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Abstract: Mesoporous silicas have a very attractive ability of sorption and enrichment of metal ions due to their huge surface area and facile functionalization by organic ligands. In this work, phosphonate-amino bifunctionalized mesoporous silica SBA-15 (PA-SBA-15) as U(VI) sorbent was fabricated through post-grafting method. The obtained mesoporous silica was characterized by SEM, XRD, NMR and nitrogen sorption/desorption experiments, which revealed the existence of ordered mesoporous structure with uniform pore diameter and large surface area. The adsorptivity of PA-SBA-15 for U(VI) from aqueous solution was investigated using batch sorption technique under different experimental conditions. The preliminary results show that the U(VI) sorption by PA-SBA-15 is very quick with equilibrium time of less than 1 h, and the U(VI) uptake is as large as 373 mg/g at pH 5.5 under 95 °C. The sorption isotherm has been successfully modeled by the Langmuir isotherm, suggesting a monolayer homogeneous sorption of U(VI) in PA-SBA-15. The sorption is pH-dependent due to the pH-dependent charge of sorbent in the aqueous solution. The thermodynamics research shows that the sorption is a feasible and endothermic process. Based on these results, PA-SBA-15 could be a promising solid phase sorbent for highly-efficient removal of U(VI) ions from waste water and enrichment of U(VI) from a solution at a very low level.

Dissolved uranium in groundwater contaminated by acid in situleaching poses a serious threat to human health and the ecosystem due to its toxicological properties. In this article, carboxy methyl cellulose (CMC) with high dispersity was used to stabilize nano zero-valent iron (nZVI), and highly dispersed CMC-stabilized nZVI (CMC-nZVI) was synthesized by a liquid-phase reduction method, characterized by multiple analysis techniques, and tested for its dispersal and antioxidizing properties. Compared with nZVI, CMC-nZVI showed great dispersal and resistance to oxidation. The effects of oxygen, pH, dosage, initial U(vi) concentration and HA concentration on U(vi) elimination by CMC-nZVI, and the U(vi) removal kinetics and mechanism were investigated. The removal capacity of U(vi) by CMC-nZVI was 400 mg g−1at pH 3.0, and the dose of 0.1 g L−1showed excellent uranium removal efficiency under acid conditions. Moreover, CMC-nZVI was used to treat groundwater from an area after acid in situleach uranium mining, and CMC-nZVI was found to be capable of decreasing the concentration of uranium in the acidic groundwater (pH < 3) from 0.321 to 0.001 mg L−1. The results indicate that CMC-nZVI has potential application prospects in the in situremediation of groundwater in areas after acid in situleach uranium mining.

Sinonasal mucosal melanoma is a rare tumor arising within the nasal cavity, paranasal sinuses, or nasopharynx (sinonasal tract). This study evaluated 90 cases diagnosed in 29 males and 61 females with median age 68 years. Most tumors involved the nasal cavity and had an epithelioid morphology. Spectrum of research techniques used in this analysis includes targeted-DNA and -RNA next-generation sequencing, Sanger sequencing, fluorescence in situ hybridization and immunohistochemistry. Sinonasal melanomas were commonly driven by RAS(38/90, 42%), especially NRAS(n= 36) mutations and rarely (4/90, 4%) displayed BRAFpathogenic variants. BRAF/RASmutants were more frequent among paranasal sinuses (10/14, 71%) than nasal (26/64, 41%) tumors. BRAF/RAS-wild type tumors occasionally harbored alterations of the key components and regulators of Ras-MAPK signaling pathway: NF1mutations (1/17, 6%) or NF1locus deletions (1/25, 4%), SPRED1(3/25, 12%), PIK3CA(3/50, 6%), PTEN(4/50, 8%) and mTOR(1/50, 2%) mutations. These mutations often occurred in a mutually exclusive manner. In several tumors some of which were NRASmutants, TP53was deleted (6/48, 13%) and/or mutated (5/90, 6%). Variable nuclear accumulation of TP53, mirrored by elevated nuclear MDM2 expression was seen in >50% of cases. Furthermore, sinonasal melanomas (n= 7) including RAS/BRAF-wild type tumors (n= 5) harbored alterations of the key components and regulators of canonical WNT-pathway: APC(4/90, 4%), CTNNB1(3/90, 3%) and AMER1(1/90, 1%). Both, TERTpromoter mutations (5/53, 9%) and fusions (2/40, 5%) were identified. The latter occurred in BRAF/RAS-wild type tumors. No oncogenic fusion gene transcripts previously reported in cutaneous melanomas were detected. Eight tumors including 7 BRAF/RAS-wild type cases expressed ADCK4::NUMBLcis-fusion transcripts. In summary, this study documented mutational activation of NRASand other key components and regulators of Ras-MAPK signaling pathway such as SPRED1in a majority of sinonasal melanomas.

Sinonasal mucosal melanoma is a rare tumor arising within the nasal cavity, paranasal sinuses, or nasopharynx (sinonasal tract). This study evaluated 90 cases diagnosed in 29 males and 61 females with median age 68 years. Most tumors involved the nasal cavity and had an epithelioid morphology. Spectrum of research techniques used in this analysis includes targeted-DNA and -RNA next-generation sequencing, Sanger sequencing, fluorescence in situ hybridization and immunohistochemistry. Sinonasal melanomas were commonly driven by RAS(38/90, 42%), especially NRAS(n= 36) mutations and rarely (4/90, 4%) displayed BRAFpathogenic variants. BRAF/RASmutants were more frequent among paranasal sinuses (10/14, 71%) than nasal (26/64, 41%) tumors. BRAF/RAS-wild type tumors occasionally harbored alterations of the key components and regulators of Ras-MAPK signaling pathway: NF1mutations (1/17, 6%) or NF1locus deletions (1/25, 4%), SPRED1(3/25, 12%), PIK3CA(3/50, 6%), PTEN(4/50, 8%) and mTOR(1/50, 2%) mutations. These mutations often occurred in a mutually exclusive manner. In several tumors some of which were NRASmutants, TP53was deleted (6/48, 13%) and/or mutated (5/90, 6%). Variable nuclear accumulation of TP53, mirrored by elevated nuclear MDM2 expression was seen in >50% of cases. Furthermore, sinonasal melanomas (n= 7) including RAS/BRAF-wild type tumors (n= 5) harbored alterations of the key components and regulators of canonical WNT-pathway: APC(4/90, 4%), CTNNB1(3/90, 3%) and AMER1(1/90, 1%). Both, TERTpromoter mutations (5/53, 9%) and fusions (2/40, 5%) were identified. The latter occurred in BRAF/RAS-wild type tumors. No oncogenic fusion gene transcripts previously reported in cutaneous melanomas were detected. Eight tumors including 7 BRAF/RAS-wild type cases expressed ADCK4::NUMBLcis-fusion transcripts. In summary, this study documented mutational activation of NRASand other key components and regulators of Ras-MAPK signaling pathway such as SPRED1in a majority of sinonasal melanomas.

Low-cost P2-type Cu/Fe/Mn-based layered oxide is considered a promising cathode material of sodium ion batteries (SIBs) for large-scale application. However, the abnormal initial Coulombic efficiency (ICE) of a P2-type Cu/Fe/Mn-based cathode is always much higher than 100% due to the difference of Na+extraction and insertion content in the first cycle, which becomes an obstacle to its commercialization. Herein, we reveal that increasing the charge capacity contribution of Mn3+/4+from an open circuit voltage to a high cutoff voltage by adjusting the initial valence state of Mn ions can effectively solve this problem. The optimized P2-type Na0.85Cu0.1Fe0.25Mn0.65O2cathode demonstrates a high energy density of 452 Wh kg–1and an ICE of 100.9%. This work provides a regulated strategy for optimizing ICE in the Na-defective layered oxides cathode in SIBs.

In this work, we investigated the dissolution behavior of U3O8and UO3in the LiCl–KCl molten salt using 2.9 or 9.5 wt % AlCl3as a chlorination agent under an argon atmosphere at 450 °C. Ultraviolet–visible/Ultraviolet–visible–near infrared absorption spectroscopy (UV–vis/UV–vis–NIR), fluorescence emission spectroscopy (FL), X-ray absorption fine structure (XAFS), and electrochemical techniques were used to systematically study the chemical species and the transformation of the dissolved products of U3O8and UO3. It was found that with the aid of AlCl3, the initial products of U3O8and UO3dissolution were different. The initial products of U3O8were UO2Cl42–and UCl62–, while the initial product of UO3dissolution was UO2Cl42–. Interestingly, regardless of U3O8or UO3, with the increase of AlCl3content, the UO2Cl42–in their dissolved products showed a tendency to transform into UCl62–. In addition, UCl4was produced by mixing 0.05 g of U3O8/UO3powders with 10 times the amount of AlCl3and heating them at 300 °C for 2 h. This work focuses on the pyrochemical reprocessing of spent oxide fuels, deepening the understanding of the dissolution of uranium oxides in higher oxidation states, and enriching the knowledge of uranium in the transformation of chemical species in molten salts.

Nitrogen (N) and phosphorus (P) are two essential nutrients that determine plant growth and many nutrient cycling processes. Increasing N and P deposition is an important driver of ecosystem changes. However, in contrast to numerous studies about the impacts of nutrient addition on forests and temperate grasslands, how plant foliar stoichiometry and nutrient resorption respond to N and P addition in alpine grasslands is poorly understood. Therefore, we conducted an N and P addition experiment (involving control, N addition, P addition, and N+P addition) in an alpine grassland on Kunlun Mountains (Xinjiang Uygur Autonomous Region, China) in 2016 and 2017 to investigate the changes in leaf nutrient concentrations (i.e., leaf N, Leaf P, and leaf N:P ratio) and nutrient resorption efficiency of Seriphidium rhodanthumand Stipa capillata, which are dominant species in this grassland. Results showed that N addition has significant effects on soil inorganic N (NO3−-N and NH4+-N) and leaf N of both species in the study periods. Compared with green leaves, leaf nutrient concentrations and nutrient resorption efficiency in senesced leaves of S. rhodanthumwas more sensitive to N addition, whereas N addition influenced leaf N and leaf N:P ratio in green and senesced leaves of S. capillata. N addition did not influence N resorption efficiency of the two species. P addition and N+P addition significantly improved leaf P and had a negative effect on P resorption efficiency of the two species in the study period. These influences on plants can be explained by increasing P availability. The present results illustrated that the two species are more sensitive to P addition than N addition, which implies that P is the major limiting factor in the studied alpine grassland ecosystem. In addition, an interactive effect of N+P addition was only discernable with respect to soil availability, but did not affect plants. Therefore, exploring how nutrient characteristics and resorption response to N and P addition in the alpine grassland is important to understand nutrient use strategy of plants in terrestrial ecosystems.

Supplemental Digital Content is available in the text.This study determined the frequency and the clinicopathologic and genetic features of colorectal carcinomas driven by oncogenic fusions of the anaplastic lymphoma kinase gene (ALK). Of the 8150 screened tumors, 12 (0.15%) were immunohistochemically ALK-positive with D5F3 antibody. These cancers harbored CAD-ALK(n=1), DIAPH2-ALK(n=2), EML4-ALK(n=2), LOC101929227-ALK(n=1), SLMAP-ALK(n=1), SPTBN1-ALK(n=4), and STRN-ALK(n=1) fusions, as detected by an RNA-based next-generation sequencing assay. ALKfusion carcinomas were diagnosed mostly in older patients with a 9:3 female predominance (median age: 72 y). All tumors, except a rectal one, occurred in the right colon. Most tumors were stage T3 (n=7) or T4 (n=3). Local lymph node and distant metastases were seen at presentation in 9 and 2 patients. These tumors showed moderate (n=6) or poor (n=3) glandular differentiation, solid medullary growth pattern (n=2), and pure mucinous morphology (n=1). DNA mismatch repair–deficient phenotype was identified in 10 cases. Tumor-infiltrating lymphocytes were prominent in 9 carcinomas. In 4 carcinomas, tumor cells showed strong, focal (n=3), or diffuse programmed death-ligand 1 immunoreactivity. CDX2 expression and loss of CK20 and MUC2 expression were frequent. CK7 was expressed in 5 tumors. Four patients died of disease within 3 years, and 7 were alive with follow-up ranging from 1 to 8 years. No mutations in BRAF, RAS, and in genes encoding components of PI3K-AKT/MTOR pathway were identified. However, 1 tumor had a loss-of-function PTENmutation. Aberration of p53 signaling, TP53mutations, and/or nuclear accumulation of p53 protein was seen in 9 cases. ALKfusion colorectal carcinomas are a distinct and rare subtype of colorectal cancers displaying some features of mismatch repair–deficient tumors.

Crystal facet engineering has attracted considerable interests in the surface gas–solid chemical reaction such as the application in gas sensing due to the unique properties derived by different atom arrangements, bond energies, and charge densities. Herein, various hierarchical SnO2nanostructures with different exposed facets including (110) facets exposed irregular decahedrons and (101) facets exposed nanorods and nanocones were successfully synthesized by different Zn doping via a hydrothermal process. We found that the difference in the exposed facets was induced by low Zn-doping energy of (101) facets compared with that of the (110) facets. Experimental and density functional theory calculation results confirmed that the Zn doping in the (101) surface of SnO2nanostructure could facilitate the generation of ionosorbed oxygen species and optimize the electronic structure. When applied to detecting triethylamine (TEA), the SnO2nanostructure with exposed well-engineered (101) facets exhibited an excellent sensitivity toward TEA with the detection limit of 50 ppb at low working temperature (70 °C). This work not only posed a new pathway to enhance facet-related properties of metal oxides semiconductors but also developed the various applications in detecting and catalyzing harmful gases in the environment.

To promote the application of a new type of bionic energy-efficient sandwich plate with light weight and high strength in the construction field, a drop hammer impact test was adopted to determine the impact mechanical properties and influencing mechanism of fiber reinforced cement-based energy-efficient honeycomb plates with different core fillers (shredded straw and glass beads). The results show that compared with unfilled honeycomb plates (CHP), the contact force–time curves of energy-efficient plates have an obvious secondary peak, and the size of the damaged area on the back side of the upper skin is significantly reduced. Additionally, the presence of fillers in the energy-efficient plates provide a certain constraint on the deformation of honeycomb walls and skins, and slightly increase the size of the secondary peak. Furthermore, this study qualitatively reveals the influence mechanisms of the flexural stiffness of the sandwich plates, the morphology of damaged skins and fillers, the deformation pattern of the honeycomb core. The results provide a reference for subsequent research on the influence of different fillers on sandwich plates.

Passive delivery of antibodies to mucosal sites may be a valuable adjunct to COVID-19 vaccination to prevent infection, treat viral carriage, or block transmission. Neutralizing monoclonal IgG antibodies are already approved for systemic delivery, and several clinical trials have been reported for delivery to mucosal sites where SARS-CoV-2 resides and replicates in early infection. However, secretory IgA may be preferred because the polymeric complex is adapted for the harsh, unstable external mucosal environment. Here, we investigated the feasibility of producing neutralizing monoclonal IgA antibodies against SARS-CoV-2. We engineered two class-switched mAbs that express well as monomeric and secretory IgA (SIgA) variants with high antigen-binding affinities and increased stability in mucosal secretions compared to their IgG counterparts. SIgAs had stronger virus neutralization activities than IgG mAbs and were protective against SARS-CoV-2 infection in an in vivomurine model. Furthermore, SIgA1 can be aerosolized for topical delivery using a mesh nebulizer. Our findings provide a persuasive case for developing recombinant SIgAs for mucosal application as a new tool in the fight against COVID-19.

HIV-1 infection remains a public health problem with no cure. Although antiretroviral therapy (ART) is effective for suppressing HIV-1 replication, it requires lifelong drug administration due to a stable reservoir of latent proviruses and may cause serious side effect and drive the emergence of drug resistant HIV-1 variants. Gene therapy represents an alternative approach to overcome the limitations of conventional treatments against HIV-1 infection. In this study, we constructed and investigated the antiviral effects of an HIV-1 Tat-dependent conditionally replicating adenovirus, which selectively replicates and expresses the diphtheria toxin A chain (Tat-CRAds-DTA) in HIV-1 infected cells both in vitro and in vivo. We found that Tat-CRAds-DTA could specifically induce cell death and inhibit virus replication in HIV-1 infected cells mediated by adenovirus proliferation and DTA expression. A low titer of progeny Tat-CRAds-DTA was also detected in HIV-1 infected cells. In addition, Tat-CRAds-DTA showed no apparent cytotoxicity to HIV-1 negative cells and demonstrated significant therapeutic efficacy against HIV-1 infection in a humanized mouse model. Findings in this study highlight the potential of Tat-CRAds-DTA as a new gene therapy for the treatment of HIV-1 infection.

Methanol oxidation reaction (MOR) in anodes is one of the significant aspects of direct methanol fuel cells (DMFCs), which also plays a critical role in achieving a carbon-neutral economy. Designing and developing efficient, cost-effective, and durable non-Pt group metal-based methanol oxidation catalysts are highly desired, but a gap still remains. Herein, we report well-defined hierarchical NiZnx@CuO nanoarray architectures as active electrocatalysts for MOR, synthesized by combining thermal oxidation treatment and magnetron sputtering deposition through a brass mesh precursor. After systematically evaluating the electrocatalytic performance of NiZnx@CuO nanoarray catalysts with different preparation conditions, we found that the NiZn1000@CuO (thermally oxidized at 500 °C for 2 h, nominal thickness of the NiZn alloy film is 1000 nm) electrode delivers a high current density of 449.3 mA cm–2at 0.8 V for MOR in alkaline media as well as excellent operation stability (92% retention after 12 h). These outstanding MOR performances can be attributed to the hierarchical well-defined structure that can not only render abundant active sites and a synergistic effect to enhance the electrocatalytic activity but also can effectively facilitate mass and electron transport. More importantly, we found that partial Zn atoms could leach from the NiZn alloy, resulting in rough surface nanorods, which would further increase the specific surface area. These results indicate that the NiZn1000@CuO nanoarray architecture could be a promising Pt group metal alternative as an efficient, cost-effective, and durable anode catalyst for DMFCs.

Up to 30% of the municipal solid waste (MSW) that is incinerated for energy recovery ends up as MSW incinerator (MSWI) ash. In light of the large volume of MSWI ash and the expenses and regulatory burden if this ash were managed as a hazardous waste, U.S. MSWI facilities place great emphasis on ensuring MSWI ashes pass the toxicity characteristic leaching procedure (TCLP). The focus on passing the TCLP has the unintended consequence of making recycling more difficult and arguably making the ash less benign. This policy analysis examines current U.S. MSWI ash management practices in relation to the TCLP, and discusses the role of the TCLP as a regulatory driver in the management of MSWI ashes. A review of existing information, example data, and common MSWI ash management practices provide insight into potential issues with the current approach and opportunities for alternative directions.

In this work, the electrochemical behaviors of Er(III) on different kinds of electrode materials (W and liquid Al-Zn cathode), as a representative of lanthanides (Lns), were studied systematically by various electrochemical techniques. This opened the door toward the development of active electrode materials for recovering actinides (Ans) over Lns in chloride molten salts. Compared to the direct deposition of Er metal on an inert cathode, the reduction of Er(III) occurs at more anodic potentials via forming binary or ternary intermetallic compounds in both co-reduction and under potential deposition processes. In addition, potentiostatic and galvanostatic electrolysis were both conducted to confirm the formation of intermetallics, and some typical related intermetallic compounds were identified by X-ray diffraction (XRD) characterization. The morphology and composition of Er-Al-Zn ternary alloys were investigated using scanning electron microscopy with energy dispersive spectroscopy (SEM-EDS).

X-linked inheritance is very rare and is estimated to account for only 1–5% of all nonsyndromic hearing loss cases. We found a multiplex family from China segregating with X-linked nonsyndromic hearing loss. After exclusive analysis of 10 common variations of three hearing loss-related genes, GJB2, mtDNA12srRNAand SLC26A4, a novel truncated variant of SMPX, c.87dupA (p.Gly30Argfs*12) (NCBI ClinVar Submission ID: SUB3136126), was identified by whole-exome sequencing. This variant was co-segregated with hearing loss in the entire family and was absent in 576 unrelated ethnically and geographically matched controls. We also detected a single nucleotide variation in two male controls with normal hearing, SMPXc.55A>G (p.Asn19Asp), which has been annotated as a rare variant in the Single Nucleotide Polymorphism (dbSNP) (rs759552778) and Exome Aggregation Consortium (ExAC) databases. This study has enriched the mutation spectrum of the SMPXgene.

This work presents the electrochemical properties of gadolinium (Gd), a significant rare earth element in spent nuclear fuel (SNF), in the LiClKCl eutectic. To explore thermodynamic properties of Gd at the liquid gallium (Ga) electrode, experiments were performed both on the inert tungsten (W) and liquid gallium (Ga) electrode at different temperatures in a range from 723 to 823 K, which show that the Gd metal can be oxidized to Gd (III) by exchanging of 3 electrons. Electrochemical techniques including cyclic voltammetry (CV), open circuit potential (OCP), potentiostatic electrolysis and galvanostatic electrolysis were utilized to detect the electrochemical behavior and evaluate standard apparent potential of the Gd(Ⅲ)/Gd couple, and EGd(Ⅲ)/Gd*=−3.456+6.2×10−4T(±0.046)(vsCl2/Cl−)is obtained. In addition, electromotive force (EMF) and coulometric titration were employed to calculate the activity and activity coefficient of Gd in metal Ga. After calculation, the activity is 1.791×10−15at 723 K and function of activity coefficient and temperature is lgγ=3.485−10927/T(±0.0875).

This work presents the electrochemical behaviors of U on a liquid Bi electrode and the formation of Bi-U intermetallic compounds in LiCl-KCl eutectic. It was found that the deposition of U on the liquid Bi electrode was a two-step process. The activity coefficient of U in the liquid Bi was determined by coulometric titration and in-situ open circuit chronpotentiometry versus two different reference electrodes at the temperature range of 723 to 813K. The solubility of U in liquid Bi was evaluated by pulse electrolysis. Furthermore, thermodynamic properties of Bi-U intermetallic compounds were measured by open circuit chronopotentiometry. The linear dependence of the Gibbs free energy of formation as a function of temperature was obtained, from which the enthalpy and entropy of formation were also determined. The activities and partial molar Gibbs free energies of U in two phase coexisting states were calculated through the measurement of electromotive force. Galvanostatic electrolysis was then conducted to prepare Bi-U intermetallic compound in the LiCl-KCl-UCl3 melt on a liquid Bi electrode. The phase composition and microstructure of the alloy was characterized by X-ray diffraction (XRD) and Scanning Electron Microscopy (SEM) with Energy Dispersive Spectroscopy (EDS).

This work presents the electrochemical behaviors of Pr (III) on a liquid Bi electrode and the formation of Bi-Pr intermetallics in LiCl-KCl eutectic melt. Galvanostatic voltammetry and open circuit chronopotentiometry techniques were employed to determine the apparent standard potential of Pr(III)/Pr couple. The reduction of Pr (III) on the liquid Bi electrode is a one step process with three electrons transferred. The activity coefficient of Pr in liquid Bi was also determined by coulometric titration and in-situ open circuit chronopotentiometry at the temperature range of 723 to 813K. In addition, the signals of five intermetallic compounds corresponding to the Bi-Pr binary phase diagram were successively detected by a series of electrochemical techniques. Thermodynamic properties for the formation of Bi-Pr intermetallic compound were measured by open circuit chronopotentiometry. The activities and partial molar Gibbs free energies of Pr in the two phase coexisting system were obtained, from which the Gibbs free energy, the enthalpy and entropy of formation were also calculated.

Electrochemical sensors now play an important role in analysis and detection of nucleic acids. In this work, we present a novel double-signal technique for electrochemically measuring the sequence and length of the d(CAG)nrepeat. The double-signal technique used an electrochemical molecular beacon (a hairpin DNA labeled with ferrocene), which was directly modified on the surface of a gold electrode, while a reporter probe (a DNA sequence labeled with horseradish peroxidase) was hybridized to the target DNA. First a simple single-signal sensor was characterized in which d(CAG)nrepeats were detected using a short reporter DNA strand labeled with horseradish peroxidase. To obtain a reliable signal that was dependent on repeat number, a double-signal biosensor was created in which the single strand capture DNA in single-signal sensor was replaced by an electrochemical molecular beacon labeled with ferrocene. When the hairpin DNA hybridized to the target–reporter DNA complex, it opened, resulting in a decreased ferrocene current. Both electrochemical biosensors exhibited high selectivity and sensitivity with low detection limits of 0.21 and 0.15 pM, respectively, for the detection of d(CAG)nrepeats. The double-signal sensor was more accurate for the determination of repeat length, which was measured from the ratio of signals for HRP and ferrocene (H/F). A linear relationship was found between H/F and the number of repeats (n), H/F = 0.1398n+ 9.89788, with a correlation coefficient of 0.974. Only 10 nM of target DNA was required for measurements based on the value of H/F in the double-signal technique. These results indicated that this new double-signal electrochemical sensor provided a reliable method for the analysis of CAG trinucleotide repeats.

Waardenburg syndrome (WS) is an autosomal dominant inherited neurogenic disorder with the combination of various degrees of sensorineural deafness and pigmentary abnormalities affecting the skin, hair and eye. The four subtypes of WS were defined on the basis of the presence or absence of additional symptoms. Mutation of human microphthalmia-associated transcription factor (MITF) gene gives rise to WS2. Here, we identified a novel WS-associated mutation at the stop codon of MITF (p.X420Y) in a Chinese WS2 patient. This mutation resulted in an extension of extra 33 amino-acid residues in MITF. The mutant MITF appeared in both the nucleus and the cytoplasm, whereas the wild-type MITF was localized in the nucleus exclusively. The mutation led to a reduction in the transcriptional activities, whereas the DNA-binding activity was not altered. We show that the foremost mechanism was haploinsufficiency for the mild phenotypes of WS2 induced in X420Y MITF.

Electrochemical properties of rare-earth elements in the LiCl-KCl eutectic are important for the pyrometallurgical recycling process of spent nuclear fuels. In this work, the electrochemical properties of Tb (III)/Tb (0) couple were studied by the cyclic voltammetry (CV) at a liquid Zn pool electrode. The results showed that this electrochemical reaction is quasi-reversible with mixed reversible diffusion control and the charge transfer control. The diffusion coefficient of Tb (III) was determined to be in the order of ~10−5cm2s−1. Moreover, kinetic parameters, such as the standard rate constants (ks) and charge transfer coefficient (α) for the electroreduction of Tb (III) to Tb (0) at the liquid Zn electrode, were calculated by the Nicholson method at 873 K. Additionally, it was found that Tb-Zn intermetallic compounds were easily to be formed in the measurements. Hence, the reduction process of Tb (III)/Tb (0) couple on the Zn-coated Mo electrode was also studied to obtain more information of the Tb-Zn intermetallic compounds. Electrochemical signals stemming from various intermetallic compounds associated with TbZn12, Tb2Zn17, Tb13Zn58, Tb3Zn11, TbZn3, TbZn2and TbZn, were observed. The thermodynamic data were thereafter estimated by applying the emf method at 823–923 K. The standard formation Gibbs energies and the standard equilibrium constant of each Tb-Zn intermetallic compounds were also calculated. Finally, enthalpies and entropies of formation and the apparent standard potentials of various Tb-Zn intermetallic compounds were also obtained.

Allogeneic hematopoietic stem cell transplantation (HSCT) is a potentially curative therapy for many malignant and nonmalignant diseases. However, chronic graft‐versus‐host disease (cGVHD) remains a significant cause of late morbidity and mortality after allogeneic HSCT. cGVHD often manifests as autoimmune syndrome. Thymic epithelial cells (TECs) play a critical role in supporting negative selection and regulatory T‐cell (Treg) generation. Studies have shown that damage in TECs is sufficient to induce cGVHD. We have previously reported that mouse embryonic stem cells (mESCs) can be selectively induced to generate thymic epithelial progenitors (TEPs) in vitro. When transplanted in vivo, mESC‐TEPs further develop into TECs that support T‐cell development. We show here that transplantation of donor‐origin mESC‐TEPs into cGVHD recipients induces immune tolerance to both donor and host antigens and prevents the development of cGVHD. This is associated with more TECs and Tregs. Our results suggest that embryonic stem cell‐derived TEPs may offer a new tool to control cGVHD. StemCellsTranslationalMedicine2017;6:121–130

The Ni5Zr alloy prepared from the mixture of nickel oxide (NiO) and zirconium oxide (ZrO2) powders by direct electrochemical reduction was conducted in molten lithium chloride (LiCl) at 923 K. The electrochemical reduction behaviors of ZrO2 and NiO-ZrO2 mixture were firstly investigated by cyclic voltammetry measurements. The influence of process parameters such as oxide composition, compression force, sintering time, and cell voltage on the electrolysis process have been comprehensively evaluated in terms of the electrochemical reducibility of ZrO2. The results demonstrated that the reduction starts with the reduction of NiO to Ni metal, and is followed by the reduction of ZrO2 on the pre-formed Ni particles to generate the intermetallic Ni5Zr. The pure Ni5Zr alloy can be prepared by direct electrochemical reduction of mixed 5NiO-ZrO2 pellets when the cell voltage of 3.2 V is applied. The reduction rate increases with higher content of NiO in a NiO-ZrO2 mixture pellet. However, the quality of formed Ni5Zr intermetallic compound particle seems unaffected under different preparation conditions.

Na3V2(PO4)3(NVP) is one of the most potential cathode materials for sodium-ion batteries (SIBs), but its actual electrochemical performance is limited by the defects of large electron and ion transfer resistance. Multicomponent design is considered an effective method to optimize the conductivity of NVP electrodes. Therefore, Cr and Si are added in NVP to form a multielement component of Na3V1.9Cr0.1(PO4)2.9(SiO4)0.1(NVP-CS). It is confirmed that 3d electrons of Cr are beneficial for improving the conductivity and increasing the average potential by activating V4+/V5+. Theoretical calculations show that the introduction of Si changes the electronic structure of V and O, thus promoting the electrochemical reaction of V3+/V4+to exert higher capacity. Due to the coordination of the two elements, a lower migration barrier is obtained in NVP-CS. Specifically, NVP-CS retains the advantages of single-doped electrodes very well (capacity retention of 90% after 300 cycles at 1 C and a high capacity of 94.1 mA h g–1at 5 C, compared to NVP with only 82.6% capacity retention at 1 C and 59.4 mA h g–1at 5 C). The excellent electrochemical performance results show that NVP can be successfully optimized by the introduction of Cr and Si. This work can provide some inspiration for multicomponent material research of cathode materials.

Herein, calcium peroxide modified mesoporous silica (CPMS) was successfully synthesized by a facile strategy and used for simultaneous adsorption and immobilization of U(VI) from uranium-containing wastewater. The batch uranium adsorption experiments reveal excellent adsorption performance of CPMS over a wide pH value. In comparison to calcium peroxide and mesoporous silica, the CPMS showed a great improvement in the removal capacity of uranium. As well, the pseudo-second-order model and Langmuir isotherm model provided a well description of adsorption kinetics and isotherm, respectively, which suggested the monolayer chemisorption governed the adsorption of CPMS for U(VI). In addition, the Langmuir isotherm model calculated the maximum adsorption capacity of CPMS for U(VI) up to 613.50 mg/g. Based on mechanistic studies of XPS, FT-IR, TEM and XRD, U(VI) is predominantly removed through synergistic adsorption of U(VI) by mesoporous silicon and immobilization of U(VI) by calcium peroxide as (UO2)O2•2 H2O (metastudtite). Furthermore, the efficient removal ability of CPMS for U(VI) in uranium tailings leachate was confirmed by column test, the U(VI) concentration of uranium tailings leachate can be reduced from 180.4 μg/L to 2.3 μg/L in 1895.2-bed volumes, which was well lower than the standard limit of WHO for U(VI) concentration in drinking water. This research provides a feasible approach and new idea for the efficient treatment of radioactive wastewater.

Combination of genistein (GT) and verapamil, a P-glycoprotein (P-gp) inhibitor, can increase GT absorption in situ perfusion technology in rat. To date, little information is yet available about the effect of verapamil on oral absorption of GT in vivo. In this study, a simple and reproducible HPLC–UV method was developed and validated for determination of total GT in rat plasma. Based on this, a pharmacokinetic experiment was designed to characterize biopharmaceutical properties of GT with or without coadministration of verapamil (10.0, 20.0, 30.0 mg/kg) in rats. The coadministration of verapamil (30.0 mg/kg) with GT caused a significant increase of the maximum GT plasma concentration (1.31-fold vs. GT, P< 0.05) and area under the curve (1.39-fold vs. GT, P< 0.05). Our data show that verapamil would increase intestinal absorption of GT in rat, suggesting there is some drug–nutrition interaction between verapamil and GT.

Imatinib mesylate resistance occurs in some patients with gastrointestinal stromal tumors (GISTs) during the course of treatment. In this study, we investigated the relationship between microRNAs (miRNAs) and imatinib-resistant GISTs, and the effect of miR-518a-5p on PIK3C2A in imatinib-resistant GISTs. A total of 20 matched-pair GIST samples from imatinib-resistant patients were included in the study. Each of the paired tumor specimens were from the same patient who had surgical removal of GISTs preimatinib and postimatinib treatment. Seven pairs of tissues were resected for microarray analysis, and the remaining 13 pairs were utilized for miRNAs analysis. Target genes were selected based on bioinformatics from multiple biological databases. Luciferase reporter assays were used to confirm the binding of miR-518a-5p to PIK3C2A 3′UTR. GIST882R-NC, 882R-miR-518a-5p-OE, and 882R-miR-518a-5p-KD cell lines were constructed using lentiviral vectors. miR-518a-5p and PIK3C2A expression in 882R-NC, 882R-OE, and 882R-KD cells was assessed by real-time PCR and western blotting. A cell counting kit was used to detect the influence of miR-518a-5p to cell proliferation. TUNEL staining was applied to detect the influence of miR-518a-5p to cell apoptosis. Microarray analysis showed that miR-518a-5p was downregulated in imatinib-resistant GISTs, and the expression of miR-518a-5p was confirmed with good concordance between real-time PCR and miRNA microarray results. Luciferase reporter assays indicated that miR-518a-5p bound to the PIK3C2A 3′UTR. Compared with 882R-OE, PIK3C2A expression was significantly increased in 882R-KD cells. MiR-518a-5p reduced 882R proliferation and promoted 882R apoptosis. In conclusion, PIK3C2A is a gene-specific target of miR-518a-5p in imatinib mesylate-resistant GISTs. Low expression of miR-518a-5p is likely to upregulate PIK3C2A and affect the cellular response to the drug, causing resistance to imatinib in GISTs.

Imatinib mesylate resistance occurs in some patients with gastrointestinal stromal tumors (GISTs) during the course of treatment. In this study, we investigated the relationship between microRNAs (miRNAs) and imatinib-resistant GISTs, and the effect of miR-518a-5p on PIK3C2A in imatinib-resistant GISTs. A total of 20 matched-pair GIST samples from imatinib-resistant patients were included in the study. Each of the paired tumor specimens were from the same patient who had surgical removal of GISTs preimatinib and postimatinib treatment. Seven pairs of tissues were resected for microarray analysis, and the remaining 13 pairs were utilized for miRNAs analysis. Target genes were selected based on bioinformatics from multiple biological databases. Luciferase reporter assays were used to confirm the binding of miR-518a-5p to PIK3C2A 3′UTR. GIST882R-NC, 882R-miR-518a-5p-OE, and 882R-miR-518a-5p-KD cell lines were constructed using lentiviral vectors. miR-518a-5p and PIK3C2A expression in 882R-NC, 882R-OE, and 882R-KD cells was assessed by real-time PCR and western blotting. A cell counting kit was used to detect the influence of miR-518a-5p to cell proliferation. TUNEL staining was applied to detect the influence of miR-518a-5p to cell apoptosis. Microarray analysis showed that miR-518a-5p was downregulated in imatinib-resistant GISTs, and the expression of miR-518a-5p was confirmed with good concordance between real-time PCR and miRNA microarray results. Luciferase reporter assays indicated that miR-518a-5p bound to the PIK3C2A 3′UTR. Compared with 882R-OE, PIK3C2A expression was significantly increased in 882R-KD cells. MiR-518a-5p reduced 882R proliferation and promoted 882R apoptosis. In conclusion, PIK3C2A is a gene-specific target of miR-518a-5p in imatinib mesylate-resistant GISTs. Low expression of miR-518a-5p is likely to upregulate PIK3C2A and affect the cellular response to the drug, causing resistance to imatinib in GISTs.

Although influenza is a common disease with characteristics of seasonality, the determinants of each season's onset, magnitude, and duration are poorly understood. This paper focuses on the role of environmental factors in spread and epidemic of seasonal influenza and explores the environmental explanatory factors for different types of influenza in mainland China. It also introduces satellite remote sensing as an important data obtaining approach, and highlights the potential of using satellite images for monitoring dynamics of climate and landscapes related to the spread of seasonal influenza. Applying Geographic Information System (GIS) technique combining with traditional statistical analysis, the paper uses influenza virus isolation rate (VIR) as the measure of influenza activity and analyzed its association with environmental factors. The results show that the spread and epidemic of influenza is influenced by various environmental factors, among which the temperature and humidity are seemed to be the determinants. However, the impacts of the environmental factors to different types of virus are varied. Low temperature and humidity conditions arere associated with a higher activity of both influenza A and B. On the contrary, high temperature and humidity conditions are associated with a higher activity of influenza A, but are associated with only a moderate or low, less consistent increase in the activity of influenza B. Recognition of this association could lead to better understanding of the mechanisms of emergence of influence epidemics and provide scientific evidence for controlling influenza.

The dramatically expanding coronavirus disease 2019 (COVID-19) needs multiple effective countermeasures. Neutralizing nanobodies (Nbs) are a potential therapeutic strategy for treating COVID-19. Here, we characterize several receptor binding domain (RBD)-specific Nbs isolated from an Nb library derived from an alpaca immunized with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein (S); among them, three Nbs exhibit picomolar potency against SARS-CoV-2 live virus, pseudotyped viruses, and circulating SARS-CoV-2 variants. To improve their efficacy, various configurations of Nbs are engineered. Nb15-NbH-Nb15, a trimer constituted of three Nbs, is constructed to be bispecific for human serum albumin (HSA) and RBD of SARS-CoV-2. Nb15-NbH-Nb15exhibits single-digit ng/ml neutralization potency against the wild-type and Delta variants of SARS-CoV-2 with a long half-life in vivo. In addition, we show that intranasal administration of Nb15-NbH-Nb15provides effective protection for both prophylactic and therapeutic purposes against SARS-CoV-2 infection in transgenic hACE2 mice. Nb15-NbH-Nb15is a potential candidate for both the prevention and treatment of SARS-CoV-2 through respiratory administration.

Electrochemical studies of UCl3and LnCl3(Ln: La, Ce, Pr, Nd) in LiCl-KCl melt were performed on inert tungsten and reactive bismuth electrodes. Galvanostatic pulse (GP) and electrochemical impedance spectroscopy (EIS) were carried out to investigate the exchange current density j0of UCl3/U on liquid Bi electrode at the temperature range of 723-873 K. The impedance data were well fitted with the equivalent circuit. The relationship between j0and the temperature was determined to model the electrowinning by using liquid Bi electrode. In addition, the electrochemical separation in low concentration uranium from multi-component lanthanide chlorides was demonstrated on liquid Bi electrode. Three electrochemical techniques, including coulometric titration, galvanostatic electrolysis and potentiostatic electrolysis, were applied for the separation of uranium. In which, the coulometric titration showed good separation results. The separation of uranium from lanthanides in terms of mole ratio (U/Ln) was determined, and the different values were discussed in detail. In general, the data from this work can provide theoretical reference for the separation process of various metals by electrochemistry.

Ni-based metallic foams possessing large specific surfaces and open cell structures are of specific interest as catalysts or catalyst carriers for electrolysis of water. Traditional fabrication of Nickel foam limits the element modification choices to several inert transition metals only on polymer foam precursor and subsequent preparation of foam-based catalysts in aqueous solution or organic electrolyte. To expand the modification horizon, molten salt with wide electrochemical window and fast ion diffusion can achieve the reduction of highly active elements. Herein, we reported is a general and facile method to deposit directly of highly reactive element La and prepare hierarchical honeycomb LaNi5alloy on Ni foam (ho-LaNi5/NF). This self-supporting electrode presents excellent electrical coupling and conductivity between the Ni foam and LaNi5, which provides a 3D self-supported heterostructure with outstanding electrocatalytic activity and excellent durability for the hydrogen evolution reaction (HER) and oxygen evolution reaction (OER). It exhibits excellent overpotential (1.86 V) comparable to commercial coupled IrO2//Pt/C (1.85 V) at a high current density of 100 mA cm−2. This work may pave the way for fabricating novel 3D self-supported honeycomb alloy that can be applied as electrode for usage of clean energy.

Electrochemical behaviors of lanthanide (i.e. La, Ce, Pr and Nd) chlorides in LiCl-KCl melt were demonstrated via cyclic voltammetry (CV) and open circuit potential (OCP) techniques at temperatures from 723 K to 873 K. An electrochemical galvanostatic intermittent titration technique (GITT) was performed to obtain the thermodynamic data of lanthanide (Ln) on liquid bismuth electrode. The relationship between activity coefficient and temperature were determined. Galvanostatic pulse (GP) and electrochemical impedance spectroscopy (EIS) as the transient measurements were performed to investigate the interfacial processes of Ln(III) on liquid Bi electrode. The exchange current densities j0of Ln(III)/Ln were determined by fitting and equivalent circuits, that showed the linear relationship with temperature. In addition, the electrodepositions of La and Ce on liquid Bi electrodes were discussed on the formation of alloys. The products of phase composition and microstructure were conducted by XRD and SEM-EDS, respectively.