The TOX-RAGE axis mediates inflammatory activation and lung injury in severe pulmonary infectious diseases.

Thymocyte selection-associated high-mobility group box (TOX) is a transcription factor that is crucial for T cell exhaustion during chronic antigenic stimulation, but its role in inflammation is poorly understood. Here, we report that TOX extracellularly mediates drastic inflammation upon severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection by binding to the cell surface receptor for advanced glycation end-products (RAGE). In various diseases, including COVID-19, TOX release was highly detectable in association with disease severity, contributing to lung fibroproliferative acute respiratory distress syndrome (ARDS). Recombinant TOX-induced blood vessel rupture, similar to a clinical signature in patients experiencing a cytokine storm, further exacerbating respiratory function impairment. In contrast, disruption of TOX function by a neutralizing antibody and genetic removal of RAGE diminished TOX-mediated deleterious effects. Altogether, our results suggest an insight into TOX function as an inflammatory mediator and propose the TOX-RAGE axis as a potential target for treating severe patients with pulmonary infection and mitigating lung fibroproliferative ARDS.

SerpinB2 deficiency is associated with delayed mammary tumor development and decreased pro-tumorigenic macrophage polarization.

The in vivo functions of SerpinB2 in tumor cells and tumor-associated macrophages (TAMs) during breast cancer development and metastasis remain elusive. SerpinB2-deficient MMTV-PyMT mice (PyMTSB2-/-) were previously produced to explore the biological roles of SerpinB2 in breast cancer. Compared with MMTV-PyMT wild-type (PyMTWT) mice, PyMTSB2-/- mice showed delayed tumor progression and reduced CK8 + tumor cell dissemination to lymph nodes. RNA-Seq data revealed significantly enriched genes associated with inflammatory responses, especially upregulated M1 and downregulated M2 macrophage marker genes in PyMTSB2-/- tumors. Decreased CD206+M2 and increased NOS2+M1 markers were detected in the primary tumors and metastatic lymph nodes of PyMTSB2-/- mice. In an in vitro study, SerpinB2 knockdown decreased the sphere formation and migration of MDA-MB-231 cells and suppressed protumorigenic M2 polarization of RAW264.7 cells. The combination of low SerpinB2, high NOS2, and low CD206 expression was favorable for survival in patients with breast cancer, as assessed in the BreastMark dataset. Our study demonstrates that SerpinB2 deficiency delays mammary tumor development and metastasis in PyMTWT mice, along with reduced sphere formation and migration abilities of tumor cells and decreased macrophage protumorigenic polarization.

Fabrication and Evaluation of Embroidery-Based Electrode for EMG Smart Wear Using Moss Stitch Technique.

Wearable 2.0 research has been conducted on the manufacture of smart fitness wear that collects bio-signals through the wearing of a textile-based electrode. Among them, the electromyography (EMG) suit measures the electrical signals generated by the muscles to check their activity, such as contraction and relaxation. General gel-type electrodes have been reported to cause skin diseases due to an uncomfortable feel and skin irritation when attached to the skin for a long time. Dry electrodes of various materials are being developed to solve this problem. Previous research has reported EMG detectio performance and conducted economic comparisons according to the size and shape of the embroidery electrode. On the other hand, these embroidery electrodes still have foreign body sensations. In this study, a moss sEMG electrode was produced with various shapes (W3 and WF) and loop lengths (1-5 mm). The optimized conditions of the embroidery-based electrodes were derived and analyzed with the tactile comfort factors and sensing performances. As the loop length of the electrode increased, MIU and Qmax increased, but the SMD decreased due to the free movement of the threads constituting the loop. Impedance and sEMG detection performance showed different trends depending on the electrode type.

Development and Characterization of Embroidery-Based Textile Electrodes for Surface EMG Detection.

The interest in wearable devices has expanded to measurement devices for building IoT-based mobile healthcare systems and sensing bio-signal data through clothing. Surface electromyography, called sEMG, is one of the most popular bio-signals that can be applied to health monitoring systems. In general, gel-based (Ag/AgCl) electrodes are mainly used, but there are problems, such as skin irritation due to long-time wearing, deterioration of adhesion to the skin due to moisture or sweat, and low applicability to clothes. Hence, research on dry electrodes as a replacement is increasing. Accordingly, in this study, a textile-based electrode was produced with a range of electrode shapes, and areas were embroidered with conductive yarn using an embroidery technique in the clothing manufacturing process. The electrode was applied to EMG smart clothing for fitness, and the EMG signal detection performance was analyzed. The electrode shape was manufactured using the circle and wave type. The wave-type electrode was more morphologically stable than the circle-type electrode by up to 30% strain, and the electrode shape was maintained as the embroidered area increased. Skin-electrode impedance analysis confirmed that the embroidered area with conductive yarn affected the skin contact area, and the impedance decreased with increasing area. For sEMG performance analysis, the rectus femoris was selected as a target muscle, and the sEMG parameters were analyzed. The wave-type sample showed higher EMG signal strength than the circle-type. In particular, the electrode with three lines showed better performance than the fill-type electrode. These performances operated without noise, even with a commercial device. Therefore, it is expected to be applicable to the manufacture of electromyography smart clothing based on embroidered electrodes in the future.

Protective Effect of Tetrahydroquinolines from the Edible Insect Allomyrina dichotoma on LPS-Induced Vascular Inflammatory Responses.

The larva of Allomyrina dichotoma (family Scarabaeidae) is an edible insect that is registered in the Korean Food Standards Codex as a food resource. The chemical study on the larvae of A. dichotoma resulted in the isolation of three new tetrahydroquinolines, allomyrinaines A-C (1-3), one new dopamine derivative, allomyrinamide A (4), and four known compounds (5-8). The structures were elucidated on the basis of 1D and 2D nuclear magnetic resonance (NMR) and MS spectroscopic data analysis. Allomyrinaines A-C (1-3) possessed three stereogenic centers at C-2, C-3, and C-4, whose relative configurations were determined by analyses of the coupling constants and the nuclear Overhauser enhancement spectroscopy (NOESY) data, as well as DP4+ calculation. The anti-inflammatory effects of compounds 1-4 were evaluated in human endothelial cells. Allomyrinaines A-C (1-3) could stabilize vascular barrier integrity on lipopolysaccharide (LPS)-induced vascular inflammation via inhibition of the nuclear factor-κB (NF-κB) pathway. The physiologically relevant concentration was confirmed by Q-TOF-MS-based quantitative analysis on allomyrinaines A-C in crude extract. This study suggests that allomyrinaines A-C (1-3) are bioactive constituents of A. dichotoma to treat vascular inflammatory disorder.

Comparison of transcriptome expression alterations by chronic exposure to low-dose bisphenol A in different subtypes of breast cancer cells.

The impacts of chronic bisphenol A (BPA) exposure suspected to be a potential risk factor for breast cancer progression are not thoroughly understood in different subtypes of breast cancer cells (BCCs). This study aimed to compare the differentially expressed genes (DEGs) and biological functions in MCF-7 (luminal A), SK-BR3 (HER2-enriched) and MDA-MB-231 (triple-negative) cells exposed to BPA at an environmentally human-relevant low dose (10-8 M) for 30 days, by using the approach of RNA sequencing and online informatics tools. BPA-exposure resulted in 172, 137, and 139 DEGs in MCF-7/BPA, SK-BR3/BPA, and MDA-MB-231/BPA, respectively. The significantly enriched gene ontology terms of DEGs in each cell were different: cellular response to gonadotropin-releasing hormone, negative regulation of fibrinolysis, choline metabolism, glutamate signaling pathways and coagulation pathway in MCF-7/BPA; positive regulation of inflammatory response and VEGF/VEGFR signaling pathways in SK-BR3/BPA; negative regulation of keratinocyte proliferation and HIF signaling pathways in MDA-MB-231/BPA cells. The immune network analysis of DEGs across the breast cancer cells indicated NKT, NK and T cell activation and dendritic cell migration by regulating the expression of immunomodulatory genes. High expression of IL19, CA9 and SPARC identified in MCF-7/BPA, SK-BR3/BPA, and MDA-MB-231/BPA are detrimental gene signatures to predict poor overall survival in luminal A, HER2-enriched and triple-negative breast cancer patients, respectively. These findings indicate chronic BPA exposure has dissimilar impacts on the regulation of gene expression and diverse biological functions, including immune modulation, in different subtypes of BCCs.

Ultravist Induces the Expression of MCP-1 and VCAM-1 in IL-4-Stimulated HUVECs.

The goal of the present study focused on the adverse reaction of contrast medium (CM) via the induction of inflammatory molecules in human umbilical vein endothelial cells (HUVECs). Ultravist-induced monocyte chemoattractant protein-1 (MCP-1) and vascular cell adhesion molecule-1 (VCAM-1) gene expression was markedly increased in interleukin-4 (IL-4)-pretreated HUVECs in a time- and dose-dependent manner and was paralleled by concomitant production of MCP-1 and VCAM-1 proteins. MCP-1 and VCAM-1 gene expression by Ultravist in combination with IL-4 was mediated by the c-Jun N-terminal kinases (JNK1/2) signaling pathway. IL-4-pretreated Ultravist-stimulated HUVECs showed greatly increased migration and adhesion of THP-1 cells. Cell migration was decreased by treatment of CCR2 antagonist, and cell adhesion was also decreased by VCAM-1 blocking antibody. Furthermore, when tested in vivo under similar conditions, MCP-1 protein was significantly increased in Ultravist combined with IL-4-injected mice. Taken together, our findings suggest that MCP-1 blocking may be crucial in preventing the endothelial dysfunction induced by contrast medium in patients with inflammatory disease and atherosclerosis.

Sulphiredoxin plays peroxiredoxin-dependent and -independent roles via the HOG signalling pathway in Cryptococcus neoformans and contributes to fungal virulence.

Mechanisms of oxidative stress resistance are crucial virulence factors for survival and proliferation of fungal pathogens within the human host. In this study we have identified and functionally characterized the role of sulphiredoxin, Srx1, in oxidative stress resistance of Cryptococcus neoformans causing fungal meningoencephalitis and regulation of peroxiredoxins, Tsa1 and Tsa3, and thioredoxins, Trx1 and Trx2. The C. neoformans HOG (High Osmolarity Glycerol response) pathway was essential for the transcriptional regulation of SRX1 under peroxide stress conditions. A gene deletion study revealed that Srx1 was required for cells to counteract peroxide stress, but not other oxidative damaging agents. HOG1 was found to be essential for the induction of adaptive response to peroxide stress with concurrent repression of ergosterol biosynthesis in an SRX1-independent manner. Consistent with this, phosphorylation of C. neoformans Hog1 was modulated by both low and high doses of exogenous hydrogen peroxide treatment. Immunoblot analysis using the C. neoformans Tsa1 specific antibody revealed that both Srx1 and Trx1 were essential for recycling of oxidized Tsa1. In addition to its role in peroxide sensing and response C. neoformans Srx1 was also found to be required for a peroxiredoxin-independent function in promoting fungicide-dependent cell swelling and growth arrest. Finally we showed the importance of C. neoformans Srx1 in fungal pathogenesis by demonstrating its requirement for full virulence using a mouse infection model.

Curcuma longa L. extract exhibits anti-inflammatory and cytoprotective functions in the articular cartilage of monoiodoacetate-injected rats.

Background: Osteoarthritis (OA), the most prevalent form of arthritis, is a degenerative joint disease marked by the progressive deterioration of articular cartilage, leading to clinical manifestations such as joint pain. Objective: This study investigated the effects of Curcuma longa L. extract (CL) containing curcumin, demethoxycurcumin, and bisdemethoxycurcumin on monosodium iodoacetate (MIA)-induced OA rats. Design: Sprague-Dawley rats with MIA-induced OA received CL supplementation at doses of 5, 25, and 40 mg/kg body weight. Results: CL extract administration suppressed mineralisation parameters and morphological modifications and decreased arachidonate5-lipoxygenase and leukotriene B4 levels in articular cartilage. Additionally, it decreased serum prostaglandin E2, NO, and glycosaminoglycanlevels as well as the protein expression of phosphorylated inhibitor kappa B-alpha, phosphorylated p65, cyclooxygenase-2, and inducible nitric oxide synthase in the cartilage of MIA-injected rats. Furthermore, it also reduced matrix metalloproteinases and elevated SMAD family member 3 phosphorylation, tissue inhibitor of metalloproteinases, aggrecan, collagen type I, and collagen type II levels in the articular cartilage of MIA-induced OA rats. Conclusions: This study's findings suggest that CL supplementation helps prevent OA development and is an effective therapy for OA.

Fabrication of Textile-Based Dry Electrode and Analysis of Its Surface EMG Signal for Applying Smart Wear.

Ag/AgCl hydrogel electrodes, which are wet electrodes, are generally used to acquire bio-signals non-invasively. Research concerning dry electrodes is ongoing due to the following limitations of wet electrodes: (1) skin irritation and disease when attached for a long time; (2) poor adhesion due to sweat; and (3) considerable cost due to disposable use. Accordingly, electrodes in film, embroidery, and knit forms were manufactured from conductive sheets and conductive yarns, which are typical textile-type dry electrode materials, using different manufacturing methods and conditions. The prepared electrodes were conducted to measure the morphology, surface resistance, skin-electrode impedance, EMG signal acquisition, and analysis. The conductive sheet type electrode exhibited a similar skin-impedance, noise, and muscle activation signal amplitude to the Ag/AgCl gel electrode due to the excellent adhesion and shape stabilization. Embroidery electrodes were manufactured based on two-dimension lock stitch (Em_LS) and three-dimension moss-stitch (Em_MS). More stable EMG signal acquisition than Em_LS was possible when manufactured with Em_MS. The knit electrode was manufactured with the typical structures of plain, purl, and interlock. Although it was possible to acquire EMG signals, considerable noise was generated as the shape and size of the electrodes were changed due to the stretch characteristics of the knit structure. Finally, the applicability of the textile-type dry electrode was confirmed by combining it with a wearable device. More stable and accurate EMG signal acquirement will be possible through more precise parameter control in the future.

Cleavage-Responsive Biofactory T Cells Suppress Infectious Diseases-Associated Hypercytokinemia.

Severe infectious diseases, such as coronavirus disease 2019 (COVID-19), can induce hypercytokinemia and multiple organ failure. In spite of the growing demand for peptide therapeutics against infectious diseases, current small molecule-based strategies still require frequent administration due to limited half-life and enzymatic digestion in blood. To overcome this challenge, a strategy to continuously express multi-level therapeutic peptide drugs on the surface of immune cells, is established. Here, chimeric T cells stably expressing therapeutic peptides are presented for treatment of severe infectious diseases. Using lentiviral system, T cells are engineered to express multi-level therapeutic peptides with matrix metallopeptidases- (MMP-) and tumor necrosis factor alpha converting enzyme- (TACE-) responsive cleavage sites on the surface. The enzymatic cleavage releases γ-carboxyglutamic acid of protein C (PC-Gla) domain and thrombin receptor agonist peptide (TRAP), which activate endothelial protein C receptor (EPCR) and protease-activated receptor-1 (PAR-1), respectively. These chimeric T cells prevent vascular damage in tissue-engineered blood vessel and suppress hypercytokinemia and lung tissue damages in vivo, demonstrating promise for use of engineered T cells against sepsis and other infectious-related diseases.

Histological Findings of Mammary Gland Development and Risk of Breast Cancer in BRCA1 Mutant Mouse Models.

PURPOSE: The breast cancer susceptibility gene, BRCA1, is involved in normal development and carcinogenesis of mammary glands. Here, we aimed to evaluate the relationship between histological findings of mammary gland development and breast cancer risk in BRCA1 mutant mice. METHODS: Five BRCA1 mutant mice and five non-mutant FVB/NJ mice were used for each group of 1-month-old (pubertal), 3-month-old (fertile), and 8-month-old (menopausal) mice. In another experiment, 15 BRCA1 mutant mice were followed up to 8 months after birth and classified into tumor-bearing (11 mice) and tumor-free (4 mice) groups. Excised mammary gland tissues were stained with Carmine Alum, and the number of terminal end buds (or alveolar buds), branching density, and duct elongation were measured using image analysis programs. Differences between the two groups were assessed using paired t-test. RESULTS: One-month-old BRCA1 mutant mice showed a higher number of terminal end buds (23.8 ± 1.0 vs. 15.6 ± 0.8, p = 0.0002), branching density (11.7 ± 0.4 vs. 9.6 ± 0.5%, p = 0.0082), and duct elongation (9.7 ± 0.7 vs. 7.3 ± 0.4 mm, p = 0.0186) than controls. However, there was no difference between the 3- and 8-month-old groups. In BRCA1 mutant mice, the tumor-bearing group showed a significantly higher number of alveolar buds (142.7 ± 5.5 vs. 105.5 ± 5.4, p = 0.0008) and branching density (30.0 ± 1.0 vs. 24.1 ± 1.1%, p = 0.008) than the tumor-free group; however, duct elongation was not different (23.9 ± 0.6 vs. 23.6 ± 0.6 mm, p = 0.8099) between the groups. CONCLUSION: BRCA1 mutant mice exhibited early pubertal mammary gland development and delayed age-related mammary gland involution was associated with breast cancer. Our results may have clinical implications for predicting breast cancer risk and developing prevention strategies for BRCA1 mutation carriers.

Electrical Heating Performance of Graphene/PLA-Based Various Types of Auxetic Patterns and Its Composite Cotton Fabric Manufactured by CFDM 3D Printer.

To evaluate the electrical heating performance by auxetic pattern, re-entrant honeycomb (RE), chiral truss (CT), honeycomb (HN), and truss (TR), using graphene/PLA (Polylactic acid) filament, were manufactured by CFDM (conveyor fused deposition modelling) 3D printer. In addition, HN and TR, which was indicated to have an excellent electrical heating property, were selected to verify the feasibility of applying fabric heating elements. The result of morphology was that the number of struts constituting the unit cell and the connected points were TR < HN < CT < RE. It was also influenced by the surface resistivity and electrical heating performance. RE, which has the highest number of struts constituting the unit cell and the relative density, had the highest value of surface resistivity, and the lowest value was found in the opposite TR. In the electrical heating performance of samples, the heat distribution of RE was limited even when the applied voltage was increased. However, HN and TR were diffused throughout the sample. In addition, the surface temperature of RE, CT, HN, and TR was about 72.4 °C, 83.1 °C, 94.9 °C, and 85.9, respectively as applied at 30 V. When the HN and TR were printed on cotton fabric, the surface resistivity of HN/cotton and TR/cotton was about 103 Ω/sq, which showed conductive material. The results of electrical heating properties indicated that the heat distribution of HN/cotton showed only in the region where power was supplied, but the TR/cotton was gradually expanded and presented stable electric heating properties. When 30 V was applied, the surface temperature of both samples showed more than 80 °C, and the shape was maintained stably due to the high thermal conductivity of the cotton fabric. Therefore, this study ensured that HN and TR show excellent electrical heating performance among four types of auxetic patterns with continuity.

Process Optimization for Manufacturing PAN-Based Conductive Yarn with Carbon Nanomaterials through Wet Spinning.

This study aimed to manufacture PAN-based conductive yarn using a wet-spinning process. Two types of carbon nanomaterials, multiwall carbon nanotubes (MWCNT) and carbon nanofiber (CNF), were used alone or in a mixture. First, to derive the optimal composite solution condition for the wet spinning process, a composite solution was prepared with carbon nanomaterials of the same total mass weight (%) and three types of mechanical stirring were performed: mechanical stirring, ultra-sonication, and ball milling. A ball milling process was finally selected by analyzing the viscosity. Based on the above results, 8, 16, 24, and 32 wt% carbon nanomaterial/PAN composite solutions were prepared to produce wet spinning-based composite films before preparing a conductive yarn, and their physical and electrical properties were examined. By measuring the viscosity of the composite solution and the surface resistance of the composite film according to the type and content of carbon nanomaterials, a suitable range of viscosity was found from 103 cP to 105 cP, and the electrical percolation threshold was from 16 wt% carbon nanomaterial/PAN, which showed a surface resistance of 106 Ω/sq or less. Wet spinning was possible with a PAN-based composite solution with a high content of carbon nanomaterials. The crystallinity, crystal orientation, tenacity, and thermal properties were improved when CNF was added up to 24 wt%. On the other hand, the properties deteriorated when CNTs were added alone due to aggregation. Mixing CNT and CNF resulted in poorer properties than with CNF alone, but superior properties to CNT alone. In particular, the electrical properties after incorporating 8 wt% CNT/16 wt% CNF into the PAN, 106 Ω/cm was similar to the PAN-based conductive yarn containing 32 wt% CNF. Therefore, this yarn is expected to be applicable to various smart textiles and wearable devices because of its improved physical properties such as strength and conductivity.

Study on the Flame Retardancy and Hazard Evaluation of Poly(acrylonitrile-co-vinylidene chloride) Fibers by the Addition of Antimony-Based Flame Retardants.

Antimony oxide (ATO) is used mainly as a flame retardant, but it is classified as a hazardous substance. Therefore, regulations on the use of antimony trioxide (ATO(3)) and antimony pentoxide (ATO(5)) in textile products are being developed. Accordingly, there is a need for alternative flame retardants. In this study, antimony tetroxide (ATO(4)), which has higher thermal stability and resistance to acids and alkalis than ATO(3) or ATO(5), was selected to assess its use as an alternative flame retardant. First, ATO(3) or ATO(4) were added to poly(acrylonitrile-co-vinylidene chloride) (PANVDC), and the film and wet-spun fiber were prepared. The PANVDC film with flame retardants was prepared to evaluate the flame retardancy and the mechanism of action of the flame retardants. Flame retardancy analysis showed that a limiting oxygen index of 31.2% was obtained when ATO(4) was added, which was higher than when ATO(3) was used. Subsequently, PANVDC fibers with antimony oxide were manufactured and showed improved mechanical and thermal properties when ATO(4) was used, compared to when ATO(3) was tested. In addition, migration analysis due to antimony in the fiber confirmed that the elution amount was below the acceptable standard when PANVDC fibers with ATO(4) were added. Therefore, based on these results, the flame-retardant and thermal properties of antimony tetroxide were superior to antimony trioxide, and it was confirmed that ATO(4) could be used as an alternative flame retardant to ATO(3).

Targeting GABAC Receptors Improves Post-Stroke Motor Recovery.

Ischemic stroke remains a leading cause of disability worldwide, with limited treatment options available. This study investigates GABAC receptors as novel pharmacological targets for stroke recovery. The expression of ρ1 and ρ2 mRNA in mice were determined in peri-infarct tissue following photothrombotic motor cortex stroke. (R)-4-amino-cyclopent-1-enyl butylphosphinic acid (R)-4-ACPBPA and (S)-4-ACPBPA were assessed using 2-elecotrode voltage electrophysiology in Xenopus laevis oocytes. Stroke mice were treated for 4 weeks with either vehicle, the α5-selective negative allosteric modulator, L655,708, or the ρ1/2 antagonists, (R)-4-ACPBPA and (S)-4-ACPBPA respectively from 3 days post-stroke. Infarct size and expression levels of GAT3 and reactive astrogliosis were determined using histochemistry and immunohistochemistry respectively, and motor function was assessed using both the grid-walking and cylinder tasks. After stroke, significant increases in ρ1 and ρ2 mRNAs were observed on day 3, with ρ2 showing a further increase on day 7. (R)- and (S)-4-ACPBPA are both potent antagonists at ρ2 and only weak inhibitors of α5ß2γ2 receptors. Treatment with either L655,708, (S)-4-ACPBPA (ρ1/2 antagonist; 5 mM only), or (R)-4-ACPBPA (ρ2 antagonist; 2.5 and 5 mM) from 3 days after stroke resulted in a significant improvement in motor recovery on the grid-walking task, with L655,708 and (R)-4-ACPBPA also showing an improvement in the cylinder task. Infarct size was unaffected, and only (R)-4-ACPBPA significantly increased peri-infarct GAT3 expression and decreased the level of reactive astrogliosis. Importantly, inhibiting GABAC receptors affords significant improvement in motor function after stroke. Targeting the ρ-subunit could provide a novel delayed treatment option for stroke recovery.

Thermosensitive Hydrogel Harboring CD146/IGF-1 Nanoparticles for Skeletal-Muscle Regeneration.

In skeletal-muscle regeneration, it is critical to promote efferocytosis of immune cells and differentiation of satellite cells/postnatal muscle stem cells at the damaged sites. With the optimized poloxamer 407 composition gelled at body temperature, the drugs can be delivered locally. The purpose of this study is to develop a topical injection therapeutic agent for muscle regeneration, sarcopenia, and cachexia. Herein, we construct an injectable, in situ hydrogel system consisting of CD146, IGF-1, collagen I/III, and poloxamer 407, termed CIC gel. The secreted CD146 then binds to VEGFR2 on the muscle surface and effectively induces efferocytosis of neutrophils and macrophages. IGF-1 promotes satellite cell differentiation, and biocompatible collagen evades immune responses of the CIC gel. Consequently, these combined molecules activate muscle regeneration via autophagy and suppress muscle inflammation and apoptosis. Conclusively, we provide an applicable concept of the myogenesis-activating protein formulation, broadening the thermoreversible hydrogel to protein therapeutics for damaged muscle recovery.

Chondroitin sulfate-hybridized zein nanoparticles for tumor-targeted delivery of docetaxel.

Chondroitin sulfate-hybridized zein nanoparticles (zein/CS NPs) were developed for targeted delivery of docetaxel, which exhibited mean diameters of 157.8 ± 3.6 nm and docetaxel encapsulation efficiency of 64.2 ± 1.9 %. Docetaxel was released from the NPs in a sustained manner (∼72 h), following first-order kinetics. The zein/CS NPs showed improved colloidal stability, maintaining the initial size in serum for 12 h. The pre-treatment of CS reduced the uptake efficiency of the NPs by 23 % in PC-3 cells, suggesting the involvement of CD44-mediated uptake mechanism. The NPs showed 2.79-fold lower IC50 values than free docetaxel. Enhanced tumor accumulation of the NPs was confirmed in PC-3 xenograft mice by near-infrared fluorescence imaging (35.3-fold, versus free Cy5.5). The NPs exhibited improved pharmacokinetic properties (9.5-fold longer terminal half-life, versus free docetaxel) and anti-tumor efficacy comparable to Taxotere with negligible systemic toxicity, suggesting zein/CS NPs could be a promising nanoplatform for targeted cancer therapy.

Long-acting nanoparticulate DNase-1 for effective suppression of SARS-CoV-2-mediated neutrophil activities and cytokine storm.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new strain of coronavirus not previously identified in humans. Globally, the number of confirmed cases and mortality rates of coronavirus disease 2019 (COVID-19) have risen dramatically. Currently, there are no FDA-approved antiviral drugs and there is an urgency to develop treatment strategies that can effectively suppress SARS-CoV-2-mediated cytokine storms, acute respiratory distress syndrome (ARDS), and sepsis. As symptoms progress in patients with SARS-CoV-2 sepsis, elevated amounts of cell-free DNA (cfDNA) are produced, which in turn induce multiple organ failure in these patients. Furthermore, plasma levels of DNase-1 are markedly reduced in SARS-CoV-2 sepsis patients. In this study, we generated recombinant DNase-1-coated polydopamine-poly(ethylene glycol) nanoparticulates (named long-acting DNase-1), and hypothesized that exogenous administration of long-acting DNase-1 may suppress SARS-CoV-2-mediated neutrophil activities and the cytokine storm. Our findings suggest that exogenously administered long-acting nanoparticulate DNase-1 can effectively reduce cfDNA levels and neutrophil activities and may be used as a potential therapeutic intervention for life-threatening SARS-CoV-2-mediated illnesses.