation. Real-time fluorescence was used to detect SARS-CoV-2 nucleic acid in nasopharyngeal swabs of all close contacts, and the colloidal gold method was used to detect serum-specific antibodies. Levels of IgM- and IgG-specific antibodies were detected quantitatively through chemiluminescence from the first nucleic acid turned negative date (0 week) and on weekly intervals of ≤1 week, 1-2 weeks, 2-3 weeks, 3-4 weeks, 4-5 weeks, 5-6 weeks, and 6-7 weeks. RESULTS: The total positive rate of the colloidal gold method (88.5%, 23/26) was significantly higher (χ2  = 59.182, p < 0.001) than that of the healthy control group (2.0%, 1/50). There was significant difference in IgG concentration at different time points (0-7 weeks) after negative nucleic acid conversion (χ2  = 14.034, p = 0.029). Serum IgG levels were significantly higher at weekly time points of 4-5 weeks (Z = -2.399, p = 0.016), 5-6 weeks (Z = -2.049, p = 0.040), and 6-7 weeks (Z = -2.197, p = 0.028) compared with 1-2 weeks after negative nucleic acid conversion. However, there was no significant difference (χ2  = 4.936, p = 0.552) in IgM concentration between time points tested (0-7 weeks) after negative nucleic acid conversion. The positive rates of IgM and IgG in asymptomatic patients (χ2  = 84.660, p < 0.001) were significantly higher than those in the healthy control group (χ2  = 9.201, p = 0.002) within 7 weeks of negative nucleic acid conversion. CONCLUSIONS: The IgG concentration in asymptomatic cases remained at a high level after nucleic acid turned negative. Nucleic acid detection combined with IgM and IgG antibody detection is an effective way to screen asymptomatic infections.

Non-Metal-Doped Porous Carbon Nitride Nanostructures for Photocatalytic Green Hydrogen Production.

Photocatalytic green hydrogen (H2) production through water electrolysis is deemed as green, efficient, and renewable fuel or energy carrier due to its great energy density and zero greenhouse emissions. However, developing efficient and low-cost noble-metal-free photocatalysts remains one of the daunting challenges in low-cost H2 production. Porous graphitic carbon nitride (gCN) nanostructures have drawn broad multidisciplinary attention as metal-free photocatalysts in the arena of H2 production and other environmental remediation. This is due to their impressive catalytic/photocatalytic properties (i.e., high surface area, narrow bandgap, and visible light absorption), unique physicochemical durability, tunable electronic properties, and feasibility to synthesize in high yield from inexpensive and earth-abundant resources. The physicochemical and photocatalytic properties of porous gCNs can be easily optimized via the integration of earth-abundant heteroatoms. Although there are various reviews on porous gCN-based photocatalysts for various applications, to the best of our knowledge, there are no reviews on heteroatom-doped porous gCN nanostructures for the photocatalytic H2 evolution reaction (HER). It is essential to provide timely updates in this research area to highlight the research related to fabrication of novel gCNs for large-scale applications and address the current barriers in this field. This review emphasizes a panorama of recent advances in the rational design of heteroatom (i.e., P, O, S, N, and B)-doped porous gCN nanostructures including mono, binary, and ternary dopants for photocatalytic HERs and their optimized parameters. This is in addition to H2 energy storage, non-metal configuration, HER fundamental, mechanism, and calculations. This review is expected to inspire a new research entryway to the fabrication of porous gCN-based photocatalysts with ameliorated activity and durability for practical H2 production.

Monitoring Mitophagy via the FRET Mechanism: Visualizing Mitochondria, Lysosomes, and Autolysosomes in Three Different Sets of Fluorescence Signals.

Mitophagy is a vital biological process playing central roles in the regulation of metabolic activity and quality control of mitochondria. The presented dual-color fluorescent probes to directly monitor mitophagy were based on the optical response to pH change during mitophagy, but pH fluctuation may lead to interference. To overcome this, herein, two fluorescent probes (G-Mito, R-Lyso) were rationally designed to visualize mitophagy directly in a dual-color manner, relying on the Förster resonance energy transfer (FRET) process for the first time. Green emissive G-Mito targeted and anchored the mitochondria via reaction with protein thiols. Red-emissive R-Lyso exclusively targeted lysosomes. Live cells loaded with the two probes demonstrated strong fluorescence in only the green channel with excitation at 405 nm. After mitophagy, G-Mito in mitochondria was delivered into the lysosomes, and red fluorescence evidently increased due to the FRET process. With the probes, mitochondria, lysosomes, and autolysosomes could be discriminatively visualized in three different sets of signals. Mitophagy induced by starvation and in normal physiological status were successfully observed. The probes revealed that a certain amount of H2O2 could induce mitophagy. We expect that the two probes can serve as molecular tools for validation of mitophagy and promote the development of related areas.

Changes of serum IL-10, IL-1ß, IL-6, MCP-1, TNF-α, IP-10 and IL-4 in COVID-19 patients.

BACKGROUND AND PURPOSE: Studies have shown that some cytokines in COVID-19 patients were elevated. This study aims to assess whether IL-10, IL-1ß, IL-6, MCP-1, TNF-α, IP-10 and IL-4 serve as potential diagnostic biomarkers of COVID-19. METHODS: The above serum cytokines in COVID-19 patients and non-COVID-19 patients were detected by ELISA and SARS-CoV-2 IgM and IgG were detected by the chemiluminescence method. The independent-sample Mann-Whitney U test was utilised to compare cytokine levels in different groups and courses, the Levene T-test and T'-test were utilised to compare they in different genders and the Spearman correlation test was utilised to analyse the correlation between the cytokine levels with ages and SARS-CoV-2 IgG and IgM. RESULTS: Serum levels of IL-10, IL-1ß, MCP-1, TNF-α and IL-4 in COVID-19 patients were significantly higher than those in non-COVID-19 patients, while IL-6 were only significantly higher than in healthy people, IP-10 were significantly lower than in other diseases patients. AUCs of COVID-19 diagnosed by IL-10, IL-1ß, IL-6, MCP-1, TNF-α, IP-10 and IL-4 were 0.735, 0.775, 0.595, 0.821, 0.848, 0.38 and 0.682, respectively. In the COVID-19 patients' serum, the levels of IL-10 and MCP-1 of male were noticeably higher than those of female, and all cytokines were significantly positively correlated with age, IL-1ß and IL-4 were significantly negatively correlated with SARS-CoV-2 IgM, while IL-10, IL-1ß, IL-6, TNF- and IP-10 were significantly negatively correlated with SARS-CoV-2 IgG. IL-10 on 43-56 days was significantly lower than at 29-42 days, TNF-α at 15-42 days was significantly higher than at 0-14 days, IP-10 at 0-14 days was the highest and IL-4 at 29-42 days was significantly higher than at 0-14 days. CONCLUSIONS: The detection of IL-10, IL-1 ß, IL-6, MCP-1, TNF-α and IL-4 would assist the clinical study of COVID-19, and IP-10 may be the cytokine of early elevation in COVID-19 patients.

Probing antiviral drugs against SARS-CoV-2 through virus-drug association prediction based on the KATZ method.

It is urgent to find an effective antiviral drug against SARS-CoV-2. In this study, 96 virus-drug associations (VDAs) from 12 viruses including SARS-CoV-2 and similar viruses and 78 small molecules are selected. Complete genomic sequence similarity of viruses and chemical structure similarity of drugs are then computed. A KATZ-based VDA prediction method (VDA-KATZ) is developed to infer possible drugs associated with SARS-CoV-2. VDA-KATZ obtained the best AUCs of 0.8803 when the walking length is 2. The predicted top 3 antiviral drugs against SARS-CoV-2 are remdesivir, oseltamivir, and zanamivir. Molecular docking is conducted between the predicted top 10 drugs and the virus spike protein/human ACE2. The results showed that the above 3 chemical agents have higher molecular binding energies with ACE2. For the first time, we found that zidovudine may be effective clues of treatment of COVID-19. We hope that our predicted drugs could help to prevent the spreading of COVID.

Assessment of heavy metal pollution and ecological risk in river water and sediments in a historically metal mined watershed, Northeast Japan.

Mining legacies continue to impact the geochemical cycles in historically mined watersheds after mine closure. The Hokuroku District in Northeast Japan is a famous metal mining area with a long mining history; however, studies on the distribution mechanisms and pollution characteristics of heavy metals in these historically mined watersheds after the boom period of mining activities are lacking. This study aims to provide fundamental insights into the effects of the mining activities and hydrological conditions on heavy metal pollution in the Kosaka watershed, Hokuroku District. Sampling was performed in terms of watershed segmentation, and the outlet of the tributary within each sub-watershed was also sampled to capture the diffusional pollution status. The distributions of Zn, Cu, Cd, Pb and As in river water and sediments, as well as their pollution characteristics and ecological risks, were analysed under different hydrological conditions. Our findings provide evidence of the ecological risk in surface water induced by Zn, Cu and Pb pollution in the Kosaka River system. In a high proportion of the sub-watershed, there was moderate to strong enrichment in Cd, Cu and Zn in the river sediments. The sub-watersheds with high pollution levels and ecological risk were highly consistent with the sub-watersheds encompassing abandoned mine sites. Suspended particles carried large amounts of Pb and Cu, especially on rainy days. The heavy metal contents in river water were very sensitive to occasional rainfall events; rainy days posed the most risk to organisms in the Kosaka River, followed by the low-water-level season and the high-water-level season.

Identifying the Activation Mechanism and Boosting Electrocatalytic Activity of Layered Perovskite Ruthenate.

SrRuO3 as a rare conductive perovskite ruthenate has attracted increasing attention for application in energy conversion. Here, the electrocatalytic activity for the hydrogen evolution reaction (HER) of thermally synthesized layered SrRuO3 is investigated and shows a considerable activation during cathodic polarization in alkaline solution. The analysis demonstrates the electrode activation is caused by the increased hydrophilicity of SrRuO3 surface, revealing the influence of the surface properties on HER performance. For further improving the catalytic activity of perovskite ruthenate, the RuO2 /SrRuO3 (RSRO) heterostructure is fabricated in situ by reducing the thermal decomposition temperature of 1000 °C for SrRuO3 to 600 °C. The appropriate lattice parameter of SrRuO3 ensures a good lattice match, which results in a strong interaction between SrRuO3 and RuO2 . Hence, the RSRO substantially outperforms the corresponding single-component oxides. In addition, the increased active sites induced by the rapid improvement of hydrophilicity of RSRO surface further highlight its structural advantage for catalytic hydrogen generation. The experimental and theoretical computation results consistently validate the positive synergistic effect among SrRuO3 and RuO2 in tuning the atomic and electronic configuration.

Dual-Wavelength Ratiometric Electrochemiluminescence Immunosensor for Cardiac Troponin I Detection.

Ratiometric electrochemiluminescence (ECL) has attracted special focus in the biological analysis field, because it could eliminate the environmental interference and allow for precise measurement. Herein, a dual-wavelength ratiometric ECL biosensor was designed for the detection of cardiac troponin I (cTnI), where (4,4'-dicarboxylic acid-2,2'-bipyridyl) ruthenium(II) (Ru(dcbpy)32+) and Au nanoparticle-loaded graphene oxide/polyethylenimine (GPRu-Au) nanomaterial acts as an acceptor, and Au nanoparticle-modified graphitic phase carbon nitride nanosheet composite (Au-CNN) acts as donor. Au-CNN shows a high and steady ECL signal centered at 455 nm, which is well-matched with the adsorption of GPRu-Au; thereby, a highly efficient electrochemiluminescent resonance energy transfer (ECL-RET) sensing platform is designed. AuNPs facilitate the immobilization of antibody on the nanomaterials through a Au-N bond. The high surface area of graphene oxide/polyethylenimine allows a large number of Ru(dcbpy)32+ to be loaded, immensely amplifying the ECL signal. This sensing platform exhibits outstanding analytical performance toward cTnI with a detection limit of 3.94 fg/mL (S/N = 3). The high reliability, selectivity, and sensitivity of this ratiometric ECL biosensor provides a versatile sensing platform for the bioanalysis.

Detection of the planetary boundary layer height by employing the Scheimpflug lidar technique and the covariance wavelet transform method.

A portable Scheimpflug lidar system has been employed for atmospheric boundary layer studies. Atmospheric backscattering signals were continuously recorded from 21 August to 28 August 2018. The covariance wavelet transform (CWT) method was utilized to identify the maximum gradient of recorded lidar curves as the planetary boundary layer (PBL) height. As the directly retrieved PBL height could be underestimated or overestimated due to the presence of residual layers and thin clouds, localized atmospheric turbulence, aerosol stratification, etc., a CWT-based quality-control algorithm has also been developed to improve the reliability of the PBL height retrieval. The temporal distribution of the final PBL height has shown a clear diurnal variation as the ambient temperature changed due to the increasing and decreasing of surface heating during a one-week continuous measurement campaign. The promising results have shown great potential in employing the Scheimpflug lidar technique and the CWT-based method in the determination of the PBL height.

Cobalt Sulfide Nanowires Core Encapsulated by a N, S Codoped Graphitic Carbon Shell for Efficient Oxygen Reduction Reaction.

Exploration of economical electrocatalysts for highly efficient and stable oxygen reduction reaction (ORR) is believed to be essential for diverse future renewable energy applications. Herein, cobalt sulfide nanowire core encapsulated in a N, S codoped graphitic carbon shell (CoS NWs@NSC) is successfully fabricated via the calcination of polydopamine-coated Co(CO3 )0.5 (OH)0.11 H2 O NWs with sulfur powder under argon atmosphere. The uniform encapsulation of CoS core by N, S codoped graphitic carbon shell favors the interaction of the core-shell structure for generating stable and numerous ORR active sites homogeneously dispersed throughout the materials. Meanwhile, the wire-like CoS NWs@NSC stacks to form 3D mesoporous conductive networks, which improves the mass and charge transport capability of catalyst. Accordingly, the resultant CoS NWs@NSC electrocatalysts possess excellent ORR activity through the four-electron pathway with superior stability and methanol tolerance over the Pt/C in 0.1 m KOH. This strategy can offer inspiration for designing and fabricating novel core-shell-structured nanomaterials with active sites derived from uniform morphology as potential electrocatalysts for various vital renewable energy devices.

A polarity-responsive lysosomes-nucleus translocation probe for the dual-emissive visualization of cell apoptosis.

Visualization of cell apoptosis is a critical task playing central roles in the fundamental studies in biology, pathology, and biomedicine. Dual-emissive fluorescent probes are desired molecular tools for study on apoptosis, which however were rarely reported. Herein, utilizing the polarity differences between lysosomes and nucleus, a translocation type of fluorescent probe (NA-S) was developed for the dual-color visualization of cell apoptosis. NA-S was designed to be polarity sensitive, bearing alkalescence group, and with DNA affinity. In living cells, NA-S targeted the lysosomes to give blue fluorescence, which translocated into the nucleus during cell apoptosis to give green emission. Thereby, the cell apoptosis could be visualized with NA-S in dual-emissive manner. With the unique probe, the cell apoptosis induced by oxidative stress, UV irradiation, rotenone, colchicine, and paclitaxel have been successfully visualized.

Protocol to induce neurodegeneration in a local area of the mouse brain by stereotaxic injection.

In vivo models of brain pathology are crucial for studying neurological diseases. Here, we present a protocol to induce a pathological condition in a mouse brain area by local injection of neurotoxic stimulus. We describe steps for preparing reagents, stereotaxic injection procedures to induce neurodegeneration in the hippocampus, and preparation of brain sections to examine the induced model. This protocol is useful for studying how local pathology affects other brain areas and neighbor cells and its functional consequences in behavior. For complete details on the use and execution of this protocol, please refer to Zhang et al.1.

Unique fluorescent probe for the recognition of late apoptosis via translocation from plasma membrane to nucleus.

Cell apoptosis is a crucial physiological process playing central roles in key biological and pathological activities. However, the current fluorescent probes for the detection of late apoptosis were "off-on" probes, which were facilely interfered by false positive signals caused by inhomogeneous staining and other factors. Herein, a unique fluorescent probe (NPn) discriminating late apoptosis from early apoptosis and heathy status with two different sets of fluorescent signals have been prepared, to overcome the possible false positive signals. NPn was designed impermeable to biomembranes and simultaneously with high affinity to DNA/RNA, which localized on the plasma membranes of living and early apoptotic cells, while relocated to the nucleus in late apoptotic cells. The hydrophilic amine unit and small ion radius were responsive for its membrane impermeability, which was confirmed with two control molecules without amine group. Using the probe, we have successfully evaluated the cell apoptosis induced by ultraviolet irradiation, rotenone, colchicine, and paclitaxel, demonstrating its potential application in biological researches.