Characterization of Silver Nanoparticles Synthesized by the Aqueous Extract of Zanthoxylum nitidum and Its Herbicidal Activity against Bidens pilosa L.

Phytosynthesis of silver nanoparticles (Ag NPs) has been progressively acquiring attractiveness. In this study, the root of Zanthoxylum nitidum was used to synthesize Ag NPs, and its pre-emergence herbicidal activity was tested. The synthesized Ag NPs by the aqueous extract from Z. nitidum were characterized by visual inspection, ultraviolet-visible spectroscopy, dynamic light scattering (DLS), X-ray diffraction (XRD), transmission electron microscopy (TEM), and energy dispersive X-ray spectroscopy (EDX). The plant-mediated synthesis was completed within 180 min and the Ag NPs exhibited a characteristic peak at around 445 nm. The results of the DLS measurement showed that the average hydrodynamic diameter was 96 nm with a polydispersity index (PDI) of 0.232. XRD results indicated the crystalline nature of the phytogenic Ag NPs. A TEM analysis revealed that the nanoparticles were spherical with an average particle size of 17 nm. An EDX spectrum confirmed the presence of an elemental silver signal. Furthermore, the Ag NPs exhibited a herbicidal potential against the seed germination and seedling growth of Bidens Pilosa L. The present work indicates that Ag NPs synthesized by plant extract could have potential for the development of a new nanoherbicide for weed prevention and control.

Acid Suspends the Circadian Clock in Hypoxia through Inhibition of mTOR.

Recent reports indicate that hypoxia influences the circadian clock through the transcriptional activities of hypoxia-inducible factors (HIFs) at clock genes. Unexpectedly, we uncover a profound disruption of the circadian clock and diurnal transcriptome when hypoxic cells are permitted to acidify to recapitulate the tumor microenvironment. Buffering against acidification or inhibiting lactic acid production fully rescues circadian oscillation. Acidification of several human and murine cell lines, as well as primary murine T cells, suppresses mechanistic target of rapamycin complex 1 (mTORC1) signaling, a key regulator of translation in response to metabolic status. We find that acid drives peripheral redistribution of normally perinuclear lysosomes away from perinuclear RHEB, thereby inhibiting the activity of lysosome-bound mTOR. Restoring mTORC1 signaling and the translation it governs rescues clock oscillation. Our findings thus reveal a model in which acid produced during the cellular metabolic response to hypoxia suppresses the circadian clock through diminished translation of clock constituents.

Cytoplasmic chromatin triggers inflammation in senescence and cancer.

Chromatin is traditionally viewed as a nuclear entity that regulates gene expression and silencing. However, we recently discovered the presence of cytoplasmic chromatin fragments that pinch off from intact nuclei of primary cells during senescence, a form of terminal cell-cycle arrest associated with pro-inflammatory responses. The functional significance of chromatin in the cytoplasm is unclear. Here we show that cytoplasmic chromatin activates the innate immunity cytosolic DNA-sensing cGAS-STING (cyclic GMP-AMP synthase linked to stimulator of interferon genes) pathway, leading both to short-term inflammation to restrain activated oncogenes and to chronic inflammation that associates with tissue destruction and cancer. The cytoplasmic chromatin-cGAS-STING pathway promotes the senescence-associated secretory phenotype in primary human cells and in mice. Mice deficient in STING show impaired immuno-surveillance of oncogenic RAS and reduced tissue inflammation upon ionizing radiation. Furthermore, this pathway is activated in cancer cells, and correlates with pro-inflammatory gene expression in human cancers. Overall, our findings indicate that genomic DNA serves as a reservoir to initiate a pro-inflammatory pathway in the cytoplasm in senescence and cancer. Targeting the cytoplasmic chromatin-mediated pathway may hold promise in treating inflammation-related disorders.

Rheology of dense suspensions of shape anisotropic particles designed to show pH-sensitive anisotropic pair potentials.

Here we investigate the flow properties of suspensions of dicolloidal particles composed of interpenetrating spheres where one sphere is rich in polystyrene and the second is rich in poly 2-vinyl pyridine. The synthesis method is designed to create both anisotropic shape and anisotropic interaction potentials that should lead to head to tail clustering. These particles are referred to as copolymer dicolloids (CDCs). The viscoelastic properties of stable and gelled suspensions of CDC particles are compared with analogs composed of homopolymer dicolloids (HDCs), having the same shape but not displaying the anisotropic attractions. After coating the particles with a nonionic surfactant to minimize van der Waals attractions, the flow properties of glassy and gelled suspensions of CDCs and HDCs are studied as a function of volume fraction, ionic strength and pH. Suspensions of HDC particles display a high kinetic arrest volume fraction (φ(g) > 0.5) over a wide range of pH and ionic strength up to [I]=0.5 M, demonstrating that the particles experience repulsive or weakly attractive pair potentials. Suspensions of CDC particles behave in a similar manner at high or low pH when [I]=0.001 M, but gel at a volume fraction of φ(g) < 0.3 and display anomalously large elastic moduli at and above the gel transition point for intermediate pH or for pH=9 when [I]=0.5 M. The gelation processes for the CDC particles are reversible by adjusting the solution pH. Interaction potential anisotropy is evident in the processes, during which the CDC particles yield on increasing oscillatory strain.

Synthesis of pH-responsive particles with shape anisotropy.

Seeded emulsion polymerization is used to produce large quantities of shape anisotropic, amphoteric particles in a size range of about 1 µm. Copolymer dicolloids (CDCs) containing pyridine groups are synthesized by swelling spherical, lightly cross-linked polystyrene seeds with a mixture of styrene and pH-responsive monomer 2-vinyl pyridine followed by secondary polymerization to contrast with their analogue homopolymer dicolloids (HDCs) where the swelling step is carried out with styrene alone. After the particles are coated with a nonionic surfactant to minimize van der Waals attractions, surface potentials and aggregation properties of dilute suspensions are studied as functions of pH and ionic strength. Compared to HDCs, which remain stable at all pH values studied (3 < pH < 9) up to an ionic strength of 5 M, the CDC particles show amphoteric behavior with strong attractions under conditions where dipolar interactions are expected to dominate.

Adoptive immunotherapy: good habits instilled at youth have long-term benefits.

Many recent advances in basic cell biology and immunology are a harbinger of progress in adoptive cell therapy (ACT) including (1) the finding that host lymphodepletion enhances engraftment and efficacy, (2) the recognition that in vitro T cell functions may not correlate with in vivo efficacy, and (3) the development of advanced ex vivo culture methods to expand lymphocytes to therapeutically effective numbers. In this article, we focus on the development of artificial antigen presenting cells (aAPCs) in our laboratory and their applicability to augment ACT protocols. We also describe how aAPCs can be used to broaden ACT to treat patients with a wide variety of cancers, chronic infectious diseases, and autoimmune manifestations.

GADD45A is a mediator of CD437 induced apoptosis in ovarian carcinoma cells.

Ovarian cancer is one of the leading causes of cancer death in women. A number of studies have suggested that synthetic retinoids may play an important role as an ovarian cancer chemotherapeutic agent. The synthetic retinoid CD 437 induces apoptosis in ovarian tumor cells by a mechanism that is not completely understood. In this study we demonstrate that CD437 treatment leads to an increase in GADD45A and GADD45B mRNA expression in CA-OV3 cells but not in CA-CD437R cells, a cell line which is resistant to CD437. This induction is specific to CD437 since no change in expression of either GADD45A or GADD45B was observed with either all-trans-RA or 4-HPR treatment. Western blot analysis demonstrated that the induction of GADD45A mRNA in the CA-OV3 cell line by CD437 was accompanied by an increase in GADD45A protein. Upregulation of GADD45A by CD437 is regulated at least in part at the post-transcriptional level. In contrast, CD437 regulates GADD45B expression by different mechanisms. The importance of GADD45A induction in mediating apoptosis was demonstrated in CA-OV3 cells overexpressing GADD45A antisense RNA (GADD45A-AS cells). Our results suggest that induction of GADD45A expression might play a role in mediating the apoptotic response of ovarian cancer cells to the synthetic retinoid CD437.