Thiophenpiperazine amide derivatives as new dual MOR and σ1R ligands for the treatment of pain.

A new series of thiophenpiperazine amide derivatives as potent dual ligands for the µ-opioid (MOR) and sigma-1 (σ1R) receptors are reported. Compound 23 exhibited good affinity to σ1R (Ki = 44.7 ± 7.05 nM) and high selectivity to σ2R. Furthermore, Compound 23 exerted MOR agonism and σ1R antagonism and potent analgesic activity in animal moldes (the abdominal constriction test (ED50 = 3.83 mg/kg) and carrageenan-induced inflammatory hyperalgesia model (ED50 = 5.23 mg/kg)). We obtained new dual ligands that might serve as starting points for preparing targeted tools. Furthermore, 23 may be a useful chemical probe for understanding more fully analgesic effects associated with MOR agonism and σ1R antagonism.

Morphological characteristics of femoral neck fractures in young and middle-aged population: a retrospective descriptive study.

BACKGROUND: A understanding of morphological characteristics are important to femoral neck fractures (FNFs) resulting in high rates of complications in the young and middle-aged adults and the detailed data is lack in the literature. We aimed to report on the detailed morphological characteristics and the relationship between them in young and middle-aged adults with femoral neck fractures (FNFs). METHODS: The postoperative CT images of one hundred and fifty-two adults with FNFs were retrospectively reviewed. After image standardization, morphological characteristics including fracture orientation, cortex comminution, and intraosseous bone defects were measured and analyzed. Additionally, the distribution and correlation of these morphological features were analyzed using Pauwels classification, the right angle of the neck axis (VNA) classification, and the anteromedial oblique angle (AMA). RESULTS: Pauwels III fractures accounted for approximately half (55.2%) of the FNFs analyzed. Pauwels II and III could be detected in all four VNA types, and the distribution of the Pauwels types in VNA classification showed significant differences (χ2 = 106.363, p < 0.001). The VNA (9.0° ± 12.1) showed positive correlation with the neck-shaft angle (139.5° ± 6.3) and modified Pauwels angle (49.8° ± 10.6) (r = 0.441, r = 0.855, all p < 0.001). Cortical comminutions were commonly observed in the posterior (86.7%) and the inferior (80.7%). AMAs within the cases without posterior and inferior cortex comminutions were significantly larger than those with comminution (t = 2.594, 2.1196; p = 0.01, 0.036), but no difference could be detected after the AMA being divided into three groups (< 85°, 85°-95°, > 95°). The MPA, VNA and AMA of the group with an intraosseous defect were significantly different compared with those without (t = 2.847, 2.314, 2.268; p = 0.005, 0.022,0.025). The incidence of intraosseous defects within the groups with coronal and axial cortex comminutions were significantly higher than those within the groups without comminutions (χ2 = 34.87, 25.303; p < 0.001). CONCLUSIONS: The present study highlights the morphological diversity and complexity within FNFs in young and middle-aged adults, which allows for more accurate simulation of FNF patterns in the future biomechanical studies.

Mechanical Bistability in Kerr-modified Cavity Magnomechanics.

Bistable mechanical vibration is observed in a cavity magnomechanical system, which consists of a microwave cavity mode, a magnon mode, and a mechanical vibration mode of a ferrimagnetic yttrium-iron-garnet sphere. The bistability manifests itself in both the mechanical frequency and linewidth under a strong microwave drive field, which simultaneously activates three different kinds of nonlinearities, namely, magnetostriction, magnon self-Kerr, and magnon-phonon cross-Kerr nonlinearities. The magnon-phonon cross-Kerr nonlinearity is first predicted and measured in magnomechanics. The system enters a regime where Kerr-type nonlinearities strongly modify the conventional cavity magnomechanics that possesses only a radiation-pressure-like magnomechanical coupling. Three different kinds of nonlinearities are identified and distinguished in the experiment. Our Letter demonstrates a new mechanism for achieving mechanical bistability by combining magnetostriction and Kerr-type nonlinearities, and indicates that such Kerr-modified cavity magnomechanics provides a unique platform for studying many distinct nonlinearities in a single experiment.

ATP5B promotes the metastasis and growth of gastric cancer by activating the FAK/AKT/MMP2 pathway.

Adenosine triphosphate (ATP) in the tumor microenvironment serves a vital role during tumor progression. ATP synthase F1 ß subunit (ATP5B) is one of the most important subunits of ATP synthase and increases cellular ATP levels. ATP5B reportedly participates in carcinogenesis in several tumors. However, the regulatory mechanisms of ATP5B remain poorly understood in gastric cancer (GC). Here, we determined that high ATP5B expression in tumor tissues of GC is positively correlated with age, the tumor size, the TNM stage, lymph node metastasis, and patients' poor prognosis. The overexpression of ATP5B in GC cells elevated the cellular ATP content and promoted migration, invasion and proliferation. The levels of MMP2 expression, phosphorylated FAK, and phosphorylated AKT were increased after ATP5B overexpression in GC cells. Additionally, ATP5B overexpression increased the extracellular ATP level through the secretion of intracellular ATP and activated the FAK/AKT/MMP2 signaling pathway. ATP5B-induced downstream pathway activation was induced through the plasma membrane P2X7 receptor. Inhibitors of P2X7, FAK, AKT, and MMP2 suppressed the proliferative, migratory, and invasive capabilities of GC cells. In conclusion, our experiments indicate that ATP5B contributes to tumor progression of GC via FAK/AKT/MMP2 pathway. ATP5B, therefore, may be a biomarker of poor prognosis and a potential therapeutic target for GC.

Surveillance of premalignant gastric cardia lesions: A population-based prospective cohort study in China.

In our study, we aimed to assess the long-term risk of gastric cardia adenocarcinoma (GCA) for patients with different histological cardia lesions to inform future guidelines for GCA screening in China. We conducted a population-based prospective study among 9740 subjects who underwent upper endoscopy screening during 2005 to 2009 and followed until December 2017. Cumulative incidence and mortality rates of GCA were calculated by the baseline histological diagnoses, and the hazard ratios (HRs), overall and by age and sex, were analyzed by Cox proportional hazards models. During a median follow-up of 10 years, we identified 123 new GCA cases (1.26%) and 31 GCA deaths (0.32%). The age-standardized incidence and mortality rates of GCA were 128.71/100 000 and 35.69/100 000 person-years, and cumulative incidence rate in patients with cardia high-grade dysplasia (CHGD), cardia low-grade dysplasia (CLGD) and atrophic carditis (AC)/cardia intestinal metaplasia (CIM) was 25%, 3.05% and 1.58%, respectively. The progression rate and cancer risk of GCA increased monotonically with each step in Correa's cascade. Individuals aged 50 to 69 years had 4.4 times higher GCA incidence than those aged 40 to 49 years. Patients with CLGD had a significantly higher 3-year GCA incidence than the normal group, while patients with AC/CIM had a comparable GCA risk during 3-year follow-up but a higher risk at 5-year intervals. Our results suggested a postponed starting age of 50 years for GCA screening, immediate treatment for patients with CHGD, a 3-year surveillance interval for patients with CLGD, and a lengthened surveillance interval of 5 years for patients with AC/CIM.

Multifunctional Dendronized Polypeptides for Controlled Adjuvanticity.

Vaccination has been playing an important role in treating both infectious and cancerous diseases. Nevertheless, many diseases still lack proper vaccines due to the difficulty to generate sufficient amounts of antigen-specific antibodies or T cells. Adjuvants provide an important route to improve and direct immune responses. However, there are few adjuvants approved clinically and many of them lack the clear structure/adjuvanticity relationship. Here, we synthesized and evaluated a series of dendronized polypeptides (denpols) functionalized with varying tryptophan/histidine (W/H) molar ratios of 0/100, 25/75, 50/50, 75/25, and 100/0 as tunable synthetic adjuvants. The denpols showed structure-dependent inflammasome activation in THP1 monocytic cells and structure-related activation and antigen cross-presentation in vitro in bone marrow-derived dendritic cells. We used the denpols with bacterial pathogen Coxiella burnetii antigens in vivo, which showed both high and tunable adjuvating activities, as demonstrated by the antigen-specific antibody and T cell responses. The denpols are easy to make and scalable, biodegradable, and have highly adjustable chemical structures. Taken together, denpols show great potential as a new and versatile adjuvant platform that allows us to adjust adjuvanticity based on structure-activity correlation with the aim to fine-tune the immune response, thus advancing vaccine development.

Identification of biomarkers associated with metabolic cardiovascular disease using mRNA-SNP-miRNA regulatory network analysis.

BACKGROUND: CVD is the leading cause of death in T2DM patients. However, few biomarkers have been identified to detect and diagnose CVD in the early stage of T2DM. The aim of our study was to identify the important mRNAs, micro (mi)RNAs and SNPs (single nucleotide polymorphisms) that are associated with metabolic cardiovascular disease. MATERIALS AND METHODS: Expression profiles and GWAS data were obtained from Gene Expression Omnibus (GEO) database. MiRNA-sequencing was conducted by Illumina HiSeq 2000 platform in T2DM patients and T2DM with CVD patients. EQTL analysis and gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted. MRNA-miRNA co-expression network and mRNA-SNP-miRNA interaction network were established and visualized by Cytoscape 3.7.2. RESULTS: In our study, we identified 56 genes and 16 miRNAs that were significantly differentially expressed. KEGG analyses results indicated that B cell receptor signaling pathway and hematopoietic cell lineage were included in the biological functions of differentially expressed genes. MRNA-miRNA co-expression network and mRNA-SNP-miRNA interaction network illustrated that let-7i-5p, RASGRP3, KRT1 and CEP41 may be potential biomarkers for the early detection and diagnosis of CVD in T2DM patients. CONCLUSION: Our results suggested that downregulated let-7i-5p, and upregulated RASGRP3, KRT1 and CEP41 may play crucial roles in molecular mechanisms underlying the initiation and development of CVD in T2DM patients.

LncRNA TUG1 functions as a ceRNA for miR-6321 to promote endothelial progenitor cell migration and differentiation.

Endothelial progenitor cell (EPC) recruitment and angiogenesis play crucial roles in aneurysm neck endothelialization, but the mechanisms of EPC recruitment and angiogenesis are still unclear. Recent studies have shown that long noncoding RNAs (lncRNAs) can regulate the function and differentiation of cells in various ways. LncRNA TUG1 is involved in liver cancer and glioma-mediated angiogenesis. The aim of this study was to investigate the role of lncRNA TUG1 in regulating EPC migration and differentiation. Overexpression and knockdown of lncRNA TUG1 with lentivirus, scratch assays, Transwell assays and tube formation assays using EPCs isolated from rat bone marrow showed that lncRNA TUG1 overexpression promoted EPC migration, invasion and differentiation. Moreover, ELISAs showed that lncRNA TUG1 overexpression increased VEGF expression. Bioinformatics prediction, luciferase assays, Western blots and RIP assays indicated that lncRNA TUG1 functions as a ceRNA (competing endogenous RNA) for miR-6321 and that miR-6321 inhibits EPC migration and differentiation through its target, ATF2. As a potential therapeutic target, lncRNA TUG1 may play a vital role in the pathogenesis of aneurysms.

Elevated serum eotaxin and IP-10 levels as potential biomarkers for the detection of esophageal squamous cell carcinoma.

BACKGROUND AND AIMS: Esophageal squamous cell cancer (ESCC) is one of the leading malignant cancers with a high incidence and mortality. Exploring novel serum biomarkers will help improve the management and monitoring of ESCC. METHODS: In the present study, we first used a ProcartaPlex Array to screen for serum proteins that were increased in 40 ESCC patients compared with matched normal controls; we found that eight proteins (IL-2, IL-5, IP-10, IL-8, eotaxin, TNF-α, HGF, and MIP-1b) had higher serum levels in ESCC patients than in normal controls. We further verified the clinical relevance of the candidate biomarkers with a larger sample of sera. RESULTS: In the 174 tested ESCC patients and 189 normal controls, the serum levels of eotaxin and IP-10 were significantly higher in patients than in normal controls (p = 0.0038, 0.0031). In particular, these two proteins were also elevated in the sera of patients with early-stage (0-IIA) ESCC (p = 0.0041, 0.0412). When combining CEA and CYFRA21-1 (in use clinically) with eotaxin or IP-10, the effectiveness of detecting ESCC was superior to that of CEA and/or CYFRA21-1 alone. Moreover, the serum level of eotaxin dropped significantly after surgical resection of primary tumors compared with that in preoperative ESCC samples (p < 0.001). CONCLUSIONS: The data suggest that serum eotaxin and IP-10 might be potential biomarkers for the detection of ESCC.

[Research on entity relationship extraction of Chinese medical literature and application in diabetes medical literature].

The medical literature contains a wealth of valuable medical knowledge. At present, the research on extraction of entity relationship in medical literature has made great progress, but with the exponential increase in the number of medical literature, the annotation of medical text has become a big problem. In order to solve the problem of manual annotation time such as consuming and heavy workload, a remote monitoring annotation method is proposed, but this method will introduce a lot of noise. In this paper, a novel neural network structure based on convolutional neural network is proposed, which can solve a large number of noise problems. The model can use the multi-window convolutional neural network to automatically extract sentence features. After the sentence vectors are obtained, the sentences that are effective to the real relationship are selected through the attention mechanism. In particular, an entity type (ET) embedding method is proposed for relationship classification by adding entity type characteristics. The attention mechanism at sentence level is proposed for relation extraction in allusion to the unavoidable labeling errors in training texts. We conducted an experiment using 968 medical references on diabetes, and the results showed that compared with the baseline model, the present model achieved good results in the medical literature, and F1-score reached 93.15%. Finally, the extracted 11 types of relationships were stored as triples, and these triples were used to create a medical map of complex relationships with 33 347 nodes and 43 686 relationship edges. Experimental results show that the algorithm used in this paper is superior to the optimal reference system for relationship extraction.

Metformin inhibits intracranial aneurysm formation and progression by regulating vascular smooth muscle cell phenotype switching via the AMPK/ACC pathway.

BACKGROUND: The regulation of vascular smooth muscle cell (VSMC) phenotype plays an important role in intracranial aneurysm (IA) formation and progression. However, the underlying mechanism remains unclear. Metformin is a 5' AMP-activated protein kinase (AMPK) agonist that has a protective effect on vasculature. The present study investigated whether metformin modulates VSMC phenotype switching via the AMPK/acetyl-CoA carboxylase (ACC) pathway during IA pathogenesis. METHODS: Adult male Sprague-Dawley rats (n = 80) were used to establish an elastase-induced IA model. The effects of metformin on AMPK activation and VSMC phenotype modulation were examined. We also established a platelet-derived growth factor (PDGF)-BB-induced VSMC model and analyzed changes in phenotype including proliferation, migration, and apoptosis as well as AMPK/ACC axis activation under different doses of metformin, AMPK antagonist, ACC antagonist, and their combinations. RESULTS: Metformin decreased the incidence and rupture rate of IA in the rat model and induced a switch in VSMC phenotype from contractile to synthetic through activation of the AMPK/ACC pathway, as evidenced by upregulation of VSMC-specific genes and decreased levels of pro-inflammatory cytokines. AMPK/ACC axis activation inhibited the proliferation, migration, and apoptosis of VSMCs, in which phenotypic switching was induced by PDGF-BB. CONCLUSIONS: Metformin protects against IA formation and rupture by inhibiting VSMC phenotype switching and proliferation, migration, and apoptosis. Thus, metformin has therapeutic potential for the prevention of IA.

Slippery Nanoparticles as a Diffusion Platform for Mucin Producing Gastrointestinal Tumors.

BACKGROUND: Treatment failure in pseudomyxoma peritonei (PMP) is partly attributed to the ineffective delivery of therapeutics through dense mucinous tumor barriers. We modified the surface of Poly (lactic-co-glycolic acid)-b-polyethylene glycol (PLGA-PEG-NPs) with a low-density, second PEG layer (PLGA-TPEG-NPs-20) to reduce their binding affinity to proteins and improve diffusion through mucin. METHODS: Nanoprecipitation was used to fabricate PLGA-PEG-NPs. To construct the second PEG layer of PLGA-TPEG-NPs-20, PEG-Thiol was conjugated to PLGA-PEG-NPs composed of 80% methoxy PLGA-PEG and 20% of PLGA-PEG-Maleimide. DiD-labeled nanoparticles (NPs) were added to the inner well of a trans-well system containing cultured LS174T or human PMP tissue. Diffusion of NPs was measured via fluorescence signal in the bottom well. In an ex vivo rat model, small intestine was treated with DiD-labeled NPs. In an in vivo murine LS174T subcutaneous tumor model, Nu/Nu nude mice received supratumoral injections (subcutaneous injection above the tumor) of DiD-labeled NPs. Thirty minutes after injection, mice were sacrificed, and tumors were collected. All tissue was cryosectioned, mounted with DAPI-containing media, and inspected via confocal microscopy. RESULTS: Diffusion profiles of NPs through PMP and cultured LS174T cells were generated. PLGA-TPEG-NPs-20 diffused faster with ~ 100% penetration versus PLGA-PEG-NPs with ~ 40% penetration after 8 h. Increased diffusion of PLGA-TPEG-NPs-20 was further observed in ex vivo rat small intestine as evidenced by elevated luminal NP fluorescence signal on the luminal surface. Subcutaneous LS174T tumors treated with PLGA-TPEG-NPs-20 demonstrated greater diffusion of NPs, showing homogenous fluorescence signal throughout the tumor. CONCLUSIONS: PLGA-TPEG-NPs-20 can be an effective mucin penetrating drug delivery system.

Cathepsin L promotes angiogenesis by regulating the CDP/Cux/VEGF-D pathway in human gastric cancer.

BACKGROUND: Increasing evidence indicates that angiogenesis plays an important role in tumor progression. The function of cathepsin L (CTSL), an endosomal proteolytic enzyme, in promoting tumor metastasis is well recognized. The mechanisms by which CTSL has promoted the angiogenesis of gastric cancer (GC), however, remains unclear. METHODS: The nuclear expression levels of CTSL were assessed in GC samples. The effects of CTSL on GC angiogenesis were determined by endothelial tube formation analysis, HUVEC migration assay, and chick embryo chorioallantoic membrane (CAM) assay. The involvement of the CDP/Cux/VEGF-D pathway was analyzed by angiogenesis antibody array, Western blot, co-immunoprecipitation (Co-IP) and dual-luciferase reporter assay. RESULTS: In this study, we found that the nuclear CTSL expression level in GC was significantly higher than that in adjacent nontumor gastric tissues and was a potential important clinical prognostic factor. Loss- and gain-of-function assays indicated that CTSL promotes the tubular formation and migration of HUVEC cells in vitro. The CAM assay also showed that CTSL promotes angiogenesis of GC in vivo. Mechanistic analysis demonstrated that CTSL can proteolytically process CDP/Cux and produce the physiologically relevant p110 isoform, which stably binds to VEGF-D and promotes the transcription of VEGF-D, thus contributing to the angiogenesis of GC. CONCLUSION: The findings of the present study suggested that CTSL plays a constructive role in the regulation of angiogenesis in human GC and could be a potential therapeutic target for GC.

Ultrashort all-fiber Fabry-Perot interferometer fabricated by a CO2 laser.

We proposed and demonstrated a method to fabricate ultrashort all-fiber Fabry-Perot interferometers by splicing a standard single-mode fiber and another single-mode fiber with a concave surface constructed by a CO2 laser pulse. The geometric parameters of the concave surface could be controlled flexibly by adjusting the laser pulse and the relative position between the laser beam and the optical fiber. In our experiments, the minimum depth of the concave surfaces is 0.12 µm, which offers a means of fabricating an all-fiber Fabry-Perot interferometer with submicrometer cavity length. Moreover, the ultralow-roughness concave surface fabricated by a CO2 laser pulse is beneficial to improve the fringe visibility of the interferometer. These advantages make it attractive for practical applications.

Smartphone Biosensor System with Multi-Testing Unit Based on Localized Surface Plasmon Resonance Integrated with Microfluidics Chip.

Detecting biomarkers is an efficient method to diagnose and monitor patients' stages. For more accurate diagnoses, continuously detecting and monitoring multiple biomarkers are needed. To achieve point-of-care testing (POCT) of multiple biomarkers, a smartphone biosensor system with the multi-testing-unit (SBSM) based on localized surface plasmon resonance (LSPR) integrated multi-channel microfluidics was presented. The SBSM could simultaneously record nine sensor units to achieve the detection of multiple biomarkers. Additional 72 sensor units were fabricated for further verification. Well-designed modularized attachments consist of a light source, lenses, a grating, a case, and a smartphone shell. The attachments can be well assembled and attached to a smartphone. The sensitivity of the SBSM was 161.0 nm/RIU, and the limit of detection (LoD) reached 4.2 U/mL for CA125 and 0.87 U/mL for CA15-3 through several clinical serum specimens testing on the SBSM. The testing results indicated that the SBSM was a useful tool for detecting multi-biomarkers. Comparing with the enzyme-linked immunosorbent assays (ELISA) results, the results from the SBSM were correlated and reliable. Meanwhile, the SBSM was convenient to operate without much professional skill. Therefore, the SBSM could become useful equipment for point-of-care testing due to its small size, multi-testing unit, usability, and customizable design.

Nrf-2 signaling inhibits intracranial aneurysm formation and progression by modulating vascular smooth muscle cell phenotype and function.

BACKGROUND: Oxidative stress and vascular smooth muscle cell (VSMC) phenotypic modulation influence intracranial aneurysm (IA) formation and progression. Oxidative stress plays an important role in phenotype switching, and nuclear factor erythroid 2-related factor 2 (Nrf-2) is one of the main antioxidant systems. Unfortunately, little is known about how Nrf-2 signaling influences VSMC phenotype switches during IA pathogenesis. METHODS: We examined the effect of Nrf-2 activation IA on formation and progression in an elastase-induced rat IA model. We also developed a hydrogen peroxide (H2O2)-induced VSMC oxidative damage model. Then, we analyzed VSMC phenotype changes in the setting of Nrf-2 activation or inhibition in vitro. The proliferation, migration ability, and apoptosis rate of VSMCs were tested. Lastly, we measured the expression levels of antioxidant enzymes and inflammatory cytokines downstream of Nrf-2. RESULTS: Nrf-2 activation suppressed IA formation and progression in vivo. We confirmed Nrf-2 nuclear translocation and a VSMC switch from the contractile to synthetic phenotype. Nrf-2 activation inhibited the proliferation, migratory ability, and apoptosis rate enhanced by H2O2. Quantitative real-time polymerase chain reaction (PCR) and western blot analysis revealed that Nrf-2 activation promoted antioxidant enzymes and VSMC-specific marker gene expressions but decreased pro-inflammatory cytokine levels. CONCLUSION: These results suggest that Nrf-2 exerts protective effects against IA development by preventing VSMCs from changing to a synthetic phenotype.

Piezoelectric Microchip for Cell Lysis through Cell-Microparticle Collision within a Microdroplet Driven by Surface Acoustic Wave Oscillation.

Cell lysis is an important and crucial step for the detection of intracellular secrets. Usually, cell lysis is based on strong ultrasonic waves or toxic chemical regents, which require a large amount of cell suspension. To obtain high efficiency cell lysis for a small amount of sample, a mechanical cell lysis method based on a surface acoustic wave (SAW) microchip is proposed. The microchip simply consists of a piece of LiNbO3 crystal substrate, interdigitated transducers (IDTs) with 80 pairs of parallel electrodes and 3M Magic Tapes. The modulated input electrical signal is coupled into the substrate through IDTs, which produces an acoustic stream in the droplet on the surface of a substrate. When a biofluid droplet containing cells and microparticles is dropped on the surface of the microchip, the cells and microparticles are accelerated and collide with each other. The fluorescence staining results illustrate that the cell membrane is efficiently destroyed and that proteins as well as nucleic acids inside the cell are released. The experimental results show that this method has a high efficiency and low sample consumption. The potential application is the pretreatment of a small amount of tested sample in a hospital or biolab.

Exploring surface sensitivity of Rayleigh anomaly in metal/dielectric multilayer gratings.

Biosensors based on Rayleigh anomaly (RA) in metal gratings exhibit impressive bulk refractive index (RI) sensitivity and narrow linewidth. However, the electric field enhancement extends far away from surface of the gratings, which limits the application on biosensor where the RI changes are restricted at the sensor interface. To overcome this shortcoming, a novel grating composed of a 8-layer Au/Al2O3 stack was optimized by numerical simulation. The electric field is limited in several hundreds of nanometers from surface. The surface sensitivity increases 10 times than that of Au gratings at the detection depth of less than 400 nm. The surface index sensitivity can be improved 5 times under oblique incidence than that under normal incidence when the thickness of cover media is 20 nm.

Label-Free Exosome Detection Based on a Low-Cost Plasmonic Biosensor Array Integrated with Microfluidics.

Localized surface plasmon resonance-based plasmonic biosensors are interesting candidates for the design of portable optical biosensor platforms owing to their integration, miniaturization, multiparameter, real-time, and label-free detection characteristics. Plasmonic biosensor arrays that have been combined with microfluidics have been developed herein to detect exosomes label-free. Gold nano-ellipsoid arrays were fabricated with low-cost anodic aluminum oxide thin films that act as shadow masks for evaporation of Au. The nano-ellipsoid arrays were integrated with a microfluidic chip to achieve multiparameter detection. The anti-CD63 antibody that is specific to the exosome transmembrane protein CD63 is modified on the surface of the nano-ellipsoids. Exosome samples were injected into the biosensor platform at different concentrations and detected successfully. The detection limit was 1 ng/mL. The proposed plasmonic biosensor array can be universally applicable for the detection of other biomarkers by simply changing the antibody on the surface of the Au nano-ellipsoids. Moreover, this biosensor platform is envisaged to be potentially useful in the development of low-cost plasmonic-based biosensors for biomarker detection and for the investigation of exosomes for noninvasive disease diagnoses.

Cell Membrane Bioconjugation and Membrane-Derived Nanomaterials for Immunotherapy.

Cell membrane engineering, including live cell membrane bioconjugation and cell membrane-derived nanomaterials is a highly promising strategy to modulate immune responses for treating diseases. Many cell membrane engineering methods have potential for translation for human clinical use in the near future. In this Topical Review, we summarize the cell membrane conjugation strategies that have been investigated for cancer immunotherapy, the prevention of immune rejection to donor cells and tissues, and the induction of antigen-specific tolerance in autoimmune diseases. Additionally, cell membrane-derived or membrane-coated nanomaterials are an emerging class of nanomaterials that is attracting significant attention in the field of nanomedicine. Some of these nanomaterials have been employed to elicit immune responses against cancer, toxins, and bacteria, although their application in establishing immune tolerance has not been explored. In addition to discussing potential problems, we provide our perspectives for promising future directions.