Search

Different from the traditional value evaluation system, EVA considers the impact of equity capital cost on enterprise value. This paper uses the EVA value evaluation model to process and analyze the financial data of Jidian Corporation from 2017 to 2021, and finds that the market value of Jidian Corporation has a small difference with EVA value. The research of this paper has certain enlightenment significance for the production and operation of power industry enterprises.

Background The CRISPR-Cas13 system is an RNA-guided RNA-targeting system and has been widely used in transcriptome engineering with potentially important clinical applications. However, it is still controversial whether Cas13 exhibits collateral activity in mammalian cells. Results Here, we find that knocking down gene expression using RfxCas13d in the adult brain neurons caused death of mice, which may result from the collateral activity of RfxCas13d rather than the loss of target gene function or off-target effects. Mechanistically, we show that RfxCas13d exhibits collateral activity in mammalian cells, which is positively correlated with the abundance of target RNA. The collateral activity of RfxCas13d could cleave 28s rRNA into two fragments, leading to translation attenuation and activation of the ZAKα-JNK/p38-immediate early gene pathway. Conclusions These findings provide new mechanistic insights into the collateral activity of RfxCas13d in mammalian cells and warn that the biosafety of the CRISPR-Cas13 system needs further evaluation before application to clinical treatments.

Inhibition of γ-secretase activity represents a potential therapeutic strategy for Alzheimer’s disease (AD). MRK-560 is a selective inhibitor with higher potency for Presenilin 1 (PS1) than for PS2, the two isoforms of the catalytic subunit of γ-secretase, although the underlying mechanism remains elusive. Here we report the cryo-electron microscopy (cryo-EM) structures of PS1 and PS2-containing γ-secretase complexes with and without MRK-560 at overall resolutions of 2.9-3.4 Å. MRK-560 occupies the substrate binding site of PS1, but is invisible in PS2. Structural comparison identifies Thr281 and Leu282 in PS1 to be the determinant for isoform-dependent sensitivity to MRK-560, which is confirmed by swapping experiment between PS1 and PS2. By revealing the mechanism for isoform-selective inhibition of presenilin, our work may facilitate future drug discovery targeting γ-secretase.

Understanding the nature of charge density waves (CDW) in cuprate superconductors has been complicated by material specific differences. A striking example is the opposite doping dependence of the CDW ordering wavevector in La-based and Y-based compounds, the two families where charge ordering is strongest and best characterized. Here we report a combined resonant soft X-ray scattering (RSXS) and neutron scattering study of charge and spin density waves in isotopically enriched La$_{1.8-x}$ Eu$_{0.2}$ Sr$_{x}$ CuO$_{4}$ over a range of doping $0.07 \leq x \leq 0.20$. For all dopings studied by RSXS, we find that the CDW amplitude is approximately temperature-independent and develops well above experimentally accessible temperatures. Surprisingly, the CDW ordering wavevector shows a non-monotonic temperature dependence, with a sudden change occurring at temperatures near the SDW onset temperature. We describe this behavior with a Landau-Ginzburg theory for an incommensurate CDW in a metallic system with a finite charge compressibility and CDW-SDW coupling. Our Landau-Ginzburg analysis suggests that the ordering wavevector at high temperatures decreases with increased doping. This behavior is opposite to the trend at low temperatures and highly reminiscent of the doping dependence seen in YBa$_2$ Cu$_3$ O$_{6+\delta}$ , suggesting a common origin of the CDW in hole-doped cuprate superconductors., Comment: Manuscript submitted to PNAS; ArXiv version formatted in Revtex4-2; Supplementary Material included as appendices; 20 pages, 14 figures (6 in the main text), and 41 references

Resistance to chemotherapy is a long-standing problem in the management of cancer, and cancer stem cells are regarded as the main source of this resistance. This study aimed to investigate metallothionein (MT)-1G involvement in the regulation of cancer stemness and provide a strategy to overcome chemoresistance in pancreatic ductal adenocarcinoma (PDAC). Methods: MT1G was identified as a critical factor related with gemcitabine resistance in PDAC cells by mRNA microarray. Its effects on PDAC stemness were evaluated through sphere formation and tumorigenicity. LC-MS/MS analysis of conditional medium revealed that activin A, a NF-κB target, was a major protein secreted from gemcitabine resistant PDAC cells. Both loss-of-function and gain-of-function approaches were used to validate that MT1G inhibited NF-κB-activin A pathway. Orthotopic pancreatic tumor model was employed to explore the effects on gemcitabine resistance with recombinant follistatin to block activin A. Results: Downregulation of MT1G due to hypermethylation of its promoter is related with pancreatic cancer stemness. Secretome analysis revealed that activin A, a NF-κB target, was highly secreted by drug resistant cells. It promotes pancreatic cancer stemness in Smad4-dependent or independent manners. Mechanistically, MT1G negatively regulates NF-κB signaling and promotes the degradation of NF-κB p65 subunit by enhancing the expression of E3 ligase TRAF7. Blockade of activin A signaling with follistatin could overcome gemcitabine resistance. Conclusions: MT1G suppresses PDAC stemness by limiting activin A secretion via NF-κB inhibition. The blockade of the activin A signaling with follistatin may provide a promising therapeutic strategy for overcoming gemcitabine resistance in PDAC.

Aberrant cleavage of amyloid precursor protein (APP) by γ-secretase is closely associated with Alzheimer’s disease (AD). γ-secretase activating protein (GSAP) specifically promotes γ-secretase–mediated cleavage of APP. However, the underlying mechanism remains enigmatic. Here, we demonstrate that the 16-kDa C-terminal fragment of GSAP (GSAP-16K) undergoes phase separation in vitro and forms puncta-like condensates in cells. GSAP-16K exerts dual modulation on γ-secretase cleavage; GSAP-16K in dilute phase increases APP–C-terminal 99-residue fragment (C99) cleavage toward preferred production of β-amyloid peptide 42 (Aβ42), but GSAP-16K condensates reduce APP-C99 cleavage through substrate sequestration. Notably, the Aβ42/Aβ40 ratio is markedly elevated with increasing concentrations of GSAP-16K. GSAP-16K stably associates with APP-C99 through specific sequence elements. These findings mechanistically explain GSAP-mediated modulation of γ-secretase activity that may have ramifications on the development of potential therapeutics.

Homozygous mutations in Ig-like domain of LMNA cause severe progeria. Unlike typical HGPS mediated by progerin due to LMNAWT/G608G mutation, it remains elusive how these homozygous mutations cause progeria. We here found that patients with LMNAR527C/R527C mutation developed an atypical progeria with autoimmune symptoms. Compare to LMNAWT/G608G mutation, this mutation led to more severe inflammation in patients. MSCs from LMNAR527C/R527C patients exhibited overt inflammation and cellular senescence. Mechanistically, LMNAR527C/R527C mutation attenuated its binding to DNA binding protein BAF, which led to aberrant aggregation of Lamin A and activation of DNA sensing pathways. Inhibition of DNA sensors, cGAS or AIM2, can suppress inflammation and rescue the senescence of patient-derived MSCs. LmnaR527C/R527C mice showed enhanced inflammation, and developed accelerated aging and dead at an early age after high-fat diet (HFD) feeding, which could be rescued by deficiency of AIM2 or treatment by a small molecule inhibitor of cGAS-STING. Therefore, we demonstrated that LMNAR527C/R527C mutation damped its interaction with DNA-binding proteins and exposed damaged DNA to the cytosolic DNA sensors, which triggered aberrant inflammatory responses and promoted the onset of accelerated aging. The present study uncovered that an inflammation driven progeria was caused by LMNA mutation and DNA sensing pathways could be potential therapeutic targets for progeria syndromes caused by homozygous mutations in Ig-like domain of LMNA.

SummaryThe CRISPR-Cas13 system is an RNA-guided RNA-targeting system, and has been widely used in transcriptome engineering with potentially important clinical applications. However, it is still controversial whether Cas13 exhibits collateral activity in mammalian cells. Here, we found that knocking down gene expression using RfxCas13d in the adult brain neurons caused death of mice, which was not resulted from the loss of target gene function or off-target effects. Mechanistically, we showed that RfxCas13d exhibited collateral activity in mammalian cells, which is positively correlated with the abundance of target RNA. The collateral activity of RfxCas13d could cleave 28s rRNA into two fragments, leading to translation attenuation and activation of the ZAKα-JNK/p38-immediate early gene (IEG) pathway. These results provide new mechanistic insights into the collateral activity of RfxCas13d and warn that the biosafety of CRISPR-Cas13 system needs further evaluation before applying it to clinical treatments.

Regulation of chromatin structure and accessibility determines the transcription activities of genes, which endows the host with function-specific patterns of gene expression. Upon viral infection, the innate immune responses provide the first line of defense, allowing rapid production of variegated antiviral cytokines. Knowledge on how chromatin accessibility is regulated during host defense against viral infection remains limited. Our previous work found that the nuclear matrix protein SAFA surveilled viral RNA and regulated antiviral immune genes expression. However, how SAFA regulates the specific induction of antiviral immune genes remains unknown. Here, through integration of RNA-seq, ATAC-seq and ChIP-seq assays, we found that the depletion of SAFA specifically decreased the chromatin accessibility, activation and expression of virus induced genes. And mutation assays suggested that the RNA-binding ability of SAFA was essential for its function in regulating antiviral chromatin accessibility. RIP-seq results showed that SAFA exclusively bound with antiviral related RNAs following viral infection. Further, we combined the CRISPR-Cas13d mediated RNA knockdown system with ATAC-qPCR, and demonstrated that the binding between SAFA and according antiviral RNAs specifically mediated the openness of the corresponding chromatin and following robust transcription of antiviral genes. Moreover, knockdown of these associated RNAs dampened the accessibility of related genes in an extranuclear signaling pathway dependent manner. Interestingly, VSV infection cleaved SAFA protein at the C-terminus which deprived its RNA binding ability for immune evasion. Thus, our results demonstrated that SAFA and the interacting RNA products collaborated and remodeled chromatin accessibility to facilitate antiviral innate immune responses.

How superconductivity interacts with charge or nematic order is one of the great unresolved issues at the center of research in quantum materials. ${\mathrm{Ba}}_{1\ensuremath{-}x}{\mathrm{Sr}}_{x}{\mathrm{Ni}}_{2}{\mathrm{As}}_{2}$ (BSNA) is a charge ordered pnictide superconductor recently shown to exhibit a sixfold enhancement of superconductivity due to nematic fluctuations near a quantum phase transition (at ${x}_{c}=0.7$) [1]. The superconductivity is, however, anomalous, with the resistive transition for $0.4lxl{x}_{c}$ occurring at a higher temperature than the specific heat anomaly. Using x-ray scattering, we discovered a new charge density wave (CDW) in BSNA in this composition range. The CDW is commensurate with a period of two lattice parameters, and is distinct from the two CDWs previously reported in this material [1,2]. We argue that the anomalous transport behavior arises from heterogeneous superconductivity nucleating at antiphase domain walls in this CDW. We also present new data on the incommensurate CDW, previously identified as being unidirectional [2], showing that it is a rotationally symmetric ``$4Q$'' state with ${C}_{4}$ symmetry. Our study establishes BSNA as a rare material containing three distinct CDWs, and an exciting test bed for studying coupling between CDW, nematic, and SC orders.

The Xishan coal mine area in Beijing, China has a long history of mining. Many landslide hazards, in addition to collapses and ground fractures, have occurred in this area. This study used multi-temporal satellite images to extract this region’s deformation information, identify landslides and analyze the deformation evolution process of these landslides. Taking the Anzigou ditch as an example, we investigate the “Quarry–Landslide–Mudslide” disaster chain model. We found that the landslide evolution process is closely related to the geological conditions, and usually goes through four stages: initial deformation, slope front swelling and collapsing, rear part connecting and rupturing, and landslide creeping. The surface deformation can be identified and tracked by high-resolution optical images and InSAR monitoring. Under the combined effects of rainfall and topographic conditions, medium and large landslides may occur and trigger a “Quarry–Landslide–Mudflow” disaster chain. The identification and analysis of these landslide hazards and the disaster chain help with geological disaster prevention, and provide reference for early identification and research of similar disasters.

Aberrant cleavage of Notch by γ-secretase leads to several types of cancer, but how γ-secretase recognizes its substrate remains unknown. Here we report the cryo-electron microscopy structure of human γ-secretase in complex with a Notch fragment at a resolution of 2.7 Å. The transmembrane helix of Notch is surrounded by three transmembrane domains of PS1, and the carboxyl-terminal β-strand of the Notch fragment forms a β-sheet with two substrate-induced β-strands of PS1 on the intracellular side. Formation of the hybrid β-sheet is essential for substrate cleavage, which occurs at the carboxyl-terminal end of the Notch transmembrane helix. PS1 undergoes pronounced conformational rearrangement upon substrate binding. These features reveal the structural basis of Notch recognition and have implications for the recruitment of the amyloid precursor protein by γ-secretase.

RNA and protein are interconnected biomolecules that can influence each other’s life cycles and functions through physical interactions. Abnormal RNA–protein interactions lead to cell dysfunctions and human diseases. Therefore, mapping networks of RNA–protein interactions is crucial for understanding cellular processes and pathogenesis of related diseases. Different practical protein-centric methods for studying RNA–protein interactions have been reported, but few robust RNA-centric methods exist. Here, we developed CRISPR-based RNA proximity proteomics (CBRPP), a new RNA-centric method to identify proteins associated with an endogenous RNA of interest in native cellular context without pre-editing of the target RNA, cross-linking or RNA–protein complexes manipulation in vitro. CBRPP is based on a fusion of dCas13 and proximity-based labelling (PBL) enzyme. dCas13 can deliver PBL enzyme to the target RNA with high specificity, while PBL enzyme labels the surrounding proteins of the target RNA, which are then identified by mass spectrometry.

How superconductivity interacts with charge or nematic order is one of the great unresolved issues at the center of research in quantum materials. Ba_{1-x}Sr_{x}Ni_{2}As_{2} (BSNA) is a charge ordered pnictide superconductor recently shown to exhibit a sixfold enhancement of superconductivity due to nematic fluctuations near a quantum phase transition (at x_{c}=0.7) [1]. The superconductivity is, however, anomalous, with the resistive transition for 0.4xx_{c} occurring at a higher temperature than the specific heat anomaly. Using x-ray scattering, we discovered a new charge density wave (CDW) in BSNA in this composition range. The CDW is commensurate with a period of two lattice parameters, and is distinct from the two CDWs previously reported in this material [1,2]. We argue that the anomalous transport behavior arises from heterogeneous superconductivity nucleating at antiphase domain walls in this CDW. We also present new data on the incommensurate CDW, previously identified as being unidirectional [2], showing that it is a rotationally symmetric "4Q" state with C_{4} symmetry. Our study establishes BSNA as a rare material containing three distinct CDWs, and an exciting test bed for studying coupling between CDW, nematic, and SC orders.

SummaryThe onset of sepsis is an important feature of COVID19 and a main cause of death. It is unknown how SARS-CoV-2 infection results in viral sepsis in human. We recently found that SARS-CoV-2 provoked an anti-bacterial like response and activation of TLR4 pathway at the very early stage of infection in animal models. This abnormal immune response led to emergency granulopoiesis and sepsis. However, the original trigger of TLR4 signaling by SARS-CoV-2 is unknown. We here identified that the trimeric spike protein of SARS-CoV-2 could bind to TLR4 directly and robustly activate downstream signaling in monocytes and neutrophils. Moreover, specific TLR4 or NFKB inhibitor, or knockout of MyD88 could significantly block IL-1B induction by spike protein. We thus reveal that spike protein of SARS-CoV-2 functions as a potent stimulus causing TLR4 activation and sepsis related abnormal responses.

Resistance to chemotherapy is a long-standing problem in the management of cancer, and cancer stem cells are regarded as the main source of this resistance. This study aimed to investigate metallothionein (MT)-1G involvement in the regulation of cancer stemness and provide a strategy to overcome chemoresistance in pancreatic ductal adenocarcinoma (PDAC). Methods: MT1G was identified as a critical factor related with gemcitabine resistance in PDAC cells by mRNA microarray. Its effects on PDAC stemness were evaluated through sphere formation and tumorigenicity. LC-MS/MS analysis of conditional medium revealed that activin A, a NF-κB target, was a major protein secreted from gemcitabine resistant PDAC cells. Both loss-of-function and gain-of-function approaches were used to validate that MT1G inhibited NF-κB-activin A pathway. Orthotopic pancreatic tumor model was employed to explore the effects on gemcitabine resistance with recombinant follistatin to block activin A. Results: Downregulation of MT1G due to hypermethylation of its promoter is related with pancreatic cancer stemness. Secretome analysis revealed that activin A, a NF-κB target, was highly secreted by drug resistant cells. It promotes pancreatic cancer stemness in Smad4-dependent or independent manners. Mechanistically, MT1G negatively regulates NF-κB signaling and promotes the degradation of NF-κB p65 subunit by enhancing the expression of E3 ligase TRAF7. Blockade of activin A signaling with follistatin could overcome gemcitabine resistance. Conclusions: MT1G suppresses PDAC stemness by limiting activin A secretion via NF-κB inhibition. The blockade of the activin A signaling with follistatin may provide a promising therapeutic strategy for overcoming gemcitabine resistance in PDAC.

Summary Development of γ-secretase inhibitors (GSIs) and modulators (GSMs) represents an attractive therapeutic opportunity for Alzheimer’s disease (AD) and cancers. However, how these GSIs and GSMs target γ-secretase has remained largely unknown. Here, we report the cryoelectron microscopy (cryo-EM) structures of human γ-secretase bound individually to two GSI clinical candidates, Semagacestat and Avagacestat, a transition state analog GSI L685,458, and a classic GSM E2012, at overall resolutions of 2.6–3.1 A. Remarkably, each of the GSIs occupies the same general location on presenilin 1 (PS1) that accommodates the β strand from amyloid precursor protein or Notch, interfering with substrate recruitment. L685,458 directly coordinates the two catalytic aspartate residues of PS1. E2012 binds to an allosteric site of γ-secretase on the extracellular side, potentially explaining its modulating activity. Structural analysis reveals a set of shared themes and variations for inhibitor and modulator recognition that will guide development of the next-generation substrate-selective inhibitors.

The SARS-CoV-2 pandemic poses an unprecedented public health crisis. Accumulating evidences suggest that SARS-CoV-2 infection causes dysregulation of immune system. However, the unique signature of early immune responses remains elusive. We characterized the transcriptome of rhesus macaques and mice infected with SARS-CoV-2. Alarmin S100A8 was robustly induced by SARS-CoV-2 in animal models as well as in COVID-19 patients. Paquinimod, a specific inhibitor of S100A8/A9, could reduce inflammatory response and rescue the pneumonia with substantial reduction of viral titers in SASR-CoV-2 infected animals. Remarkably, Paquinimod treatment resulted in 100% survival of mice in a lethal model of mouse coronavirus (MHV) infection. A novel group of neutrophils that contributed to the uncontrolled inflammation and onset of COVID-19 were dramatically induced by coronavirus infections. Paquinimod treatment could reduce these neutrophils and regain antiviral responses, unveiling key roles of S100A8/A9 and noncanonical neutrophils in the pathogenesis of COVID-19, highlighting new opportunities for therapeutic intervention. Funding: This work was supported by the National Natural Science Foundation of China (31570891; 31872736), the National Key Research and Development Program of China (2016YFA0500302; 2020YFA0707800), the National Key Research and Development Program (2020YFA0707500) and the Strategic Priority Research Program (XDB29010000). Xiangxi Wang was supported by Ten Thousand Talent Program and the NSFS Innovative Research Group (81921005). We thank National Mega projects of China for Major Infectious Diseases (2017ZX10304402), CAMS initiative for Innovative Medicine of China (2016-12M-2-006) and The National Natural Science Foundation of China (82041008) for the support on the animal model study. Conflict of Interest: The authors have no conflicts of interest to declare. Ethical Approval: All experiments with live SARS-CoV-2 viruses were carried out in the enhanced biosafety level 3 (P3+) facilities in the Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS) approved by the National Health Commission of the People’s Republic of China. All animals care and use were in accordance with the Guide for the Care and Use of Laboratory Animals of the Chinese Association for Laboratory Animal Science. All procedures of animal handling were approved by the Animal Care Committee of Peking University Health Science Center.

Identifying what broken symmetries are present in the cuprates has become a major area of research. Many authors have reported evidence for so-called "$Q \sim 0$" order that involves broken inversion, mirror, chiral, or time-reversal symmetry that is uniform in space. Not all these observations are well understood and new experimental probes are needed. Here we use resonant soft x-ray scattering (RSXS) to search for $Q \sim 0$ order in Bi$_{2.1}$Sr$_{1.9}$CaCu$_2$O$_{8+x}$ (Bi-2212) by measuring the region of a forbidden Bragg peak, $(0,0,3)$, which is normally extinguished by symmetry but may become allowed on resonance if valence band order is present. Using circularly polarized light, we found that this reflection becomes allowed on the Cu $L_3$ resonance for temperatures $T_c < T < T^\ast$, though remains absent in linear polarization and at other temperatures. This observation suggests the existence of spatially uniform valence band order near the pseudogap temperature. In addition, we observed periodic oscillations in the specular reflectivity from the sample surface that resemble thin film interference fringes, though no known film is present. These fringes are highly resonant, appear in all polarizations, and exhibit a period that depends on the location where the beam strikes the sample surface. We speculate that these fringes arise from interaction between some intrinsic valence band instability and extrinsic structural surface morphologies of the material. Our study supports the existence of some kind of $Q \sim 0$ broken symmetry state in Bi-2212 at intermediate temperatures, and calls for further study using a microfocused beam that could disentangle microscopic effects from macroscopic heterogeneities., 9 pages, 4 figures

The aspect ratio dependence of the electroconvection phenomenon in a suspended nematic liquid crystal film with a rectangular boundary is investigated. Two-dimensional global stability analysis is carried out on the coupled electrohydrodynamic system to calculate the instability boundary of the phenomenon for different aspect ratios. The calculated critical $R$ number (Rayleigh-like number) shows a rapidly decreasing trend in the low-aspect-ratio region (roughly $\unicode[STIX]{x1D6FE}, where $\unicode[STIX]{x1D6FE}$ is defined as the aspect ratio of the film), and then the variation becomes slow until $\unicode[STIX]{x1D6FE}\approx 2.5$, where the critical $R$ number starts to increase slightly. Convective patterns of liquid films with different aspect ratios are also obtained from stability analysis and validated by particle image velocimetry measurement.

The effect of widely different corrosion rates of Mg alloys on four parameters of interest for in vivo characterization was evaluated: (1) the effectiveness of transdermal H 2 measurements with an electrochemical sensor for noninvasively monitoring biodegradation compared to the standard techniques of in vivo X-ray imaging and weight loss measurement of explanted samples, (2) the chemical compositions of the corrosion layers of the explanted samples by XPS, (3) the effect on animal organs by histology, and (4) the accumulation of corrosion by-products in multiple organs by ICP-MS. The in vivo biodegradation of three magnesium alloys chosen for their widely varying corrosion rates – ZJ41 (fast), WKX41 (intermediate) and AZ31 (slow) – were evaluated in a subcutaneous implant mouse model. Measuring H 2 with an electrochemical H 2 sensor is a simple and effective method to monitor the biodegradation process in vivo by sensing H 2 transdermally above magnesium alloys implanted subcutaneously in mice. The correlation of H 2 levels and biodegradation rate measured by weight loss shows that this non-invasive method is fast, reliable and accurate. Analysis of the insoluble biodegradation products on the explanted alloys by XPS showed all of them to consist primarily of Mg(OH) 2 , MgO, MgCO 3 and Mg 3 (PO 4 ) 2 with ZJ41 also having ZnO. The accumulation of magnesium and zinc were measured in 9 different organs by ICP-MS. Histological and ICP-MS studies reveal that there is no significant accumulation of magnesium in these organs for all three alloys; however, zinc accumulation in intestine, kidney and lung for the faster biodegrading alloy ZJ41 was observed. Although zinc accumulates in these three organs, no toxicity response was observed in the histological study. ICP-MS also shows higher levels of magnesium and zinc in the skull than in the other organs. Statement of significance Biodegradable devices based on magnesium and its alloys are promising because they gradually dissolve and thereby avoid the need for subsequent removal by surgery if complications arise. In vivo biodegradation rate is one of the crucial parameters for the development of these alloys. Promising alloys are first evaluated in vivo by being implanted subcutaneously in mice for 1 month. Here, we evaluated several magnesium alloys with widely varying corrosion rates in vivo using multiple characterization techniques. Since the alloys biodegrade by reacting with water forming H 2 gas, we used a recently demonstrated, simple, fast and noninvasive method to monitor the biodegradation process by just pressing the tip of a H 2 sensor against the skin above the implant. The analysis of 9 organs (intestine, kidney, spleen, lung, heart, liver, skin, brain and skull) for accumulation of Mg and Zn revealed no significant accumulation of magnesium in these organs. Zinc accumulation in intestine, kidney and lung was observed for the faster corroding implant ZJ41. The surfaces of explanted alloys were analyzed to determine the composition of the insoluble biodegradation products. The results suggest that these tested alloys are potential candidates for biodegradable implant applications.

Magnesium (Mg) and its alloys have increasingly been considered as implant materials for orthopedic, craniofacial, and cardiovascular applications. These materials generally have mechanical properties close to those of human bone and they biodegrade in aqueous environments. The biodegradation properties can be tailored to fit the desired application by changing the alloying elements and/or by addition of surface coatings. To test and compare the biodegradation properties of different materials, immersion tests in solutions ranging from simple salt solutions to complex biological media are commonly done that yield some information about the biodegradation rate and the biodegradation products on the surface after completion of the test. Here we report on a method that allows the continuous real-time monitoring of the biodegradation process using electrochemical sensors for pH and H2 during immersion of Mg samples in the cell culture medium DMEM/F12 with different concentrations of fetal bovine serum and in the presence of living cells. The sensors effectively indicated the biodegradation behavior of Mg samples in real-time. This system could be very useful for immersion tests and even supporting biocompatibility testing of implant materials.

The machinery behind amyloid peptides β-Amyloid peptides, which are derived from amyloid precursor protein (APP), form the plaques in the brain that are characteristic of Alzheimer's disease. Zhou et al. report a high-resolution structure of a transmembrane segment of APP bound to human γ-secretase, the transmembrane protease that cleaves APP to give β-amyloid peptides (see the Perspective by Lichtenthaler and Güner). Disease-associated mutations within presenilin-1, the catalytic subunit of APP, likely affect how the substrate is bound and thus which peptides are generated, with some being more amyloidogenic. It may now be possible to exploit the features of substrate binding to design inhibitors. Science , this issue p. eaaw0930 ; see also p. 690

Magnesium and its alloys exhibit properties such as high strength, light weight, and in vivo corrosion that make them promising candidates for the development of biodegradable metallic implant materials for bone repair, stents and other medical applications. Sensors have been used to monitor the corrosion of magnesium and its alloys by measuring the concentrations of the following corrosion products: magnesium ions, hydroxyl ions and hydrogen gas. The corrosion characterization system with home-made capillary pH and Mg2+ microsensors has been developed for real-time detection of magnesium corrosion in vitro. A hydrogen gas sensor was used to monitor the corrosion of magnesium by measuring the concentration of the hydrogen gas reaction product in vivo. The high permeability of hydrogen through skin allows transdermal monitoring of the biodegradation of a magnesium alloy implanted beneath the skin by detecting hydrogen gas at the skin surface. The sensor was used to map hydrogen concentration in the vicinity of an implanted magnesium alloy.

The epoxy-acrylate (EA) was mixed with Ag-plated graphene (Ag-G), which was used as the conductive filler, to prepare the dual-curable electrical conductive adhesive (ECA). The characterization of Ag-G has been carried out by transmission electron microscope, X-ray diffraction, Raman spectrum, and X-ray photoelectron spectroscopy. Results showed that the Ag-G has been successfully prepared and the relative amount of Ag nanoparticles was 11.25 At%. The mechanical and conductive properties together with thermal stability of ECA have also been investigated. The shear strength reached to 4.67 MPa and the electrical conductivity of ECA reached to 0.41 S/cm when the content of conductive filler was 25 wt%, respectively. This content was regarded as the optimum. And, thermal analysis indicated that ECA exhibited better thermal stability than EA.

Carbon nanotube (CNT) threads are a type of CNT arrays that consist of super long CNTs. CNT threads inherit the advantages of CNTs, while avoiding the potential toxicity caused by individual CNTs. Electrodes based on CNT threads were fabricated and used for simultaneous detection of trace levels of Cu2+, Pb2+ Cd2+ and Zn2+ by anodic stripping voltammetry (ASV). The detection limits are 0.27 nM, 1.5 nM, 1.9 nM and 1.4 nM for Cu2+, Pb2+, Cd2+ and Zn2+, respectively, in 0.1 M acetate buffer pH 4.5. The CNT thread electrode gives well-defined, reproducible and sharp stripping signals for individual and simultaneous detection of heavy metals.

This study gives the first-time evidence for China that the geographical heterogeneity of the acute effects of outdoor PM 10 can be partially explained by differences in indoor exposure to PM 10 of outdoor origin. We used data from the China Air Pollution and Health Effects Study (CAPES), which demonstrated a geographical heterogeneity of the acute effect of particulate air pollution (particulate matter with an aerodynamic diameter smaller than 10 μm, or PM 10 ) on mortality in 16 Chinese cities. Given that a large fraction of the exposure to PM 10 of outdoor origin occurs indoors, we made the hypothesis that this heterogeneity might be partially explained by inter-city differences in indoor exposure to PM 10 of outdoor origin. In our analysis, we estimated PM 10 exposure coefficients (the change in the estimated personal exposure to PM 10 of outdoor origin per unit change in outdoor PM 10 concentration) in these 16 Chinese cities and examined their correlation with PM 10 mortality coefficients (the increase in mortality associated with a given increase in the concentrations of outdoor PM 10 ). We showed that the PM 10 mortality coefficients and the PM 10 exposure coefficients were significantly correlated, with an R -squared ( R 2 ) value of 0.549 (95% confidence interval: 0.201, 0.771; p

Carbon nanotubes (CNTs) have attracted intense interest due to their excellent properties, such as increased electrode surface area, fast electron transfer rate, significant mechanical strength and good chemical stability. CNT threads, spun from shorter CNTs, inherit the advantages of CNTs, while avoiding the potential toxicity caused by individual CNTs. In this work, microelectrodes based on CNT threads were used to detect trace zinc by anodic stripping voltammetry with an estimated detection limit of 1.4 nM without mercury or bismuth films. CNT threads showed promise for measuring trace metals in small sample volumes without stirring such as encountered in some in vivo and in vitro applications.

Solid contact (SC) ion-selective electrodes (ISEs) have been recognized as the next generation of ISEs. In this work, the electrical conductivity and mechanical strength of a carbon nanotube (CNT) tower enable it to play the dual roles of transducer and substrate for micro SC-ISEs. The electrode had a close to Nernstian slope of 35 mV/decade aCa2+, a linear range of four orders of magnitude of calcium ion activity (10−5.6 to 10−1.8 M), and a detection limit of 1.6×10−6 M. The simplified fabrication by a one-step drop casting makes miniaturizing SC-ISEs and fabricating sensor arrays easier to achieve.

The effect of widely different corrosion rates of Mg alloys on four parameters of interest for in vivo characterization was evaluated: (1) the effectiveness of transdermal HBiodegradable devices based on magnesium and its alloys are promising because they gradually dissolve and thereby avoid the need for subsequent removal by surgery if complications arise. In vivo biodegradation rate is one of the crucial parameters for the development of these alloys. Promising alloys are first evaluated in vivo by being implanted subcutaneously in mice for 1month. Here, we evaluated several magnesium alloys with widely varying corrosion rates in vivo using multiple characterization techniques. Since the alloys biodegrade by reacting with water forming H

Carbon coating of fine particles of Li 4 Ti 5 O 12 synthesized under hydrothermal condition is carried out by amphiphilic carbonaceous material (ACM) in aqueous solution, followed by carbonization at 800 °C for 2 h. The particles prepared are comprised of highly-crystalline spinel-type Li 4 Ti 5 O 12 with the size in the range of 100–400 nm without any agglomeration, of which surface is uniformly covered by a thin carbon layer. Their electrochemical performance as an anode in lithium-ion batteries is evaluated. The initial discharge capacity of carbon-coated Li 4 Ti 5 O 12 at 20 C rate is 137 mA h g −1 and remains as high as 125 mA h g −1 after 100 cycles (91% retention), exhibiting good rate and cyclic performance. Carbon coating by using ACM as carbon precursor gives the Li 4 Ti 5 O 12 particles an enhanced performance as an anode in lithium-ion batteries, owing to the improvement in electrical conductivity, polarization and ability of dispersion. This non-organic coating process may present a new economic, facile, and green pathway for the preparation of carbon-coated Li 4 Ti 5 O 12 as a high power anode material in lithium-ion batteries.

Anodic stripping voltammetry (ASV) determination of Pb2+, Cd2+, and Zn2+ was done using metal catalyst free carbon nanotube (MCFCN) electrodes. Osteryoung square wave stripping voltammetry (OSWSV) was selected for detection. The MCFCNTs are synthesized via Carbo Thermal Carbide Conversion method which leads to residual transition metal free in the CNT structure. The new material shows very good results in detecting heavy metal ions, such as Pb2+, Cd2+, and Zn2+. The calculated limits of detection were 13 nM, 32 nM and 50 nM for Pb2+, Cd2+ and Zn2+, respectively with a deposition time of 150 s.

A label-free biosensor for Escherichia coli (E. coli) ORN 178 based on faradaic electrochemical impedance spectroscopy (EIS) was developed. α-Mannoside or β-galactoside was immobilized on a gold disk electrode using a self-assembled monolayer (SAM) via a spacer terminated in a thiol functionality. Impedance measurements (Nyquist plot) showed shifts due to the binding of E. coli ORN 178, which is specific for α-mannoside. No significant change in impedance was observed for E. coli ORN 208, which does not bind to α-mannoside. With increasing concentrations of E. coli ORN 178, electron-transfer resistance (R(et)) increases before the sensor is saturated. After the Nyquist plot of E. coli/mixed SAM/gold electrode was modeled, a linear relationship between normalized R(et) and the logarithmic value of E. coli concentrations was found in a range of bacterial concentration from 10(2) to 10(3) CFU/mL. The combination of robust carbohydrate ligands with EIS provides a label-free, sensitive, specific, user-friendly, robust, and portable biosensing system that could potentially be used in a point-of-care or continuous environmental monitoring setting.

Anodic stripping voltammetry (ASV) trace detection of the heavy metals ions Pb2+, Cd2+, Cu2+ and Zn2+ was done at highly aligned multi-wall carbon nanotube tower electrodes (CNT tower electrodes). The CNT tower electrode is one type of CNT array that consists of millions of ordered super long CNTs. Osteryoung square-wave stripping voltammetry was used for the stripping step. This electrode material shows good resolution for individual detection of these four metal ions with calculated detection limits of 12 nM, 25 nM, 44 nM and 67 nM for Pb2+, Cd2+, Cu2+ and Zn2+, respectively, for a deposition time of 120 s. The detectable limit was as low as 0.5 nM for a 10 min deposition.

Development of biodegradable metal implants is a complex problem because it combines engineering and medical requirements for a material. This article discusses the development of sensing and corrosion control techniques that can help in the design of biodegradable metallic implants. Biodegradable metallic implants dissolve as new tissue is formed. One of the most important factors in the design of biodegradable implants is to study the active interface, which should be monitored and controlled to address the medical concern of biocompatibility. Thus miniaturized and nanotechnology-based sensors that measure the activities of the degradation process and the formation of tissue are discussed for use with in vitro and in vivo experiments. These sensors can monitor chemical components and also cell activity and can provide new knowledge about biodegradable interfaces and how to actively control the interface to provide the best bioactivity to regenerate new tissue in a short time. Development of new alloys, nano-materials, miniature sensors, corrosion control coatings, and auxiliary applications such as biodegradable drug delivery capsules is expected to open up a new era in the engineering of materials for medicine.

The surface properties of glass fiber were quantificationally analyzed by inverse gas chromatography (IGC). Five n-alkanes (C6, C7, C8, C9, and C10) were chosen as apolar probes to characterize the dispersive component of surface free energy. Trichloromethane (CHCl3), acetone, and tetrahydrofuran (THF) were chosen as polar probes to detect the Lewis acid-base parameters. It is found that the dispersive components of free energy are 32.3, 30.5, 27.5, and 26.9 mJ/m2 at 70, 80, 90, and 100 °C, respectively. The Lewis acidic number Ka of the glass fiber is 0.512 4, and the basic number Kb is 2.862. The results mean the glass fiber is a Lewis basic material.

Li 4 Ti 5 O 12 ultrafine powders were synthesized by hydrothermal method using aqueous TiCl 4 solution and LiOH·H 2 O as raw materials. The prepared particles comprise crystalline spinel-type Li 4 Ti 5 O 12 with the size in the range of 100–400 nm without any agglomerate. Electrochemical measurements were then carried out to evaluate the anode performances of Li 4 Ti 5 O 12 samples in lithium-ion batteries. The initial discharge capacity is 172.8 mAh g − 1 at 0.1 C and 142.4 mAh g − 1 at 10 C. It maintained its capacitance to as high as 122.2 mAh g − 1 (87.3% retention) at 10 C even after 100 cycles, indicating a good rate and cyclic performance. This novel non-organic hydrothermal method presented an economical, facile and green pathway for Li 4 Ti 5 O 12 as anode material in lithium-ion batteries of high power densities.

A Nafion film loaded with novel catalyst-free multiwalled carbon nanotubes (MWCNTs) was used to modify a glassy carbon (GC) electrode to detect trace concentrations of metal ions, with europium ion (Eu(3+)) as a model. The interaction between the sidewalls of MWCNTs and the hydrophobic backbone of Nafion allows the MWCNTs to be dispersed in Nafion, which was then coated as a thin film on the GC electrode surface. The electrochemical response to Eu(3+) was found to be ∼10 times improved by MWCNT concentrations between 0.5 and 2 mg/mL, which effectively expanded the electrode surface into the Nafion film and thereby reduced the diffusion distance of Eu(3+) to the electrode surface. At low MWCNT concentrations of 0.25 and 0.5 mg/mL, no significant improvement in signal was obtained compared with Nafion alone. Scanning electron microscopy and electrochemical impedance spectroscopy were used to characterize the structure of the MWCNT-Nafion film, followed by electrochemical characterization with Eu(3+) via cyclic voltammetry and preconcentration voltammetry. Under the optimized conditions, a linear range of 1-100 nM with a calculated detection limit of 0.37 nM (signal/noise = 3) was obtained for determination of Eu(3+) by Osteryoung square-wave voltammetry after a preconcentration time of 480 s.

Understanding Mg corrosion is important to the development of biomedical implants made from Mg alloys. Mg corrodes readily in aqueous environments, producing H2, OH- and Mg2+. The rate of formation of these corrosion products is especially important in biomedical applications where they can affect cells and tissue near the implant. We have developed a corrosion characterization system (CCS) that allows realtime monitoring of the solution soluble corrosion products OH-, Mg2+, and H2 during immersion tests commonly used to study the corrosion of Mg materials. Instrumentation was developed to allow the system to also record electrochemical impedance spectra simultaneously in the same solution to monitor changes in the Mg samples. We demonstrated application of the CCS by observing the corrosion of Mg (99.9%) in three different corrosion solutions: NaCl, HEPES buffer, and HEPES buffer with NaCl at 37°C for 48 h. The solution concentrations of the corrosion products measured by sensors correlated with the results using standard weight loss measurements to obtain corrosion rates. This novel approach gives a better understanding of the dynamics of the corrosion process in realtime during immersion tests, rather than just providing a corrosion rate at the end of the test, and goes well beyond the immersion tests that are commonly used to study the corrosion of Mg materials. The system has the potential to be useful in systematically testing and comparing the corrosion behavior of different Mg alloys, as well as protective coatings.

A biosensor is an electronic device that measures biologically important parameters. An example is a sensor that measures the chemicals and materials released during corrosion of a biodegradable magnesium implant that impact surrounding cells, tissues and organs. A responsive biosensor is a biosensor that responds to its own measurements. An example is a sensor that measures the corrosion of an implant and automatically adjusts (slows down or speeds up) the corrosion rate. The University of Cincinnati, the University of Pittsburgh, North Carolina A&T State University, and the Hannover Medical Institute are collaborators in an NSF Engineering Research Center (ERC) for Revolutionizing Metallic Biomaterials (RBM). The center will use responsive sensors in experimental test beds to develop biodegradable magnesium implants. Our goal is to develop biodegradable implants that combine novel bioengineered materials based on magnesium alloys, miniature sensor devices that monitor and control the corrosion, and coatings that slow corrosion and release biological factors and drugs that will promote healing in surrounding tissues. Responsive biosensors will monitor what is happening at the interface between the implant and tissue to ensure that the implant is effective, biosafe, and provides appropriate strength while degrading. Corrosion behavior is a critical factor in the design of the implant. The corrosion behavior of implants will be studied using biosensors and through mathematical modeling. Design guidelines will be developed to predict the degradation rate of implants, and to predict and further study toxicity arising from corrosion products (i.e., Mg ion concentrations, pH levels, and hydrogen gas evolution). Knowing the corrosion rate will allow estimations to be made of implant strength and toxicity risk throughout the degradation process.Copyright © 2009 by ASME

The flower-like Cu 2 O nanostructures were hydrothermally synthesized without using any template or surfactant. The influences of hydrothermal temperature, reaction time and reactants concentrations on the growth of nanostructures were investigated in detail. The samples were characterized by scanning electron microscope (SEM) and X-ray powder diffraction (XRD). Cu 2 O crystals with different shapes, i.e., flower-like (F-product) cubic box (CB-product) and cubic box with holes in each face (CBH-product), were synthesized by controlling the synthesis parameters and explored for CO catalytic oxidation. It was found that F-product showed higher catalytic than others.

Ag @ C core–shell structures were prepared using hydrothermal methods by AgNO 3 reduction with ascorbic acid in the presence of polyacrylamide (PAM). Temperature plays a key role in the formation of the core–shell structures. The roles of reactants, surfactant concentrations and reaction time on the morphologies of core–shell nanoparticles were investigated in detail. This synthetic method is one-pot synthesis, which is fast, high-yield and environmental-friendly for fabrication of Ag @ C core–shell structures. The surface properties of core–shell Ag @ C nanoparticles were characterized by Raman spectroscopy.

One-step synthetic route has been developed for the preparation of Nd ( OH )3 nanorods in the presence of n-butylamine. The as-prepared sample is in hexagonal phase with good crystallinity, and made up of highly dispersed nanorods of 14–15 nm in diameter and up to 40–50 nm in length at 120°C for 24 h. Optical measurements show that these nanorods have intensive photoluminescence (PL) at room temperature and have the potential to become optical materials. Thermogravimetric analysis (TGA) of the Nd ( OH )3 nanorods reveals that the nanorods remain stable up to 220°C and decompose to the derived oxide of Nd 2 O 3 at higher temperatures. The derived oxides show the promise active catalyst for the oxidation of carbon monoxide. In addition, this synthetic route has been developed for the synthesis of a series of other lanthanide hydroxides nanorods including Pr ( OH )3, Sm ( OH )3, Eu ( OH )3, Gd ( OH )3, Tb ( OH )3 and Dy ( OH )3, and their PL properties, thermostability and catalytic properties are investigated.

not Available.