A pH-Responsive Protein Assembly through Clustering of a Charge-Tunable Single Amino Acid Repeat.

Specific targeting of tumor cells is a key to achieving high therapeutic efficacy while minimizing off-target side effects. As a general approach to targeting diverse tumor cells, considerable attention has been paid to the tumor microenvironment, particularly its slightly acidic pH (6.5-6.

Intense pulsed light annealing of solution-based indium-gallium-zinc-oxide semiconductors with printed Ag source and drain electrodes for bottom gate thin film transistors.

In this study, an intense pulsed light (IPL) annealing process for a printed multi-layered indium-gallium-zinc-oxide (IGZO) and silver (Ag) electrode structure was developed for a high performance all-printed inorganic thin film transistor (TFT). Through a solution process using IGZO precursor and Ag ink, the bottom gate structure TFT was fabricated. The spin coating method was used to form the IGZO semiconductor layer on a heavily-doped silicon wafer covered with thermally grown silicon dioxide.

Dexmedetomidine Stereotaxic Injection Alleviates Neuronal Loss Following Bilateral Common Carotid Artery Occlusion Up-Regulation of BDNF Expression.

Background/aim: Neurogenesis is an important process in the recovery from neurological damage caused by ischemic lesions. Endogenous neurogenesis is insufficient to restore neuronal damage following cerebral ischemia. Dexmedetomidine (DEX) exerts neuroprotective effects against cerebral ischemia and ischemia/reperfusion injury.

Engineering of a Fluorescent Protein for a Sensing of an Intrinsically Disordered Protein through Transition in the Chromophore State.

Intrinsically disordered proteins (IDPs) not only play important roles in biological processes but are also linked with the pathogenesis of various human diseases. Specific and reliable sensing of IDPs is crucial for exploring their roles but remains elusive due to structural plasticity. Here, we present the development of a new type of fluorescent protein for the ratiometric sensing and tracking of an IDP.

A pH-Responsive Virus-Like Particle as a Protein Cage for a Targeted Delivery.

A stimuli-responsive protein self-assembly offers promising utility as a protein nanocage for biotechnological and medical applications. Herein, the development of a virus-like particle (VLP) that undergoes a transition between assembly and disassembly under a neutral and acidic pH, respectively, for a targeted delivery is reported. The structure of the bacteriophage P22 coat protein is used for the computational design of coat subunits that self-assemble into a pH-responsive VLP.

A bivalent form of a RBD-specific synthetic antibody effectively neutralizes SARS-CoV-2 variants.

Coronavirus Disease 2019 (COVID-19) pandemic is severely impacting the world, and tremendous efforts have been made to deal with it. Despite many advances in vaccines and therapeutics, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants remains an intractable challenge. We present a bivalent Receptor Binding Domain (RBD)-specific synthetic antibody, specific for the RBD of wild-type (lineage A), developed from a non-antibody protein scaffold composed of LRR (Leucine-rich repeat) modules through phage display.

Oligomeric states of ASC specks regulate inflammatory responses by inflammasome in the extracellular space.

Inflammasomes are multi-protein complexes and play a crucial role in host defense against pathogens. Downstream inflammatory responses through inflammasomes are known to be related to the oligomerization degree of ASC specks, but the detailed mechanism still remains unexplored. Here, we demonstrate that oligomerization degrees of ASC specks regulate the caspase-1 activation in the extracellular space.

Vertebral Artery Dissection Following Anterior Cervical Decompression and Artificial Disc Replacement.

Vertebral artery dissection (VAD) is a rare vascular cause of acute stroke. Although VAD may be classified as spontaneous or traumatic, it is increasingly recognized that trivial mechanical stress typically precipitates this potentially dangerous condition. Herein, we report a rare case of VAD and acute stroke following anterior cervical decompression and artificial disc replacement (ADR).

A conformation-selective protein binder for a KRAS mutant inhibits the interaction between RAS and RAF.

Small GTPases are key signaling nodes that regulate the cellular processes and subcellular events, and their abnormal activities and dysregulations are closely linked with diverse cancers. Here, we report the development of conformation-selective protein binders for a KRAS mutant. The conformation-specific protein binders were selected from a repebody scaffold composed of LRR (Leucine-rich repeat) modules through phage display and modular engineering against constitute active conformation of KRAS.

Construction and Functionalization of a Clathrin Assembly for a Targeted Protein Delivery.

Protein assemblies have drawn much attention as platforms for biomedical applications, including gene/drug delivery and vaccine, due to biocompatibility and functional diversity. Here, the construction and functionalization of a protein assembly composed of human clathrin heavy chain and light chain for a targeted protein delivery, is presented. The clathrin heavy and light chains are redesigned and associated with each other, and the resulting triskelion unit further self-assembled into a clathrin assembly with the size of about 28 nm in diameter.

Primary Malignant Lymphoma Presenting as an Isolated Epidural Mass.

Primary central nervous system lymphoma is a rare form of extranodal non-Hodgkin's lymphoma that occurs in the brain, spinal cord, leptomeninges, or eyes and typically remains confined to the central nervous system. Among them, malignant lymphoma presenting as a primary tumor of the spinal cord is extremely uncommon, and epidural mass formation is known to occur in only 0.8-2.

Enhanced half-life and antitumor activity of interleukin-15 through genetic fusion of a serum albumin-specific protein binder.

Human interleukin-15 (hIL-15) has attracted a considerable attention as a promising cancer immunotherapeutic due to its function to directly stimulate the proliferation and cytotoxic activity of NK and T cells. Nevertheless, a relatively short half-life of hIL-15 requires repeated administration and higher doses, causing serious side effects. Here, we demonstrate an enhanced blood half-life and biological activity of hIL-15 through genetic fusion of a human serum albumin-specific protein binder (rHSA).

Computational epitope binning reveals functional equivalence of sequence-divergent paratopes.

The therapeutic efficacy of a protein binder largely depends on two factors: its binding site and its binding affinity. Advances in library display screening and next-generation sequencing have enabled accelerated development of strong binders, yet identifying their binding sites still remains a major challenge. The differentiation, or "binning", of binders into different groups that recognize distinct binding sites on their target is a promising approach that facilitates high-throughput screening of binders that may show different biological activity.

Dendrimer-Like Supramolecular Assembly of Proteins with a Tunable Size and Valency Through Stepwise Iterative Growth.

The assembly of proteins in a programmable manner provides insight into the creation of novel functional nanomaterials for practical applications. Despite many advances, however, a rational protein assembly with an easy scalability in terms of size and valency remains a challenge. Here, a simple bottom-up approach to the supramolecular protein assembly with a tunable size and valency in a programmable manner is presented.

Design of 3D printable prosthetic foot to implement nonlinear stiffness behavior of human toe joint based on finite element analysis.

Toe joint is known as one of the critical factors in designing a prosthetic foot due to its nonlinear stiffness characteristic. This stiffness characteristic provides a general feeling of springiness in the toe-off and it also affects the ankle kinetics. In this study, the toe part of the prosthetic foot was designed to improve walking performance.

Fabrication of solderable intense pulsed light sintered hybrid copper for flexible conductive electrodes.

Additively printed circuits provide advantages in reduced waste, rapid prototyping, and versatile flexible substrate choices relative to conventional circuit printing. Copper (Cu) based inks along with intense pulsed light (IPL) sintering can be used in additive circuit printing. However, IPL sintered Cu typically suffer from poor solderability due to high roughness and porosity.

Nonphosphorylatable PEA15 mutant inhibits epithelial-mesenchymal transition in triple-negative breast cancer partly through the regulation of IL-8 expression.

Background: Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype that lacks targeted therapies. Patients with TNBC have a very poor prognosis because the disease often metastasizes. New treatment approaches addressing drivers of metastasis and tumor growth are crucial to improving patient outcomes.

Epitopes of Protein Binders Are Related to the Structural Flexibility of a Target Protein Surface.

Protein binders including antibodies are known not to bind to random sites of target proteins, and their functional effectiveness mainly depends on the binding region, called the epitope. For the development of protein binders with desired functions, it is thus critical to understand which surface region protein binders prefer (or do not prefer) to bind. The current methods for epitope prediction focus on static indicators such as structural geometry or amino acid propensity, whereas protein binding events are in fact a consequence of dynamic interactions.

Computationally-guided design and affinity improvement of a protein binder targeting a specific site on HER2.

A protein binder with a desired epitope and binding affinity is critical to the development of therapeutic agents. Here we present computationally-guided design and affinity improvement of a protein binder recognizing a specific site on domain IV of human epidermal growth factor receptor 2 (HER2). As a model, a protein scaffold composed of Leucine-rich repeat (LRR) modules was used.

Biomechanical evaluation of the stability of extra-articular distal radius fractures fixed with volar locking plates according to the length of the distal locking screw.

Surgeons usually used short screws to avoid extensor tendon problems during volar locking plate fixation in distal radius fracture. However, the stability according to the length of distal locking screws have not been fully understood. We investigated this issue through finite element analysis and compression test using synthetic radius.

Structure-guided rational design of the substrate specificity and catalytic activity of an enzyme.

The quest for an enzyme with desired property is high for biocatalyic production of valuable products in industrial biotechnology. Synthetic biology and metabolic engineering also increasingly require an enzyme with unusual property in terms of substrate spectrum and catalytic activity for the construction of novel circuits and pathways. Structure-guided enzyme engineering has demonstrated a prominent utility and potential in generating such an enzyme, even though some limitations still remain.

Computer-guided binding mode identification and affinity improvement of an LRR protein binder without structure determination.

Precise binding mode identification and subsequent affinity improvement without structure determination remain a challenge in the development of therapeutic proteins. However, relevant experimental techniques are generally quite costly, and purely computational methods have been unreliable. Here, we show that integrated computational and experimental epitope localization followed by full-atom energy minimization can yield an accurate complex model structure which ultimately enables effective affinity improvement and redesign of binding specificity.

Site-Specific Lipidation of a Small-Sized Protein Binder Enhances the Antitumor Activity through Extended Blood Half-Life.

Protein and peptide therapeutics tend to have a short blood circulation time mainly caused by rapid clearance in kidney, leading to a low therapeutic efficacy. Here, we demonstrate that the antitumor activity of a small-sized protein binder can be significantly enhanced by prolonged blood half-life through site-specific lipidation. An unnatural amino acid was genetically incorporated into a specific site with the highest accessibility in a human interleukin-6 (IL-6)-targeting protein binder with a size of 30.

Functionalized gold nanoparticles with zinc finger-fused proteins as a colorimetric immunoassay platform.

The quest for highly sensitive and specific detection of disease biomarkers is high, despite many advances in analysis system. Here, we present a sensitive immunoassay platform using DNA-tethered gold nanoparticles and DNA-binding zinc fingers (ZFs). Monomeric alkaline phosphatase (mAP) and human TNF-α were employed as a signal generator and a disease biomarker, respectively.