Fermentative aminopyrrolnitrin production by metabolically engineered Corynebacterium glutamicum.

Aminopyrrolnitrin (APRN), a natural halogenated phenylpyrrole derivative (HPD), has strong antifungal and antiparasitic activities. Additionally, it showed 2.8-fold increased photostability compared to pyrrolnitrin, a commercially available HPD with antimicrobial activity. For microbial production of APRN, we first engineered anthranilate phosphoribosyltransferase encoded by trpD from Corynebacterium glutamicum, resulting in a TrpDA162D mutation that exhibits feedback-resistant against L-tryptophan and higher substrate affinity compared to wild-type TrpD. Plasmid-borne expression of trpDA162D in C. glutamicum TP851 strain with two copies of trpDA162D in the genome led to the production of 3.1 g/L L-tryptophan in flask culture. Subsequent step for L-tryptophan chlorination into 7-chloro-L-tryptophan was achieved by introducing diverse sources of genes encoding tryptophan 7-halogenase (PrnA or RebH) and flavin reductase (Fre, PrnF, or RebF). The combined expression of prnA from Serratia grimesii or Serratia plymuthica with flavin reductase gene from Escherichia coli, Pseudomonas fluorescens, or Lechevalieria aerocolonigenes yielded higher production of 7-chloro-L-tryptophan in comparison to other sets of two-component systems. In the next step, production of putative monodechloroaminopyrrolnitrin (MDAP) from 7-chloro-L-tryptophan was achieved through the expression of prnB encoding MDAP synthase from S. plymuthica or P. fluorescens. Finally, an artificial APRN biosynthetic pathway was constructed by simultaneously expressing genes coding for tryptophan 7-halogenase, flavin reductase, MDAP synthase, and MDAP halogenase (PrnC) from different microbial sources within the L-tryptophan-producing TP851 strain. As prnC from S. grimesii or S. plymuthica was introduced into the host strain, which carried plasmids expressing prnA from S. plymuthica, fre from E. coli, and prnB from S. plymuthica, APN3639 and APN3638 accumulated 29.5 mg/L and 28.1 mg/L of APRN in the culture broth. This study represents the first report on the fermentative APRN production by metabolically engineered C. glutamicum.

Addition of recombinant human bone morphogenic protein-2 to the graft materials improves the clinical outcomes of implants placed in grafted maxillary sinus.

Background/purpose: The long-term outcomes of implants placed in grafted sinuses using recombinant human bone morphogenetic protein-2 (rhBMP-2) are unclear. This study aimed to compare 3- and 5-year implant survival rates and marginal bone loss (MBL) during functional loading. Materials and methods: In this retrospective study, we analyzed 63 implants inserted after maxillary sinus floor augmentation (MSFA) in 45 patients between January 2016 and April 2019. The outcome variables were: 1) 3- and 5-year cumulative survival rates of the implants and 2) MBL after functional loading. Other assessed variables included patient demographic information, preoperative residual bone height (RBH), surgical site, implant length and diameter, graft material, healing period before loading, prosthetic type, and opposing dentition. Results: The cumulative 3- and 5-year survival rates of the implants were 100% in the rhBMP-2 group and 95.5% and 86.4% in the non-rhBMP-2 group, respectively. The average 3- and 5-year MBL were 1.14 ± 0.67 mm, 1.30 ± 0.74 mm in the rhBMP-2 group and 1.68 ± 0.90 mm, 2.27 ± 1.29 mm in the non-rhBMP-2 group, respectively. Significant differences were observed between 3 and 5 years between the two groups. Conclusion: Addition of the rhBMP-2 to the graft materials positively affects implant placement in the grafted maxillary sinus in terms of implant survival and MBL when preoperative RBH is unfavorable.

The Effect of Induction Therapy on Antibody-Mediated Rejection in Kidney Transplantation: A Network Meta-Analysis Using Recent Data.

BACKGROUND: Various induction regimens are available for kidney transplantation (KT); however, which is superior remains unclear. Moreover, although the induction regimens are effective and important for reducing side effects, their respective relationships with antibody-mediated rejection (AMR) after transplantation remain unclear. Therefore, this study aimed to elucidate the most effective induction regimen for AMR reduction through network analysis. METHODS: We performed a comprehensive search of databases, including basiliximab, alemtuzumab, antithymocyte globulin (ATG), and daclizumab as induction regimens for KT from inception to September 1, 2022. Using a network meta-analysis, we investigated the priorities of 5 induction regimens for patient survival, graft failure, and graft rejection after ABO-incompatible KT. RESULTS: In total, 25 studies comprising 1768 people were included in this network meta-analysis. The primary outcome was the AMR rate of other induction regimens compared with that of basiliximab, whereas the secondary outcomes were heart failure, stroke, hospitalization, peripheral artery disease, myocardial infarction, anemia, leukopenia, herpes zoster, or adverse events. Notably, ATG reduced the AMR rate by 59% (odds ratio, 0.41; 95% credible interval, 0.20-0.90), whereas the other drugs did not show statistical significance. Furthermore, secondary outcomes did not significantly differ between the induction regimens. CONCLUSION: ATG is widely used in KT induction regimens. Our results showed that ATG reduced the risk of AMR in KT recipients when compared with other induction drugs; therefore, it appears to be an efficient choice of induction regimen to reduce AMR after KT.

Effect of Induction Therapy Dose on Survival in Abo-Incompatible Kidney Transplantation: A Network Meta-Analysis Using Recent Data.

BACKGROUND: Rituximab is an essential induction immunosuppressant for ABO-incompatible kidney transplantation (KT) (ABOi-KT). However, studies on the optimal dose of rituximab are insufficient, and there are dosage differences between transplant centers and countries. Therefore, we conducted a study to determine the survival outcomes of patients receiving the most effective and safe dose of rituximab during ABOi-KT. METHODS: Studies on rituximab dose were divided into four groups: ABO compatible, 1) placebo, 2) rituximab 200 mg, 3) rituximab 200-500 mg, and 4) rituximab 500 mg. We searched the CENTRAL, MEDLINE, EMBASE, and Science Citation Index Expanded databases from 1970 to February 2022.9 . The inclusion criteria were adult patients (>18 years old). Reviews, observational studies, and clinical trials that did not clearly define outcomes or that did not have graft failure as an outcome were excluded. We performed direct and indirect network meta-analyses using Bayesian models and ranked different rituximab doses using a generation mixed treatment comparison (GeMTC) and Stata version 13. The NMA approach was evaluated using the GRADE framework, which specifies four levels of certainty for a given result: high, moderate, low, and very low. The outcomes included patient survival, graft failure, and bacterial and viral infections. RESULTS: Twenty-five trials, including 5,378 subjects, were divided into the following four groups: 1) placebo, 2) rituximab 200 mg, 3) rituximab 200-500 mg, and 4) rituximab 500 mg. We focused on survival outcomes according to the dose of rituximab when patients received induction therapy for ABOi-KT. The mortality rate was significantly lower in the ABO-compatible and rituximab 200 mg groups (odds ratio [OR] 0.27, 95% CrI: 0.071-0.91 and OR 0.14, 95% CrI 0.036-0.47), compared with that in the placebo group. CONCLUSIONS: We found that low-dose rituximab in ABO-i KT was effective compared to the high-dose and placebo in maintaining the survival rate. However, large-scale and long-term data are necessary for further validation of our findings. Additionally, the use of smaller doses of rituximab will require further discussion.

Effect of Plasmapheresis on the Efficacy of Rituximab in Antibody-Mediated Rejection Patients.

BACKGROUND: Rituximab and plasmapheresis (PP) suppress and eliminate antibody production in patients experiencing antibody-mediated rejection (AMR). Herein, we discuss a case where rituximab was less effective after PP for treating AMR. CASE: A 55-year-old male patient underwent kidney transplantation. His renal function remained normal for 1 year. Subsequently, renal function declined, and (donor-specific antibodies showed positive results. A biopsy of the transplanted kidney revealed AMR. On the day of the biopsy, the medical staff administered 200 mg of rituximab, followed by IV immunoglobulin (IVIg) and PP the next day. The time interval between PP + IVIg treatment and rituximab was 12 h. As a result, the B-cell markers CD19 and CD20 did not decrease sufficiently, and the patient's creatinine and glomerular filtration rate muscles did not recover adequately. CONCLUSION: We report a case in which PP was administered shortly after rituximab injection, resulting in insufficient B-cell inhibition due to the removal of rituximab.

High-Dose Intravenous Immunoglobulin to Treat Anti-Thymocyte Globulin Induction-Related BK Virus and Cytomegalovirus Infection in Patients with ABO-Incompatible Kidney Transplantation.

BACKGROUND: ABO-incompatible (ABOi) transplantation is a novel method transplantation method that carries a heightened risk of infection caused by the use of high immunosuppressant doses. This elevated risk is particularly concerning for viral infections, such as cytomegalovirus (CMV) and the BK virus (BKV) increases. Herein, we present a case where high-dose intravenous immunoglobulin (IVIG) was effective in treating viral infections after transplantation. METHODS: A 41-year-old man underwent an ABOi transplantation. The initial isoagglutinin titer was 1:32. The patient received 200 mg of rituximab, and 3 rounds of plasmapheresis were performed. Subsequently, renal function remained normal; however, 7 months later, the renal function declined, and BK nephropathy and CMV infection were diagnosed through biopsy and serologic tests. The FK level was reduced, and mycophenolate mofetil was discontinued. Although ciprofloxacin and leflunomide were administered, their effects were minimal. Therefore, high-dose IVIG (1 g/kg) was administered 5 times over 5 weeks, which led to a reduction in BK viral load and CMV infectivity in the serum. CONCLUSIONS: High-dose IVIG may serve as a promising alternative treatment to mitigate early transplant rejection and BKV and CMV infections.

BMP-2-immobilized PCL 3D printing scaffold with a leaf-stacked structure as a physically and biologically activated bone graft.

Although three-dimensional (3D) printing techniques are used to mimic macro- and micro-structures as well as multi-structural human tissues in tissue engineering, efficient target tissue regeneration requires bioactive 3D printing scaffolds. In this study, we developed a bone morphogenetic protein-2 (BMP-2)-immobilized polycaprolactone (PCL) 3D printing scaffold with leaf-stacked structure (LSS) (3D-PLSS-BMP) as a bioactive patient-tailored bone graft. The unique LSS was introduced on the strand surface of the scaffold via heating/cooling in tetraglycol without significant deterioration in physical properties. The BMP-2 adsorbed on3D-PLSS-BMPwas continuously released from LSS over a period of 32 d. The LSS can be a microtopographical cue for improved focal cell adhesion, proliferation, and osteogenic differentiation.In vitrocell culture andin vivoanimal studies demonstrated the biological (bioactive BMP-2) and physical (microrough structure) mechanisms of3D-PLSS-BMPfor accelerated bone regeneration. Thus, bioactive molecule-immobilized 3D printing scaffold with LSS represents a promising physically and biologically activated bone graft as well as an advanced tool for widespread application in clinical and research fields.

Nano/Micro Biosensors for Biomedical Applications.

Advances in nano/micro technologies in recent years have significantly improved biosensors in terms of their viability for biomedical purposes, from diagnostic to therapeutic applications, allowing for effective early detection and personalized treatment modalities [...].

Predictive factors of lymph node metastasis in papillary thyroid cancer.

This study aimed to evaluate factors that predict lymph node metastasis (LNM) in papillary thyroid cancer (PTC). This retrospective cross-sectional study compared the demographic, clinical, and ultrasonographic findings of patients with PTC with and without LNM. Subgroup analysis was conducted for micro-PTCs (<1 cm). Among total (n = 512; mean age, 47.3 ± 12.7 years) and micro-PTC patients (n = 312), 35.7% and 19.6% had LNM, respectively. Younger age, male sex, tumor size, bilaterality, and suspicious ultrasound features of the tumor were associated with LNM. In multiple logistic regression analysis, among all patients, age, tumor size, and extrathyroidal extension were independent risk factors for LNM (all p<0.05). In the micro-PTC subgroup, age, extrathyroidal extension, bilaterality of tumor, and presence of autoimmune thyroid disease were independent risk and protective factors for LNM (all p<0.05). In the receiver operating characteristic analysis, the accuracy of the multivariable logistic regression model for predicting LNM among all patients and micro-PTC was acceptable (area under the curve = 0.729 and 0.733, respectively). Age, sex, tumor size, and extrathyroidal extension can assist in predicting LNM in PTC patients. Additionally, the bilaterality of tumors and presence of autoimmune thyroid disease can assist in predicting LNM in micro-PTCs.

Early outcomes of robotic transabdominal preperitoneal inguinal hernia repair: a retrospective single-institution study in Korea.

Purpose: Robotic hernia repair has increased in popularity since the introduction of da Vinci robots (Intuitive Surgical). However, we lack quantitative analyses of its potential benefits. Herein, we report our initial experience with robotic transabdominal preperitoneal (R-TAPP) inguinal hernia repair. Methods: We retrospectively reviewed the data from patients who underwent R-TAPP inguinal hernia repair with a prosthetic mesh using the da Vinci platform. Data on patient characteristics and surgical outcomes were also collected. Results: Twenty-one patients (including 20 male patients [95.2%]) with a mean age of 54.1 ±16.4 years and body mass index of 23.8 ± 1.9 kg/m2 underwent R-TAPP inguinal hernia repair. Bilateral hernia repair was performed in two patients (9.5%), and six patients (28.5%) with scrotal hernia underwent R-TAPP hernia repair. A sigmoid colon sliding hernia was present in three patients (14.3%). The mean operation and console times were 91.8 ± 20.4 minutes and 154.5 ± 26.2 minutes, and 61.4 ± 16.9 minutes and 128.0 ± 25.5 minutes for unilateral and bilateral inguinal hernia, respectively. Spermatic vessel injury was identified intraoperatively in one patient. Two minor postoperative complications, postoperative ileus, and wound seroma were reported. The mean duration of hospitalization was 3.8 ± 0.9 days. No recurrence or conversion to open surgery was required. Conclusion: Our findings suggest that R-TAPP inguinal hernia repair is safe and feasible. Its cost-effectiveness, optimal procedural steps, and indications for a robotic approach require further investigation.

Impact of adjuvant therapy in patients with invasive intraductal papillary mucinous neoplasms of the pancreas: an international multicenter cohort study.

BACKGROUND: Adjuvant therapy prolongs survival in patients with pancreatic ductal adenocarcinoma. However, no clear guidelines are available regarding the oncologic effects of adjuvant therapy (AT) in resected invasive intraductal papillary mucinous neoplasms (IPMN). The aim was to investigate the potential role of AT in patients with resected invasive IPMN. MATERIALS AND METHODS: From 2001 to 2020, 332 patients with invasive pancreatic IPMN were retrospectively reviewed in 15 centres in eight countries. Propensity score-matched and stage-matched survival analyses were conducted. RESULTS: A total of 289 patients were enroled in the study after exclusion (neoadjuvant therapy, unresectable disease, uncertain AT status, and stage IV). A total of 170 patients were enroled in a 1:1 propensity score-matched analysis according to the covariates. In the overall cohort, disease-free survival was significantly better in the surgery alone group than in the AT group ( P =0.003), but overall survival (OS) was not ( P =0.579). There were no significant differences in OS in the stage-matched analysis between the surgery alone and AT groups (stage I, P =0.402; stage II, P =0.179). AT did not show a survival benefit in the subgroup analysis according to nodal metastasis (N0, P =0.481; N+, P =0.705). In multivariate analysis, node metastasis (hazard ratio, 4.083; 95% CI, 2.408-6.772, P <0.001), and cancer antigen 19-9 greater than or equal to 100 (hazard ratio, 2.058; 95% CI, 1.247-3.395, P =0.005) were identified as adverse prognostic factors in resected invasive IPMN. CONCLUSION: The current AT strategy may not be recommended to be performed with resected invasive IPMN in stage I and II groups, unlike pancreatic ductal adenocarcinoma. Further investigations of the potential role of AT in invasive IPMN are recommended.

Aptameric Fluorescent Biosensors for Liver Cancer Diagnosis.

Liver cancer is a prevalent global health concern with a poor 5-year survival rate upon diagnosis. Current diagnostic techniques using the combination of ultrasound, CT scans, MRI, and biopsy have the limitation of detecting detectable liver cancer when the tumor has already progressed to a certain size, often leading to late-stage diagnoses and grim clinical treatment outcomes. To this end, there has been tremendous interest in developing highly sensitive and selective biosensors to analyze related cancer biomarkers in the early stage diagnosis and prescribe appropriate treatment options. Among the various approaches, aptamers are an ideal recognition element as they can specifically bind to target molecules with high affinity. Furthermore, using aptamers, in conjunction with fluorescent moieties, enables the development of highly sensitive biosensors by taking full advantage of structural and functional flexibility. This review will provide a summary and detailed discussion on recent aptamer-based fluorescence biosensors for liver cancer diagnosis. Specifically, the review focuses on two promising detection strategies: (i) Förster resonance energy transfer (FRET) and (ii) metal-enhanced fluorescence for detecting and characterizing protein and miRNA cancer biomarkers.

Molecularly imprinted polymers (MIPs): emerging biomaterials for cancer theragnostic applications.

Cancer is a disease caused by abnormal cell growth that spreads through other parts of the body and threatens life by destroying healthy tissues. Therefore, numerous techniques have been employed not only to diagnose and monitor the progress of cancer in a precise manner but also to develop appropriate therapeutic agents with enhanced efficacy and safety profiles. In this regard, molecularly imprinted polymers (MIPs), synthetic receptors that recognize targeted molecules with high affinity and selectivity, have been intensively investigated as one of the most attractive biomaterials for theragnostic approaches. This review describes diverse synthesis strategies to provide the rationale behind these synthetic antibodies and provides a selective overview of the recent progress in the in vitro and in vivo targeting of cancer biomarkers for diagnosis and therapeutic applications. Taken together, the topics discussed in this review provide concise guidelines for the development of novel MIP-based systems to diagnose cancer more precisely and promote successful treatment. Molecularly imprinted polymers (MIPs), synthetic receptors that recognize targeted molecules with high affinity and selectivity, have been intensively investigated as one of the most attractive biomaterials for cancer theragnostic approaches. This review describes diverse synthesis strategies to provide the rationale behind these synthetic antibodies and provides a selective overview of the recent progress in the in vitro and in vivo targeting of cancer biomarkers for diagnosis and therapeutic applications. The topics discussed in this review aim to provide concise guidelines for the development of novel MIP-based systems to diagnose cancer more precisely and promote successful treatment.

Heat-Killed Enterococcus faecalis Inhibit FL83B Hepatic Lipid Accumulation and High Fat Diet-Induced Fatty Liver Damage in Rats by Activating Lipolysis through the Regulation the AMPK Signaling Pathway.

Continuous consumption of high-calorie meals causes lipid accumulation in the liver and liver damage, leading to non-alcoholic fatty liver disease (NAFLD). A case study of the hepatic lipid accumulation model is needed to identify the mechanisms underlying lipid metabolism in the liver. In this study, the prevention mechanism of lipid accumulation in the liver of Enterococcus faecalis 2001 (EF-2001) was extended using FL83B cells (FL83Bs) and high-fat diet (HFD)-induced hepatic steatosis. EF-2001 treatment inhibited the oleic acid (OA) lipid accumulation in FL83B liver cells. Furthermore, we performed lipid reduction analysis to confirm the underlying mechanism of lipolysis. The results showed that EF-2001 downregulated proteins and upregulated AMP-activated protein kinase (AMPK) phosphorylation in the sterol regulatory element-binding protein 1c (SREBP-1c) and AMPK signaling pathways, respectively. The effect of EF-2001 on OA-induced hepatic lipid accumulation in FL83Bs enhanced the phosphorylation of acetyl-CoA carboxylase and reduced the levels of lipid accumulation proteins SREBP-1c and fatty acid synthase. EF-2001 treatment increased the levels of adipose triglyceride lipase and monoacylglycerol during lipase enzyme activation, which, when increased, contributed to increased liver lipolysis. In conclusion, EF-2001 inhibits OA-induced FL83B hepatic lipid accumulation and HFD-induced hepatic steatosis in rats through the AMPK signaling pathway.

Plasmon Modulated Upconversion Biosensors.

Over the past two decades, lanthanide-based upconversion nanoparticles (UCNPs) have been fascinating scientists due to their ability to offer unprecedented prospects to upconvert tissue-penetrating near-infrared light into color-tailorable optical illumination inside biological matter. In particular, luminescent behavior UCNPs have been widely utilized for background-free biorecognition and biosensing. Currently, a paramount challenge exists on how to maximize NIR light harvesting and upconversion efficiencies for achieving faster response and better sensitivity without damaging the biological tissue upon laser assisted photoactivation. In this review, we offer the reader an overview of the recent updates about exciting achievements and challenges in the development of plasmon-modulated upconversion nanoformulations for biosensing application.

Micro-Current Stimulation Can Modulate the Adipogenesis Process by Regulating the Insulin Signaling Pathway in 3T3-L1 Cells and ob/ob Mice.

Obesity is a disease in which fat is abnormally or excessively accumulated in the body, and many studies have been conducted to overcome it with various techniques. In this study, we evaluated whether micro-current stimulation (MCS) can be applied to prevent obesity by regulating the adipogenesis through 3T3-L1 cells and ob/ob mice. To specify the intensity of MCS, Oil Red O staining was conducted with various intensities of MCS. Based on these, subsequent experiments used 200 and 400 µA for the intensity of MCS. The expressions of insulin signaling pathway-related proteins, including phosphorylation of IGF-1 and IR, were decreased in all MCS groups, and in turn, downstream signals such as Akt and ERK were decreased. In addition, MCS reduced the nucleus translocation of PPAR-γ and decreased the protein expression of C/EBP-α. In the ob/ob mouse model, MCS reduced body weight gain and abdominal adipose tissue volume. In particular, the concentration of triglycerides in serum was also decreased. Taken together, our findings showed that MCS inhibited lipid accumulation by regulating insulin signaling in 3T3-L1, and it was effective at reducing body weight and adipose tissue volume in ob/ob mice. These suggest that MCS may be a useful treatment approach for obesity.

Bioactive Porous Particles as Biological and Physical Stimuli for Bone Regeneration.

Even though bony defects can be recovered to their original condition with full functionality, critical-sized bone injuries continue to be a challenge in clinical fields due to deficiencies in the scaffolding matrix and growth factors at the injury region. In this study, we prepared bone morphogenetic protein-2 (BMP-2)-loaded porous particles as a bioactive bone graft for accelerated bone regeneration. The porous particles with unique leaf-stacked morphology (LSS particles) were fabricated by a simple cooling procedure of hot polycaprolactone (PCL) solution. The unique leaf-stacked structure in the LSS particles provided a large surface area and complex release path for the sufficient immobilization of BMP-2 and sustained release of BMP-2 for 26 days. The LSS was also recognized as a topographical cue for cell adhesion and differentiation. In in vitro cell culture and in vivo animal study using a canine mandible defect model, BMP-2-immobilized LSS particles provided a favorable environment for osteogenic differentiation of stem cells and bone regeneration. In vitro study suggests a dual stimulus of bone mineral-like (leaf-stacked) structure (a physical cue) and continuously supplied BMP-2 (a biological cue) to be the cause of this improved healing outcome. Thus, LSS particles containing BMP-2 can be a promising bioactive grafting material for effective new bone formation.

Distribution of Mn Oxidation States in Grassland Soils and Their Relationships with Soil Pores.

Manganese (Mn) is known to be an active contributor to processing and cycling of soil organic carbon (C), yet the exact mechanisms behind its interactions with C are poorly understood. Plant diversity in terrestrial ecosystems drives feedback links between plant C inputs and soil pores, where the latter, in turn, impact the redox environment and Mn. This study examined associations between soil pores (>36 µm Ø) and Mn within intact soils from two grassland ecosystems, after their >6-year implementation in a replicated field experiment. We used µ-XRF imaging and XANES spectroscopy to explore spatial distribution patterns of Mn oxidation states, combined with X-ray computed microtomography and 2D zymography. A high plant diversity system (restored prairie) increased soil C and modified spatial distribution patterns of soil pores as compared to a single species system (monoculture switchgrass). In switchgrass, the abundance of oxidized and reduced Mn oxidation states varied with distance from pores consistently with anticipated O2 diffusion, while in the soil from restored prairie, the spatial patterns suggested that biological activity played a greater role in influencing Mn distributions. Based on the findings, we propose a hypothesis that Mn transformations promote C gains in soils of high plant diversity grasslands.

Introduction of Nanomaterials to Biosensors for Exosome Detection: Case Study for Cancer Analysis.

Exosomes have been gaining attention for early cancer diagnosis owing to their biological functions in cells. Several studies have reported the relevance of exosomes in various diseases, including pancreatic cancer, retroperitoneal fibrosis, obesity, neurodegenerative diseases, and atherosclerosis. Particularly, exosomes are regarded as biomarkers for cancer diagnosis and can be detected in biofluids, such as saliva, urine, peritoneal fluid, and blood. Thus, exosomes are advantageous for cancer liquid biopsies as they overcome the current limitations of cancer tissue biopsies. Several studies have reported methods for exosome isolation, and analysis for cancer diagnosis. However, further clinical trials are still required to determine accurate exosome concentration quantification methods. Recently, various biosensors have been developed to detect exosomal biomarkers, including tumor-derived exosomes, nucleic acids, and proteins. Among these, the exact quantification of tumor-derived exosomes is a serious obstacle to the clinical use of liquid biopsies. Precise detection of exosome concentration is difficult because it requires clinical sample pretreatment. To solve this problem, the use of the nanobiohybrid material-based biosensor provides improved sensitivity and selectivity. The present review will discuss recent progress in exosome biosensors consisting of nanomaterials and biomaterial hybrids for electrochemical, electrical, and optical-based biosensors.

Recent Advances in DNA Nanotechnology for Plasmonic Biosensor Construction.

Since 2010, DNA nanotechnology has advanced rapidly, helping overcome limitations in the use of DNA solely as genetic material. DNA nanotechnology has thus helped develop a new method for the construction of biosensors. Among bioprobe materials for biosensors, nucleic acids have shown several advantages. First, it has a complementary sequence for hybridizing the target gene. Second, DNA has various functionalities, such as DNAzymes, DNA junctions or aptamers, because of its unique folded structures with specific sequences. Third, functional groups, such as thiols, amines, or other fluorophores, can easily be introduced into DNA at the 5' or 3' end. Finally, DNA can easily be tailored by making junctions or origami structures; these unique structures extend the DNA arm and create a multi-functional bioprobe. Meanwhile, nanomaterials have also been used to advance plasmonic biosensor technologies. Nanomaterials provide various biosensing platforms with high sensitivity and selectivity. Several plasmonic biosensor types have been fabricated, such as surface plasmons, and Raman-based or metal-enhanced biosensors. Introducing DNA nanotechnology to plasmonic biosensors has brought in sight new horizons in the fields of biosensors and nanobiotechnology. This review discusses the recent progress of DNA nanotechnology-based plasmonic biosensors.