Hierarchically Patterned Self-Cleaning Polymer Composites for Daytime Radiative Cooling.

Passive daytime radiative cooling (PDRC) has the potential to reduce energy demand and mitigate global warming. However, surface contamination from dust and bacterial buildup limits practical PDRC applications. Here, we develop a hierarchically patterned nanoporous composite (HPNC) using a facile template-molding fabrication method to integrate PDRC materials with self-cleaning and antibacterial functions. The HPNC design decouples multifunctional control into different characteristic length scales that can be optimized simultaneously. The nanoporous polymer matrix embedded with tunable fillers enables 7.8 and 4.4 °C temperature reduction for outdoor personal and building cooling, respectively, under intense solar irradiance. Meanwhile, a microscale pillar array pattern integrated into the HPNC enables superhydrophobicity with self-cleaning and antisoiling functions to mitigate surface contamination. Moreover, the surface coating of photocatalytic agents can generate photoinduced antibacterial effects. The scalable fabrication and multifunctional capabilities of our HPNC design offer a promising solution for practical PDRC applications with minimal maintenance needs.

Tailored Polypeptide Star Copolymers for 3D Printing of Bacterial Composites Via Direct Ink Writing.

Hydrogels hold much promise for 3D printing of functional living materials; however, challenges remain in tailoring mechanical robustness as well as biological performance. In addressing this challenge, the modular synthesis of functional hydrogels from 3-arm diblock copolypeptide stars composed of an inner poly(l-glutamate) domain and outer poly(l-tyrosine) or poly(l-valine) blocks is described. Physical crosslinking due to ß-sheet assembly of these star block copolymers gives mechanical stability during extrusion printing and the selective incorporation of methacrylate units allows for subsequent photocrosslinking to occur under biocompatible conditions. This permits direct ink writing (DIW) printing of bacteria-based mixtures leading to 3D objects with high fidelity and excellent bacterial viability. The tunable stiffness of different copolypeptide networks enables control over proliferation and colony formation for embedded Escherichia coli bacteria as demonstrated via isopropyl ß-d-1-thiogalactopyranoside (IPTG) induction of green fluorescent protein (GFP) expression. This translation of molecular structure to network properties highlights the versatility of these polypeptide hydrogel systems with the combination of writable structures and biological activity illustrating the future potential of these 3D-printed biocomposites.

Global Issues of Radiopharmaceutical Access and Availability: A Nuclear Medicine Global Initiative Project.

The Nuclear Medicine Global Initiative was formed in 2012 by 13 international organizations to promote human health by advancing the field of nuclear medicine and molecular imaging by supporting the practice and application of nuclear medicine. The first project focused on standardization of administered activities in pediatric nuclear medicine and resulted in 2 articles. For its second project the Nuclear Medicine Global Initiative chose to explore issues impacting on access and availability of radiopharmaceuticals around the world. Methods: Information was obtained by survey responses from 35 countries on available radioisotopes, radiopharmaceuticals, and kits for diagnostic and therapeutic use. Issues impacting on access and availability of radiopharmaceuticals in individual countries were also identified. Results: Detailed information on radiopharmaceuticals used in each country, and sources of supply, was evaluated. Responses highlighted problems in access, particularly due to the reliance on a sole provider, regulatory issues, and reimbursement, as well as issues of facilities and workforce, particularly in low- and middle-income countries. Conclusion: Strategies to address access and availability of radiopharmaceuticals are outlined, to enable timely and equitable patient access to nuclear medicine procedures worldwide. In the face of disruptions to global supply chains by the coronavirus disease 2019 outbreak, renewed focus on ensuring a reliable supply of radiopharmaceuticals is a major priority for nuclear medicine practice globally.

Helicobacter pylori Infection Modulates Host Cell Metabolism through VacA-Dependent Inhibition of mTORC1.

Helicobacter pylori (Hp) vacuolating cytotoxin (VacA) is a bacterial exotoxin that enters host cells and induces mitochondrial dysfunction. However, the extent to which VacA-dependent mitochondrial perturbations affect overall cellular metabolism is poorly understood. We report that VacA perturbations in mitochondria are linked to alterations in cellular amino acid homeostasis, which results in the inhibition of mammalian target of rapamycin complex 1 (mTORC1) and subsequent autophagy. mTORC1, which regulates cellular metabolism during nutrient stress, is inhibited during Hp infection by a VacA-dependent mechanism. This VacA-dependent inhibition of mTORC1 signaling is linked to the dissociation of mTORC1 from the lysosomal surface and results in activation of cellular autophagy through the Unc 51-like kinase 1 (Ulk1) complex. VacA intoxication results in reduced cellular amino acids, and bolstering amino acid pools prevents VacA-mediated mTORC1 inhibition. Overall, these studies support a model that Hp modulate host cell metabolism through the action of VacA at mitochondria.

IQGAP1 and IQGAP3 Serve Individually Essential Roles in Normal Epidermal Homeostasis and Tumor Progression.

IQ motif-containing GTPase-activating protein (IQGAP) scaffolding proteins regulate many essential cellular processes including growth factor receptor signaling, cytoskeletal rearrangement, adhesion, and proliferation and are highly expressed in many cancers. Using genetically engineered human skin tissue in vivo, we demonstrate that diminished, sub-physiologic expression of IQGAP1 or IQGAP3 is sufficient to maintain normal epidermal homeostasis, whereas significantly higher levels are required to support tumorigenesis. To target this tumor-specific IQGAP requirement in vivo, we engineered epidermal keratinocytes to express individual IQGAP protein domains designed to compete with endogenous IQGAPs for effector protein binding. Expression of the IQGAP1-IQ motif decoy domain in epidermal tissue in vivo inhibits oncogenic Ras-driven mitogen-activated protein kinase signaling and antagonizes tumorigenesis, without disrupting normal epidermal proliferation or differentiation. These findings define essential non-redundant roles for IQGAP1 and IQGAP3 in the epidermis and demonstrate the potential of IQGAP antagonism for cancer therapy.

Opposing mechanisms involving RNA and lipids regulate HIV-1 Gag membrane binding through the highly basic region of the matrix domain.

Membrane binding of Gag, a crucial step in HIV-1 assembly, is facilitated by bipartite signals within the matrix (MA) domain: N-terminal myristoyl moiety and the highly basic region (HBR). We and others have shown that Gag interacts with a plasma-membrane-specific acidic phospholipid, phosphatidylinositol-(4,5)-bisphosphate [PI(4,5)P(2)], via the HBR, and that this interaction is important for efficient membrane binding and plasma membrane targeting of Gag. Generally, in protein-PI(4,5)P(2) interactions, basic residues promote the interaction as docking sites for the acidic headgroup of the lipid. In this study, toward better understanding of the Gag-PI(4,5)P(2) interaction, we sought to determine the roles played by all of the basic residues in the HBR. We identified three basic residues promoting PI(4,5)P(2)-dependent Gag-membrane binding. Unexpectedly, two other HBR residues, Lys25 and Lys26, suppress membrane binding in the absence of PI(4,5)P(2) and prevent promiscuous intracellular localization of Gag. This inhibition of nonspecific membrane binding is likely through suppression of myristate-dependent hydrophobic interaction because mutating Lys25 and Lys26 enhances binding of Gag with neutral-charged liposomes. These residues were reported to bind RNA. Importantly, we found that RNA also negatively regulates Gag membrane binding. In the absence but not presence of PI(4,5)P(2), RNA bound to MA HBR abolishes Gag-liposome binding. Altogether, these data indicate that the HBR is unique among basic phosphoinositide-binding domains, because it integrates three regulatory components, PI(4,5)P(2), myristate, and RNA, to ensure plasma membrane specificity for particle assembly.

Functional brain imaging in pure akinesia with gait freezing: [18F] FDG PET and [18F] FP-CIT PET analyses.

Pure akinesia with gait freezing (PAGF) has characteristic features, including freezing of gait and prominent speech disturbance without rigidity or tremor. The purpose of this study was to investigate changes in brain glucose metabolism and presynaptic dopaminergic function in PAGF. By using [(18)F] fluorodeoxyglucose (FDG) PET, 11 patients with PAGF were compared with 14 patients with probable progressive supranuclear palsy (PSP), 13 patients with Parkinson's disease (PD), and 11 normal controls. [(18)F] N-(3-fluoropropyl)-2beta-carbon ethoxy-3beta-(4-iodophenyl) nortropane (FP-CIT) PET was performed in 11 patients with PAGF and with 10 normal controls. The PAGF patients showed decreased glucose metabolism in the midbrain when compared with normal controls. PSP patients showed a similar topographic distribution of glucose hypometabolism with additional areas, including the frontal cortex, when compared with normal controls. The FP-CIT PET findings in patients with PAGF revealed severely decreased uptake bilaterally in the basal ganglia. These findings suggest that both PAGF and PSP may be part of the same pathophysiologic spectrum of disease. However, the reason why PAGF manifests clinically in a different manner needs to be further elucidated.

Efficient targeting of gastric cancer cells using radiolabeled anti-carcinoembryonic antigen-specific T84.66 fragments in experimental radioimmunoguided surgery.

BACKGROUND: Radioimmunoguided surgery (RIGS) appears as an efficient tool for accurate tumor detection up to the level of micrometastases by detecting radiolabeled antibody-bound tumor cells during operation. Anti-CEA-specific T84.66 fragments were examined as to whether they efficiently detected gastric cancer cells in experimental RIGS. T84.66, anti-CEA-specific antibody, has widely been used as an immune carrier in the preclinical and clinical trials of radioimmunotherapy and radioimmunoscintiscan. MATERIALS AND METHODS: Fifty-one tumors from two human gastric carcinoma cell lines with profuse (MKN45) and low (RF48) CEA expression were successfully implanted subcutaneously in the backs of 32 nude mice. Tumors were localized after 125I-labeled T84.66 F(ab')2 and Fab' injection. RESULTS: The radioactivity of F(ab')2-pretreated mice was greater than that of Fab'-pretreated in all organs and tumors (p<0.001-0.035). Localization indices of the tumor in various organs revealed 7.4 to 32.5 in F(ab')2-pretreated and 1 to 7.1 in Fab'-pretreated mice. Silver grains and immune staining were predominantly distributed in tumor cells regardless of fragment types and cell lines. There was no false-negative evaluation of tumor in F(ab')2-pretreated mice. Sensitivity and specificity of tumor localization by RIGS were the highest in the F(ab')2-pretreated mice (95% for MKN45- and 82% for RF46-xenografted mice) and the least in the Fab'-pretreated mice (66% for MKN45- and 67% for RF46-xenografted mice). In all organs, three quarters of the false-positive evaluations occurred from silver grains as radioimmune complex or dissociated nuclides in the circulation that can be eliminated with time. CONCLUSION: Anti-CEA-specific T84.66 fragments achieved a great affinity and avidity with accurate localization of gastric carcinoma in experimental RIGS.

Enhancement of colorectal tumor targeting using a novel biparatopic monoclonal antibody against carcinoembryonic antigen in experimental radioimmunoguided surgery.

Biparatopic CEA, carcinoembryonic antigen (MAb) was newly designed and tested as to whether it enhanced the accuracy of tumor detection by reducing non-specific binding in experimental radioimmunoguided surgery. Biparatopic MAb was prepared by using cross-linking of reduced Fab' fragments from PR1A3 and T84.66. Fifty-nine tumors from 2 human colorectal carcinoma cell lines with high (KM-12c) and low (Clone A) carcinoembryonic antigen (CEA) expression were successfully implanted subcutaneously on the backs of 42 nude mice. Tumors were localized using 125I-labeled MAbs: IgG, F(ab')(2) and Fab' of PR1A3, and biparatopic MAb of PR1A3 and T84.66. Radioactivity counted on a portable radioisotope detector correlated well with that counted on a gamma counter (p < 0.001). Accumulations of radioactivity in control mice without tumorigenesis were the greatest in PR1A3 IgG-pretreated mice and the least in biparatopic MAb-pretreated mice. Tumors of 2 cell lines did not differ in the distribution of radiolabeled MAbs. Localization indices of the tumor in various organs revealed 1.3 to 4.1 in PR1A3 IgG-pretreated mice, 2.4 to 6.6 in fragment MAbs of PR1A3-pretreated mice and 2 to 4.6 in biparatopic MAb-pretreated mice. Silver grains and immune staining were predominantly distributed in tumor cells of all types of MAb-pretreated mice. Sensitivity and specificity of tumor localization by radioimmunoguided surgery (RIGS) were the highest in the biparatopic MAb-pretreated mice (90.9% and 94.5%, respectively) and the least in the PR1A3 IgG-pretreated mice (50% and 72%). The biparatopic MAb using 2 anti-CEA MAbs against different epitopes achieved a great affinity and avidity with accurate localization of colorectal carcinoma in experimental radioimmunoguided surgery.