Combinatory Nanovesicle with siRNA-Loaded Extracellular Vesicle and IGF-1 for Osteoarthritis Treatments.

Extracellular vesicles (EVs) have been found to have the characteristics of their parent cells. Based on the characteristics of these EVs, various studies on disease treatment using mesenchymal stem cell (MSC)-derived EVs with regenerative activity have been actively conducted. The therapeutic nature of MSC-derived EVs has been shown in several studies, but in recent years, there have been many efforts to functionalize EVs to give them more potent therapeutic effects. Strategies for functionalizing EVs include endogenous and exogenous methods. In this study, human umbilical cord MSC (UCMSC)-derived EVs were selected for optimum OA treatments with expectation via bioinformatics analysis based on antibody array. And we created a novel nanovesicle system called the IGF-si-EV, which has the properties of both cartilage regeneration and long-term retention in the lesion site, attaching positively charged insulin-like growth factor-1 (IGF-1) to the surface of the UCMSC-derived Evs carrying siRNA, which inhibits MMP13. The downregulation of inflammation-related cytokine (MMP13, NF-kB, and IL-6) and the upregulation of cartilage-regeneration-related factors (Col2, Acan) were achieved with IGF-si-EV. Moreover, the ability of IGF-si-EV to remain in the lesion site for a long time has been proven through an ex vivo system. Collectively, the final constructed IGF-si-EV can be proposed as an effective OA treatment through its successful MMP13 inhibition, chondroprotective effect, and cartilage adhesion ability. We also believe that this EV-based nanoparticle-manufacturing technology can be applied as a platform technology for various diseases.

Extracellular vesicle encapsulated nicotinamide delivered via a trans-scleral route provides retinal ganglion cell neuroprotection.

The progressive and irreversible degeneration of retinal ganglion cells (RGCs) and their axons is the major characteristic of glaucoma, a leading cause of irreversible blindness worldwide. Nicotinamide adenine dinucleotide (NAD) is a cofactor and metabolite of redox reaction critical for neuronal survival. Supplementation with nicotinamide (NAM), a precursor of NAD, can confer neuroprotective effects against glaucomatous damage caused by an age-related decline of NAD or mitochondrial dysfunction, reflecting the high metabolic activity of RGCs. However, oral supplementation of drug is relatively less efficient in terms of transmissibility to RGCs compared to direct delivery methods such as intraocular injection or delivery using subconjunctival depots. Neither method is ideal, given the risks of infection and subconjunctival scarring without novel techniques. By contrast, extracellular vesicles (EVs) have advantages as a drug delivery system with low immunogeneity and tissue interactions. We have evaluated the EV delivery of NAM as an RGC protective agent using a quantitative assessment of dendritic integrity using DiOlistics, which is confirmed to be a more sensitive measure of neuronal health in our mouse glaucoma model than the evaluation of somatic loss via the immunostaining method. NAM or NAM-loaded EVs showed a significant neuroprotective effect in the mouse retinal explant model. Furthermore, NAM-loaded EVs can penetrate the sclera once deployed in the subconjunctival space. These results confirm the feasibility of using subconjunctival injection of EVs to deliver NAM to intraocular targets.

Multiplexed PLGA scaffolds with nitric oxide-releasing zinc oxide and melatonin-modulated extracellular vesicles for severe chronic kidney disease.

INTRODUCTION: With prevalence of chronic kidney disease (CKD) in worldwide, the strategies to recover renal function via tissue regeneration could provide alternatives to kidney replacement therapies. However, due to relatively low reproducibility of renal basal cells and limited bioactivities of implanted biomaterials along with the high probability of substance-inducible inflammation and immunogenicity, kidney tissue regeneration could be challenging. OBJECTIVES: To exclude various side effects from cell transplantations, in this study, we have induced extracellular vesicles (EVs) incorporated cell-free hybrid PMEZ scaffolds. METHODS: Hybrid PMEZ scaffolds incorporating essential bioactive components, such as ricinoleic acid grafted Mg(OH)2 (M), extracellular matrix (E), and alpha lipoic acid-conjugated ZnO (Z) based on biodegradable porous PLGA (P) platform was successfully manufactured. Consecutively, for functional improvements, melatonin-modulated extracellular vesicles (mEVs), derived from the human umbilical cord MSCs in chemically defined media without serum impurities, were also loaded onto PMEZ scaffolds to construct the multiplexed PMEZ/mEV scaffold. RESULTS: With functionalities of Mg(OH)2 and extracellular matrix-loaded PLGA scaffolds, the continuous nitric oxide-releasing property of modified ZnO and remarkably upregulated regenerative functionalities of mEVs showed significantly enhanced kidney regenerative activities. Based on these, the structural and functional restoration has been practically achieved in 5/6 nephrectomy mouse models that mimicked severe human CKD. CONCLUSION: Our study has proved the combinatory bioactivities of the biodegradable PLGA-based multiplexed scaffold for kidney tissue regeneration in 5/6 nephrectomy mouse representing a severe CKD model. The optimal microenvironments for the morphogenetic formations of renal tissues and functional restorations have successfully achieved the combinatory bioactivities of remarkable components for PMEZ/mEV, which could be a promising therapeutic alternative for CKD treatment.

Recent advances in extracellular vesicle engineering and its applications to regenerative medicine.

Extracellular vesicles (EVs) are nanosized particles that are released from cells and reflect the characteristics of the mother cell. Recently, the EVs have been used in several types of studies across many different fields. In the field of EV research, multiple cell culture and EV isolation techniques have been highlighted in importance. Various strategies, including exclusive component culture media, three-dimensional (3D) cultures, and hypoxic conditions, have been proposed for the cell culture to control function of the EVs. Ultracentrifugation, ultrafiltration, precipitation, and tangential flow filtration (TFF) have been utilized for EV isolation. Although isolated EVs have their own functionalities, several researchers are trying to functionalize EVs by applying various engineering approaches. Gene editing, exogenous, endogenous, and hybridization methods are the four well-known types of EV functionalization strategies. EV engineered through these processes has been applied in the field of regenerative medicine, including kidney diseases, osteoarthritis, rheumatoid arthritis, nervous system-related diseases, and others. In this review, it was focused on engineering approaches for EV functionalization and their applications in regenerative medicine.

Kidney tissue regeneration using bioactive scaffolds incorporated with differentiating extracellular vesicles and intermediate mesoderm cells.

BACKGROUND: To overcome the limitations of current alternative therapies for chronic kidney disease (CKD), tissue engineering-mediated regeneration strategies have demonstrated the possibilities for complete kidney tissue regeneration. Given the challenges associated with the reproducibility of renal basal cells, the incorporation of intermediate mesoderm (IM) cells and bioactive materials to control bioactivities of cells with supported scaffolds should be considered as a viable approach to enable the regeneration of the complex kidney structure via renal differentiation. METHODS: We developed PMEZ scaffolds by combining crucial bioactive components, such as ricinoleic acid-grafted Mg(OH)2 (M), extracellular matrix (E), and alpha lipoic acid-conjugated ZnO (Z) integrated into biodegradable porous PLGA (P) platform. Additionally, we utilized differentiating extracellular vesicles (dEV) isolated during intermediate mesoderm differentiation into kidney progenitor cells, and IM cells were serially incorporated to facilitate kidney tissue regeneration through their differentiation into kidney progenitor cells in the 3/4 nephrectomy mouse model. RESULTS: The use of differentiating extracellular vesicles facilitated IM differentiation into kidney progenitor cells without additional differentiation factors. This led to improvements in various regeneration-related bioactivities including tubule and podocyte regeneration, anti-fibrosis, angiogenesis, and anti-inflammation. Finally, implanting PMEZ/dEV/IM scaffolds in mouse injury model resulted in the restoration of kidney function. CONCLUSIONS: Our study has demonstrated that utilizing biodegradable PLGA-based scaffolds, which include multipotent cells capable of differentiating into various kidney progenitor cells along with supporting components, can facilitate kidney tissue regeneration in the mouse model that simulates CKD through 3/4 nephrectomy.

Saving Stabilizing Structure Treatment With Bilateral-Contralateral Decompression for Spinal Stenosis in Degenerative Spondylolisthesis Using Unilateral Biportal Endoscopy.

OBJECTIVE: This study aimed to evaluate the treatment of spinal stenosis with spondylolisthesis using bilateral-contralateral unilateral biportal endoscopic (UBE) decompression to minimize facet joint damage. METHODS: We retrospectively evaluated 42 patients with grade 1 spondylolisthesis who underwent bilateral-contralateral UBE decompression between July 2018 and September 2019. To identify segmental instability, static and dynamic images from preoperative and postoperative procedures and final follow-up radiographs were reviewed. Lateral radiograph slippage ratio, sagittal motion, and facet joint preservation were evaluated. Clinical assessments were conducted using the visual analogue scale (VAS), Oswestry Disability Index (ODI), and modified MacNab criteria. RESULTS: The average final follow-up period was 26.5 ± 1.3 months. The average preoperative slip percentage was 15.70% ± 5.25%, which worsened to 18.80% ± 5.41% at the final follow-up (p < 0.005). The facet joint preservation rate was 95.6% ± 4.1% on the contralateral side. Improvements in the VAS scores (leg pain: from 7.9 ± 2.2 to 3.1 ± 0.7; p < 0.005; back pain: from 7.2 ± 3.0 to 2.8 ± 1.0; p < 0.005) were observed at the final follow-up. The mean preoperative ODI was 26.19 ± 3.42, which improved to 9.6 ± 1.0 (p < 0.005). Thirteen patients exhibited delayed focal segmental instability following decompression. Despite the absence of symptoms or improvement with conservative treatment in the majority of patients with delayed instability, two patients required fusion surgery to address the instability. Additionally, 2 patients developed facet synovial cysts, while 2 experienced spinous process fractures. CONCLUSION: Bilateral decompression with a contralateral UBE approach could be an effective and alternative treatment method to reduce instability in spinal stenosis with grade 1 spondylolisthesis.

Acidonemycins A-C, Glycosylated Angucyclines with Antivirulence Activity Produced by the Acidic Culture of Streptomyces indonesiensis.

The genome of Streptomyces indonesiensis is highly enriched with cryptic biosynthetic gene clusters (BGCs). The majority of these cryptic BGCs are transcriptionally silent in normal laboratory culture conditions as determined by transcriptome analysis. When cultured in acidic pH (pH 5.4), this strain has been shown to produce a set of new metabolites that were not observed in cultures of neutral pH (pH 7.4). The organic extract of the acidic culture displayed an antivirulence activity against methicillin-resistant Staphylococcus aureus (MRSA). Here, we report the structures of new glycosylated aromatic polyketides, named acidonemycins A-C (1-3), belonging to the family of angucyclines. Type II polyketide synthase BGC responsible for the production of 1-3 was identified by a transcriptome comparison between acidic (pH 5.4) and neutral (pH 7.4) cultures and further confirmed by heterologous expression in Streptomyces albus J1074. Of the three new compounds, acidonemycins A and B (1 and 2) displayed antivirulence activity against MRSA. The simultaneous identification of both antivirulent compounds and their BGC provides a starting point for the future effort of combinatorial biosynthesis.

Time-resolved proteomic analyses of senescence highlight metabolic rewiring of mitochondria.

Mitochondrial dysfunction and cellular senescence are hallmarks of aging. However, the relationship between these two phenomena remains incompletely understood. In this study, we investigated the rewiring of mitochondria upon development of the senescent state in human IMR90 fibroblasts. Determining the bioenergetic activities and abundance of mitochondria, we demonstrate that senescent cells accumulate mitochondria with reduced OXPHOS activity, resulting in an overall increase of mitochondrial activities in senescent cells. Time-resolved proteomic analyses revealed extensive reprogramming of the mitochondrial proteome upon senescence development and allowed the identification of metabolic pathways that are rewired with different kinetics upon establishment of the senescent state. Among the early responding pathways, the degradation of branched-chain amino acid was increased, whereas the one carbon folate metabolism was decreased. Late-responding pathways include lipid metabolism and mitochondrial translation. These signatures were confirmed by metabolic flux analyses, highlighting metabolic rewiring as a central feature of mitochondria in cellular senescence. Together, our data provide a comprehensive view on the changes in mitochondrial proteome in senescent cells and reveal how the mitochondrial metabolism is rewired in senescent cells.

Multimodal therapy strategy based on a bioactive hydrogel for repair of spinal cord injury.

Traumatic spinal cord injury results in permanent and serious neurological impairment, but there is no effective treatment yet. Tissue engineering approaches offer great potential for the treatment of SCI, but spinal cord complexity poses great challenges. In this study, the composite scaffold consists of a hyaluronic acid-based hydrogel, decellularized brain matrix (DBM), and bioactive compounds such as polydeoxyribonucleotide (PDRN), tumor necrosis factor-α/interferon-γ primed mesenchymal stem cell-derived extracellular vesicles (TI-EVs), and human embryonic stem cell-derived neural progenitor cells (NPC). The composite scaffold showed significant effects on regenerative prosses including angiogenesis, anti-inflammation, anti-apoptosis, and neural differentiation. In addition, the composite scaffold (DBM/PDRN/TI-EV/NPC@Gel) induced an effective spinal cord regeneration in a rat spinal cord transection model. Therefore, this multimodal approach using an integrated bioactive scaffold coupled with biochemical cues from PDRN and TI-EVs could be used as an advanced tissue engineering platform for spinal cord regeneration.

Prognostic Significance of ARID1A Expression Patterns Varies with Molecular Subtype in Advanced Gastric Cancer.

Background/Aims: AT-rich interactive domain 1A (ARID1A) is frequently mutated in gastric cancer (GC), especially Epstein-Barr virus (EBV)-associated and microsatellite instability high GC. The loss of ARID1A expression has been reported as a poor prognostic marker in GC. However, the relationships between ARID1A alteration and EBV-associated and microsatellite instability high GC, which are known to have a favorable prognosis, has hampered proper evaluation of the prognostic significance of ARID1A expression in GC. We aimed to analyze the true prognostic significance of ARID1A expression by correcting confounding variables. Methods: We evaluated the ARID1A expression in a large series (n=1,032) of advanced GC and analyzed the relationships between expression pattern and variable parameters, including clinicopathologic factors, key molecular features such as EBV-positivity, mismatch repair protein deficiency, and expression of p53 and several receptor tyrosine kinases including human epidermal growth factor receptor 2, epidermal growth factor receptor, and mesenchymal-epithelial transition factor. Survival analysis of the molecular subtypes was done according to the ARID1A expression patterns. Results: Loss of ARID1A expression was found in 52.5% (53/101) of mutL homolog 1 (MLH1)-deficient and 35.8% (24/67) of EBV-positive GCs, compared with only 9.6% (82/864) of the MLH1-proficient and EBV-negative group (p<0.001). The loss of ARID1A expression was associated only with MLH1 deficiency and EBV positivity. On survival analysis, the loss of ARID1A expression was associated with worse prognosis only in MLH1-proficient and EBV-negative GC. Multivariate analysis revealed that both loss of ARID1A and decreased ARID1A expression were independent worse prognostic factors in patients with advanced GC. Conclusions: Only in MLH1-proficient and EBV-negative GC, the loss of ARID1A expression is related to poorer prognosis.

The proteomic landscape shows oncologic relevance in cystitis glandularis.

BACKGROUND: The relationship between cystitis glandularis (CG) and bladder malignancy remains unclear. METHODS: We identified the oncologic significance of CG at the molecular level using liquid chromatography-tandem mass spectrometry-based proteomic analysis of 10 CG, 12 urothelial carcinoma (UC), and nine normal urothelium (NU) specimens. Differentially expressed proteins (DEPs) were identified based on an analysis of variance false discovery rate < 0.05, and their functional enrichment was analyzed using a network model, Gene Set Enrichment Analysis, and Gene Ontology annotation. RESULTS: We identified 9,890 proteins across all samples and 1,139 DEPs among the three entities. A substantial number of DEPs overlapped in CG/NU, distinct from UC. Interestingly, we found that a subset of DEP clusters (n = 53, 5%) was differentially expressed in NU but similarly between CG and UC. This "UC-like signature" was enriched for reactive oxygen species (ROS) and energy metabolism, growth and DNA repair, transport, motility, epithelial-mesenchymal transition, and cell survival. Using the top 10 shortlisted DEPs, including SOD2, PRKCD, CYCS, and HCLS1, we identified functional elements related to ROS metabolism, development, and transport using network analysis. The abundance of these four molecules in UC/CG than in NU was consistent with the oncologic functions in CG. CONCLUSIONS: Using a proteomic approach, we identified a predominantly non-neoplastic landscape of CG, which was closer to NU than to UC. We also confirmed a small subset of common DEPs in UC and CG, suggesting that altered ROS metabolism might imply potential cancerous risks in CG.

Endogenous stimulus-responsive nitric oxide releasing bioactive liposome for a multilayered drug-eluting balloon.

Drug-eluting balloon (DEB) system has been widely utilized for percutaneous coronary intervention (PCI), treating atherosclerosis to overcome the limitations of cardiovascular stents. With the anti-proliferative drug, everolimus (EVL), nitric oxide (NO) plays a key bioregulator role to facilitate the angiogenesis of endothelial cells (ECs) and inhibit the cell proliferation of smooth muscle cells (SMCs) in the lesions of cardiovascular diseases. Due to the very short lifetime and limited exposure area of NO in the body, the continuous release and efficient delivery of NO must be carefully considered. In this respect, a liposome-containing disulfide bonding group was introduced as a delivery vehicle of EVL and NO with the continuous release of NO via successive reaction cycles with GSH and SNAP in the blood vessel without the need for exogenous stimulations. With a multilayer coating platform consisting of a polyvinylpyrrolidone (PVP)/EVL-laden liposome with NO (EVL-NO-Lipo)/PVP, we precluded the loss of the EVL-encapsulated liposome with NO release during the transition time and maximized the transfer rate from the surface of DEB to the tissues. The sustained release of NO was monitored using a nitric oxide analyzer (NOA), and the synergistic bioactivities of EVL and NO were proved in EC and SMC with angiogenesis and cell proliferation-related assays. From the results of hemocompatibility and ex vivo studies, the feasibility was provided for future in vivo applications of the multilayer-coated DEB system.

CaExTun: Mitigating Cas9-Related Toxicity in Streptomyces through Species-Specific Expression Tuning with Randomized Constitutive Promoters.

The CRISPR/Cas9 system provides an efficient tool for engineering genomes. However, its application to Streptomyces genome engineering has been hampered by excessive toxicity associated with overexpression of Cas9 protein. As the level of Cas9 toxicity varies significantly between Streptomyces species, species-specific optimization of Cas9 expression is a strategy to mitigate its toxicity while maintaining sufficient double-strand break (DSB) activity for genome engineering. Using a pool of randomized constitutive promoters and a blue pigment indigoidine biosynthetic gene (IndC) as a reporter, we developed the CaExTun (Cas9 Expression Tuning) platform, which enables rapid screening of a large pool of promoter-Cas9 constructs to quickly recover the one with high DSB activity and no apparent toxicity. We demonstrate the utility of CaExTun using four model Streptomyces species. We also show that CaExTun can be applied to the CRISPRi system by allowing the construction of a library of promoter-dCas9 constructs that confer a wide range of gene repression levels. As demonstrated here, CaExTun is a versatile tool for the rapid optimization of the CRISPR/Cas9 system in a species-specific manner and thus will facilitate CRISPR/Cas9-based genome engineering efforts in Streptomyces.

Iatrogenic Ankle Charcot Neuropathic Arthropathy after Spinal Surgery: A Case Report and Literature Review.

Charcot neuropathic arthropathy is a relatively rare, chronic disease that leads to joint destruction and reduced quality of life of patients. Early diagnosis of Charcot arthropathy is essential for a good outcome. However, the diagnosis is often based on the clinical course and longitudinal follow-up of patients is required. Charcot arthropathy is suspected in patients with suggestive symptoms and an underlying etiology. Failed spinal surgery is not a known cause of Charcot arthropathy. Herein we report a patient with ankle Charcot neuropathic arthropathy that developed after failed spinal surgery. A 58-year-old man presented to the emergency room due to painful swelling of the left ankle for 2 weeks that developed spontaneously. He underwent spinal surgery 8 years ago that was associated with nerve damage, which led to weakness of great toe extension and ankle dorsiflexion, and sensory loss below the knee. CT and T2-weighted sagittal MRI showed a fine erosive lesion, subluxation, sclerosis, fragmentation, and large bone defects. Based on the patient's history and radiological findings, Charcot arthropathy was diagnosed. However, the abnormal blood parameters, positive blood cultures, and severe pain despite the decreased sensation suggested a diagnosis of septic arthritis. Therefore, diagnostic arthroscopy was performed. The ankle joint exhibited continued destruction after the initial surgery. Consequently, several repeat surgeries were performed over the next 2 years. Despite the early diagnosis and treatment of Charcot arthropathy, the destruction of the ankle joint continued. Given the chronic disease course and poor prognosis of Charcot arthropathy, it is essential to consider this diagnosis in patients with neuropathy.

Bolstering the secretion and bioactivities of umbilical cord MSC-derived extracellular vesicles with 3D culture and priming in chemically defined media.

Human mesenchymal stem cells (hMSCs)-derived extracellular vesicles (EVs) have been known to possess the features of the origin cell with nano size and have shown therapeutic potentials for regenerative medicine in recent studies as alternatives for cell-based therapies. However, extremely low production yield, unknown effects derived from serum impurities, and relatively low bioactivities on doses must be overcome for translational applications. As several reports have demonstrated the tunability of secretion and bioactivities of EVs, herein, we introduced three-dimensional (3D) culture and cell priming approaches for MSCs in serum-free chemically defined media to exclude side effects from serum-derived impurities. Aggregates (spheroids) with 3D culture dramatically enhanced secretion of EVs about 6.7 times more than cells with two-dimensional (2D) culture, and altered surface compositions. Further modulation with cell priming with the combination of TNF-α and IFN-γ (TI) facilitated the production of EVs about 1.4 times more than cells without priming (9.4 times more than cells with 2D culture without priming), and bioactivities of EVs related to tissue regenerations. Interestingly, unlike changing 2D to 3D culture, TI priming altered internal cytokines of MSC-derived EVs. Through simulating characteristics of EVs with bioinformatics analysis, the regeneration-relative properties such as angiogenesis, wound healing, anti-inflammation, anti-apoptosis, and anti-fibrosis, for three different types of EVs were comparatively analyzed using cell-based assays. The present study demonstrated that a combinatory strategy, 3D cultures and priming MSCs in chemically defined media, provided the optimum environments to maximize secretion and regeneration-related bioactivities of MSC-derived EVs without impurities for future translational applications.

The Upregulation of Regenerative Activity for Extracellular Vesicles with Melatonin Modulation in Chemically Defined Media.

Extracellular vesicles (EVs) derived from human mesenchymal stem cells (hMSCs) have been widely known to have therapeutic effects by representing characteristics of the origin cells as an alternative for cell-based therapeutics. Major limitations of EVs for clinical applications include low production yields, unknown effects from serum impurities, and relatively low bioactivities against dose. In this study, we proposed a cell modulation method with melatonin for human umbilical cord MSCs (hUCMSCs) cultured in serum-free chemically defined media (CDM) to eliminate the effects of serum-derived impurities and promote regeneration-related activities. miRNAs highly associated with regeneration were selected and the expression levels of them were comparatively analyzed among various types of EVs depending on culture conditions. The EVs derived from melatonin-stimulated hUCMSCs in CDM (CDM mEVs) showed the highest expression levels of regeneration-related miRNAs, and 7 times more hsa-let-7b-5p, 5.6 times more hsa-miR-23a-3p, and 5.7 times more hsa-miR-100-5p than others, respectively. In addition, the upregulation of various functionalities, such as wound healing, angiogenesis, anti-inflammation, ROS scavenging, and anti-apoptosis, were proven using in vitro assays by simulating the characteristics of EVs with bioinformatics analysis. The present results suggest that the highly regenerative properties of hUCMSC-derived EVs were accomplished with melatonin stimulation in CDM and provided the potential for clinical uses of EVs.

Utility of Epstein-Barr Viral Load in Blood for Diagnosing and Predicting Prognosis of Lymphoma: A Comparison with Epstein-Barr Virus-Encoded RNA in Situ Hybridization.

Epstein-Barr virus (EBV) is a ubiquitous pathogen that persists in a small portion of B cells after primary infection and is etiologically associated with multiple lymphoma subtypes. We evaluated the clinical utility of EBV real-time quantitative PCR in comparison with the widely used Epstein-Barr virus-encoded RNA (EBER) in situ hybridization (ISH) method in 912 patients with four lymphoma subtypes: diffuse large B-cell lymphoma (DLBCL), extranodal natural killer/T-cell lymphoma (ENKTCL), peripheral T-cell lymphoma (PTCL), and Hodgkin lymphoma. We also assessed the impact of EBV positivity determined from each method or a combination of both methods on mortality using Kaplan-Meier survival analysis and Cox proportional hazard regression. EBV real-time quantitative PCR identified more positive cases than EBER-ISH for all subtypes, except ENKTCL. EBV DNA-positive patients with ENKTCL and PTCL displayed poorer overall survival (OS) than EBV DNA-negative patients (P = 0.0016 and P = 0.0013, respectively). In addition, among those with EBER-positive DLBCL and ENKTL and those with EBER-negative PTCL, OS was significantly worse for EBV DNA-positive patients (P = 0.027, P = 0.0016, and P = 0.0018, respectively). EBER positivity was associated with worse OS for DLBCL (P = 0.037), in reanalyses including only the 862 patients with unambiguous EBER-ISH results. Overall, EBV DNA positivity is a more effective prognostic marker than EBER-ISH status for patients with certain lymphoma subtypes.

High Color Purity Plasmonic Color Filter by One-Dimensional Photonic Crystals.

Structural colors have been reported instead of conventional dye- or pigment-based color filters. Color selectivity can degrade as structure-based optical resonances are accompanied by several resonance modes. In this work, we suggest a simple and effective design of the plasmonic color filter (PCF) that integrated the PCF with the one-dimensional (1D) photonic crystal (PhC). The introduced PhC creates an optical band gap and suppresses undesired peaks of the PCF caused by the high-order resonance mode. Finally, the suggested structure provides a high color purity. This study can be a guideline for technology that replaces conventional color filters.

Exploring dopant effects in stannic oxide nanoparticles for CO2 electro-reduction to formate.

The electrosynthesis of formate from CO2 can mitigate environmental issues while providing an economically valuable product. Although stannic oxide is a good catalytic material for formate production, a metallic phase is formed under high reduction overpotentials, reducing its activity. Here, using a fluorine-doped tin oxide catalyst, a high Faradaic efficiency for formate (95% at 100 mA cm-2) and a maximum partial current density of 330 mA cm-2 (at 400 mA cm-2) is achieved for the electroreduction of CO2. Furthermore, the formate selectivity (≈90%) is nearly constant over 7 days of operation at a current density of 100 mA cm-2. In-situ/operando spectroscopies reveal that the fluorine dopant plays a critical role in maintaining the high oxidation state of Sn, leading to enhanced durability at high current densities. First-principle calculation also suggests that the fluorine-doped tin oxide surface could provide a thermodynamically stable environment to form HCOO* intermediate than tin oxide surface. These findings suggest a simple and efficient approach for designing active and durable electrocatalysts for the electrosynthesis of formate from CO2.