A Type I Photosensitizer-Polymersome Boosts Reactive Oxygen Species Generation by Forcing H-Aggregation for Amplifying STING Immunotherapy.

Activation of the innate immune Stimulator of Interferon Genes (STING) pathway potentiates antitumor immunity. However, delivering STING agonists systemically to tumors presents a formidable challenge, and resistance to STING monotherapy has emerged in clinical trials with diminishing natural killer (NK) cell proliferation. Here, we encapsulated the STING agonist diABZI within polymersomes containing a Type I photosensitizer (NBS), creating a nanoagonist (PNBS/diABZI) for highly responsive tumor immunotherapy.

Fundamental theory on multiple energy resources and related case studies.

Herein, I methodically optimize a distributed energy resource in terms of the production, management, utilization, and/or transaction of renewable energies during the deployment process. I deliver a theoretical mathematical model that allows users to visualize three critical output functions of their energy preference, including output power, energy economy, and carbon footprint. The model delivers three eigenstates derived by a power utility matrix (PUM) model.

Structural and immunological differences in Plasmodium falciparum sexual stage transmission-blocking vaccines comprised of Pfs25-EPA nanoparticles.

Development of a malaria vaccine that blocks transmission of different parasite stages to humans and mosquitoes is considered critical for elimination efforts. A vaccine using Pfs25, a protein on the surface of zygotes and ookinetes, is under investigation as a transmission-blocking vaccine (TBV) that would interrupt parasite passage from mosquitoes to humans. The most extensively studied Pfs25 TBVs use Pichia pastoris-produced recombinant forms of Pfs25, chemically conjugated to a recombinant carrier protein, ExoProtein A (EPA).

Rational design of semiconducting polymer brushes as cancer theranostics.

Photonic theranostics (PTs) generally contain optical agents for the optical sensing of biomolecules and therapeutic components for converting light into heat or chemical energy. Semiconducting polymer nanoparticles (SPNs) as advanced PTs possessing good biocompatibility, stable photophysical properties, and sensitive and tunable optical responses from the ultraviolet to near-infrared (NIR) II window (300-1700 nm) have recently aroused great interest. Although semiconducting polymers (SPs) with various building blocks have been synthesized and developed to meet the demands of biophotonic applications, most of the SPNs were made by a nanoprecipitation method that used amphiphilic surfactants to encapsulate SPs.

Rational Design of All-Organic Nanoplatform for Highly Efficient MR/NIR-II Imaging-Guided Cancer Phototheranostics.

Organic theranostic nanomedicine has precision multimodel imaging capability and concurrent therapeutics under noninvasive imaging guidance. However, the rational design of desirable multifunctional organic theranostics for cancer remains challenging. Rational engineering of organic semiconducting nanomaterials has revealed great potential for cancer theranostics largely owing to their intrinsic diversified biophotonics, easy fabrication of multimodel imaging platform, and desirable biocompatibility.

Complementary and Alternative Medicine in Chronic Rhinosinusitis: A Systematic Review and Qualitative Analysis.

Background: Complementary and alternative medicine (CAM) is frequently used in the treatment of chronic rhinosinusitis (CRS) in developed countries. With a plethora of CAM therapies available, their effectiveness and safety are poorly understood in the context of CRS.

Objectives: This article aims to critically appraise the evidence for CAM use in CRS through a systematic review of current literature that investigate the effects of CAM on symptoms and clinical status of adults with CRS.

Effects of gold nanoparticles on lipid packing and membrane pore formation.

Gold nanoparticles (AuNPs) have been increasingly integrated in biological systems, making it imperative to understand their interactions with cell membranes, the first barriers to be crossed to enter cells. Herein, liposomes composed of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) as a model membrane system were treated with citrate stabilized AuNPs from 5 to 30 nm at various concentrations. The fluorescence shifts of Laurdan probes reveal that AuNPs in general made liposomes more fluidic.

Clathrin-coat disassembly illuminates the mechanisms of Hsp70 force generation.

Hsp70s use ATP hydrolysis to disrupt protein-protein associations and to move macromolecules. One example is the Hsc70- mediated disassembly of the clathrin coats that form on vesicles during endocytosis. Here, we exploited the exceptional features of these coats to test three models-Brownian ratchet, power-stroke and entropic pulling-proposed to explain how Hsp70s transform their substrates.

Developing instrumentation to characterize thermoelectric generator modules.

Based on the law of physics, known as "Seebeck effect," a thermoelectric generator (TEG) produces electricity when the temperature differential is applied across the TEG. This article reports a precision method in characterizing TEG modules. A precision instrument is constructed to study thermoelectric conversion in terms of output power and efficiency of TEG modules.

Optical and photoacoustic dual-modality imaging guided synergistic photodynamic/photothermal therapies.

Phototherapies such as photodynamic therapy (PDT) and photothermal therapy (PTT), due to their specific spatiotemporal selectivity and minimal invasiveness, have been widely investigated as alternative treatments of malignant diseases. Graphene and its derivatives not only have been used as carriers to deliver photosensitizers for PDT, but also as photothermal conversion agents (PTCAs) for PTT. Herein, we strategically designed and produced a novel photo-theranostic platform based on sinoporphyrin sodium (DVDMS) photosensitizer-loaded PEGylated graphene oxide (GO-PEG-DVDMS) for enhanced fluorescence/photoacoustic (PA) dual-modal imaging and combined PDT and PTT.

Enhanced fluorescence imaging guided photodynamic therapy of sinoporphyrin sodium loaded graphene oxide.

Extensive research indicates that graphene oxide (GO) can effectively deliver photosensitives (PSs) by π-π stacking for photodynamic therapy (PDT). However, due to the tight complexes of GO and PSs, the fluorescence of PSs are often drastically quenched via an energy/charge transfer process, which limits GO-PS systems for photodiagnostics especially in fluorescence imaging. To solve this problem, we herein strategically designed and prepared a novel photo-theranostic agent based on sinoporphyrin sodium (DVDMS) loaded PEGylated GO (GO-PEG-DVDMS) with improved fluorescence property for enhanced optical imaging guided PDT.

Versatile RNA interference nanoplatform for systemic delivery of RNAs.

Development of nontoxic, tumor-targetable, and potent in vivo RNA delivery systems remains an arduous challenge for clinical application of RNAi therapeutics. Herein, we report a versatile RNAi nanoplatform based on tumor-targeted and pH-responsive nanoformulas (NFs). The NF was engineered by combination of an artificial RNA receptor, Zn(II)-DPA, with a tumor-targetable and drug-loadable hyaluronic acid nanoparticle, which was further modified with a calcium phosphate (CaP) coating by in situ mineralization.

Targeted therapeutic nanotubes influence the viscoelasticity of cancer cells to overcome drug resistance.

Resistance to chemotherapy is the primary cause of treatment failure in over 90% of cancer patients in the clinic. Research in nanotechnology-based therapeutic alternatives has helped provide innovative and promising strategies to overcome multidrug resistance (MDR). By targeting CD44-overexpressing MDR cancer cells, we have developed in a single-step a self-assembled, self-targetable, therapeutic semiconducting single-walled carbon nanotube (sSWCNT) drug delivery system that can deliver chemotherapeutic agents to both drug-sensitive OVCAR8 and resistant OVCAR8/ADR cancer cells.

Development of a Pfs25-EPA malaria transmission blocking vaccine as a chemically conjugated nanoparticle.

Successful efforts to control infectious diseases have often required the use of effective vaccines. The current global strategy for control of malaria, including elimination and eradication will also benefit from the development of an effective vaccine that interrupts malaria transmission. To this end, a vaccine that disrupts malaria transmission within the mosquito host has been investigated for several decades targeting a 25 kDa ookinete specific surface protein, identified as Pfs25.

Unraveling protein-protein interactions in clathrin assemblies via atomic force spectroscopy.

Atomic force microscopy (AFM), single molecule force spectroscopy (SMFS), and single particle force spectroscopy (SPFS) are used to characterize intermolecular interactions and domain structures of clathrin triskelia and clathrin-coated vesicles (CCVs). The latter are involved in receptor-mediated endocytosis (RME) and other trafficking pathways. Here, we subject individual triskelia, bovine-brain CCVs, and reconstituted clathrin-AP180 coats to AFM-SMFS and AFM-SPFS pulling experiments and apply novel analytics to extract force-extension relations from very large data sets.

Fabrication of hydrogels with steep stiffness gradients for studying cell mechanical response.

Many fundamental cell processes, such as angiogenesis, neurogenesis and cancer metastasis, are thought to be modulated by extracellular matrix stiffness. Thus, the availability of matrix substrates having well-defined stiffness profiles can be of great importance in biophysical studies of cell-substrate interaction. Here, we present a method to fabricate biocompatible hydrogels with a well defined and linear stiffness gradient.

Analysis of the conformation and function of the Plasmodium falciparum merozoite proteins MTRAP and PTRAMP.

Thrombospondin repeat (TSR)-like domains are structures involved with cell adhesion. Plasmodium falciparum proteins containing TSR domains play crucial roles in parasite development. In particular, the preerythrocytic P.

AFM visualization of clathrin triskelia under fluid and in air.

Atomic force microscopy (AFM) is used to characterize the structure and interactions of clathrin triskelia. Time sequence images of individual, wet triskelia resting on mica surfaces clearly demonstrate conformational fluctuations of the triskelia. AFM of dried samples yields images having nanometric resolution comparable to that obtainable by electron microscopy of shadowed samples.

Structure of the Plasmodium falciparum circumsporozoite protein, a leading malaria vaccine candidate.

The Plasmodium falciparum circumsporozoite protein (CSP) is critical for sporozoite function and invasion of hepatocytes. Given its critical nature, a phase III human CSP malaria vaccine trial is ongoing. The CSP is composed of three regions as follows: an N terminus that binds heparin sulfate proteoglycans, a four amino acid repeat region (NANP), and a C terminus that contains a thrombospondin-like type I repeat (TSR) domain.

Characterization of a protective Escherichia coli-expressed Plasmodium falciparum merozoite surface protein 3 indicates a non-linear, multi-domain structure.

Immunization with a recombinant yeast-expressed Plasmodium falciparum merozoite surface protein 3 (MSP3) protected Aotus nancymai monkeys against a virulent challenge infection. Unfortunately, the production process for this yeast-expressed material was not optimal for human trials. In an effort to produce a recombinant MSP3 protein in a scaleable manner, we expressed and purified near-full-length MSP3 in Escherichia coli (EcMSP3).

A Mycobacterium tuberculosis-derived lipid inhibits membrane fusion by modulating lipid membrane domains.

Tuberculosis is an infectious and potentially fatal disease caused by the acid-fast bacillus Mycobacterium tuberculosis (MTB). One hallmark of a tuberculosis infection is the ability of the bacterium to subvert the normal macrophage defense mechanism of the host immune response. Lipoarabinomannan (LAM), an integral component of the MTB cell wall, is released when MTBs are taken into phagosomes and has been reported to be involved in the inhibition of phago-lysosomal (P-L) fusion.

Measuring the elasticity of clathrin-coated vesicles via atomic force microscopy.

Using a new scheme based on atomic force microscopy (AFM), we investigate mechanical properties of clathrin-coated vesicles (CCVs). CCVs are multicomponent protein and lipid complexes of approximately 100 nm diameter that are implicated in many essential cell-trafficking processes. Our AFM imaging resolves clathrin lattice polygons and provides height deformation in quantitative response to AFM-substrate compression force.

Titin PEVK segment: charge-driven elasticity of the open and flexible polyampholyte.

The giant protein titin spans half of the sarcomere length and anchors the myosin thick filament to the Z-line of skeletal and cardiac muscles. The passive elasticity of muscle at a physiological range of stretch arises primarily from the extension of the PEVK segment, which is a polyampholyte with dense and alternating-charged clusters. Force spectroscopy studies of a 51 kDa fragment of the human fetal titin PEVK domain (TP1) revealed that when charge interactions were reduced by raising the ionic strength from 35 to 560 mM, its mean persistence length increased from 0.

Evaluation of a mobile diabetes care telemedicine clinic serving Aboriginal communities in Northern British Columbia, Canada.

Introduction: In British Columbia, Aboriginal diabetes prevalence, hospitalization and mortality rates are all more than twice as high as in the rest of the population. We describe and evaluate a program to improve access to diabetes care for Aboriginal people in northern communities.

Study Design: Cost-effectiveness evaluation.