Soilborne bacterium Klebsiella pneumoniae promotes cluster root formation in white lupin through ethylene mediation.

Cluster roots of white lupin are induced by low phosphorus (LP) to efficiently access unavailable P, but how soilborne microbes are associated with cluster root formation (CRF) is unclear. We investigated the roles of soilborne bacteria in CRF response to LP by high-throughput sequencing and root-bacteria interactions. Cluster root number was significantly decreased in plants grown in sterilized soil compared with nonsterilized soil.

Direct Tie2 Agonists Stabilize Vasculature for the Treatment of Diabetic Macular Edema.

Purpose: Diabetic macular edema (DME) is the leading cause of vision loss and blindness among working-age adults. Although current intravitreal anti-vascular endothelial growth factor (VEGF) therapies improve vision for many patients with DME, approximately half do not achieve the visual acuity required to drive. We therefore sought additional approaches to resolve edema and improve vision for these patients.

Dramatic activation of an antibody by a single amino acid change in framework.

Antibody function is typically entirely dictated by the Complementarity Determining Regions (CDRs) that directly bind to the antigen, while the framework region acts as a scaffold for the CDRs and maintains overall structure of the variable domain. We recently reported that the rabbit monoclonal antibody 4A11 (rbt4A11) disrupts signaling through both TGFβ2 and TGFβ3 (Sun et al. in Sci Transl Med, 2021.

Co-delivery of anionic epitope/CpG vaccine and IDO inhibitor by self-assembled cationic liposomes for combination melanoma immunotherapy.

Immunotherapy is revolutionizing cancer treatment. Vaccination of antigenic peptides has been identified as a promising strategy for cancer immunotherapy while insufficient immune responses were stimulated due to low antigenicity. Moreover, immune checkpoint blockade therapy is still limited by a low objective response rate.

Reproducible quantification of IgG uptake at endogenous and overexpressed FcRn levels at pH 7.4: Comparison of a wild type IgG and a stronger FcRn binding variant.

IgG antibodies have been used to treat many diseases including cancer. IgG antibody-drug conjugates (ADCs) deliver cytotoxic drugs to target cells for cell elimination, but they have dose limiting toxicity due to target-independent uptake, including pinocytotic uptake. Neonatal Fc receptor (FcRn) recycles pinocytosed IgG in a pH-dependent manner and is the receptor responsible for the long half-life of IgG.

Hybrid Fiber Optic Sensor, Based on the Fabry⁻Perot Interference, Assisted with Fluorescent Material for the Simultaneous Measurement of Temperature and Pressure.

Herein we design a fiber sensor able to simultaneously measure the temperature and the pressure under harsh conditions, such as strong electromagnetic interference and high pressure. It is built on the basis of the fiber-optic Fabry⁻Perot (F⁻P) interference and the temperature sensitive mechanism of fluorescent materials. Both halogen lamps and light-emitting diodes (LED) are employed as the excitation light source.

Graphene-Ag Hybrids on Laser-Textured Si Surface for SERS Detection.

Surface-enhanced Raman scattering (SERS) has been extensively investigated as an effective approach for trace species detection. Silver nanostructures are high-sensitivity SERS substrates in common use, but their poor chemical stability impedes practical applications. Herein, a stable and sensitive SERS substrate based on the hybrid structures of graphene/silver film/laser-textured Si (G/Ag/LTSi) was developed, and a simple, rapid, and low-cost fabrication approach was explored.

Laser-assisted chemical vapor deposition setup for fast synthesis of graphene patterns.

An automatic setup based on the laser-assisted chemical vapor deposition method has been developed for the rapid synthesis of graphene patterns. The key components of this setup include a laser beam control and focusing unit, a laser spot monitoring unit, and a vacuum and flow control unit. A laser beam with precision control of laser power is focused on the surface of a nickel foil substrate by the laser beam control and focusing unit for localized heating.

Design and Pharmacokinetic Characterization of Novel Antibody Formats for Ocular Therapeutics.

Purpose: To design and select the next generation of ocular therapeutics, we performed a comprehensive ocular and systemic pharmacokinetic (PK) analysis of a variety of antibodies and antibody fragments, including a novel-designed bispecific antibody.

Methods: Molecules were administrated via intravitreal (IVT) or intravenous (IV) injections in rabbits, and antibody concentrations in each tissue were determined by ELISA. A novel mathematical model was developed to quantitate the structure-PK relationship.

Framework selection can influence pharmacokinetics of a humanized therapeutic antibody through differences in molecule charge.

Pharmacokinetic (PK) testing of a humanized (κI, VH3 framework) and affinity matured anti-hepatitis C virus E2-glycoprotein (HCV-E2) antibody (hu5B3.κ1VH3.v3) in rats revealed unexpected fast clearance (34.

[A meibomian gland massage mechanism for upper and lower eyelids based on anti-phase rolling and enveloping movement].

During the course of meibomian gland dysfunction (MGD) treatment, meibomian gland massage is an effective auxiliary method. Based on an extrusion method using anti-phase massage rollers and a theory on envelope plane, a massage mechanism was proposed in this paper for the defect of the traditional mechanical assist massage structure to discharge obstruction of Meibomian gland more smoothly and to enlarge massage coverage. Meanwhile, for the case that the power of motor was significantly limited by size, an evaluation, about the input, output and loss, was carried out to initially verify the feasibility of the designed mechanism.

Real-time immuno-polymerase chain reaction in a 384-well format: detection of vascular endothelial growth factor and epidermal growth factor-like domain 7.

Immuno-polymerase chain reaction (immuno-PCR) combines the specificity of antibodies with the amplification power of PCR to detect low levels of proteins. Here, we describe the development of a 384-well immuno-PCR method that uses streptavidin coated on a PCR plate to capture complexes of biotinylated capture antibody, antigen, and DNA-labeled detection antibody. Unbound molecules are removed by a wash step using a standard plate washer.

An interleukin-17-mediated paracrine network promotes tumor resistance to anti-angiogenic therapy.

Although angiogenesis inhibitors have provided substantial clinical benefit as cancer therapeutics, their use is limited by resistance to their therapeutic effects. While ample evidence indicates that such resistance can be influenced by the tumor microenvironment, the underlying mechanisms remain incompletely understood. Here, we have uncovered a paracrine signaling network between the adaptive and innate immune systems that is associated with resistance in multiple tumor models: lymphoma, lung and colon.

Detection of hepatocyte growth factor (HGF) ligand-c-MET receptor activation in formalin-fixed paraffin embedded specimens by a novel proximity assay.

Aberrant activation of membrane receptors frequently occurs in human carcinomas. Detection of phosphorylated receptors is commonly used as an indicator of receptor activation in formalin-fixed paraffin embedded (FFPE) tumor specimens. FFPE is a standard method of specimen preparation used in the histological analysis of solid tumors.

The therapeutic role of very low-density lipoprotein receptor gene in hyperlipidemia in type 2 diabetic rats.

Hyperlipidemia is a common feature of type 2 diabetes and is related to cardiovascular disease. The very low-density lipoprotein receptor (VLDLR) binds to and internalizes triglyceride-rich lipoproteins with high specificity. In this study, we evaluated the role of VLDLR in hyperlipidemia in type 2 diabetic rats.

EGFR over-expression and activation in high HER2, ER negative breast cancer cell line induces trastuzumab resistance.

HER2 is gene amplified or over-expressed in 20-25% of breast cancers resulting in elevated HER2 activation. Trastuzumab (Herceptin), a humanized monoclonal antibody, targets activated HER2 and is clinically effective in HER2-over-expressing breast cancers. However, despite prolonged survival, treated breast cancer patients develop resistance.

The ubiquitin-conjugating enzyme E2-EPF is overexpressed in primary breast cancer and modulates sensitivity to topoisomerase II inhibition.

We identified the ubiquitin-conjugating enzyme E2-EPF mRNA as differentially expressed in breast tumors relative to normal tissues and performed studies to elucidate its putative role in cancer. We demonstrated that overexpression of E2-EPF protein correlated with estrogen receptor (ER) negativity in breast cancer specimens and that its expression is cell cycle-regulated, suggesting a potential function for E2-EPF in cell cycle progression. However, reduction of E2-EPF protein levels by > 80% using RNAi had no significant effects on the proliferation of HeLa cervical cancer cells or ER(-) MDA-MB-231 or MDA-MB-453 breast cancer cells.

Anti-EphA2 antibodies decrease EphA2 protein levels in murine CT26 colorectal and human MDA-231 breast tumors but do not inhibit tumor growth.

The EphA2 receptor tyrosine kinase has been shown to be over-expressed in cancer and a monoclonal antibody (mAb) that activates and down-modulates EphA2 was reported to inhibit the growth of human breast and lung tumor xenografts in nude mice. Reduction of EphA2 levels by treatment with anti-EphA2 siRNA also inhibited tumor growth, suggesting that the anti-tumor effects of these agents are mediated by decreasing the levels of EphA2. As these studies employed human tumor xenograft models in nude mice with reagents whose cross reactivity with murine EphA2 is unknown, we generated a mAb (Ab20) that preferentially binds, activates, and induces the degradation of murine EphA2.

aph-1 and pen-2 are required for Notch pathway signaling, gamma-secretase cleavage of betaAPP, and presenilin protein accumulation.

Presenilins are components of the gamma-secretase protein complex that mediates intramembranous cleavage of betaAPP and Notch proteins. A C. elegans genetic screen revealed two genes, aph-1 and pen-2, encoding multipass transmembrane proteins, that interact strongly with sel-12/presenilin and aph-2/nicastrin.