The Role of Damaged DNA Binding Protein 2 in Colon Cancer

Deregulation of the Wnt/β-catenin signaling pathway drives the development of colorectal cancer (CRC) but understanding of this pathway remains incomplete. Here we report that the damage-specific DNA-binding protein DDB2 is critical for β-catenin-mediated activation of RNF43, which restricts Wnt-signaling by removing Wnt receptors from the cell surface. Reduced expression of DDB2 and RNF43 was observed in human hyperplastic colonic foci. DDB2 recruited EZH2 and β-catenin at an upstream site in the Rnf43 gene, enabling functional interaction with distant TCF4/β-catenin binding sites in the intron of Rnf43. This novel activity of DDB2 was required for RNF43 function as a negative feedback regulator of Wnt-signaling. Mice genetically deficient in DDB2 exhibited increased susceptibility to colon tumor development in a manner associated with higher abundance of the Wnt receptor-expressing cells and greater activation of the downstream Wnt-pathway. Our results identify DDB2 as both a partner and regulator of Wnt-signaling with an important role in suppressing colon cancer development

Unimolecular Micelles of Amphiphilic Cyclodextrin-Core Star-Like Copolymers with Covalent pH-Responsive Linkage of Anticancer Prodrugs

Multifunctional stable and stimuli-responsive drug delivery systems are important for efficient cancer treatment due to their advantages such as enhanced cancer-targeting efficiency, improved pharmacokinetics, minimized drug leaching, and reduced undesirable side effects. Here we report a robust and pH-responsive anticancer drug delivery system based on unimolecular micelles of star-like amphiphilic copolymers. The polymers (denoted as <b>CPOFs</b>) were facilely synthesized via one-step atom transfer radical polymerization of functionalizable benzoaldehyde and hydrophilic poly­[(oligo ethylene glycol) methyl ether methacrylate] as comonomers from the core of heptakis [2,3,6-tri-<i>o</i>-(2-bromo-2-methyl propionyl]-β-cyclodextrin as the initiator. Doxorubicin (DOX) as an anticancer drug was covalently linked to the benzoaldehyde groups of <b>CPOFs</b> through pH-sensitive Schiff-base bonds. The DOX-conjugated polymers, denoted as <b>CPOF–DOX</b>, formed robust unimolecular micelles with an average diameter of 18 nm in aqueous media. More importantly, these unimolecular micelles showed higher drug loading capacity and more controllable drug release characteristics, compared to our previous unimolecular micelles of β-cyclodextrin-poly­(lactic acid)-<i>b</i>-poly­[(oligo ethylene glycol) methyl ether methacrylates] that physically encapsulated DOX via hydrophobic interaction. Moreover, the <b>CPOF–DOX</b> unimolecular micelles could be internalized by human cervical cancer HeLa cells in a stepwise way and showed less cytotoxicity compared to carrier-free DOX. We foresee that <b>CPOF–DOX</b> would provide a promising robust and controllable anticancer drug delivery system for future animal study and clinical trials for cancer treatment

Additional file 1: Figure S1. of The fate of systemically administrated allogeneic mesenchymal stem cells in mouse femoral fracture healing

Cell surface markers and differentiation capacities of mouse MSCs. (A) Flow cytometry analysis results confirmed that isolated BM-MSCs were negative for hematopoietic marker CD45. (B) Cells were negative for endothelial cell marker CD31. (C, D) Cells were positive for MSC markers CD44 and CD90. (E) The Alizarin red staining demonstrated that mineralized nodules formed after 4 weeks of the osteogenic induction. (F) Intracellular Oil red O-stained lipid-rich vacuoles appeared after 2 weeks of the adipogenic induction. BM-MSC bone marrow-derived mesenchymal stem cell, MSC mesenchymal stem cell. (TIFF 468 kb

Near-Infrared Light-Responsive Semiconductor Polymer Composite Hydrogels: Spatial/Temporal-Controlled Release via a Photothermal “Sponge” Effect

Near-infrared (NIR) light-responsive hydrogels are important for biomedical applications, such as remote-controlled release, but the NIR agents previously used were largely limited to heavy-metal inorganic materials such as gold nanoparticles. In this article, we report a new type of NIR photothermal-responsive hydrogel that can undergo structural changes in response to NIR light for biomedical applications in drug delivery and controlled release. The hydrogels synthesized by integrating a narrow-bandgap semiconductor polymer poly­(diketopyrrolopyrrole-<i>alt</i>-3,4-ethylenedioxythiophene) with the polymerization of <i>N</i>-isopropylacrylamide show rapid and reversible mechanical shrinkage upon NIR light irradiation and can serve as carriers for anticancer drug loading and spatial/temporal control of drug release. These stimuli-responsive hydrogels, which can be prepared in different sizes and shapes, integrate photothermal properties and hydrogel characteristics and can provide on-demand, repeated, remote-controlled drug delivery for biomedical applications such as cancer treatment

Nanopore Signatures of Nucleoside Drugs

Nucleoside drugs, which are analogues of natural nucleosides, have been widely applied in the clinical treatment of viral infections and cancers. The development of nucleoside drugs, repurposing of existing drugs, and combined use of multiple drug types have made the rapid sensing of nucleoside drugs urgently needed. Nanopores are emerging single-molecule sensors that have high resolution to resolve even minor structural differences between chemical compounds. Here, an engineered Mycobacterium smegmatis porin A hetero-octamer was used to perform general nucleoside drug analysis. Ten nucleoside drugs were simultaneously detected and fully discriminated. An accuracy of >99.9% was consequently reported. This sensing capacity was further demonstrated in direct nanopore analysis of ribavirin buccal tablets, confirming its sensing reliability against complex samples and environments. No sample separation is needed, however, significantly minimizing the complexity of the measurement. This technique may inspire nanopore applications in pharmaceutical production and pharmacokinetics measurements

Nanopore Signatures of Nucleoside Drugs

Nucleoside drugs, which are analogues of natural nucleosides, have been widely applied in the clinical treatment of viral infections and cancers. The development of nucleoside drugs, repurposing of existing drugs, and combined use of multiple drug types have made the rapid sensing of nucleoside drugs urgently needed. Nanopores are emerging single-molecule sensors that have high resolution to resolve even minor structural differences between chemical compounds. Here, an engineered Mycobacterium smegmatis porin A hetero-octamer was used to perform general nucleoside drug analysis. Ten nucleoside drugs were simultaneously detected and fully discriminated. An accuracy of >99.9% was consequently reported. This sensing capacity was further demonstrated in direct nanopore analysis of ribavirin buccal tablets, confirming its sensing reliability against complex samples and environments. No sample separation is needed, however, significantly minimizing the complexity of the measurement. This technique may inspire nanopore applications in pharmaceutical production and pharmacokinetics measurements

Nanopore Signatures of Nucleoside Drugs

Nucleoside drugs, which are analogues of natural nucleosides, have been widely applied in the clinical treatment of viral infections and cancers. The development of nucleoside drugs, repurposing of existing drugs, and combined use of multiple drug types have made the rapid sensing of nucleoside drugs urgently needed. Nanopores are emerging single-molecule sensors that have high resolution to resolve even minor structural differences between chemical compounds. Here, an engineered Mycobacterium smegmatis porin A hetero-octamer was used to perform general nucleoside drug analysis. Ten nucleoside drugs were simultaneously detected and fully discriminated. An accuracy of >99.9% was consequently reported. This sensing capacity was further demonstrated in direct nanopore analysis of ribavirin buccal tablets, confirming its sensing reliability against complex samples and environments. No sample separation is needed, however, significantly minimizing the complexity of the measurement. This technique may inspire nanopore applications in pharmaceutical production and pharmacokinetics measurements

Additional file 1: of Characteristics of cardio-Cerebrovascular modulation in patients with generalized anxiety disorder: an observational study

Available data in patients with generalized anxiety disorder and healthy controls. Data of age, supine arterial pressure, standing arterial pressure, cerebral blood flow velocity, Heart rate, and HAMA score in patients with generalized anxiety disorder and healthy controls. (XLSX 14 kb

What is the right scale for REDD?

Recent developments in nanopore sequencing have inspired new concepts in precision medicine but limited in throughput. By optically encoding calcium flux from an array of nanopores, parallel measurements from hundreds of nanopores were reported, while lateral drifts of biological nanopores set obstacles for signal processing. In this paper, optical single-channel recording (oSCR) serves to track nanopores with high precision and a general principle of nanopore motion kinetics is quantitatively investigated. By finely adjusting the osmosis-oriented interactions between the lipid/substrate interfaces, motions of nanopores could be controllably restricted. Improved signal-to-noise ratio is observed from motion-restricted nanopores, which is experimentally demonstrated. To systematically evaluate oSCR with asymmetric salt concentrations, a finite element method simulation is established. oSCR with an array of immobilized nanopores suggests new strategies for sequencing DNA by microscopic imaging in high throughput and is widely applicable to the investigation of other transmembrane proteins

Mussel Inspired Modification for Aluminum Oxide/Silicone Elastomer Composites with Largely Improved Thermal Conductivity and Low Dielectric Constant

Inspired by unparalleled adhesion of mussels, bioinspired poly­(dopamine) (PDA) has been used to functionalize the surface of aluminum oxide (Al₂O₃) nanoparticles aiming at improving the thermal conductivity of silicone rubber (SR). The successful and effective preparation of PDA modified Al₂O₃ nanoparticles (Al₂O₃–PDA) was confirmed by XPS, HR-TEM, and XRD. The PDA coating on the Al₂O₃ nanoparticles improved its interfacial interaction between polymeric matrix and facilitated the uniform-dispersion of filler, leading to the 30 vol % Al₂O₃–PDA/SR composite that exhibited a high thermal conductivity (0.585 W/((m·K))), which was almost 400% of pure silicone rubber (0.147 W/(m·K)). In addition, the 30 vol % Al₂O₃–PDA/SR composite displayed a relatively low dielectric constant (4.06 at 1 kHz), which was a bit higher than that of pure SR (2.59 at 1 kHz), a big advantage for the electronic or electrical engineering application. With advantages of efficient, easy handling, controllable, and eco-friendly, this modification method provides a new universal route to improve the thermal conductivity of composites