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Ethyl ferulate (EF) is abundant in Rhizoma Chuanxiong and grains (e.g., rice and maize) and possesses antioxidative, antiapoptotic, antirheumatic, and anti-inflammatory properties. However, its effect on lipopolysaccharide (LPS)-induced acute lung injury (ALI) is still unknown. In the present study, we found that EF significantly alleviated LPS-induced pathological damage and neutrophil infiltration and inhibited the gene expression of proinflammatory cytokines (TNF-α, IL-1β, and IL-6) in murine lung tissues. Moreover, EF reduced the gene expression of TNF-α, IL-1β, IL-6, and iNOS and decreased the production of NO in LPS-stimulated RAW264.7 cells and BMDMs. Mechanistic experiments revealed that EF prominently activated the AMPK/Nrf2 pathway and promoted Nrf2 nuclear translocation. AMPK inhibition (Compound C) and Nrf2 inhibition (ML385) abolished the beneficial effect of EF on the inflammatory response. Furthermore, the protective effect of EF on LPS-induced ALI was not observed in Nrf2 knockout mice. Taken together, the results of our study suggest that EF ameliorates LPS-induced ALI in an AMPK/Nrf2-dependent manner. These findings provide a foundation for developing EF as a new anti-inflammatory agent for LPS-induced ALI/ARDS therapy. [Image: see text]

Dan Chen,1,* Zhi-qi Gao,1,* Ying-ying Wang,1 Bin-bin Wan,1 Gang Liu,1 Jun-liang Chen,1 Ya-xian Wu,1 Qin Zhou,2 Shan-yu Jiang,2 Ren-qiang Yu,2 Qing-feng Pang1 1Department of Physiopathology, Wuxi School of Medicine, Jiangnan University, Wuxi, 214122, Jiangsu Province, People’s Republic of China; 2Department of Neonatology, The Affiliated Wuxi Maternity and Child Health Care Hospital of Nanjing Medical University, Wuxi, 214002, Jiangsu Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ren-qiang Yu 48 Huaishu Lane, Liangxi District, Wuxi, Jiangsu Province, People’s Republic of ChinaTel +86510-82709790Fax +86-510-82725094Email yurenqiang553@163.comQing-feng Pang 1800 Lihu Avenue, Binhu District, Wuxi, Jiangsu Province, People’s Republic of ChinaTel +8651052430172Fax +86-510-85329042Email qfpang@jiangnan.edu.cnBackground: Alveolar arrest and the impaired angiogenesis caused by chronic inflammation and oxidative stress are two main factors in bronchopulmonary dysplasia (BPD). Short-chain fatty acids (SCFAs), especially propionate, possess anti-oxidant and anti-inflammatory effects. The present study was designed to examine the roles of sodium propionate (SP) on lipopolysaccharide (LPS)-challenged BPD and its potential mechanisms.Methods: WT, Nrf2-/- mice and pulmonary microvascular endothelial cells (HPMECs) were used in this study. LPS was performed to mimic BPD model both in vivo and vitro. Lung histopathology, inflammation and oxidative stress-related mRNA expressions in lungs involved in BPD pathogenesis were investigated. In addition, cell viability and angiogenesis were also tested.Results: The increased nuclear factor erythroid 2-related factor (Nrf2) and decreased Kelch-like ECH-associated protein-1 (Keap-1) expressions were observed after SP treatment in the LPS-induced neonatal mouse model of BPD. In LPS-induced wild-type but not Nrf2-/- neonatal mice, SP reduced pulmonary inflammation and oxidative stress and exhibited obvious pathological alterations of the alveoli. Moreover, in LPS-evoked HPMECs, SP accelerated Nrf2 nuclear translocation presented and exhibited cytoprotective and pro-angiogenesis effects. In addition, SP diminished the LPS-induced inflammatory response by blocking the activation of nuclear factor-kappa B pathway. Moreover, pretreatment with ML385, an Nrf2 specific inhibitor, offsets the beneficial effects of SP on inflammation, oxidative stress and angiogenesis in LPS-evoked HPMECs.Conclusion: SP protects against LPS-induced lung alveolar simplification and abnormal angiogenesis in neonatal mice and HPMECs in an Nrf2-dependent manner.Keywords: sodium propionate, lipopolysaccharide, Nrf2, angiogenesis, bronchopulmonary dysplasia

Indole-3-acetic acid (IAA) plays an important role in the growth and development of plants. In this study, a series of predominant strains were isolated and identified as Enterobacter sp. with remarkable IAA-producing capabilities. The IAA-producing strains are mainly tryptophan-dependent and have significantly high yields of IAA (3477 μg mL−1 and 3378 μg mL−1). The ipdC gene encoding indole-3-pyruvate decarboxylase was identified by genomic analysis and RT-qPCR analysis, indicating the involvement of the indole-3-pyruvic acid (IPyA) pathway of IAA biosynthesis. The IPyA pathway was also confirmed by the intermediate assay. The IAA product of microbial metabolites was isolated, purified and characterized. These microbes exhibiting IAA production significantly promoted the growth of maize, increasing root length, plant height, fresh weight and dry weight. Thus, Enterobacter sp. with high IAA production has great prospects in agricultural and industrial applications.

Highly selective activation of multiple sites of C–H bonds in a complex organic compound is a huge challenge. Herein, diverse novel fused polycyclic- and multi-substituted 2-oxyl naphthalene benzimidazole derivatives were selectively synthesized via Rh(III)-catalyzed tandem C–H activation/cyclization. The efficient strategy for the construction of diverse annulation products was precisely controlled by changing the reaction conditions.

The α‐mannosidase Ams1 is involved in catabolism of oligosaccharides and is transported from the cytoplasm into vacuoles by selective autophagy pathways in yeasts. The cryo‐EM structure of S. pombe Ams1 determined at 3.2 Å resolution reveals the detailed interactions mediating tetramerization, the configuration of the active site, and the differences with a low‐resolution structure of S. cerevisiae Ams1., Fungal α‐mannosidase Ams1 and its mammalian homolog MAN2C1 hydrolyze terminal α‐linked mannoses in free oligosaccharides released from misfolded glycoproteins or lipid‐linked oligosaccharide donors. Ams1 is transported by selective autophagy into vacuoles. Here, we determine the tetrameric structure of Ams1 from the fission yeast Schizosaccharomyces pombe at 3.2 Å resolution by cryo‐electron microscopy. Distinct from a low resolution structure of S. cerevisiae Ams1, S. pombe Ams1 has a prominent N‐terminal tail that mediates tetramerization and an extra β‐sheet domain. Ams1 shares a conserved active site with other enzymes in glycoside hydrolase family 38, to which Ams1 belongs, but contains extra N‐terminal domains involved in tetramerization. The atomic structure of Ams1 reported here will aid understanding of its enzymatic activity and transport mechanism.

Phosphate-solubilizing microorganisms have been considered as a novel alternative approach to provide phosphate fertilizers that promote plant growth. In this study, three strains were isolated and identified as Penicillium oxalicum FJG21, Penicillium oxalicum FJQ5, and Bacillus subtilis BPM12, with a relatively high phosphate-solubilizing activity. Various phosphate sources were investigated, and Ca3(PO4)2 was identified as the effective phosphate source. Factors governing the phosphate-solubilizing activity of the strains included carbon and nitrogen sources, initial pH, and fermentation time. A high soluble phosphorus content was achieved with 529.0 μg·mL-1, 514.0 μg·mL-1, and 330.7 μg·mL-1 for Penicillium oxalicum FJG21, Penicillium oxalicum FJQ5, and Bacillus subtilis BPM12, respectively. An inverse correlation of the quantity of soluble phosphorus content and the pH value of the medium was observed. In addition, Bacillus subtilis BPM12 displayed a prominent capability of producing indole acetic acid. Penicillium oxalicum FJG21 and Penicillium oxalicum FJQ5 exhibited high cellulase activities. These phosphate-solubilizing microorganisms with good phosphate-solubilizing capability and growth-promoting ability are the promising strains for agricultural utilization.

In this study, nano-sized SnO2 decorated on carbon cloth (SnO2/CC) is prepared through a simple and facile solid method. The nano-sized SnO2 is uniformly distributed on the surface of carbon fibers in carbon cloth, providing sufficient free space to relieve volume expansion and reduce electrode pulverization during cycling. The as-prepared SnO2/CC as a flexible, self-supporting and additive-free anode electrode for sodium-ion/lithium-ion batteries (SIBs/LIBs) can demonstrate outstanding electrochemical performance. SnO2/CC after annealing at 350 °C (SC-350) as an anode for SIBs can deliver a reversible capacity of 0.587 mA h cm−2 at the current density of 0.3 mA cm−2 after 100 cycles. In addition, when cycling at 1.5 mA cm−2, SC-350 can maintain 1.69 mA h cm−2 after 500 cycles when used as LIB anode. These results illustrate that the as-prepared SnO2/CC can be a promising flexible anode material for flexible SIBs/LIBs and provide a simple and practical method for designing new flexible electrode materials.

Background Lignocellulosic biomass upgrading has become a promising alternative route to produce transportation fuels in response to energy security and environmental concerns. As the second most abundant polysaccharide in nature, hemicellulose mainly containing xylose is an important carbon source that can be used for the bioconversion to fuels and chemicals. However, the adaptation phenomena could appear and influence the bioconversion performance of xylose when Saccharomyces cerevisiae strain was transferred from the glucose to the xylose environment. Therefore, it is crucial to elucidate the mechanism of this adaptation phenomena, which can guide the strategy exploration to improve the efficiency of xylose utilization. Results In this study, xylose-utilizing strains had been constructed to effectively consume xylose. It is found that the second incubation of yYST218 strain in synthetic complete-xylose medium resulted in a 1.24-fold increase in xylose consumption ability as compared with the first incubation in synthetic complete-xylose medium. The results clearly showed that growing S. cerevisiae again in synthetic complete-xylose medium can significantly reduce the stagnation time and thus achieved a faster growth rate, by comparing the growth status of the strain in synthetic complete-xylose medium for the first and second time at the single-cell level through Microfluidic technology. Although these xylose-utilizing strains possessed different xylose metabolism pathways, they exhibited the “transient memory” phenomenon of xylose metabolism after changing the culture environment to synthetic complete-xylose medium, which named ‘xylose consumption memory (XCM)’ of S. cerevisiae in this study. According to the identification of protein acetylation, partial least squares analysis and the confirmatory test had verified that H4K5Ac affected the state of “XCM” in S. cerevisiae. Knockout of the acetylase-encoding genes GCN5 and HPA2 enhanced the “XCM” of the strain. Protein acetylation analysis suggested that xylose induced perturbation in S. cerevisiae stimulated the rapid adaptation of strains to xylose environment by regulating the level of acetylation. Conclusions All these results indicated protein acetylation modification is an important aspect that protein acetylation regulated the state of “XCM” in S. cerevisiae and thus determine the environmental adaptation of S. cerevisiae. Systematically exploiting the regulation approach of protein acetylation in S. cerevisiae could provide valuable insights into the adaptation phenomena of microorganisms in complex industrial environments.

Phycospheric bacteria may be the key biological factors affecting the growth of algae. However, the studies about interaction between Isochrysis galbana and its phycospheric bacteria are limited. Here, we show that a marine heterotrophic bacterium, Alteromonas macleodii, enhanced the growth of I. galbana, and inhibited non-photochemical quenching (NPQ) and superoxide dismutase (SOD) activities of this microalgae. Further, we explored this phenomenon via examining how the entire transcriptomes of I. galbana changed when it was co-cultured with A. macleodii. Notable increase was observed in transcripts related to photosynthesis, carbon fixation, oxidative phosphorylation, ribosomal proteins, biosynthetic enzymes, and transport processes of I. galbana in the presence of A. macleodii, suggesting the introduction of the bacterium might have introduced increased production and transport of carbon compounds and other types of biomolecules. Besides, the transcriptome changed largely corresponded to reduced stress conditions for I. galbana, as inferred from the depletion of transcripts encoding DNA repair enzymes, superoxide dismutase (SOD) and other stress-response proteins. Taken together, the presence of A. macleodii mainly enhanced photosynthesis and biosynthesis of I. galbana and protected it from stress, especially oxidative stress. Transfer of fixed organic carbon, but perhaps other types of biomolecules, between the autotroph and the heterotroph might happen in I. galbana-A. macleodii co-culture. The present work provides novel insights into the transcriptional consequences of I. galbana of mutualism with its heterotrophic bacterial partner, and mutually beneficial associations existing in I. galbana-A. macleodii might be explored to improve productivity and sustainability of aquaculture algal rearing systems.

Misplaced or excessive hypochlorous acid in lysosomes has a close association with lots of diseases, so monitoring hypochlorous acid in lysosomes is particularly necessary. In the present work, a novel lysosome-targetable fluorescent probe (Lyso-R-HClO) for hypochlorous acid based on a HClO-mediated cyclization reaction was developed. In the fluorescent probe, the morpholine unit and the site of a HClO-mediated cyclization reaction were, respectively, used as the lysosome-targetable group and the response group. The probe has high selectivity and high sensitivity to hypochlorous acid, with a linear range from 5.0 × 10

Pulmonary endothelial cell dysfunction plays an important role in ionizing radiation (IR)-induced lung injury. Whether pulmonary endothelial cell ferroptosis occurs after IR and what are the underlying mechanisms remain elusive. Here, we demonstrate that 15-Gy IR induced ferroptosis characterized by lethal accumulation of reactive oxygen species (ROS), lipid peroxidation, mitochondria shrinkage, and decreased glutathione peroxidase 4 (GPX4) and SLC7A11 expression in pulmonary endothelial cells. The phenomena could be mimicked by Yoda1, a specific activator of mechanosensitive calcium channel PIEZO1. PIEZO1 protein expression was upregulated by IR in vivo and in vitro. The increased PIEZO1 expression after IR was accompanied with increased calcium influx and increased calpain activity. The effects of radiation on lung endothelial cell ferroptosis was partly reversed by inhibition of PIEZO1 activity using the selective inhibitor GsMTx4 or inhibition of downstreaming Ca2+/calpain signaling using PD151746. Both IR and activation of PIEZO1 led to increased degradation of VE-cadherin, while PD151746 blocked these effects. VE-cadherin knockdown by specific siRNA causes ferroptosis-like phenomena with increased ROS and lipid peroxidation in the lung endothelial cells. Overexpression of VE-cadherin partly recused the ferroptosis caused by IR or PIEZO1 activation as supported by decreased ROS production, lipid peroxidation and mitochondria shrinkage compared to IR or PIEZO1 activation alone. In summary, our study reveals a previously unrecognized role of PIEZO1 in modulating ferroptosis, providing a new target for future mitigation of radiation-induced lung injury.

Nickel–cobalt oxide has been given more attention to being used as the supercapacitor's electrode materials due to its two-dimensional layered structure, good electron conductivity, and excellent stability. In this work, NiCo2O4 nanosheets were successfully prepared by the simple solvothermal reaction and the thermal treatment process. Under the three-electrode system, it exhibits a maximum specific capacitance of 978 F/g at 1.5 A/g and good cycle stability. Meanwhile, a freestanding of partially reduced graphene oxides/carbon nanotubes (PRGO/CNTs) film was obtained by the vacuum filter and solvothermal methods, which can provide a wide potential window of − 1 ~ 0 V and a maximum specific capacitance of 236 F/g at 0.5 A/g. Finally, an asymmetric supercapacitor of PRGO/CNTs//NiCo2O4 was assembled, which exhibits good electrochemical performance, such as specific capacitance of 82 F/g at 0.5 A/g, energy density of 18.8 Wh/kg at 0.32 kW/kg, and 99.5% of capacitance retention after 5000 cycles at 5 A/g. This test results reveal that PRGO/CNTs//NiCo2O4 ASC has great potential for practical application in energy storage systems.

Objective We investigated whether Piezo1 could regulate oxygen-glucose deprivation/reoxygenation injury of neurons through Ca2+/calpain signaling. Methods Piezo1 expression in rat brain cortex and PC12 cells were confirmed by immunohistochemistry, immunofluorescence and Western blotting. The effects of Yoda1 and GsMTx4 on OGD/R-induced decrease in cell viability, increase in cell apoptosis and activation of downstreaming Ca2+/calpain signaling were investigated. Furthermore, calpain signaling was inhibited by PD151746 to see whether Ca2+/calpain signaling participated in the neurotoxic effects of Piezo1 activation. Results Piezo1 expression was increased in rat cerebral cortex after ischemia/reperfusion and in PC12 cells after OGD/R. Activation of Piezo1 by Yoda1 enhanced OGD/R-induced cell viability inhibition, apoptosis, increase intracellular calcium levels and enhanced calpain activity while GsMTx4 showed the opposite effects. The effects of Piezo1 activation on cell viability and apoptosis were reversed by PD151746. Conclusion Piezo1 could regulate neuron oxygen-glucose deprivation/reoxygenation injury via activation of Ca2+/calpain signaling.

Hypothyroidism is a common hormone deficiency condition. Regenerative medicine approaches, such as a bioengineered thyroid, have been proposed as potential therapeutic alternatives for patients with hypothyroidism. This study demonstrates a novel approach to generate thyroid grafts using decellularized rat thyroid matrix.Isolated rat thyroid glands were perfused with 1% sodium dodecyl sulfate to generate a decellularized thyroid scaffold. The rat thyroid scaffold was then recellularized with rat thyroid cell line to reconstruct the thyroid by perfusion seeding technique. As a pilot study, the decellularized rat thyroid scaffold was perfused with human-derived thyrocytes and parathyroid cells.The decellularization process retained the intricate three-dimensional microarchitecture with a perfusable vascular network and native extracellular matrix components, allowing efficient reseeding of the thyroid matrix with the FRTL-5 rat thyroid cell line generating three-dimensional follicular structures in vitro. In addition, the recellularized thyroid showed successful cellular engraftment and thyroid-specific function, including synthesis of thyroglobulin and thyroid peroxidase. Moreover, the decellularized rat thyroid scaffold could further be recellularized with human-derived thyroid cells and parathyroid cells to reconstruct a humanized bioartificial endocrine organ, which maintained expression of critical genes such as thyroglobulin, thyroid peroxidase, and parathyroid hormone.These findings demonstrate the utility of a decellularized thyroid extracellular matrix scaffold system for the development of functional, bioengineered thyroid tissue, which could potentially be used to treat hypothyroidism.

Highly efficient rhodium(III) catalysis was developed for obtaining structurally divergent pyrazolone analogues from pyrazolones and non-activated free allyl alcohols. Notably, this new C–H activation reaction generated unexpected pyrazolo[1,2-α]cinnoline derivatives besides γ-ketone substituted edaravone derivatives, and the selectivity of this coupling reaction could be controlled by changing the conditions.

Sodium ion batteries are in great need of electrode materials with high specificity and rate capability being developed. The sluggish reaction kinetics of SnO2-based materials has impeded their applications as anodes of SIBs. Designing electrode materials with high pseudocapacitive contribution can increase the near-surface faradaic reaction, which helps to improve their kinetics and achieve high rate capability. Here, we designed a high-pseudocapacitance sodium storage anode SnO2/N-rGO by downsizing the particle size of SnO2 and constructing an N-doped graphene wrapped structure. The ultrafine structure of SnO2 ensures the high faradaic near-surface reaction, while the N-doped graphene matrix guarantees the superior electron and Na+ diffusion. Meanwhile, the wrapped N-doped graphene acts as a buffer layer to alleviate the volumetric changes of the active SnO2. The obtained ultrafine SnO2/N-graphene composite exhibits a high capacity of 607.6 mA h g-1 at 50 mA g-1 with an impressive rate capability (261.8 mA h g-1 at 2 A g-1) in Na+ half-cells. Furthermore, a good performance with a capacity of 133.3 mA h g-1 at 2.4 A g-1 in Na+ full-cells can also be achieved, which makes it a promising anode material for SIBs.

Cadmium (Cd), a toxic heavy metal, is harmful to plants and human health. Glutathione (GSH) could alleviate Cd toxicity of plant species, whereas its mechanism responsible for wheat remains poorly understood. Here, we found that exogenous GSH application significantly increased the fresh and dry weight, root elongation, chlorophyll contents, while decreased the contents of malondialdehyde (MDA) and GSH, and translocation factor of Cd compared with Cd treatment. Moreover, GSH application significantly increased activities of antioxidant enzymes and expression of related genes, which involved in GSH synthesis, especially in roots. In addition, we found that GSH application suppressed Cd-induced expression of metal transporter genes TaNramp1, TaNramp5, TaHMA2, TaHMA3, TaLCT1 and TaIRT2 in roots. Taken together, our results suggested that GSH could alleviate Cd toxicity in wheat by increasing GSH synthesis gene expression or suppressing Cd transporter genes expression, and further affecting Cd uptake and translocation in wheat plants.

Lysosome of phagocyte is the main site of hypochlorous acid (HClO) production, and HClO can be employed as the biomarker for the diagnosis and treatment evaluation of arthritis. In recent years, developing fluorescent probes for lysosomal HClO has attracted considerable attention, but most of them still have some defects, such as autofluorescence, phototoxicity and photobleaching because of their excitation and emission located in short-wavelength region. Due to the advantages of two-photon fluorescent probes with near-infrared emissions, a lysosome-targetable two-photon fluorescent probe (Lyso-TP-HClO) with a near-infrared emission was reported in this paper. Lyso-TP-HClO has a high selectivity and a high sensitivity to HClO in the linear range (10.0 × 10−8 to 5.0 × 10−6 M), with a detection limit of 3.0 × 10−8 M. Due to the two-photon excited near-infrared emission, Lyso-TP-HClO has excellent imaging performances, such as small autofluorescence, excellent photostability, and large imaging depth. Furthermore, Lyso-TP-HClO was successfully employed for visualizing lysosomal HClO in bacteria-infected cells. At last, we have successfully used Lyso-TP-HClO to image the arthritis and evaluate the treatment of arthritis in mice. All the results confirm that Lyso-TP-HClO is a useful chemical tool for imaging of lysosomal HClO, the diagnosis of arthritis, and treatment evaluation of arthritis.

We developed a novel auto-nucleation suppressed mechanism (ANSM) for direct synthesis of EM-visible gold nanoparticles (AuNPs) on cysteine-rich tags (e.g., metallothionein) in cells for single-molecule detection with electron microscopy (it accompanies our Nature Method manuscript, Jiang et al. 2020 [1]). Both tagged-fusion proteins expressed in cells (e.g.bacteria, yeast and mammalian cells) and antigens stained with antibody-tag fusion proteins can be visualized by this protocol. Here we describe the typical protocols (both the chemical fixation and the high pressure freezing cases) developed for ANSM-based AuNP synthesis in HeLa cells expressing metallothionein (MTn) tags (Figure 1). This approach should be widely applicable to many systems for EM visualization of single-molecule in mammalian cells.

We developed a novel auto-nucleation suppressed mechanism (ANSM) for direct synthesis of EM-visible gold nanoparticles (AuNPs) on cysteine-rich tags (e.g., metallothionein) in cells for single-molecule detection with electron microscopy (it accompanies our Nature Method manuscript, Jiang et al. 2020 [1]). Both tagged-fusion proteins expressed in cells (e.g.bacteria, yeast and mammalian cells) and antigens stained with antibody-tag fusion proteins can be visualized by this protocol. Here we describe the typical protocols (both the chemical fixation and the high pressure freezing cases) developed for ANSM-based AuNP synthesis in yeast cells expressing metallothionein (MTn) tags (Figure 1). This approach should be useful for EM visualization of single-molecule in yeast cells, and easier adapted for bacterial cells.

Objective: Herpes simplex viruses (HSVs) are widely spread throughout the world, causing infections from oral, and genital mucous membrane ulcerations to severe viral encephalitis. Glycoprotein B (gB) was the first HSV envelope glycoprotein identified to induce cell fusion. This glycoprotein initiates viral entry and thereby determines the infectivity of HSV, as well as oncolytic HSV (oHSV). Clarifying its molecular characterization and enlarging its motif reservoir will help to engineer oHSV and in cancer treatment applications. Only in recent years has the importance of gB been acknowledged in HSV infection and oHSV engineering. Although gB-modified oHSVs have been developed, the detailed molecular biology of gB needs to be illustrated more clearly in order to construct more effective oHSVs. Method: Here, we performed a systematic comparative sequence analysis of gBs from the 9 HSV-1 and 2 HSV-2 strains, including HSV-1-LXMW, which was isolated by our lab. Online software was implemented to predict gB secondary structure and motifs. Based on extensive literature reviews, a functional analysis of the predicted motifs was performed. Results: Here, we reported the DNA and predicted amino acid sequences of our recently isolated HSV-1-LXMW and found that the strain was evolutionarily close to HSV-1 strains F, H129, and SC16 based on gB analysis. The 22 novel motifs of HSV gB were identified for the first time. An amino acid sequence alignment of the 11 HSV strains showed that the gB motifs are conserved among HSV strains, suggesting that they are functional in vivo. Additionally, we found that certain amino acids within the 13 motifs out of the 22 were reported to be functional in vivo. Furthermore, the gB mutants and gB-engineered oHSVs were also summarized. Conclusion: Our identification of the 22 novel motifs shed light on HSV gB biology and provide new options for gB engineering to improve the efficiency and safety of oHSVs.

Drug-induced liver injury (DILI) has been a hot issue of public health, owing to its unpredictability and serious harm to public health. Peroxynitrite (ONOO−) is an important biomarker for the assessment and diagnosis of DILI. In this article, based on a kind of rhodamine analogue with a near-infrared (NIR) emission (610 nm–800 nm) and a two-photon absorption cross section (54 GM), a two-photon excited NIR fluorescence probe (NIR-ONOO) for ONOO− was developed. With a high selectivity and a high sensitivity to ONOO−, NIR-ONOO has a linear range for detection of ONOO− from 5.0 × 10−8 to 1.0 × 10−5 M, a good detection limit (15 nM) and a large fluorescence enhancement (340-fold). In addition, NIR-ONOO has been used to monitor ONOO− in cells with satisfactory results. Because of its two-photon excied NIR emission, NIR-ONOO also showed excellent performances for imaging ONOO− including low autofluorescence, stable and persistent fluorescence, and a deep penetration (204 μm). Finally, NIR-ONOO was successfully employed to image ONOO− in inflammatory mouse, drug-induced hepatotoxicity in cells and its remediation. All the results indicated that NIR-ONOO is a powerful chemical tool to image ONOO− and assay drug-induced hepatotoxicity.

Sophoricoside (SOP), an isoflavone glycoside isolated from seed of Sophora japonica L., has been reported to have various pharmacological activities, including anti-cancer, anti-allergy and anti-inflammation. However, the effect of SOP on lipopolysaccharides (LPS)-acute lung injury (ALI) is completely unclear. Here, we found that SOP pretreatment significantly ameliorated LPS-induced pathological damage, tissue permeability, neutrophil infiltration and the production of pro-inflammatory cytokines (TNF-α, IL-1β and IL-6) in a murine model of ALI. Besides, SOP reduced the production of pro-inflammatory mediators such as iNOS, NO and inflammatory cytokines including TNF-α, IL-1β and IL-6 in LPS-stimulated RAW264.7 cells and bone marrow derived macrophages. Interestingly, treatment with SOP exhibited no effect on the activation of NF-κB and MAPKs in macrophages but prominently accelerated the expression and nuclear translocation of Nrf2. By using ML385, a specific Nrf2 inhibitor, we found that inhibition of Nrf2 abolished the inhibitory effect of SOP on LPS-induced iNOS expression, NO production as well as pro-inflammatory cytokine generation. SOP also activated AMPK, an upstream protein of Nrf2, under LPS stimuli. Furthermore, we demonstrated that the accelerated expression of Nrf2 induced by SOP was reversed by interference with the AMPK inhibitor Compound C. Taken together, our results suggested that SOP attenuated LPS-induced ALI in AMPK/Nrf2 dependent manner and indicated that SOP might be a potential therapeutic candidate for treating ALI/ARDS.

Due to the Earth’s scarcity of lithium, replacing lithium with earth-abundant and low-cost sodium for sodium-ion batteries (SIBs) has recently become a promising substitute for lithium-ion batterie...

Objective To investigate the correlation of M-type phospholipase A2 receptor (PLA2R) expression and serum anti-PLA2R antibody with the clinical parameters and prognosis of patients with idiopathic membranous nephropathy (IMN). Methods A literature search for relevant original articles published between January 2009 and October 2019 was conducted on domestic and foreign databases. RevMan 5.3 software was used for meta-analysis. Results Eighteen studies were included in this meta-analysis. There were 1235 anti-PLA2R antibody-positive and PLA2R-positive patients, and 407 serum anti-PLA2R antibody-negative and PLA2R-negative patients. Compared with negative group, patients in the serum PLA2R antibody -positive group had lower serum albumin [SMD = -1.11, 95% CI (− 1.82, − 0.40), P P P P P = 0.002]. No significant difference was observed between anti-PLA2R antibody -positive and -negative groups with respect to adverse events. Serum anti-PLA2R antibody titer did not affect the adverse event rate. Conclusion As compared to PLA2R, serum anti-PLA2R antibody is more closely related with IMN disease progression.

Androgen deprivation therapy (ADT) via surgical or chemical castration frequently fails to halt lethal castration-resistant prostate cancer (CRPC), which is induced by multiple mechanisms involving constitutive androgen receptor (AR) splice variants, AR mutation, and/or de novo androgen synthesis. The AR N-terminal domain (NTD) possesses most transcriptional activity and is proposed as a potential target for CRPC drug development. We constructed a screening system targeting AR-NTD transcription activity to screening a compound library and identified a novel small molecule compound named QW07. The function evaluation and mechanism investigation of QW07 were carried out in vitro and in vivo. QW07 bound to AR-NTD directly, blocked the transactivation of AR-NTD, blocked interactions between co-regulatory proteins and androgen response elements (AREs), inhibited the expression of genes downstream of AR, and inhibited prostate cancer growth in vitro and in vivo. QW07 was demonstrated as an AR-NTD-specific antagonist with the potential to inhibit both canonical and variant-mediated AR signaling to regress the CRPC xenografts and is proposed as a lead compound for a specific antagonist targeting AR-NTD.

Diabetic nephropathy is the most common microvascular complications of diabetes. Berberine is the main active ingredient of Coptis chinensis and previous studies have been showed that berberine could delay the progression of diabetic nephropathy by regulating related cytokines and signaling pathways. Glomerular mesangial cells and podocytes are two vital indigenous cells of kidney and interaction between these two cellular components via exosomes might affect function of glomerulus in diabetic nephropathy condition. On the basis of our previous studies, transwell systems were used to demonstrate that the exosomes released by glomerular mesangial cells induced by the high glucose were involved in podocytes injury. The current study demonstrates that berberine can reduce TGFβ1 in exosomes released by high glucose-induced glomerular mesangial cells. Berberine-treated high glucose-induced exosomes which are secreted by glomerular mesangial cells can protect damage of podocytes by reducing apoptosis and increasing adhesion. These results suggest that berberine could protect the function of podocytes through inhibiting the transfer of TGFβ1 from the glomerular mesangial cells to the podocytes, which is one of the potential mechanisms of protective effect of berberine on diabetic nephropathy.

In order to ascertain the effect of carbon networks with various dimension on the Li-storage properties of Fe 3 O 4 anode material, three Fe 3 O 4 -based nanocomposites with different dimensional carbon networks, including zero-dimensional C/Fe 3 O 4 (0D-C/F), one-dimensional carbon nanotubes/Fe 3 O 4 (1D-CNTs/F) and two-dimensional graphene/Fe 3 O 4 (2D-G/F) nanocomposites, are successfully prepared via precisely controlling the preparation processes and parameters. Their morphology, conductivity, reaction kinetics, and electrochemical properties are discussed in detail. The results show that the addition of 1D-CNTs or 2D-G in the Fe 3 O 4 results in a smaller size of Fe 3 O 4 particles, which shortens the diffusion distance of Li + , and provides a faster electron conduction pathways, as well as the flexible carbon networks will effectively relieve the internal strain during charge and discharge processes. Most importantly, it is revealed that 2D-G/F with the large surface area leads to a faster electrochemical reaction kinetic which is mainly controlled by pseudocapacitive behavior, while the electrochemical reaction kinetic of 1D-CNTs/F is dominated by the slow Li + insert process. As a result, 2D-G/F shows the best Li-storage performance with a reversible capacity of 1014 mAh g −1 in the first cycle at 0.1 C and even at a high rate of 5 C, the reversible capacity is still 513.5 mAh g −1 . Furthermore, after 100 cycles at 0.5 C, it still delivers a reversible capacity of 1125.6 mAh g −1 without capacity decay.

A novel core–shell Fe3O4@FeS composed of Fe3O4 core and FeS shell with the morphology of regular octahedra has been prepared via a facile and scalable strategy via employing commercial Fe3O4 as the precursor. When used as anode material for sodium-ion batteries (SIBs), the prepared Fe3O4@FeS combines the merits of FeS and Fe3O4 with high Na-storage capacity and superior cycling stability, respectively. The optimized Fe3O4@FeS electrode shows ultralong cycle life and outstanding rate capability. For instance, it remains a capacity retention of 90.8% with a reversible capacity of 169 mAh g–1 after 750 cycles at 0.2 A g–1 and 151 mAh g–1 at a high current density of 2 A g–1, which is about 7.5 times in comparison to the Na-storage capacity of commercial Fe3O4. More importantly, the prepared Fe3O4@FeS also exhibits excellent full-cell performance. The assembled Fe3O4@FeS//Na3V2(PO4)2O2F sodium-ion full battery gives a reversible capacity of 157 mAh g–1 after 50 cycles at 0.5 A g–1 with a capacity retention of...

Oncolytic herpes simplex viruses (oHSVs) have been approved for clinical usage and become more and more popular for tumor virotherapy. However, there are still many issues for the oHSVs used in clinics and clinical trials. The main issues are the limited anti-tumor effects, intratumor injection, and some side effects. To overcome such challenges, here we review the genetic engineering of the envelope glycoproteins for oHSVs to target tumors specifically, and at the same time we summarize the many neutralization antibodies against the envelope glycoproteins and align the neutralization epitopes with functional domains of the respective glycoproteins for future identification of new functions of the glycoproteins and future engineering of the epitopes to escape from host neutralization.

Most of the widely used vaginal lubricants in the U.S. and Europe are strongly hyperosmolal, formulated with high concentrations of glycerol, propylene glycol, polyquaternary compounds or other ingredients that make these lubricants 4 to 30 times the osmolality of healthy vaginal fluid. Hyperosmolal formulations have been shown to cause marked toxicity to human colorectal epithelia in vivo, and significantly increase vaginal transmission of genital herpes infections in the mouse/HSV model. They also cause toxicity to explants of vaginal epithelia, to cultured vaginal epithelial cells, and increase susceptibility to HIV in target cells in cell cultures. Here, we report that the osmolality of healthy vaginal fluid is 370 ± 40 mOsm/Kg in women with Nugent scores 0–3, and that a well-characterized three-dimensional human vaginal epithelium tissue model demonstrated that vaginal lubricants with osmolality greater than 4 times that of vaginal fluid (>1500 mOsm/Kg) markedly reduce epithelial barrier properties and showed damage in tissue structure. Four out of four such lubricants caused disruption in the parabasal and basal layers of cells as observed by histological analysis and reduced barrier integrity as measured by trans-epithelial electrical resistance (TEER). No epithelial damage to these layers was observed for hypo- and iso-osmolal lubricants with osmolality of

Aluminum oxynitride (AlON) powders were synthesized using the raw materials of γ-Al 2 O 3 and carbon black through the carbothermal reduction and nitridation process. The carbon content in the γ-Al 2 O 3 /C mixture and heating temperature were investigated. The AlON powders were synthesized by calcination for 2 h at 1750 °C when the carbon content in the γ-Al 2 O 3 /C mixture was 5.8 wt%. The particle size of powder is important to the transparency of ceramics, but the size of the synthesized powder was large. Therefore, a few methods, such as freeze-drying, ultrasonic dispersion, and liquid nitrogen ball milling, were used to reduce the particle size of powders. Among the three methods, liquid nitrogen milling had the best results.

A few thousand tons of nanoparticles and quantum dots (QDs) are produced yearly worldwide, and a significant amount is released into ecosystems. This knowledge has stimulated numerous studies on the toxicological properties of these nanomaterials. However, an important ecotoxicological aspect has been largely overlooked: the activation of silent viruses in bacteria (the so-called prophages). This is particularly important because, once the prophages are activated, phage replication using bacterial hosts is an autocatalytic process with a potentially exponential rate of bacteria killing under certain conditions. To shed light on these underestimated processes, the interactions of differently functionalized CdTe QDs with E. coli containing lambda prophages were investigated. We found that prophages can be activated with as little as a nanomolar concentration range of QDs. DNA damage due to oxidative stress induced by the CdTe QDs was revealed as the main reason for the prophage activation. The contribution of freely dissociated Cd2+ to prophage activation was on the order of 15 to 25%. Our pioneering work is intended to provide the first examination to better understand the role of nanoparticles in aquatic ecosystems.

In this study, the double transition metal selenide Ni1.5CoSe5 with cube-like nanoaggregate morphology was successfully embedded into a three-dimensional (3D) dual N-doped carbon network, developing an advanced anode material for sodium-ion batteries (SIBs). In the prepared composite, Ni1.5CoSe5 nanoparticles were first coated by N-doped carbon (NC), which further aggregated to form nanocubes, and finally embedded into interconnected N-doped reduced graphene oxide (rGO) nanosheets; hence, the material was abbreviated as Ni1.5CoSe5@NC@rGO. It delivered a reversible Na-storage capacity of 582.5 mA h g−1 at a low current density of 0.05 A g−1 and exhibited ultra-fast rate properties (e.g., with the specific capacities of 180.8 and 96.3 mA h g−1 at high current densities of 30 and 50 A g−1, respectively). The much enhanced Na-storage properties were ascribed to the highly conductive 3D network constructed by dual N-doped carbonaceous materials, which acted not only as a highway for ultrafast charge transfer but also as an effective protector for the active Ni1.5CoSe5 material and cube-like nanoaggregates with nanometer-sized primary particles. More significantly, the Ni1.5CoSe5@NC@rGO electrode also exhibited superior energy storage performance in sodium-ion full cells when coupled with a high-voltage Na3V2(PO4)2O2F cathode, making it a promising anode material for practical SIBs.

This study aimed to investigate the antibacterial actions of glycinin basic peptide against the oxidative phosphorylation system of Aspergillus niger (A. niger). The structural disruption and lipid peroxidation of the A. niger membrane were assessed via changes in 1,6-diphenyl-1,3,5-hexatriene fluorescence intensity and malondialdehyde content. Glycinin basic peptide decreased the fluorescence intensity of 1,6-diphenyl-1,3,5-hexatriene and increased the malondialdehyde content in A. niger cells. These results indicated that glycinin basic peptide disrupted the structural and functional integrity of the A. niger membrane and triggered severe lipid peroxidation. Moreover, the types and quantities of A. niger proteins decreased after exposure to glycinin basic peptides, as determined by protein electrophoresis. The activities of five key enzymes in the A. niger oxidative phosphorylation system were significantly inhibited after exposure to glycinin basic peptide. As observed by fluorescence quantitative polymerase chain reaction, glycinin basic peptide could significantly downregulate genes related to these enzymes (expression level of these genes decreased more than 50% when glycinin basic peptide reached 3.00 mg/mL). The inactivation of key enzymes and downregulation of corresponding genes indicated that glycinin basic peptide disrupted oxidative phosphorylation system, resulting in cell death of A. niger.

The physicochemical and antioxidant properties of tree peony seed protein (TPSP) hydrolysates by Alcalase, Neutrase, Papain, Protamex, and Flavourzyme were investigated in this study. The physicochemical properties were characterized by SDS-PAGE, particle size distribution, fourier transform infrared and fluorescence spectroscopy etc. The antioxidant activities were determined by DPPH radical, ABTS radical, Fe2+ chelating, and reducing power. The results showed five proteases produced hydrolysates with a significantly reduced average particle size, α-helices, and surface hydrophobicity compared to TPSP. Alcalase and Neutrase hydrolysis enhanced the nutritional value of the hydrolysates. Alcalase hydrolysates possessed the highest degree of hydrolysis (27.97%) and lowest molecular weight (

Two metal complexes [(Me)2Sn(L)(OAc)] (1), and [Pd(L)Cl] (2) based on 2-benzoylpyridine N(4)-cyclohexylthiosemicarbazone have been synthesized and structurally characterized. X-ray crystallography reveals that in title compounds, each thiosemicarbazone adopts tridentate NNS manner to coordinate with the metal center, and the metal coordination geometry can be described as a distorted pentagonal bipyramid in 1 and a contorted square-planar in 2, respectively. Growth inhibition assays have indicated that two compounds can effectively inhibit the growth of HepG2 cancer cell lines at micromolar concentrations. In addition, apoptosis mechanisms of 2 on HepG2 cells were further investigated. The results show that 2 can promote the apoptosis of HepG2 cells and the apoptosis is associated with the activation of caspase-3.

Herein, ultrafine nano-Si has been prepared via a NaCl-assisted magnesiothermic reduction with scalable silicate as Si source. In the high-temperature procedures of magnesiothermic reduction, as an effective heat scavenger, adjuvant NaCl promote the formation of interconnected Si nanoparticles with ultra-small size of 5–10 nm. When used as anode materials for lithium-ion batteries, reduced graphene oxide (rGO) plays a significant role in enhancing the electrochemical performance due to its high conductivity and flexibility by forming the nano-Si/rGO composite. The nano-Si/rGO composite exhibits much improved Li-storage properties in terms of superior high-rate capabilities and excellent cycle stability compared to the pure nano-Si as well as the micro-Si prepared from no addition of NaCl. It can deliver a high specific capacity of 1955 mA h g−1 at 100 mA g−1 with high initial columbic efficiency of >80%. In addition, nano-Si/rGO exhibits superior rate capability (891 mA h g−1 at 5 A g−1). The significantly enhanced Li-storage properties could be attributed to the synergistic effects of highly conductive rGO and nanosized Si particles in the nano-Si/rGO. While the former can improve the electrical conductivity, the latter will decrease the Li+ diffusion length, improve the capacity and optimize the cycling stability.

Oxidative stress is mainly caused by reactive oxygen species (ROS). The damage causes a net stress on normal organs, leading to a gradual loss of vital physiological function. ROS, such as free radicals, represent a class of molecules which are derived from the metabolism of oxygen and exist inherently. However, excessive produced ROS can damage all aerobic organisms. Ginseng is one of the most commonly used alternative herbal medicines, also as a traditional Chinese medicine. The aim of this study is to investigate the antioxidant potential function of ginsenoside Rg1 against cisplatin-caused hepatic damage. Male mice were treated with cisplatin to induce oxidative stress to mimic the side effect of anti-cancer drug cisplatin. Ginsenoside Rg1 effectively prevented against cisplatin-induced hepatotoxicity, alleviating histological lesions. Antioxidant functions of Rg1 were restrained by the activation of p62-Keap1-Nrf2 signaling pathway, simultaneously accompanied with expression of protein products. Accumulative p62 and increased activation of JNK in hepatocytes promoted the activation of Nrf2. For the other, degradation of Nrf2 was guided by tyrosine phosphorylation, ubiquitin, and Keap1. In summary, Rg1 prevents hepatotoxicity mainly by inhibiting the binding of Keap1 and Nrf2, partly by p62 accumulation, and more importantly by increasing the production of antioxidative proteins associated to Nrf2. Pharmacological activation of Nrf2 is an effective way in combating against liver injury.

Background Cancer-initiating cell (CIC), a functionally homogeneous stem-like cell population, is resonsible for driving the tumor maintenance and metastasis, and is a source of chemotherapy and radiation-therapy resistance within tumors. Targeting CICs self-renewal has been proposed as a therapeutic goal and an effective approach to control tumor growth. BMI-1, a critical regulator of self-renewal in the maintenance of CICs, is identified as a potential target for colorectal cancer therapy. Methods Colorectal cancer stem-like cell lines HCT116 and HT29 were used for screening more than 500 synthetic compounds by sulforhodamine B (SRB) cell proliferation assay. The candidate compound was studied in vitro by SRB cell proliferation assay, western blotting, cell colony formation assay, quantitative real-time PCR, flow cytometry analysis, and transwell migration assay. Sphere formation assay and limiting dilution analysis (LDA) were performed for measuring the effect of compound on stemness properties. In vivo subcutaneous tumor growth xenograft model and liver metastasis model were performed to test the efficacy of the compound treatment. Student’s t test was applied for statistical analysis. Results We report the development and characterization of a small molecule inhibitor QW24 against BMI-1. QW24 potently down-regulates BMI-1 protein level through autophagy-lysosome degradation pathway without affecting the BMI-1 mRNA level. Moreover, QW24 significantly inhibits the self-renewal of colorectal CICs in stem-like colorectal cancer cell lines, resulting in the abrogation of their proliferation and metastasis. Notably, QW24 significantly suppresses the colorectal tumor growth without obvious toxicity in the subcutaneous xenograft model, as well as decreases the tumor metastasis and increases mice survival in the liver metastasis model. Moreover, QW24 exerts a better efficiency than the previously reported BMI-1 inhibitor PTC-209. Conclusions Our preclinical data show that QW24 exerts potent anti-tumor activity by down-regulating BMI-1 and abrogating colorectal CICs self-renewal without obvious toxicity in vivo, suggesting that QW24 could potentially be used as an effective therapeutic agent for clinical colorectal cancer treatment.

Heat stroke is a symptom of hyperthermia with a temperature of more than 40 °C, which usually leads to all kinds of physical discomfort and even death. It is necessary to study the mechanism of action of heat stroke on cells or organelles (such as cytotoxicity of heat) and the processes of cells or organelles during heat stroke. Recent studies have shown that there is a certain correlation between heat stroke and lysosome acidity. In order to clarify their relationship, Lyso-NIR-pH, a photostable Si-rhodamine-based near-infrared fluorescent probe, was developed for sensing pH changes in lysosomes during heat stroke in this paper. For Lyso-NIR-pH, a morpholine group is employed as the lysosome-targeting unit and a H+-triggered openable deoxylactam is employed as the response unit to pH. Lyso-NIR-pH can detect pH with a high selectivity and a sensitivity, and its pKa is 4.63. Lyso-NIR-pH also has outstanding imaging performances, such as excellent lysosome-targeting ability, low autofluorescence and photostable fluorescence signal, which are in favor of long-term imaging of pH with accurate fluorescence signals. Moreover, we successfully applied Lyso-NIR-pH to monitor lysosomal pH increases induced by chloroquine and apoptosis in live cells. Finally, we successfully applied Lyso-NIR-pH for monitoring changes of lysosomal pH during heat stroke. These results confirmed that Lyso-NIR-pH is a powerful tool to monitor pH change in lysosomes and study its possible effects.

Allelopathy is a central process in crop&ndash, weed interactions and is mediated by the release of allelochemicals that result in adverse growth effects on one or the other plant in the interaction. The genomic mechanism for the biosynthesis of many critical allelochemicals is unknown but may involve the clustering of non-homologous biosynthetic genes involved in their formation and regulatory gene modules involved in controlling the coordinated expression within these gene clusters. In this study, we used the transcriptomes from mono- or co-cultured rice and barnyardgrass to investigate the nature of the gene clusters and their regulatory gene modules involved in the allelopathic interactions of these two plants. In addition to the already known biosynthetic gene clusters in barnyardgrass we identified three potential new clusters including one for quercetin biosynthesis and potentially involved in allelopathic interaction with rice. Based on the construction of gene networks, we identified one gene regulatory module containing hub transcription factors, significantly positively co-regulated with both the momilactone A and phytocassane clusters in rice. In barnyardgrass, gene modules and hub genes co-expressed with the gene clusters responsible for 2,4-dihydroxy-7-methoxy-1,4-benzoxazin-3-one (DIMBOA) biosynthesis were also identified. In addition, we found three genes in barnyardgrass encoding indole-3-glycerolphosphate synthase that regulate the expression of the DIMBOA cluster. Our findings offer new insights into the regulatory mechanisms of biosynthetic gene clusters involved in allelopathic interactions between rice and barnyardgrass, and have potential implications in controlling weeds for crop protection.

Hypochlorite (ClO−), one of reactive oxygen species (ROS), is closely related with many physiological and pathological processes. Especially as one of cellular reactive oxygen species in mitochondria, ClO− can induce mitochondrial permeability, which leads to apoptosis. Thus, developing an effective method which is able to sense ClO− in mitochondria is important. Although fluorescent probe has become a powerful tool for imaging ClO− in mitochondria, most of them suffered from phototoxicity to biosamples, autofluorescence, and photobleaching phenomenon due to their short-wavelength excitations and emissions. Based on advantages of two-photon fluorescent probe and far-red to NIR fluorescent probe, a mitochondria-targetable two-photon fluorescent probe with a turn-on signal in far-red to NIR region, Mito-TP-ClO, was developed for ClO− in this paper. Mito-TP-ClO is consisted of a triphenylphosphonium cations as a mitochondria-targetable unit and a structure of dibenzoylhydrazine as a response unit to ClO−. Mito-TP-ClO exhibited a high sensitivity and a high selectivity to ClO−, with a linear range from 6.0 × 10−8 to 1.0 × 10−5 M and a detection limit of 2.5 × 10−8 M. Due to its large two-photon cross section (267 GM) and far-red to NIR emission, Mito-TP-ClO exhibits excellent performances including low autofluorescence, photostable fluorescence signal, and deep tissue penetration (230 μM). Moreover, Mito-TP-ClO was successfully used to detect endogenous ClO− in bacteria-infected cells and inflammatory mouse model, which confirmed that Mito-TP-ClO is a powerful tool to monitor ClO− in mitochondria and study on effects of hypochlorite on mitochondria.

Genetically encoded tags for single-molecule imaging in electron microscopy (EM) are long-awaited. Here, we report an approach for directly synthesizing EM-visible gold nanoparticles (AuNPs) on cysteine-rich tags for single-molecule visualization in cells. We first uncovered an auto-nucleation suppression mechanism that allows specific synthesis of AuNPs on isolated tags. Next, we exploited this mechanism to develop approaches for single-molecule detection of proteins in prokaryotic cells and achieved an unprecedented labeling efficiency. We then expanded it to more complicated eukaryotic cells and successfully detected the proteins targeted to various organelles, including the membranes of endoplasmic reticulum (ER) and nuclear envelope, ER lumen, nuclear pores, spindle pole bodies and mitochondrial matrices. We further implemented cysteine-rich tag-antibody fusion proteins as new immuno-EM probes. Thus, our approaches should allow biologists to address a wide range of biological questions at the single-molecule level in cellular ultrastructural contexts.

Single-molecule visualization in cells with genetically encoded tags for electron microscopy (EM) has been a long-awaited but unimplemented tool for cell biologists. Here, we report an approach for directly synthesizing EM-visible gold nanoparticles (AuNPs) on cysteine-rich tags for single-molecule visualization in cells. We first uncovered an auto-nucleation suppression mechanism that allows specific synthesis of AuNPs on isolated cysteine-rich tags. We next exploited this mechanism to develop an approach for single-molecule detection of proteins in prokaryotic cells and achieved an unprecedented labeling efficiency. We then expanded it to more complicated eukaryotic cells and successfully detected the proteins targeted to various organelles, including the membranes of endoplasmic reticulum (ER) and nuclear envelope, ER lumen, nuclear pores, spindle pole bodies, and mitochondrial matrix. Thus, our implementation of genetically encoded tags for EM should allow cell biologists to address an enormous range of biological questions at single-molecule level in diverse cellular ultrastructural contexts without using antibodies.

In order to develop promising anode materials for lithium-ion batteries (LIBs), a unique nanocomposite abbreviated as G⊥FP@C-NA, in which a carbon-coated FeP nanorod array (FP@C-NA) is vertically grown on a conductive reduced graphene oxide (G) network, has been successfully prepared via a scalable strategy. Benefiting from the distinctive structure, G⊥FP@C-NA exhibits much improved conductivity, structural stability and pseudocapacitance-boosted ultrafast electrochemical kinetics for Li storage. As a result, the G⊥FP@C-NA delivers a high Li-storage capacity (1106 mA h g-1 at 50 mA g-1), outstanding rate capability (565 mA h g-1 at 5000 mA g-1) and long-term cycling stability (1009 mA h g-1 at 500 mA g-1 after 500 cycles and 310 mA h g-1 at 2000 mA g-1 after 2000 cycles) when used as an anode material for LIBs. As expected, this kind of nanoarray structure is attractive and can also be extended to other electrode materials for various energy storage systems.

This study aimed to explore effects and mechanisms of 004 (IMM-H004), a novel coumarin derivative, in OKA (okadaic acid)-induced AD (Alzheimer's disease)-like model. In vitro, MTT, LDH, and Annexin V/FITC flow cytometry assay were used to test cell survival. In vivo, OKA microinjection was conducted to simulate AD-like neuropathology. Morris water maze and Nissl staining were used to detect spatial memory function and neuronal damage respectively. Western blot and immunohistochemistry were used to study the mechanisms of 004 in Tau pathology. The results showed that 004 reduced cell death and increased survival in PC12 cells, and decreased neuronal injury in the hippocampus in rats. 004 improved learning and memory functions in OKA-treated rats. The mechanistic studies indicated that 004 inhibited phosphorylation of Tau protein by down-regulating the activity of protein kinases CDK5 and GSK3β and increasing PP2A activity. Overall, 004 improved spatial memory impairments and neuron cells injury induced by OKA; on the other hand, 004 inhibited Tau hyperphosphorylation by regulating CDK5, GSK3β and PP2A.