Constructing Hierarchical Porous MoO2 @Mo2 N@C Composite via a Confined Pyrolysis Synthetic Strategy Towards Lithium-Ion Battery Anodes.

Molybdenum dioxide (MoO2 ) demonstrates a big potential toward lithium-ion storage due to its high theoretical capacity. The sluggish reaction kinetics and large volume change during cycling process, however, unavoidably lead to inferior electrochemical performance, thus failing to satisfy the requirements of practical applications. Herein, we developed a molybdenum-based oxyacid salt confined pyrolysis strategy to achieve a novel hierarchical porous MoO2 @Mo2 N@C composite. A two-step successive annealing process was proposed to obtain a hybrid phase of MoO2 and Mo2 N, which was used to further improve the electrochemical performance of MoO2 -based anode. We demonstrate that the well-dispersed MoO2 nanoparticles can ensure ample active sites exposure to the electrolyte, while conductive Mo2 N quantum dots afford pseudo-capacitive response, which conduces to the migration of ions and electrons. Additionally, the interior voids could provide buffer spaces to surmount the effect of volume change, thereby avoiding the fracture of MoO2 nanoparticles. Benefiting from the aforesaid synergies, the as-obtained MoO2 @Mo2 N@C electrode demonstrates a striking initial discharge capacity (1760.0 mAh g-1 at 0.1 A g-1 ) and decent long-term cycling stability (652.5 mAh g-1 at 1.0 A g-1 ). This work provides a new way for the construction of advanced anode materials for lithium-ion batteries.

Construction of N-Doped Carbon-Modified Ni/SiO2 Catalyst Promoting Cinnamaldehyde Selective Hydrogenation.

At present, the selective hydrogenation of α, ß-unsaturated aldehydes remains a challenge due to competition between unsaturated functional groups (C=C and C=O). In this study, N-doped carbon deposited on silica-supported nickel Mott-Schottky type catalysts (Ni/SiO2@NxC) was prepared for the selective hydrogenation of cinnamaldehyde (CAL) by using the respective hydrothermal method and high-temperature carbonization method. The prepared optimal Ni/SiO2@N7C catalyst achieved 98.9% conversion and 83.1% selectivity for 3-phenylpropionaldehyde (HCAL) in the selective hydrogenation reaction of CAL. By constructing the Mott-Schottky effect, the electron transfer from metallic Ni to N-doped carbon at their contact interface was promoted, and the electron transfer was demonstrated by XPS and UPS. Experimental results indicated that by modulating the electron density of metallic Ni, the catalytic hydrogenation of C=C bonds was preferentially performed to obtain higher HCAL selectivity. Meanwhile, this work also provides an effective way to design electronically adjustable type catalysts for more selective hydrogenation reactions.

Novel variant in BRAT1 with the lethal neonatal rigidity and multifocal seizure syndrome.

BACKGROUND: Lethal neonatal rigidity and multifocal seizure syndrome (RMFSL) is caused by variants in BRAT1 (BRCA1-associated protein required for ATM activation-1). However, the molecular mechanism of RMFSL is still unclear. METHODS: An RMFSL infant was recruited and the peripheral blood samples from his trio-family were collected. The genomic DNA was extracted, and then the whole-exome sequencing was performed. The expression of BRAT1 was analyzed by Western blotting. The subcellular localization of BRAT1 and MitoSOX (mitochondrial superoxide level) was investigated by confocal microscopy. The RNA samples were obtained from transfected cells, and then the RNA sequencing was performed. RESULTS: In this study, a novel homozygous BRAT1 variant c.233G > C with amino acid change of R with P at residue 78 (R78P) was identified. This variant altered the peptide structure and subcellular localization, as well as the expression in vitro. However, R78P did not alter the ability of BRAT1 to downregulate MitoSOX in mitochondria. Meanwhile, R78P BRAT1 was positively correlated with temporal lobe epilepsy, autosomal recessive primary microcephaly, defective/absent horizontal voluntary eye movements, and neuron apoptotic process as indicated by gene set enrichment analysis (GSEA). CONCLUSIONS: The BRAT1 variant spectrum has been expanded, which will be helpful for genetic counseling. We also explored the molecular mechanism altered by R78P, which will provide a better understanding of the pathogenesis of RMFSL. IMPACT: The detailed course of an infant with lethal neonatal RMFSL was depicted. A novel disease-causing variant R78P in BRAT1 for lethal neonatal RMFSL was identified. R78P led to reduced BRAT1 expression and nuclear localization in vitro. R78P did not alter the ability of BRAT1 to downregulate MitoSOX in the mitochondria. The variant R78P in BRAT1 was positively correlated with temporal lobe epilepsy, autosomal recessive primary microcephaly, defective/absent horizontal voluntary eye movements, and neuron apoptotic process as indicated by GSEA.

Molecular organization of mammalian meiotic chromosome axis revealed by expansion STORM microscopy.

During prophase I of meiosis, chromosomes become organized as loop arrays around the proteinaceous chromosome axis. As homologous chromosomes physically pair and recombine, the chromosome axis is integrated into the tripartite synaptonemal complex (SC) as this structure's lateral elements (LEs). While the components of the mammalian chromosome axis/LE-including meiosis-specific cohesin complexes, the axial element proteins SYCP3 and SYCP2, and the HORMA domain proteins HORMAD1 and HORMAD2-are known, the molecular organization of these components within the axis is poorly understood. Here, using expansion microscopy coupled with 2-color stochastic optical reconstruction microscopy (STORM) imaging (ExSTORM), we address these issues in mouse spermatocytes at a resolution of 10 to 20 nm. Our data show that SYCP3 and the SYCP2 C terminus, which are known to form filaments in vitro, form a compact core around which cohesin complexes, HORMADs, and the N terminus of SYCP2 are arrayed. Overall, our study provides a detailed structural view of the meiotic chromosome axis, a key organizational and regulatory component of meiotic chromosomes.

Single-molecule analysis reveals multi-state folding of a guanine riboswitch.

Guanine-responsive riboswitches undergo ligand-dependent structural rearrangements to control gene expression by transcription termination. While the molecular basis for ligand recognition is well established, the associated structural rearrangements and the kinetics involved in the formation of the aptamer domain are less well understood. Using high-resolution optical tweezers, we followed the folding trajectories of a single molecule of the xpt-pbuX guanine aptamer from Bacillus subtilis. We report a rapid six-state conformational rearrangement, in which three of the states are guanine dependent, during the transition from the linear to the native receptor conformation. The folding completes in <1 s. The force-dependent equilibrium kinetics and the mutational data indicated that the flexible J2-J3 junction undergoes a ligand-dependent conformational switching, which triggers the formation of the long-range tertiary interactions and the P1 helix. In the absence of the right ligand, the junction failed to initiate the series of conformational rearrangements required for the riboswitch activities.

Patterned Synthesis of ZnO Nanorod Arrays for Nanoplasmonic Waveguide Applications.

We report the patterned synthesis of ZnO nanorod arrays of diameters between 50 nm and 130 nm and various spacings. This was achieved by patterning hole arrays in a polymethyl methacrylate layer with electron beam lithography, followed by chemical synthesis of ZnO nanorods in the patterned holes using the hydrothermal method. The fabrication of ZnO nanorod waveguide arrays is also demonstrated by embedding the nanorods in a silver film using the electroplating process. Optical transmission measurement through the nanorod waveguide arrays is performed and strong resonant transmission of visible light is observed. We have found the resonance shifts to a longer wavelength with increasing nanorod diameter. Furthermore, the resonance wavelength is independent of the nanowaveguide array period, indicating the observed resonant transmission is the effect of a single ZnO nanorod waveguide. These nanorod waveguides may be used in single-molecule imaging and sensing as a result of the nanoscopic profile of the light transmitted through the nanorods and the controlled locations of these nanoscale light sources.

Soliton-mediated orientational ordering of gold nanorods and birefringence in plasmonic suspensions.

We report on the soliton-mediated orientational ordering of gold nanorods in a colloidal plasmonic suspension. Due to the nonlinear optical response of the suspension, a light beam forms an optical spatial soliton which creates an effective optical waveguide. The orientation of the nanorods along the waveguide is regulated by the optical torque exerted by the linearly polarized soliton beam. By measuring the polarization transmission spectrum of a probe beam at a wavelength far from the plasmonic resonance, we observe orientation-enhanced birefringence along the soliton channel, suggesting a disorder-to-order transition of nanorods due to the action of the soliton beam. This approach may be applied in other colloidal systems with optical force-induced nonlinearity.

Localized Plasmon-Stimulated Nanochemistry of Graphene Oxide on a SERS Substrate.

In recent years, there has been remarkable progress in the reduction and functionalization of graphene oxide (GO) using nanoparticles and high-energy optical photons. Most of these reactions are carried out in solutions, whereas the local modification of GO on solid substrates still remains a challenge. In this work, we demonstrate the local reduction of GO and its further destruction, leading to the synthesis of polyaromatic hydrocarbons (PAHs) stimulated by localized surface plasmons (LSPs). The reduction of GO and the synthesis of PAHs have been carried out on a substrate designed for surface-enhanced Raman spectroscopy (SERS). We found that LSPs initiate the destruction of water molecules entrapped in the nanogaps between silver nanoparticles after the deposition of GO from the aqueous suspension. It was demonstrated that OH radicals, as a result of water decomposition, initiate the reduction of GO, leading to the synthesis of PAHs. The reactions have been observed in real time by using SERS. The measurement of current-voltage (I-V) characteristics through conductive atomic force microscopy (AFM), recorded in an LSP-stimulated area, have shown the increased electrical conductivity (more than ten times) compared with the conductivity of GO. The synthesis of new compounds in the LSP-stimulated area has been confirmed by the appearance of new peaks in the Raman spectra and nonlinear I-V characteristics typical for PAHs. We show that the used method allows the local modification of electrical properties of GO and controlled nanopattering of organic compounds on the surface.

Genetic diversity and molecular phylogeography of Chinese domestic goats by large-scale mitochondrial DNA analysis.

Mitochondrial DNA (mtDNA) D-loop sequences of 666 individuals (including 109 new individuals, 557 individuals retrieved from GenBank) from 33 Chinese domestic goat breeds throughout China were used to investigate their mtDNA variability and molecular phylogeography. The results showed that all goat breeds in this study proved to be extremely diverse, and the average haplotype diversity and nucleotide diversity were 0.990 ± 0.001 and 0.032 ± 0.001, respectively. The 666 sequences gave 326 different haplotypes. Phylogenetic analyses revealed that there were 4 mtDNA haplogroups identified in Chinese domestic goats, in which haplogroup A was predominant and widely distributed. Our finding was consistent with archaeological data and other genetic diversity studies. Amova analysis showed there was significant geographical structuring. Almost 84.31% of genetic variation was included in the within-breed variance component and only 4.69% was observed among the geographic distributions. This genetic diversity results further supported the previous view of multiple maternal origins of Chinese domestic goats, and the results on the phylogenetic relationship contributed to a better understanding of the history of goat domestication and modern production of domestic goats.

Single-cell transcriptome sequencing partially revealed the changes of T cells in the early stage of aging kidney.

Aging is a gradual, inevitable physiologic process. The organ aging is related to the persistence of chronic inflammation, but the understanding of inflammatory state during renal aging is lacking currently. Single-cell transcriptome sequencing was performed on aging mouse kidney to reveal the molecular phenotype and composition changes of different cell types. In the early stage of aging, immune cells such as T, B cells and mononuclear macrophages increased in kidney. The molecular state of T cells in aging kidney changed and polarized. Among them, we identified a group of GZMK+ CD8 + T cells with high expression of Eomes, Pdcd1 and Ifng and a group of Il17a+ T cells with high expression of Il17a and Il23r. Moreover, the cytokines and inflammations can aggravate tissue damage eventually. Furthermore, we found the interaction between different types of epithelial cells and T cells increased during the renal aging. These results identify the changes of T cells in the early stage of aging kidney and suggest that GZMK+CD8+ T cells might be a potential target to ameliorate age-associated dysfunctions of kidney(Graphical Abstract).

Insufficiency of Mrpl40 disrupts testicular structure and semen parameters in a murine model.

Approximately 31% of patients with 22q11.2 deletion syndrome (22q11.2DS) have genitourinary system disorders and 6% of them have undescended testes. Haploinsufficiency of genes on chromosome 22q11.2 might contribute to the risk of 22q11.2DS. In this study, we used mice with single-allele deletion in mitochondrial ribosomal protein L40 (Mrpl40 +/- ) as models to investigate the function of Mrpl40 in testes and spermatozoa development. The penetrance of cryptorchidism in Mrpl40 +/- mice was found to be higher than that in wild-type (WT) counterparts. Although the weight of testes was not significantly different between the WT and Mrpl40 +/- mice, the structure of seminiferous tubules and mitochondrial morphology was altered in the Mrpl40 +/- mice. Moreover, the concentration and motility of spermatozoa were significantly decreased in the Mrpl40 +/- mice. In addition, data-independent acquisition mass spectrometry indicated that the expression of genes associated with male infertility was altered in Mrpl40 +/- testes. Our study demonstrated the important role of Mrpl40 in testicular structure and spermatozoa motility and count. These findings suggest that Mrpl40 is potentially a novel therapeutic target for cryptorchidism and decreased motility and count of spermatozoa.

The Efficiency of Pest Control Options against Two Major Sweet Corn Ear Pests in China.

Helicoverpa armigera (Hübner) and Ostrinia furnacalis (Guenée) are the most devastating insect pests at the ear stage of maize, causing significant losses to the sweet corn industry. Pesticide control primarily relies on spraying during the flowering stage, but the effectiveness is inconsistent since larvae are beneath husks within hours to a day, making pesticide treatments simpler to avoid. Insufficient understanding of pest activity patterns impedes precise and efficient pesticide control. H. armigera and O. furnacalis in corn fields were monitored in the last few years in Beijing China, and we observed a higher occurrence of both moths during the R1 stage of sweet corn. Moth captures reached the maximum during this stage, with 555-765 moths per hectare corn field daily. The control efficiency of nine synthetic insecticides and five biopesticides was assessed in the field during this period. Virtako, with mineral oil as the adjuvant, appeared to be the most effective synthetic insecticide, with the efficiencies reaching 88% and 87% on sweet and waxy corn, respectively. Pesticide residue data indicated that the corn is safe after 17 days of its use. The most effective bioinsecticide was Beauveria bassiana combined with mineral oil, with 88% and 80% control efficiency in sweet and waxy corn, respectively. These results suggested that spraying effective insecticides 5 days after corn silking could effectively control corn ear pests H. armigera and O. furnacalis. Our findings provide valuable insights for the development of ear pest management strategies in sweet corn.

Expanding the toolset of fluorescent covalent staining of biological samples by labeling carboxylate and phosphate groups.

Recently, fluorescent covalent staining methods have been developed for visualization of anatomical structures in cells and tissues. Coupled with expansion microscopy, these stains revealed various ultrastructural details. However, the covalently stainable chemical groups have been limited to amines, carbohydrates, and thiols. Here, we developed procedures for covalently labeling tissues for carboxylate and phosphate groups, utilizing carbodiimide crosslinker chemistry. In porcine kidney tissues, the carboxylate and phosphate stain provides 1.8-4.8-fold higher signal intensity than those from the three existing stains. In cancer cells, such stain allows 2-8-fold more accurate identification of nucleoli than the amine stain. In expansion microscopy samples, such stain reveals a variety of sub-cellular structures in tissues when combined with the amine stain. Such stain also allows imaging of lipid-based structures in cultured cells. With these advantages, this new covalent staining method further expands the toolset for fluorescent visualization of histology.

Single-Molecule Force Spectroscopy of Deoxyribonucleic Acid and Deoxyribonucleic Acid Polymerase Activity Impacted by Alkylating Agents.

DNA alkylating agents are widely used in anticancer pharmacology. Although shown to induce cross-linking and/or methylation of DNA, how they affect the mechanical properties of DNA and activity of DNA enzymes remains to be elucidated. Here, we perform single-molecule optical tweezer experiments on DNA treated with alkylating agents, including melphalan, cisplatin, and dacarbazine. While all three drugs induce a significant increase of overstretching force and a reduction of hysteresis, suggesting stabilization of DNA against shearing forces, their effects on elasticity of DNA were quite different, with the largest change in persistence length induced by cisplatin. Furthermore, we find that these alkylating-agent-induced changes on DNA have different effects on processivity of DNA polymerase, with melphalan and cisplatin showing significantly reduced activity and dacarbazine showing little effect. Overall, our results provide new insights into the effects for these alkylating agents, which could potentially facilitate a better design of related drugs.

Exploring characteristics of bioelectricity generation and dye decolorization of mixed and pure bacterial cultures from wine-bearing wastewater treatment.

This study uncovered microbial characteristics of bioelectricity generation and dye decolorization in single-chamber microbial fuel cells (MFCs) using activated sludge for wine-containing wastewater treatment. Phylogenetic tree analysis on 16S rRNA gene fragments indicated that the predominant strains on anodic biofilm in acclimatized MFCs were Gamma-Proteobacteria Aeromonas punctata NIU-P9, Pseudomonas plecoglossicida NIU-Y3, Pseudomonas koreensis NIU-X8, Acinetobacter junii NIU-Y8, Stenotrophomonas maltophila NIU-X2. Our findings showed that the current production capabilities of these pure strains were only ca. 10% of those of their mother activated sludge, indicating that synergistic interactions among microbes might be the most influential factor to maximize power generation in MFCs. Plus, these electrochemically active strains also performed reductive decolorization of C.I. reactive blue 160, suggesting that bioelectricity generation might be directly associated to azo dye decolorization to deal with electron transfer on anodic biofilm in MFCs.

Nanowaveguide-illuminated fluorescence correlation spectroscopy for single molecule studies.

Fluorescence Correlation Spectroscopy (FCS) is a method of investigating concentration fluctuations of fluorescent particles typically in the nM range as a result of its femtoliter-sized sample volume. However, biological processes on cell membranes that involve molecules in the µM concentration range require sample volumes well below the conventional FCS limit as well as nanoscale confinement in the longitudinal direction. In this study, we show that an effective measurement volume down to the zeptoliter range can be achieved via the introduction of a nanowire waveguide, resulting in an illumination spot of about 50 nm in lateral dimensions and a longitudinal confinement of around 20 nm just above the waveguide exit surface. Using illumination profiles obtained from finite element method simulations of dielectric nanowaveguides, we perform Monte Carlo simulations of fluorescence fluctuations for two scenarios of fluorophore movement: fluorophores freely diffusing in the three-dimensional (3D) space above the nanowaveguide and fluorophores moving in a two-dimensional (2D) membrane situated directly above the nanowaveguide exit surface. We have developed analytical functions to fit the simulation results and found that an effective illumination size of about 150 zl and 4 × 10-3 µm2 can be obtained for the 3D and 2D scenarios, respectively. Given the flat surface geometry and the deep-subwavelength confinement of its illumination spot, this nanowaveguide-illuminated fluorescence correlation spectroscopy technique may be well suited for studying the concentration and dynamics of densely distributed protein molecules on cell membranes.

Screening of a Plesiomonas shigelloides phage and study of the activity of its lysis system.

Plesiomonas shigelloides is an important fish pathogen that causes significant losses in aquaculture. Phage therapy is a new approach to overcome the problem of multidrug-resistant bacteria. Herein, a virulent phage of P. shigelloides was isolated from the intestines of grass carp. This phage belongs to the Siphoviridae family and was designated PSP01. The optimal multiplicity of infection of PSP01 was 1 with a latent period of 30 min and a lytic period of 140 min. Good activity was observed over a wide range of temperatures (-20 °C-50 °C), pH values (3-12), and NaCl concentrations (0.1-3.5%). The phage PSP01 lysis cassette is composed of 3 genes, HolPSP, LysPSP-1 and LysPSP-2. Expression of HolPSP or LysPSP-2 in Escherichia coli resulted in bacterial lysis, and a synergistic effect was observed when the HolPSP and LysPSP-1 proteins were co-expressed. In-frame deletion uncovered an important role of the transmembrane domain (TMD) in HolPSP and the signal peptide (SP) in LysPSP-2 for bacterial lysis function. The protective effects of phage PSP01 were investigated by intraperitoneal injection into grass carp infected with P. shigelloides, showing a 33.3% increase in the survival rate of the infected grass carp. Pathological analysis of the spleens from the infected grass carp revealed alleviation of the pathological symptoms. In conclusion, isolation and bacterial lysis investigations of phage PSP01 provide a new tool for the control of fish pathogens and possesses potential for aquaculture applications.

Measurement of expansion factor and distortion for expansion microscopy using isolated renal glomeruli as landmarks.

Expansion microscopy has enabled super resolution imaging of biological samples. The accurate measurement of expansion factor and distortion typically requires locating and imaging the same region of interest in the sample before and after expansion, which is often time-consuming to achieve. Here we introduce a convenient method for relocation by utilizing isolated porcine glomeruli as landmarks during expansion. Following heat denaturation and proteinase K digestion protocols, the glomeruli exhibit expansion factor of 3.5 to 4 (only 7%-16% less expanded than the hydrogel), and 1% to 2% of relative distortion. Due to its appropriate size of 100 to 300 µm, the location of the glomerulus in the sample are visible to eyes, while its detailed shape only requires bright field microscopy. For expansion factors ranging from 3 to 10, the region in the vicinity of the glomerulus can be easily re-identified, and sometimes allows quantification of expansion factor and distortion under bright field without fluorescent labels.

Controlled synthesis of mesoporous single-crystalline TiO2 nanoparticles for efficient photocatalytic H2 evolution.

Mesoporous single-crystals have emerged as a unique family of functional materials, exhibiting excellent performance in various applications, owing to their well-defined accessible mesoporosity and highly single-crystalline structures. Precise tailoring structures of mesoporous single-crystals at the nanoscale remains an unsolved scientific and technical challenge. Herein, we report a facile and general approach for the synthesis of mesoporous single-crystalline TiO2 nanoparticles (designated as MSC-TNs) with distinctive traits including tunable morphologies, controllable particle sizes, well dispersity, high hydrophilicity, well-defined mesoporosity and single-crystal nature. Specifically, the amount of water employed in the precursor solution was seen to give fine control over the particle sizes and morphologies of MSC-TNs. MSC-TNs with different sizes show excellent photocatalytic activity in production of hydrogen from water. Under the illumination of 300 W Xe lamp, MSC-TNs were shown to provide good photodegradation performance with Rhodamine 6 G, as well as H2 production when loaded 1 wt % Pt. In a CH3OH solution H2 was evolved with a rate of 8.98 mmol h-1 g-1, which is significantly higher than with commercial P25 nanoparticles (4.02 mmol h-1 g-1).

Type I Interferon Regulates a Coordinated Gene Network to Enhance Cytotoxic T Cell-Mediated Tumor Killing.

Type I interferons (IFN), which activate many IFN-stimulated genes (ISG), are known to regulate tumorigenesis. However, little is known regarding how various ISGs coordinate with one another in developing antitumor effects. Here, we report that the ISG UBA7 is a tumor suppressor in breast cancer. UBA7 encodes an enzyme that catalyzes the covalent conjugation of the ubiquitin-like protein product of another ISG (ISG15) to cellular proteins in a process known as "ISGylation." ISGylation of other ISGs, including STAT1 and STAT2, synergistically facilitates production of chemokine-receptor ligands to attract cytotoxic T cells. These gene-activation events are further linked to clustering and nuclear relocalization of STAT1/2 within IFN-induced promyelocytic leukemia (PML) bodies. Importantly, this coordinated ISG-ISGylation network plays a central role in suppressing murine breast cancer growth and metastasis, which parallels improved survival in patients with breast cancer. These findings reveal a cooperative IFN-inducible gene network in orchestrating a tumor-suppressive microenvironment. SIGNIFICANCE: We report a highly cooperative ISG network, in which UBA7-mediated ISGylation facilitates clustering of transcription factors and activates an antitumor gene-expression program. These findings provide mechanistic insights into immune evasion in breast cancer associated with UBA7 loss, emphasizing the importance of a functional ISG-ISGylation network in tumor suppression.This article is highlighted in the In This Issue feature, p. 327.