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Extracellular vesicles (EVs) are major contributors to immunological responses following solid organ transplantation. Donor derived EVs are best known for their role in transplant rejection through transferring donor major histocompatibility complex proteins to recipient antigen presenting cells, a phenomenon known as ‛cross‐decoration'. In contrast, donor liver‐derived EVs are associated with organ tolerance in small animal models. Therefore, the cellular source of EVs and their cargo could influence their downstream immunological effects. To investigate the immunological effects of EVs released by the liver in a physiological and transplant‐relevant model, we isolated EVs being produced during normothermic ex vivo liver perfusion (NEVLP), a novel method of liver storage prior to transplantation. We found EVs were produced by the liver during NEVLP, and these EVs contained multiple anti‐inflammatory miRNA species. In terms of function, liver‐derived EVs were able to cross‐decorate allogeneic cells and suppress the immune response in allogeneic mixed lymphocyte reactions in a concentration‐dependent fashion. In terms of cytokine response, the addition of 1 × 109 EVs to the mixed lymphocyte reactions significantly decreased the production of the inflammatory cytokines TNF‐α, IL‐10 and IFN‐γ. In conclusion, we determined physiologically produced liver‐derived EVs are immunologically regulatory, which has implications for their role and potential modification in solid organ transplantation. [ABSTRACT FROM AUTHOR]

PURPOSE: There are currently no predictive molecular biomarkers to identify patients with oligometastatic disease (OMD) who will benefit from definitive-intent radiation therapy (RT). We prospectively characterized circulating tumor cell (CTC) kinetics in patients with OMD undergoing definitive-intent RT. METHODS: This prospective correlative biomarker study included patients with any solid malignancy ≤5 metastatic sites in ≤3 anatomic organ systems undergoing definitive-intent RT to all disease sites. Circulating tumor cells (CTCs) were captured and enumerated using a biomimetic cell rolling and nanotechnology-based assay functionalized with antibodies against epithelial cell adhesion molecule, against human epidermal growth factor receptor 2, and against epidermal growth factor receptor before and during RT and at follow-up visits up to 2 years post-RT. RESULTS: We enrolled 43 patients with a median follow-up of 14.3 months. The pretreatment CTC level (cells captured/mL) was not associated with the number of disease sites (median one metastatic site/patient, range 1-5) or metastasis location (bone, brain, visceral) on Wilcoxon signed-rank test, P >.05. Post-RT, 56% of patients received systemic therapy, and 72% of patients experienced subsequent local or systemic progression. For 90% of patients, a CTC level <15 within 130 days post-RT corresponded to a durable control of irradiated lesions. Patients with a favorable versus an unfavorable clearance profile experienced significantly longer progression-free survival after RT (median 13 v 4 months, log-rank test, P =.0011). On logistic regression, CTC level >15 at a given time point was associated with clinical disease progression within the subsequent 6 months (odds ratio 3.31, P =.007). In 26% of patients with disease progression, a CTC level >15 preceded radiographic or clinical progression. CONCLUSION: CTCs may serve as a biomarker for disease control in OMD and may predict disease progression before standard assessments for patients receiving diverse cancer-directed therapies. [ABSTRACT FROM AUTHOR]

Owing to their unique optical and chemical properties, gold nanorods (AuNRs) are among the most frequently used nanomaterials for biomedical applications, including cancer therapy, imaging, and drug delivery. In particular, the longitudinal dipole plasmon wavelength of AuNRs can be verified from the visible to the near‐infrared (NIR) region, allowing AuNRs to be used as photodynamic/photothermal and imaging contrast agents. At the same time, the silica shell is important as it enhances stability and facilitates the functionalization and biocompatibility of AuNRs, offering numerous advantages in biomedical applications. In this review, silica‐coated AuNRs from a bioapplication perspective are focused. First, the importance of AuNRs for biomedical applications is explained and the purpose of silica coating on AuNRs is discussed. Then, recent studies on the development of silica‐coated AuNRs from a biomedical perspective are reviewed. Subsequently, various strategies for engineering silica coatings and their properties in the biomedical field are reviewed. This review is expected to promote further research on next‐generation silica‐coated AuNRs for biomedical applications. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is characterized by misfolding, oligomerization, and accumulation of amyloid-β (Aβ) peptides in the brain. Aβ monomers transform into Aβ oligomers, which are toxic species, inducing tau hyperphosphorylation and the downstream effects on microglia and astrocytes, triggering synaptic and cognitive dysfunctions. The oligomers then deposit into Aβ plaques, primarily composed of β-stranded fibrils, required for definitive AD diagnosis. As amyloid burden plays the pivotal role in AD pathogenesis, many efforts are devoted in preventing amyloidosis as a therapeutic approach to impede the disease progression. Here, we discovered carprofen, a non-steroidal anti-inflammatory drug, accelerates Aβ aggregating into fibrils and increases Aβ plaques when intraperitoneally injected to 5XFAD transgenic mouse model. However, the drug seems to alleviate the key Alzheimer-like phenotypes induced by Aβ aggregation as we found attenuated neuroinflammation, improved post-synaptic density expression, associated with synaptic plasticity, and decreased phosphorylated tau levels. Carprofen also rescued impaired working memory as we discovered improved spontaneous alternation performance through Y-maze test assessed with Aβ(1–42)-infused mouse model. Collectively, while carprofen accelerates the conversion of Aβ monomers into fibrils in vitro, the drug ameliorates the major pathological hallmarks of AD in vivo. [ABSTRACT FROM AUTHOR]

Background: The tyrosine kinase receptors Axl and MerTK are highly overexpressed in head and neck cancer (HNC) cells, where they are critical drivers of survival, proliferation, metastasis, and therapeutic resistance. Methods: We investigated the role of Axl and MerTK in creating an immunologically "cold" tumor immune microenvironment (TIME) by targeting both receptors simultaneously with a small molecule inhibitor of Axl and MerTK (INCB081776). Effects of INCB081776 and/or anti‐PDL1 on mouse oral cancer (MOC) cell growth and on the TIME were evaluated. Results: Targeting Axl and MerTK can reduce M2 and induce M1 macrophage polarization. In vivo, INCB081776 treatment alone or with anti‐PDL1 appears to slow MOC tumor growth, increase proinflammatory immune infiltration, and decrease anti‐inflammatory immune infiltration. Conclusions: This data indicates that simultaneous targeting of Axl and MerTK with INCB081776, either alone or in combination with anti‐PDL1, slows tumor growth and creates a proinflammatory TIME in mouse models of HNC. [ABSTRACT FROM AUTHOR]

Poly(dimethylsiloxane) (PDMS) has been widely employed in biomedical disciplines due to its several advantages, including biocompatibility, nontoxicity, and low‐cost preparation. However, the intrinsic hydrophobicity of this material encourages biofouling and reduces cell regulation capacity, thereby limiting its biomedical applicability. The purpose of this study is to explore the surface modification and functionalization of PDMS and PDMS‐based biomaterials to improve their properties for biomedical applications. The content of this review is organized based on physical and chemical surface modification strategies to improve surface hydrophilicity to enhance antibiofouling and the regulation of immunomodulation and cell modulation on the surface of PDMS and PDMS‐based biomaterials. Future developments in this area are also discussed. [ABSTRACT FROM AUTHOR]

Rosa gallica has been previously reported to display anti‐inflammatory, anti‐oxidative, and anti‐skin wrinkle activities. However, the effect of Rosa gallica on skin hydration and its active components are largely unknown. Herein, we aimed to investigate the skin hydration effect of rose petal extract (RPE) in humans and elucidate the underlying molecular mechanism. A double‐blinded clinical study was performed to investigate the effect of RPE on skin hydration. Stratum corneum moisture analysis demonstrated that RPE treatment significantly improved hydration levels in human skin. Furthermore, HAS2 and hyaluronic acid levels were notably increased by RPE in keratinocytes and 3D human skin equivalent model. By comparing the modulatory effect on HAS2 expression, cyanidin‐3,5‐O‐diglucoside (CDG) was identified as the most potent compound in RPE likely responsible for skin hydration. The kinase activity of GLK, an upstream regulator of MAPK signaling, was increased by CDG in a dose‐dependent manner. Importantly, silencing GLK reversed CDG‐mediated HAS2 upregulation, further supporting the involvement of GLK in the CDG‐mediated effects. Binding of CDG to GLK was confirmed by pull‐down assay and computer modeling. These findings suggest that RPE and its active component CDG increases skin hydration by upregulating HAS2 expression through modulating the GLK‐MAP2K‐MAPK signaling pathway. [ABSTRACT FROM AUTHOR]

Extracellular vesicle (EV) secretion is an important mechanism used by cells to release biomolecules. A common necroptosis effector—mixed lineage kinase domain like (MLKL)—was recently found to participate in the biogenesis of small and large EVs independent of its function in necroptosis. The objective of the current study is to gain mechanistic insights into EV biogenesis during necroptosis. Assessing EV number by nanoparticle tracking analysis revealed an increased number of EVs released during necroptosis. To evaluate the nature of such vesicles, we performed a newly adapted, highly sensitive mass spectrometry‐based proteomics on EVs released by healthy or necroptotic cells. Compared to EVs released by healthy cells, EVs released during necroptosis contained a markedly higher number of unique proteins. Receptor interacting protein kinase‐3 (RIPK3) and MLKL were among the proteins enriched in EVs released during necroptosis. Further, mouse embryonic fibroblasts (MEFs) derived from mice deficient of Rab27a and Rab27b showed diminished basal EV release but responded to necroptosis with enhanced EV biogenesis as the wildtype MEFs. In contrast, necroptosis‐associated EVs were sensitive to Ca2+ depletion or lysosomal disruption. Neither treatment affected the RIPK3‐mediated MLKL phosphorylation. An unbiased screen using RIPK3 immunoprecipitation‐mass spectrometry on necroptotic EVs led to the identification of Rab11b in RIPK3 immune‐complexes. Our data suggests that necroptosis switches EV biogenesis from a Rab27a/b dependent mechanism to a lysosomal mediated mechanism. [ABSTRACT FROM AUTHOR]

Simple Summary: Circulating cell-free DNA (cfDNA) has attracted a great deal of scientific interest as a predictive biomarker for the diagnosis and prognosis of hepatocellular carcinoma (HCC). HCC result in high mortality due to the absence of blood biomarkers for early diagnosis and prognosis. We established cfDHCC as a new scoring system by applying a machine learning algorithm that integrates the expression profiles of cfDNA. Based on this, it was possible to accurately predict the clinico-pathological characteristics of patients with HCC as well as improve their survival. (1) Background: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide. Although various serum enzymes have been utilized for the diagnosis and prognosis of HCC, the currently available biomarkers lack the sensitivity needed to detect HCC at early stages and accurately predict treatment responses. (2) Methods: We utilized our highly sensitive cell-free DNA (cfDNA) detection system, in combination with a machine learning algorithm, to provide a platform for improved diagnosis and prognosis of HCC. (3) Results: cfDNA, specifically alpha-fetoprotein (AFP) expression in captured cfDNA, demonstrated the highest accuracy for diagnosing malignancies among the serum/plasma biomarkers used in this study, including AFP, aspartate aminotransferase, alanine aminotransferase, albumin, alkaline phosphatase, and bilirubin. The diagnostic/prognostic capability of cfDNA was further improved by establishing a cfDNA score (cfDHCC), which integrated the total plasma cfDNA levels and cfAFP-DNA expression into a single score using machine learning algorithms. (4) Conclusion: The cfDHCC score demonstrated significantly improved accuracy in determining the pathological features of HCC and predicting patients' survival outcomes compared to the other biomarkers. The results presented herein reveal that our cfDNA capture/analysis platform is a promising approach to effectively utilize cfDNA as a biomarker for the diagnosis and prognosis of HCC. [ABSTRACT FROM AUTHOR]

The development of minimally invasive tests for cancer diagnosis and prognosis will aid in the research of new treatments and improve survival rates. Liquid biopsies seek to derive actionable information from tumor material found in routine blood samples. The relative scarcity of tumor material in this complex mixture makes isolating and detecting cancerous material such as proteins, circulating tumor DNA, exosomes, and whole circulating tumor cells a challenge for device engineers. This review describes the chemistry and applications of branched and hyperbranched to improve the performance of liquid biopsy devices. These polymers can improve the performance of a liquid biopsy through several mechanisms. For example, polymers designed to increase the affinity of capture enhance device sensitivity. On the other hand, polymers designed to increase binding avidity or repel nonspecific adsorption enhance device specificity. Branched and hyperbranched polymers can also be used to amplify the signal from small amounts of detected material. The further development of hyperbranched polymers in liquid biopsy applications will enhance device capabilities and help these critical technologies reach the oncology clinic where they are sorely needed. This article is categorized under:Diagnostic Tools > BiosensingDiagnostic Tools > Diagnostic Nanodevices [ABSTRACT FROM AUTHOR]

Background: The receptor tyrosine kinase (RTK) epidermal growth factor receptor (EGFR) is overexpressed and an important therapeutic target in Head and Neck cancer (HNC). Cetuximab is currently the only EGFR-targeting agent approved by the FDA for treatment of HNC; however, intrinsic and acquired resistance to cetuximab is a major problem in the clinic. Our lab previously reported that AXL leads to cetuximab resistance via activation of HER3. In this study, we investigate the connection between AXL, HER3, and neuregulin1 (NRG1) gene expression with a focus on understanding how their interdependent signaling promotes resistance to cetuximab in HNC.Methods: Plasmid or siRNA transfections and cell-based assays were conducted to test cetuximab sensitivity. Quantitative PCR and immunoblot analysis were used to analyze gene and protein expression levels. Seven HNC patient-derived xenografts (PDXs) were evaluated for protein expression levels.Results: We found that HER3 expression was necessary but not sufficient for cetuximab resistance without AXL expression. Our results demonstrated that addition of the HER3 ligand NRG1 to cetuximab-sensitive HNC cells leads to cetuximab resistance. Further, AXL-overexpressing cells regulate NRG1 at the level of transcription, thereby promoting cetuximab resistance. Immunoblot analysis revealed that NRG1 expression was relatively high in cetuximab-resistant HNC PDXs compared to cetuximab-sensitive HNC PDXs. Finally, genetic inhibition of NRG1 resensitized AXL-overexpressing cells to cetuximab.Conclusions: The results of this study indicate that AXL may signal through HER3 via NRG1 to promote cetuximab resistance and that targeting of NRG1 could have significant clinical implications for HNC therapeutic approaches. [ABSTRACT FROM AUTHOR]

Immunosuppressive cells residing in the tumor microenvironment, especially tumor associated macrophages (TAMs), hinder the infiltration and activation of T cells, limiting the anti-cancer outcomes of immune checkpoint blockade. Here, we report a biocompatible alginate-based hydrogel loaded with Pexidartinib (PLX)-encapsulated nanoparticles that gradually release PLX at the tumor site to block colony-stimulating factor 1 receptors (CSF1R) for depleting TAMs. The controlled TAM depletion creates a favorable milieu for facilitating local and systemic delivery of anti-programmed cell death protein 1 (aPD-1) antibody-conjugated platelets to inhibit post-surgery tumor recurrence. The tumor immunosuppressive microenvironment is also reprogrammed by TAM elimination, further promoting the infiltration of T cells into tumor tissues. Moreover, the inflammatory environment after surgery could trigger the activation of platelets to facilitate the release of aPD-1 accompanied with platelet-derived microparticles binding to PD-1 receptors for re-activating T cells. All these results collectively indicate that the immunotherapeutic efficacy against tumor recurrence of both local and systemic administration of aPD-1 antibody-conjugated platelets could be strengthened by local depletion of TAMs through the hydrogel reservoir. Increased density of tumor associated macrophages has been correlated with tumor recurrence following surgery. Here the authors design an alginate-based hydrogel encapsulating anti-PD-1-conjugated platelets and nanoparticles loaded with the macrophage-depleting CSF-1R inhibitor pexidartinib, showing inhibition of post-surgery tumor recurrence in preclinical models. [ABSTRACT FROM AUTHOR]

Cancer immunotherapy, or the utilization of a patient's own immune system to treat cancer, has shifted the paradigm of cancer treatment. Despite meaningful responses being observed in multiple studies, currently available immunotherapy platforms have only proven effective to a small subset of patients. To address this, nanoparticles have been utilized as a novel carrier for immunotherapeutic drugs, achieving robust anti‐tumor effects with increased adaptive and durable responses. Specifically, dendrimer nanoparticles have attracted a great deal of scientific interest due to their versatility in various therapeutic applications, resulting from their unique physicochemical properties and chemically well‐defined architecture. This review offers a comprehensive overview of dendrimer‐based immunotherapy technologies, including their formulations, biological functionalities, and therapeutic applications. Common formulations include: (1) modulators of cytokine secretion of immune cells (adjuvants); (2) facilitators of the recognition of tumorous antigens (vaccines); (3) stimulators of immune effectors to selectively attack cells expressing specific antigens (antibodies); and (4) inhibitors of immune‐suppressive responses (immune checkpoint inhibitors). On‐going works and prospects of dendrimer‐based immunotherapies are also discussed. Overall, this review provides a critical overview on rapidly growing dendrimer‐based immunotherapy technologies and serves as a guideline for researchers and clinicians who are interested in this field. This article is categorized under:Nanotechnology Approaches to Biology > Nanoscale Systems in BiologyTherapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic DiseaseTherapeutic Approaches and Drug Discovery > Emerging Technologies [ABSTRACT FROM AUTHOR]

The multivalent binding effect has been the subject of extensive studies to modulate adhesion behaviors of various biological and engineered systems. However, precise control over the strong avidity‐based binding remains a significant challenge. Here, a set of engineering strategies are developed and tested to systematically enhance the multivalent binding of peptides in a stepwise manner. Poly(amidoamine) (PAMAM) dendrimers are employed to increase local peptide densities on a substrate, resulting in hierarchically multivalent architectures (HMAs) that display multivalent dendrimer–peptide conjugates (DPCs) with various configurations. To control binding behaviors, effects of the three major components of the HMAs are investigated: i) poly(ethylene glycol) (PEG) linkers as spacers between conjugated peptides; ii) multiple peptides on the DPCs; and iii) various surface arrangements of HMAs (i.e., a mixture of DPCs each containing different peptides vs DPCs cofunctionalized with multiple peptides). The optimized HMA configuration enables significantly enhanced target cell binding with high selectivity compared to the control surfaces directly conjugated with peptides. The engineering approaches presented herein can be applied individually or in combination, providing guidelines for the effective utilization of biomolecular multivalent interactions using DPC‐based HMAs. [ABSTRACT FROM AUTHOR]

The multivalent binding effect has been the subject of extensive studies to modulate adhesion behaviors of various biological and engineered systems. However, precise control over the strong avidity‐based binding remains a significant challenge. Here, a set of engineering strategies are developed and tested to systematically enhance the multivalent binding of peptides in a stepwise manner. Poly(amidoamine) (PAMAM) dendrimers are employed to increase local peptide densities on a substrate, resulting in hierarchically multivalent architectures (HMAs) that display multivalent dendrimer–peptide conjugates (DPCs) with various configurations. To control binding behaviors, effects of the three major components of the HMAs are investigated: i) poly(ethylene glycol) (PEG) linkers as spacers between conjugated peptides; ii) multiple peptides on the DPCs; and iii) various surface arrangements of HMAs (i.e., a mixture of DPCs each containing different peptides vs DPCs cofunctionalized with multiple peptides). The optimized HMA configuration enables significantly enhanced target cell binding with high selectivity compared to the control surfaces directly conjugated with peptides. The engineering approaches presented herein can be applied individually or in combination, providing guidelines for the effective utilization of biomolecular multivalent interactions using DPC‐based HMAs. [ABSTRACT FROM AUTHOR]

The multivalent binding effect has been the subject of extensive studies to modulate adhesion behaviors of various biological and engineered systems. However, precise control over the strong avidity‐based binding remains a significant challenge. Here, a set of engineering strategies are developed and tested to systematically enhance the multivalent binding of peptides in a stepwise manner. Poly(amidoamine) (PAMAM) dendrimers are employed to increase local peptide densities on a substrate, resulting in hierarchically multivalent architectures (HMAs) that display multivalent dendrimer–peptide conjugates (DPCs) with various configurations. To control binding behaviors, effects of the three major components of the HMAs are investigated: i) poly(ethylene glycol) (PEG) linkers as spacers between conjugated peptides; ii) multiple peptides on the DPCs; and iii) various surface arrangements of HMAs (i.e., a mixture of DPCs each containing different peptides vs DPCs cofunctionalized with multiple peptides). The optimized HMA configuration enables significantly enhanced target cell binding with high selectivity compared to the control surfaces directly conjugated with peptides. The engineering approaches presented herein can be applied individually or in combination, providing guidelines for the effective utilization of biomolecular multivalent interactions using DPC‐based HMAs. [ABSTRACT FROM AUTHOR]

Viruses are infectious agents that pose significant threats to plants, animals, and humans. The current coronavirus disease 2019 pandemic, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), has spread globally and resulted in over 2 million deaths and immeasurable financial losses. Rapid and sensitive virus diagnostics become crucially important in controlling the spread of a pandemic before effective treatment and vaccines are available. Gold nanoparticle (AuNP)‐based testing holds great potential for this urgent unmet biomedical need. In this review, we describe the most recent advances in AuNP‐based viral detection applications. In addition, we discuss considerations for the design of AuNP‐based SARS‐CoV‐2 testings. Finally, we highlight and propose important parameters to consider for the future development of effective AuNP‐based testings that would be critical for not only this COVID‐19 pandemic, but also potential future outbreaks. This article is categorized under:Diagnostic Tools > BiosensingDiagnostic Tools > In Vitro Nanoparticle‐Based Sensing [ABSTRACT FROM AUTHOR]

Accurate and efficient estimation and prediction of the nonlinear behavior of materials during plastic working is a major issue in academic and industrial settings. Studies on property meta-models are being conducted to estimate and predict plastic working results. However, accurately representing strong nonlinear properties using power-law and exponential models, which are typical meta-models, is difficult. The combination meta-model can be used to solve this problem, but the possible number of parameters increases. This causes a cost problem when using FE simulation. In this study, the accuracy of the nonlinear properties of materials and the number of iterations were compared for three typical meta-models and the proposed advanced meta-models considering stress–strain properties. A material property test was conducted using ASTM E8/E8M, and the meta-model was initialized using ASTM E646 and MATLAB Curve Fitting Toolbox. A finite element (FE) simulation was conducted for the meta-models, and the test and simulation results were compared in terms of the engineering stress–strain curve and the root-mean-square error (RMSE). In addition, an inverse method was applied for the FE simulation to estimate the true stress–strain properties, and the results were analyzed in terms of the RMSE and the number of iterations and simulations. Finally, the need for an advanced meta-model that exhibits strong nonlinearity was suggested. [ABSTRACT FROM AUTHOR]

A ghost-cell immersed boundary method for unified simulations of flow over finite- and zero-thickness moving bodies at large Courant-Friedrichs-Lewy (CFL) numbers is presented. In order to handle such bodies in a unified manner, algorithms for interface construction and cell demarcation are proposed. The main challenge in treating zero-thickness bodies is to maintain sharpness and accuracy even at large CFL numbers with diminished spurious force oscillations. Thus, the effect of large CFL numbers on the solution accuracy of fluid-structure interaction (FSI) problems involving zero-thickness bodies is investigated and necessary treatments to preserve solution accuracy even at large CFL numbers are suggested. The present study suggests two treatments which are important in preserving the accuracy and stability of the solution: backward time integration for computational cells called 'swept-cells' and pressure boundary condition with mass conservation. Composite implicit time integration for the dynamic equation of a thin elastic structure is employed for a stable simulation of FSI at large CFL numbers. By using large time step sizes, the present method not only enhances computational efficiency, but also suppresses spurious force oscillations while maintaining the sharpness of an infinitesimally thin body. The efficacy and accuracy of the present method are examined through numerical examples. [ABSTRACT FROM AUTHOR]

It is known that 2,2,6,6-tetramethylpiperidinyl-1-oxy (or TEMPO) is a stable, radical-containing molecule, which has been utilized in various areas of organic synthesis, catalysis, polymer chemistry, electrochemical reactions, and materials chemistry. Its unique stability, attributable to its structural features, and molecular tunability allows for the modification of various materials, including the heterogenization of solid materials. Metal–organic frameworks (MOFs) and covalent organic frameworks (COFs) are porous and tunable because of their ligand or linker portion, and both have been extensively studied for use in catalytic applications. Therefore, synergistically combining the chemistry of TEMPO with the properties of MOFs and COFs is a natural choice and should allow for significant advancements, including improved recyclability and selectivity. This article focuses on TEMPO-bearing MOFs and COFs for use in catalytic applications. In addition, recent strategies related to the use of these functional porous materials in catalytic reactions are also discussed. [ABSTRACT FROM AUTHOR]

Dear Editor, Lung cancer is one of the most common cancers.1 Although its primary risk factor is smoking,2 15-20% and >50% of male and female lung cancer patients, respectively, are nonsmokers,3,4 which indicates the involvement of other risk factors. Shannon's diversity index of the oral microbiome was significantly lower in patients, and the overall oral microbiome structure differed significantly between patients and controls (Figure 1A). We investigated the oral and gut microbiomes of never-smoking lung adenocarcinoma patients to identify microbial signatures of lung cancer, which can be used for diagnosis and prognosis. Recently, alteration of the oral and gut microbiomes was observed in lung cancer patients,5,6 suggesting potential roles of microbiota in lung cancer. [Extracted from the article]

CTCs were only found in 65.3% of cancer patients, exosomes were elevated in both benign and malignant tumor patients, and cfDNA levels of early-stage patients were similar to those of the non-cancer cohorts. Tri-modal liquid biopsy: Combinational analysis of circulating tumor cells, exosomes, and cell-free DNA using machine learning algorithm Analysis of tumor biomarkers in circulation, commonly known as liquid biopsy, has been highlighted as an effective real-time monitoring technique for the surveillance of therapeutic responses and tumor progression.1-3 However, existing liquid biopsy assays that utilize a single tumor biomarker lack the sensitivity and specificity required to obtain clinically reliable information.4 In this study, we established a multimodal liquid biopsy (MMLB) system that integrates the expression profiles of the three different tumor biomarkers, circulating tumor cells (CTCs), exosomes, and cell-free DNA (cfDNA), using a machine learning algorithm (Figure 1). GLO:F2H7/01aug21:ctm2499-fig-0001.jpg PHOTO (COLOR): 1 Schematic illustration of the machine learning-based multimodal analysis of the triple tumor biomarkers - CTCs, exosomes, and cfDNA: (A) A graphical abstract of the multimodal liquid biopsy analysis. [Extracted from the article]

Frailty is a common geriatric syndrome associated with the risk of adverse health outcomes. Recently, 2 key pathophysiological characteristics of frailty, altered energy metabolism and dysregulated immunity, have been reported to be associated with gut microbiome dysbiosis, indicating that the gut microbiome plays a role in frailty. However, few studies have directly examined the relationship between the gut microbiome and frailty. Here, we investigated the association of frailty measures with the gut microbiome using 16S rRNA gene sequencing data obtained from the fecal samples of 176 Korean older adults. Overall frailty was scored using the Korean Frailty Index (FI). Grip strength and Geriatric Depression Scale (GDS) scores were used as physical and mental frailty measures, respectively. In contrast to age, metabolic, and inflammatory biomarkers, the frailty measures were associated with interindividual variations in microbial composition (false discovery rate [FDR] < 0.2). Both FI and GDS scores were negatively associated with microbial diversity (FDR < 0.2). Frailty measures showed distinct associations with specific microbial taxa and metabolic functions. Particularly, the Bacteroides enterotype was found only in subjects categorized in the frail group. Moreover, we observed that the abundance of beneficial taxa, such as Prevotella copri and Coprococcus eutactus, was reduced in frailer individuals, whereas that of detrimental taxa, such as Bacteroides fragilis and Clostridium hathewayi, was increased (FDR < 0.2). Our findings suggest that the gut microbiome can be used an indicator of an increased risk of frailty or a target for improving health in frail older adults. [ABSTRACT FROM AUTHOR]

Metal–organic frameworks (MOFs), which are porous inorganic–organic hybrid materials, act as versatile catalyst platforms for various organic transformations. In particular, the aerobic oxidation of alcohols to the corresponding aldehydes (or ketones) has been extensively studied using various MOFs and their analogs. In this account, we summarize the performance of MOF‐based catalysts for the aerobic oxidation of alcohols based on the position of the catalytic species and the type of functionalization. Moreover, recent advances in MOF‐based catalysts for aerobic oxidation are discussed in terms of catalytic efficiency and substrate size discrimination. [ABSTRACT FROM AUTHOR]

Amylosucrase (ASase, E.C. 2.4.1.4) is a powerful transglycosylation enzyme that can transfer glucose from sucrose to the hydroxyl (-OH) group of various compounds. In this study, recombinant ASases from Deinococcus geothermalis (DgAS) and Bifidobacterium thermophilum (BtAS) were used to synthesize biosurfactants based on the computational analysis of predicted docking simulations. Successful predictions of the binding affinities, conformations, and three-dimensional structures of three surfactants were computed from receptor-ligand binding modes. DgAS and BtAS were effective in the synthesis of biosurfactants from glyceryl caprylate, glyceryl caprate, and polyglyceryl-2 caprate. The results of the transglycosylation reaction were consistent for both ASases, with glyceryl caprylate acceptor showing the highest concentration, as confirmed by thin layer chromatography. Furthermore, the transglycosylation reactions of DgAS were more effective than those of BtAS. Among the three substrates, glyceryl caprylate glycoside and glyceryl caprate glycoside were successfully purified by liquid chromatography–mass spectrometry (LC–MS) with the corresponding molecular weights. [ABSTRACT FROM AUTHOR]

Although circulating cell-free DNA (cfDNA) is a promising biomarker for the diagnosis and prognosis of various tumors, clinical correlation of cfDNA with gastric cancer has not been fully understood. To address this, we developed a highly sensitive cfDNA capture system by integrating polydopamine (PDA) and silica. PDA-silica hybrids incorporated different molecular interactions to a single system, enhancing cfDNA capture by 1.34-fold compared to the conventional silica-based approach (p = 0.001), which was confirmed using cell culture supernatants. A clinical study using human plasma samples revealed that the diagnostic accuracy of the new system to be superior than the commercially available cfDNA kit, as well as other serum antigen tests. Among the cancer patients, plasma cfDNA levels exhibited a good correlation with the size of a tumor. cfDNA was also predicative of distant metastasis, as the median cfDNA levels of metastatic cancer patients were ~60-fold higher than those without metastasis (p = 0.008). Furthermore, high concordance between tissue biopsy and cfDNA genomic analysis was found, as HER2 expression in cfDNA demonstrated an area under ROC curve (AUC) of 0.976 (p <0.001) for detecting patients with HER2-positive tumors. The new system also revealed high prognostic capability of cfDNA, as the concentration of cfDNA was highly associated with the survival outcomes. Our novel technology demonstrates the potential to achieve efficient detection of cfDNA that may serve as a reliable biomarker for gastric tumor. [ABSTRACT FROM AUTHOR]

The gut microbiome is related to various host health conditions through metabolites produced by microbiota. Investigating their relationships involves association analysis of the population-level microbiome and metabolome data, which requires the appropriate collection, handling, and storage of specimens. Simplification of the specimen handling processes will facilitate such investigations. As a pilot study for population-level studies, we collected the fecal samples from three volunteers and tested whether a single sample collection procedure, particularly using OMNIgene-GUT, can be used to reliably obtain both microbiome and metabolome data. We collected fecal samples from three young and healthy Korean adults, stored them at room temperature with and without OMNIgene-GUT solution up to three weeks, and analyzed their microbiome and metabolite profiles. We found that the microbiome profiles were stably maintained in OMNIgene-GUT solution for 21 days, and the abundance relationships among metabolites were well preserved, although their absolute abundances slightly varied over time. Our results show that a single sampling procedure suffices to obtain a fecal sample for collecting gut microbiome and gut metabolome data of an individual. We expect that the health effects of gut microbiome via fecal metabolites can be further understood by increasing the sampling size to the population level. [ABSTRACT FROM AUTHOR]

Ischemic stroke is a leading cause of death and disability worldwide and is in urgent need of new treatment options. The only approved treatment for stroke restores blood flow to the brain, but much of the tissue damage occurs during the subsequent reperfusion. Antioxidant therapies that directly address ischemia-reperfusion injury have shown promise in preclinical results. In this review, we discuss that reformulating antioxidant therapies as nanomedicine can potentially overcome the barriers that have kept these therapies from succeeding in the clinic. We begin by reviewing the pathophysiology of ischemic stroke with a focus on the effects of reperfusion injury. Next, we review nanotherapeutic systems designed to treat the disease with a focus on those addressing reperfusion injury. Mechanisms of passive and active transport required to traverse a blood–brain barrier are discussed. Finally, we conclude by outlining design parameters for potentially successful nanomedicines as front-line therapeutics for ischemic stroke. [ABSTRACT FROM AUTHOR]

A continuous‐wave blue laser annealing (BLA) system (λ ~ 440 nm) is applied to delineate the physical phenomenon of low‐temperature crystallization from amorphous Si (a‐Si) thin film to poly‐Si film on glass substrates for potential industrial application. At various scanning speeds and laser intensities, crystallization mechanism of BLA has been studied. It shows that BLA can achieve high quality, smooth poly‐Si film with laterally grown grains with sizes of 4×10 µm, as studied by optical microscopy, Raman spectroscopy, and AFM. The p‐channel poly‐Si TFT on glass exhibited the field‐effect mobility of 120.82 cm2/Vs and subthreshold swing of 284mV/dec. Therefore, it proves that BLA can substitute conventional annealing processes as a reliable, scalable, and economical tool. [ABSTRACT FROM AUTHOR]

Blue diode laser annealing (BLA) systems have been successfully developed for low‐temperature crystallization from amorphous silicon film on glass substrates. It is demonstrated that it can achieve high quality poly‐Si film with large grain sizes, as studied by optical microscopy, Raman spectroscopy and AFM measurements. The p‐channel poly‐Si TFT on glass using BLA exhibited the field‐effect mobility of 168.05 cm2/Vs and subthreshold swing of 220 mV/dec. BLA is scalable to large‐scale display manufacturing and significantly lowers the capital expense and operating cost, since diode lasers are highly reliable and rugged, remarkably efficient, and maintenance‐free, allowing 24/7 operations without the need of consumables. The BLA system consists of an array of high‐power blue diode lasers (λ ~ 450 nm) and beam‐shaping optics to produce a line‐shaped beam which can be scanned at high speed to anneal the Si film in a single scan, where the high scan speed minimizes thermal stress. The scan‐to‐scan is seamless to cover a large panel such as G6 or G8 without glass damage. The physical phenomena responsible for melting and recrystallization are explained by heat transfer simulations for process optimization. [ABSTRACT FROM AUTHOR]

Advances in nanotechnology have had profound impacts on therapeutic delivery, leading to the development of nanomaterials engineered with large carrying capabilities and targeting functionalities. Among the nanomaterials, dendrimers have garnered particular attention from researchers owing to their well-defined structure, near-monodispersity, and ease of multifunctionalization. As hyperbranched, three-dimensional macromolecules, dendrimers can be engineered to target and deliver a wide range of therapeutic agents, including small molecules, peptides, and genes, reducing their systemic toxicities and enhancing efficacies. In this review, we provide a comprehensive overview of the commonly employed dendrimer-based nanocarrier designs, including dendrimer conjugates, Janus dendrimers, and linear-dendritic block copolymers. The discussion will progress through the basic synthetic strategies of dendrimer-based nanocarriers, followed by the potential clinical applications related to their unique structural properties. Finally, the major challenges that these nanocarriers are currently facing in their clinical translation and possible solutions to address these issues will be discussed, with the aim to provide researchers in the drug delivery field a good understanding of the potential utilities of dendrimer-based nanocarriers. WIREs Nanomed Nanobiotechnol 2017, 9:e1409. doi: 10.1002/wnan.1409 For further resources related to this article, please visit the . [ABSTRACT FROM AUTHOR]

Although circulating tumor cells ( CTCs) in blood have been widely investigated as a potential biomarker for diagnosis and prognosis of metastatic cancer, their inherent rarity and heterogeneity bring tremendous challenges to develop a CTC detection method with clinically significant specificity and sensitivity. With advances in nanotechnology, a series of new methods that are highly promising have emerged to enable or enhance detection and separation of CTCs from blood. In this review, we systematically categorize nanomaterials, such as gold nanoparticles, magnetic nanoparticles, quantum dots, graphenes/graphene oxides, and dendrimers and stimuli-responsive polymers, used in the newly developed CTC detection methods. This will provide a comprehensive overview of recent advances in the CTC detection achieved through application of nanotechnology as well as the challenges that these existing technologies must overcome to be directly impactful on human health. WIREs Nanomed Nanobiotechnol 2016, 8:223-239. doi: 10.1002/wnan.1360 For further resources related to this article, please visit the . [ABSTRACT FROM AUTHOR]

Water molecules play an important role in protein folding and protein interactions through their structural association with proteins. Examples of such structural association can be found in protein crystal structures, and can often explain protein functionality in the context of structure. We herein report the systematic analysis of the local structures of proteins interacting with water molecules, and the characterization of their geometric features. We first examined the interaction of water molecules with a large local interaction environment by comparing the preference of water molecules in three regions, namely, the protein-protein interaction (PPI) interfaces, the crystal contact (CC) interfaces, and the non-interfacial regions. High preference of water molecules to the PPI and CC interfaces was found. In addition, the bound water on the PPI interface was more favorably associated with the complex interaction structure, implying that such water-mediated structures may participate in the shaping of the PPI interface. The pairwise water-mediated interaction was then investigated, and the water-mediated residue-residue interaction potential was derived. Subsequently, the types of polar atoms surrounding the water molecules were analyzed, and the preference of the hydrogen bond acceptor was observed. Furthermore, the geometries of the structures interacting with water were analyzed, and it was found that the major structure on the protein surface exhibited planar geometry rather than tetrahedral geometry. Several previously undiscovered characteristics of water-protein interactions were unfolded in this study, and are expected to lead to a better understanding of protein structure and function. [ABSTRACT FROM AUTHOR]

Nanoparticles have shown great promise in the treatment of cancer, with a demonstrated potential in targeted drug delivery. Among a myriad of nanocarriers that have been recently developed, dendrimers have attracted a great deal of scientific interests due to their unique chemical and structural properties that allow for precise engineering of their characteristics. Despite this, the clinical translation of dendrimers has been hindered due to their drawbacks, such as scale-up issues, rapid systemic elimination, inefficient tumor accumulation and limited drug loading. In order to overcome these limitations, a series of reengineered dendrimers have been recently introduced using various approaches, including: (i) modifications of structure and surfaces; (ii) integration with linear polymers and (iii) hybridization with other types of nanocarriers. Chemical modifications and surface engineering have tailored dendrimers to improve their pharmacokinetics and tissue permeation. Copolymerization of dendritic polymers with linear polymers has resulted in various amphiphilic copolymers with self-assembly capabilities and improved drug loading efficiencies. Hybridization with other nanocarriers integrates advantageous characteristics of both systems, which includes prolonged plasma circulation times and enhanced tumor targeting. This review provides a comprehensive summary of the newly emerging drug delivery systems that involve reengineering of dendrimers in an effort to precisely control their nano–bio interactions, mitigating their inherent weaknesses. [ABSTRACT FROM PUBLISHER]

ABSTRACT This article presents a 60 GHz low insertion loss double-pole double-throw (DPDT) switch implemented in 65 nm standard CMOS process. To achieve the low insertion loss, various techniques are used such as the double-well body-floating, gate-floating, high-performance thin-film microstrip line, resonating the capacitance of the off-state transistor, and the transmission line based matching network. To achieve both high performance and small area, EM simulations are intensely performed to model passive components. The DPDT switch achieves insertion loss of less than 2.7 dB, and return loss of better than 10 dB over the 52-66 GHz band. The measured IIP3 is 18 dBm (simulated IP1dB is 11.4 dBm). The fabricated DPDT switch has an effective area of 0.073 mm2. © 2014 Wiley Periodicals, Inc. Microwave Opt Technol Lett 56:2864-2867, 2014 [ABSTRACT FROM AUTHOR]

Endoxifen (EDX) is an active metabolite of tamoxifen that has been proven effective in the prevention and treatment of estrogen-positive breast cancer; however, oral administration of tamoxifen often causes severe side effects. Here, the topical delivery of EDX is explored using polymeric micelles to achieve localized drug delivery with potentially minimal side effects. EDX is encapsulated into dendron micelles (DM) with various surface groups (-NH2, -COOH, or -Ac) and into cationic liposomes as a control. End-group modification significantly affects the drug loading, where the DM-COOH micelles allow the most efficient encapsulation. Furthermore, unlike the burst release from the liposomes, all DMs show sustained release of EDX over 6 days. Each formulation is evaluated for its potential to deliver EDX across the skin layers. DMs substantially enhance the permeation of EDX through both mouse (up to 20-fold) and human (up to 4-fold) skin samples relative to ethanol, a chemical penetration enhancer. Franz diffusion cell experiments reveal that DM-COOH induces the highest flux of EDX among all groups. The enhanced drug loading, controlled release profiles, and enhanced skin permeation all demonstrate that DMs are a useful platform for the topical delivery of EDX, offering a potential alternative administration route for chemoprevention. [ABSTRACT FROM AUTHOR]

The ability of cancer-targeted nanoparticles (NPs) to reach their site of action and evoke a desired biological response after intravenous injection is critical to achieve clinically significant in vivo efficacy. Throughout their journey in the body, NPs must successfully traverse biological environments such as blood circulation and tumor microenvironments. The interactions that occur at the interface between NPs and biological components are complex, requiring a thorough understanding of the “nano-bio” interactions to design NPs with maximal therapeutic indices. In this article, we review the challenges presented by the multiscale, important biocompartments that NPs face, describe the crucial nano-bio interactions present at each stage, and discuss potential strategies to overcome those challenges. This review suggests design considerations for NPs to optimally modulate their physicochemical properties to achieve desired biological responses, which are expected to aid chemists, engineers, and clinical scientists to design and develop highly effective delivery platforms for cancer therapy. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) have been highlighted as novel drug carriers due to their unique structural properties and intrinsic features, including high stability, biocompatibility, and cell-targeting properties. Although many efforts have been made to harness these features to develop a clinically effective EV-based therapeutic system, the clinical translation of EV-based nano-drugs is hindered by their low yield and loading capacity. Herein, we present an engineering strategy that enables upscaled EV production with increased loading capacity through the secretion of EVs from cells via cytochalasin-B (CB) treatment and reduction of EV intravesicular contents through hypo-osmotic stimulation. CB (10 µg/mL) promotes cells to extrude EVs, producing ~three-fold more particles than through natural EV secretion. When CB is induced in hypotonic conditions (223 mOsm/kg), the produced EVs (hypo-CIMVs) exhibit ~68% less intravesicular protein, giving 3.4-fold enhanced drug loading capacity compared to naturally secreted EVs. By loading doxorubicin (DOX) into hypo-CIMVs, we found that hypo-CIMVs efficiently deliver their drug cargos to their target and induce up to ~1.5-fold more cell death than the free DOX. Thus, our EV engineering offers the potential for leveraging EVs as an effective drug delivery vehicle for cancer treatment. [ABSTRACT FROM AUTHOR]

Nanotechnology is an up-and-coming branch of science that studies and designs materials with at least one dimension sized from 1-100 nm. These nanomaterials have unique functions at the cellular, atomic, and molecular levels. The term "nanotechnology" was first coined in 1974. Since then, it has evolved dramatically and now consists of distinct and independent scientific fields. Nanotechnology is a highly studied topic of interest, as nanoparticles can be applied to various fields ranging from medicine and pharmacology, to chemistry and agriculture, to environmental science and consumer goods. The rapidly evolving field of nanomedicine incorporates nanotechnology with medical applications, seeking to give rise to new diagnostic means, treatments, and tools. Over the past two decades, numerous studies that underscore the successful fusion of nanotechnology with novel medical applications have emerged. This has given rise to promising new therapies for a variety of diseases, especially cancer. It is becoming abundantly clear that nanotechnology has found a place in the medical field by providing new and more efficient ways to deliver treatment. Ophthalmology can also stand to benefit significantly from the advances in nanotechnology research. As it relates to the eye, research in the nanomedicine field has been particularly focused on developing various treatments to prevent and/or reduce corneal neovascularization among other ophthalmologic disorders. This review article aims to provide an overview of corneal neovascularization, currently available treatments, and where nanotechnology comes into play. [ABSTRACT FROM AUTHOR]