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By introducing anisotropy into nonlinear propagations, off-axis vortex beams exhibit significantly different characteristics compared to the isotropic case. The orbital angular momentum (OAM) is non-conservative and can periodically change between positive and negative values. Accordingly, the rotation of phase singularity can transit between clockwise and counterclockwise directions. Furthermore, the phase singularity can move to infinity when the OAM approaches zero. By using the Ehrenfest theorem, the motion of the beam center is obtained. Its trajectory can be circular and parabolic or follow other complex shapes, depending closely on the anisotropy of the nonlinearity. The rotational velocity of the beam center can be modulated by the nonlinearity anisotropy and can far exceed the initial value during its propagation. These results may find potential applications in beam shaping and optical manipulation.
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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).
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Envejecimiento , Linfocitos T CD8-positivos , Riñón , Análisis de la Célula Individual , Transcriptoma , Animales , Envejecimiento/inmunología , Envejecimiento/genética , Ratones , Riñón/inmunología , Transcriptoma/genética , Análisis de la Célula Individual/métodos , Linfocitos T CD8-positivos/inmunología , Ratones Endogámicos C57BL , Masculino , Linfocitos T/inmunología , Perfilación de la Expresión Génica/métodosRESUMEN
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.
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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.
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Colorantes , Fosfatos , Animales , Porcinos , Coloración y Etiquetado , Microscopía , Aminas , Colorantes FluorescentesRESUMEN
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 (1760.0â mAh g-1 at 0.1â A g-1 ) and decent long-term cycling stability (652.5â mAh g-1 at 1.0â A g-1 ). This work provides a new way for the construction of advanced anode materials for lithium-ion batteries.
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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.
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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.
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Alquilantes , Melfalán , Alquilantes/farmacología , Melfalán/farmacología , Cisplatino , Antineoplásicos Alquilantes/farmacología , Dacarbazina , ADN , Análisis EspectralRESUMEN
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.
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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.
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Epilepsia del Lóbulo Temporal , Epilepsia , Microcefalia , Humanos , Lactante , Recién Nacido , Microcefalia/genética , Mutación , Proteínas Nucleares/genética , Linaje , Convulsiones/genéticaRESUMEN
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.
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Bacteriófagos , Carpas , Plesiomonas , Animales , Acuicultura , Bacteriófagos/genética , Escherichia coli , Plesiomonas/genéticaRESUMEN
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.
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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.
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Hidrogeles , Microscopía , Animales , PorcinosRESUMEN
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).
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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.
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Neoplasias de la Mama/genética , Interferón Tipo I/genética , Factor de Transcripción STAT1/genética , Factor de Transcripción STAT2/genética , Enzimas Activadoras de Ubiquitina/genética , Animales , Neoplasias de la Mama/inmunología , Neoplasias de la Mama/patología , Proliferación Celular/genética , Femenino , Regulación Neoplásica de la Expresión Génica/genética , Redes Reguladoras de Genes/inmunología , Humanos , Ratones , Linfocitos T/inmunología , Factores de Transcripción/genética , Ubiquitinas/genética , Ubiquitinas/inmunologíaRESUMEN
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.
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Cromosomas de los Mamíferos/química , Cromosomas de los Mamíferos/metabolismo , Microscopía/métodos , Animales , Proteínas de Ciclo Celular/metabolismo , Proteínas de Unión al ADN/metabolismo , Masculino , Mamíferos/genética , Meiosis , Ratones , Espermatocitos/metabolismo , Coloración y Etiquetado , Complejo Sinaptonémico/metabolismoRESUMEN
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.
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By applying a controlled mechanical load using optical tweezers, we measured the diffusive barrier crossing in a 49 nt long P5ab RNA hairpin. We find that in the free-energy landscape the barrier height (G) and transition distance (x) are dependent on the loading rate (r) along the pulling direction, x, as predicted by Bell. The barrier shifted toward the initial state, whereas ΔG reduced significantly from 50 to 5 kT, as r increased from 0 to 32 pN/s. However, the equilibrium work (ΔG) during strand separation, as estimated by Crook's fluctuation theorem, remained unchanged at different rates. Previously, helix formation and denaturation have been described as two-state (F â U) transitions for P5ab. Herein, we report three intermediate states I1, I, and I2 located at 4, 11, and 16 nm respectively, from the folded conformation. The intermediates were observed only when the hairpin was subjected to an optimal r, 7.6 pN/s. The results indicate that the complementary strands in P5ab can zip and unzip through complex routes, whereby mismatches act as checkpoints and often impose barriers. The study highlights the significance of loading rates in force-spectroscopy experiments that are increasingly being used to measure the folding properties of biomolecules.
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Pliegue del ARN , ARN/química , Termodinámica , Secuencias Invertidas Repetidas , Fenómenos Mecánicos , Modelos Químicos , Modelos Moleculares , Pinzas Ópticas , Transición de FaseRESUMEN
The expression of breast cancer resistant protein (BCRP) in lung cancer is correlated with development of multidrug resistance (MDR) and therefore leads to lower response to chemotherapy. ZM323881, a previously developed selective VEGFR-2 inhibitor, was found to have inhibitory effects on BCRP-mediated MDR in this investigation. ZM323881 significantly decreased the cytotoxic doses of mitoxantrone and SN-38 in BCRP-overexpressing NCI-H460/MX20 cells. Mechanistic studies revealed that ZM323881 effected by inhibiting BCRP-mediated drug efflux, leading to intracellular accumulation of BCRP substrates. No significant alteration in the expression levels and localization pattern of BCRP was observed when BCRP-overexpressing cells were exposed to ZM323881. Stimulated bell-shaped ATPase activities were observed. Molecular docking suggested that ZM323881 binds to the modulator site of BCRP and the binding pose is stable validated by 100ns molecular dynamic simulation. Overall, our results indicated that ZM323881 reversed BCRP-related MDR by inhibiting its efflux function. These findings might be useful in developing combination chemotherapy for MDR cancer treatment.
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Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2/fisiología , Resistencia a Múltiples Medicamentos/efectos de los fármacos , Proteínas de Neoplasias/fisiología , Quinazolinas/farmacología , Receptor 2 de Factores de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Bencimidazoles/metabolismo , Línea Celular Tumoral , Doxorrubicina/farmacología , Células HEK293 , Humanos , Mitoxantrona/metabolismo , Simulación de Dinámica MolecularRESUMEN
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.
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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.