Activin A, a Novel Chemokine, Induces Mouse NK Cell Migration via AKT and Calcium Signaling.

Natural killer (NK) cells can migrate quickly to the tumor site to exert cytotoxic effects on tumors, and some chemokines, including CXCL8, CXCL10 or and CXCL12, can regulate the migration of NK cells. Activin A, a member of the transforming growth factor ß (TGF-ß) superfamily, is highly expressed in tumor tissues and involved in tumor development and immune cell activation. In this study, we focus on the effects of activin A on NK cell migration. In vitro, activin A induced NK cell migration and invasion, promoted cell polarization and inhibited cell adhesion. Moreover, activin A increased Ca2+, p-SMAD3 and p-AKT levels in NK cells. An AKT inhibitor and Ca2+ chelator partially blocked activin A-induced NK cell migration. In vivo, exogenous activin A increased tumor-infiltrating NK cells in NS-1 cell solid tumors and inhibited tumor growth, and blocking endogenous activin A with anti-activin A antibody reduced tumor-infiltrating NK cells in 4T-1 cell solid tumors. These results suggest that activin A induces NK cell migration through AKT signaling and calcium signaling and may enhance the antitumor effect of NK cells by increasing tumor-infiltrating NK cells.

Tensile Strain-Mediated Bimetallene Nanozyme for Enhanced Photothermal Tumor Catalytic Therapy.

Nanozymes have demonstrated significant potential in combating malignant tumor proliferation through catalytic therapy. However, the therapeutic effect is often limited by insufficient catalytic performance. In this study, we propose the utilization of strain engineering in metallenes to fully expose the active regions due to their ultrathin nature. Here, we present the first report on a novel tensile strain-mediated local amorphous RhRu (la-RhRu) bimetallene with exceptional intrinsic photothermal effect and photo-enhanced multiple enzyme-like activities. Through geometric phase analysis, electron diffraction profile, and X-ray diffraction, it is revealed that crystalline-amorphous heterophase boundaries can generate approximately 2 % tensile strain in the bimetallene. The ultrathin structure and in-plane strain of the bimetallene induce an amplified strain effect. Both experimental and theoretical evidence support the notion that tensile strain promotes multiple enzyme-like activities. Functioning as a tumor microenvironment (TME)-responsive nanozyme, la-RhRu exhibits remarkable therapeutic efficacy both in vitro and in vivo. This work highlights the tremendous potential of atomic-scale tensile strain engineering strategy in enhancing tumor catalytic therapy.

Endoscopic endonasal transsphenoidal surgery for unusual sellar lesions: eight cases and review of the literature.

Background: Preoperative imaging for some unusual lesions in the sellar region can pose challenges in establishing a definitive diagnosis, impacting treatment strategies. Methods: This study is a retrospective analysis of eight cases involving unusual sellar region lesions, all treated with endoscopic endonasal transsphenoidal surgery (EETS). We present the clinical, endocrine, and radiological characteristics, along with the outcomes of these cases. Results: Among the eight cases, the lesions were identified as follows: Solitary fibrous tumor (SFT) in one case, Lymphocytic hypophysitis (LYH) in one case, Cavernous sinus hemangiomas (CSH) in one case, Ossifying fibroma (OF) in two cases; Sphenoid sinus mucocele (SSM) in one case, Pituitary abscess (PA) in two cases. All patients underwent successful EETS, and their diagnoses were confirmed through pathological examination. Postoperatively, all patients had uneventful recoveries without occurrences of diabetes insipidus or visual impairment. Conclusion: Our study retrospectively analyzed eight unusual lesions of the sellar region. Some lesions exhibit specific imaging characteristics and clinical details that can aid in preoperative diagnosis and inform treatment strategies for these unusual sellar diseases.

An extracellular matrix-mimicking magnetic microrobot for targeted elimination of circulating cancer cells.

Cancer cells disseminate through the bloodstream, leading to metastasis in distant sites within the body. One promising strategy to prevent metastasis is to eliminate circulating tumor cells. However, this remains challenging due to the lack of an active and targeted biomedical tool for efficient cancer cell elimination. Here, we developed a magnetic microrobot by using natural materials derived from the extracellular matrix (ECM) to mimic the ligand-receptor interaction between cancer cells and the ECM, offering targeted elimination of cancer cells. The ECM-mimicking microrobot is designed with a biodegradable hydrogel matrix, incorporating a cancer cell ligand and magnetic microparticles for cancer cell capture and active locomotion. This microrobot was fabricated based on an interface-shearing method, enabling controllable magnetic response and size scalability (30 µm-500 µm). The presented ECM-mimicking microrobot can actively approach and capture single cancer cells and cell clusters under the control of specific magnetic fields. The experiment was conducted in a blood vessel-mimicking simulator. The microrobot demonstrates an outstanding elimination efficacy of 92.3% on MDA-MB-231 cancer cells and a stable transport capability of the captured cells over long distances to a designed recycling site, inhibiting cell metastasis. This magnetic ECM-mimicking microrobot based on a bioinspired binding mechanism represents a promising candidate for the efficient elimination of cancer cells and other biological waste in the blood.

Paclitaxel Aggravating Radiation-Induced Pulmonary Fibrosis Is Associated with the Down-Regulation of the Negative Regulatory Function of Spry2.

Paclitaxel (PTX) is capable of aggravating radiation-induced pulmonary fibrosis (RIPF), but the mechanism is unknown. Spry2 is a negative regulator of receptor tyrosine kinase-related Ras/Raf/extracellular signal regulated kinase (ERK) pathway. This experiment was aimed at exploring whether the aggravation of RIPF by PTX is related to Spry2. The RIPF model was established with C57BL/6 mice by thoracic irradiation, and PTX was administered concurrently. Western blot was used to detect the expression level of ERK signaling molecules and the distribution of Spry2 in the plasma membrane/cytoplasm. Co-immunoprecipitation (co-IP) and immunofluorescence were used to observe the colocalization of Spry2 with the plasma membrane and tubulin. The results showed that PTX-concurrent radiotherapy could aggravate fibrotic lesions in RIPF, downregulate the content of membrane Spry2, and upregulate the levels of p-c-Raf and p-ERK in lung tissue. It was found that knockdown of Spry2 in fibroblast abolished the upregulation of p-c-Raf and p-ERK by PTX. Both co-IP results and immunofluorescence staining showed that PTX increased the binding of Spry2 to tubulin, and microtubule depolymerizing agents could abolish PTX's inhibition of Spry2 membrane distribution and inhibit PTX's upregulation of Raf/ERK signaling. Both nintedanib and ERK inhibitor were effective in relieving PTX-exacerbated RIPF. Taken together, the mechanism of PTX's aggravating RIPF was related to its ability to enhance Spry2's binding to tubulin, thus attenuating Spry2's negative regulation on Raf/ERK pathway. SIGNIFICANCE STATEMENT: This study revealed that paclitaxel (PTX) concurrent radiation therapy exacerbates radiation-induced pulmonary fibrosis during the treatment of thoracic tumors, which is associated with PTX restraining Spry2 and upregulating the Raf/extracellular signal regulated kinase signaling pathway, and provided drug targets for mitigating this complication.

Glycyrrhetinic Acid Mitigates Radiation-Induced Pulmonary Fibrosis via Inhibiting the Secretion of TGF-ß1 by Treg Cells.

PURPOSE: Radiation-induced pulmonary fibrosis (RIPF) is a common side effect of radiation therapy for thoracic tumors without effective prevention and treatment methods at present. The aim of this study was to explore whether glycyrrhetinic acid (GA) has a protective effect on RIPF and the underlying mechanism. METHODS AND MATERIALS: A RIPF mouse model administered GA was used to determine the effect of GA on RIPF. The cocultivation of regulatory T (Treg) cells with mouse lung epithelial-12 cells or mouse embryonic fibroblasts and intervention with GA or transforming growth factor-ß1 (TGF-ß1) inhibitor to block TGF-ß1 was conducted to study the mechanism by which GA alleviates RIPF. Furthermore, injection of Treg cells into GA-treated RIPF mice to upregulate TGF-ß1 levels was performed to verify the roles of TGF-ß1 and Treg cells. RESULTS: GA intervention improved the damage to lung tissue structure and collagen deposition and inhibited Treg cell infiltration, TGF-ß1 levels, epithelial mesenchymal transition (EMT), and myofibroblast (MFB) transformation in mice after irradiation. Treg cell-induced EMT and MFB transformation in vitro were prevented by GA, as well as a TGF-ß1 inhibitor, by decreasing TGF-ß1. Furthermore, reinfusion of Treg cells upregulated TGF-ß1 levels and exacerbated RIPF in GA-treated RIPF mice. CONCLUSIONS: GA can improve RIPF in mice, and the corresponding mechanisms may be related to the inhibition of TGF-ß1 secreted by Treg cells to induce EMT and MFB transformation. Therefore, GA may be a promising therapeutic candidate for the clinical treatment of RIPF.

Solitary fibrous tumor in the saddle area treated with neuroendoscopic surgery and proton therapy: A case report and literature review.

Solitary fibrous tumor (SFT) of the central nervous system is a rare fibroblastic tumor of mesenchymal origin. SFTs in the saddle area are much less common. In January 2022, a 43-year-old female patient was admitted with SFT 3 months following partial resection of a microscopic transsphenoidal saddle area tumor at a different hospital. Magnetic resonance imaging indicated that the unresected part of the tumor was significantly enhanced on T1 enhancement, which strongly indicated a recurrence. Subsequently, the patient underwent transnasal endoscopic saddle area tumor resection at our hospital and the tumor was successfully removed. By using postoperative pathology examination, immunohistochemical analysis of Bcl-2, cluster of differentiation 99, STAT6 and vimentin, and a fusion gene test performed by high-throughput sequencing technology, the SFT was definitively diagnosed. Following 3 months of follow-up, the patient was found to have tumor recurrence in the cavernous sinus and absence of tumor growth in the pituitary fossa. Therefore, the patient received proton therapy and tumor growth was controlled effectively.

Follistatin is a crucial chemoattractant for mouse decidualized endometrial stromal cell migration by JNK signalling.

Follistatin (FST) and activin A as gonadal proteins exhibit opposite effects on follicle-stimulating hormone (FSH) release from pituitary gland, and activin A-FST system is involved in regulation of decidualization in reproductive biology. However, the roles of FST and activin A in migration of decidualized endometrial stromal cells are not well characterized. In this study, transwell chambers and microfluidic devices were used to assess the effects of FST and activin A on migration of decidualized mouse endometrial stromal cells (d-MESCs). We found that compared with activin A, FST exerted more significant effects on adhesion, wound healing and migration of d-MESCs. Similar results were also seen in the primary cultured decidual stromal cells (DSCs) from uterus of pregnant mouse. Simultaneously, the results revealed that FST increased calcium influx and upregulated the expression levels of the migration-related proteins MMP9 and Ezrin in d-MESCs. In addition, FST increased the level of phosphorylation of JNK in d-MESCs, and JNK inhibitor AS601245 significantly attenuated FST action on inducing migration of d-MESCs. These data suggest that FST, not activin A in activin A-FST system, is a crucial chemoattractant for migration of d-MESCs by JNK signalling to facilitate the successful uterine decidualization and tissue remodelling during pregnancy.

Activin A is a novel chemoattractant for migration of microglial BV2 cells.

BACKGROUND: Microglia are involved in many neurodegenerative diseases and repairment of traumatic injury to the CNS. Activin A is a neurotrophic and neuroprotective factor that can regulate the activities of macrophages/microglia. However, the effects of activin A on the migration of microglia are still unclear. In this study, the role of activin A in regulation of the microglia migration was investigated with the murine microglial BV2 cell. METHODS: The levels of cytokines were detected by enzyme-linked immunosorbent assay (ELISA). The protein expression was examined by Western blotting. The adhesion of BV2 cells was assayed by real-time cell analysis (RTCA). The migration of BV2 cells was determined by transwell chamber and microfluidics device. Smad3 was overexpressed or knocked down in BV2 cells by transfection of Smad3 or Smad3 shRNA-expressing plasmids. RESULTS: Activin A inhibited the release of nitric oxide (NO) and inflammatory cytokines of TNF-α and IL-6 and the expression of TNF-α and IL-6 mRNA by BV2 cells. In contrast, activin A promoted the production of TGF-ß1. Activin A inhibited adhesion, promoted wound healing and migration which is related to the expression of N-cadherin and E-cadherin expression. Additionally, Smad3 overexpression in BV2 cells decreased the levels of TNF-α and IL-6, and promoted the wound healing, whereas Smad3 knockdown showed the opposite effects. CONCLUSIONS: These findings revealed that activin A regulated the biological behavior of BV2 cells via Smad3 signaling, suggesting that activin A may serve as a potential treatment target for neuroinflammation and glia scar formation in nervous system.

Regulation of Drought and Salt Tolerance by OsSKL2 and OsASR1 in Rice.

Abiotic stresses such as salinity and drought greatly impact the growth and production of crops worldwide. Here, a shikimate kinase-like 2 (SKL2) gene was cloned from rice and characterized for its regulatory function in salinity and drought tolerance. OsSKL2 was localized in the chloroplast, and its transcripts were significantly induced by drought and salinity stress as well as H2O2 and abscisic acid (ABA) treatment. Meanwhile, overexpression of OsSKL2 in rice increased tolerance to salinity, drought and oxidative stress by increasing antioxidant enzyme activity, and reducing levels of H2O2, malondialdehyde, and relative electrolyte leakage. In contrast, RNAi-induced suppression of OsSKL2 increased sensitivity to stress treatment. Interestingly, overexpression of OsSKL2 also increased sensitivity to exogenous ABA, with an increase in reactive oxygen species (ROS) accumulation. Moreover, OsSKL2 was found to physically interact with OsASR1, a well-known chaperone-like protein, which also exhibited positive roles in salt and drought tolerance. A reduction in ROS production was also observed in leaves of Nicotiana benthamiana showing transient co-expression of OsSKL2 with OsASR1. Taken together, these findings suggest that OsSKL2 together with OsASR1 act as important regulatory factors that confer salt and drought tolerance in rice via ROS scavenging.

Recent advances in microfluidics-based cell migration research.

Cell migration is crucial for many biological processes, including normal development, immune response, and tissue homeostasis and many pathological processes such as cancer metastasis and wound healing. Microfluidics has revolutionized the research in cell migration since its inception as it reduces the cost of studies and allows precise manipulation of different parameters that affect cell migratory response. Over the past decade, the field has made great strides in many directions, such as techniques for better control of the cellular microenvironment, application-oriented physiological-like models, and machine-assisted cell image analysis methods. Here we review recent developments in the field of microfluidic cell migration through the following aspects: 1) the co-culture models for studying host-pathogen interactions at single-cell resolution; 2) the spatiotemporal manipulation of the chemical gradients guiding cell migration; 3) the organ-on-chip models to study cell transmigration; and 4) the deep learning image processing strategies for cell migration data analysis. We further discuss the challenges, possible improvement and future perspectives of using microfluidic techniques to study cell migration.

Establishing pteridine metabolism in a progressive isogenic breast cancer cell model - part II.

INTRODUCTION: Determining the biological significance of pteridines in cancer development and progression remains an important step in understanding the altered levels of urinary pteridines seen in certain cancers. Our companion study revealed that several folate-derived pteridines and lumazines correlated with tumorigenicity in an isogenic, progressive breast cancer cell model, providing direct evidence for the tumorigenic origin of pteridines. OBJECTIVES: This study sought to elucidate the pteridine biosynthetic pathway in a progressive breast cancer model via direct pteridine dosing to determine how pteridine metabolism changes with tumorigenicity. METHODS: First, MCF10AT breast cancer cells were dosed individually with 15 pteridines to determine which pteridines were being metabolized and what metabolic products were being produced. Second, pteridines that were significantly metabolized were dosed individually across the progressive breast cancer cell model (MCF10A, MCF10AT, and MCF10ACA1a) to determine the relationship between each metabolic reaction and breast cancer tumorigenicity. RESULTS: Several pteridines were found to have altered metabolism in breast cancer cell lines, including pterin, isoxanthopterin, xanthopterin, sepiapterin, 6-biopterin, lumazine, and 7-hydroxylumazine (p < 0.05). In particular, isoxanthopterin and 6-biopterin concentrations were differentially expressed (p < 0.05) with respect to tumorigenicity following dosing with pterin and sepiapterin, respectively. Finally, the pteridine biosynthetic pathway in breast cancer cells was proposed based on these findings. CONCLUSIONS: This study, along with its companion study, demonstrates that pteridine metabolism becomes disrupted in breast cancer tumor cells. This work highlights several key metabolic reactions within the pteridine biosynthetic pathway that may be targeted for further investigation and clinical applications.

Boron rich nanotube drug carrier system is suited for boron neutron capture therapy.

Boron neutron capture therapy (BNCT) is a two-step therapeutic process that utilizes Boron-10 in combination with low energy neutrons to effectively eliminate targeted cells. This therapy is primarily used for difficult to treat head and neck carcinomas; recent advances have expanded this method to cover a broader range of carcinomas. However, it still remains an unconventional therapy where one of the barriers for widespread adoption is the adequate delivery of Boron-10 to target cells. In an effort to address this issue, we examined a unique nanoparticle drug delivery system based on a highly stable and modular proteinaceous nanotube. Initially, we confirmed and structurally analyzed ortho-carborane binding into the cavities of the nanotube. The high ratio of Boron to proteinaceous mass and excellent thermal stability suggest the nanotube system as a suitable candidate for drug delivery into cancer cells. The full physicochemical characterization of the nanotube then allowed for further mechanistic molecular dynamic studies of the ortho-carborane uptake and calculations of corresponding energy profiles. Visualization of the binding event highlighted the protein dynamics and the importance of the interhelical channel formation to allow movement of the boron cluster into the nanotube. Additionally, cell assays showed that the nanotube can penetrate outer membranes of cancer cells followed by localization around the cells' nuclei. This work uses an integrative approach combining experimental data from structural, molecular dynamics simulations and biological experiments to thoroughly present an alternative drug delivery device for BNCT which offers additional benefits over current delivery methods.

Development of a HPLC-MS/MS method for assessment of thiol redox status in human tear fluids.

Oxidative stress is reported to be part of the pathology of many ocular diseases. For the diagnosis of ocular diseases, tear fluid has unique advantages. Although numerous analytical methods exist for the measurement of different types of biomolecules in tear fluid, few have been reported for comprehensive understanding of oxidative stress-related thiol redox signaling. In this study, a high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method was developed to determine a panel of twelve metabolites that systematically covered several thiol metabolic pathways. With optimization of MS/MS parameters and HPLC mobile phases, this method was sensitive (LOQ as low as 0.01 ng/ml), accurate (80-125% spike recovery) and precise (<10% RSD). This LC-MS/MS method combined with a simple tear fluid collection with Schirmer test strip followed by ultrafiltration allowed the high-throughput analysis for efficient determination of metabolites associated with thiol redox signaling in human tear fluids. The method was then applied to a small cohort of tear fluids obtained from healthy individuals. The method presented here provides a new technique to facilitate future work aiming to determine the complex thiol redox signaling in tear fluids for accurate assessment and diagnosis of ocular diseases.

A Novel Glucose Metabolism-Related Gene Signature for Overall Survival Prediction in Patients with Glioblastoma.

INTRODUCTION: Glioblastoma (GBM) is one of the most frequent primary intracranial malignancies, with limited treatment options and poor overall survival rates. Alternated glucose metabolism is a key metabolic feature of tumour cells, including GBM cells. However, due to high cellular heterogeneity, accurately predicting the prognosis of GBM patients using a single biomarker is difficult. Therefore, identifying a novel glucose metabolism-related biomarker signature is important and may contribute to accurate prognosis prediction for GBM patients. METHODS: In this research, we performed gene set enrichment analysis and profiled four glucose metabolism-related gene sets containing 327 genes related to biological processes. Univariate and multivariate Cox regression analyses were specifically completed to identify genes to build a specific risk signature, and we identified ten mRNAs (B4GALT7, CHST12, G6PC2, GALE, IL13RA1, LDHB, SPAG4, STC1, TGFBI, and TPBG) within the Cox proportional hazards regression model for GBM. RESULTS: Depending on this glucose metabolism-related gene signature, we divided patients into high-risk (with poor outcomes) and low-risk (with satisfactory outcomes) subgroups. The results of the multivariate Cox regression analysis demonstrated that the prognostic potential of this ten-gene signature is independent of clinical variables. Furthermore, we used two other GBM databases (Chinese Glioma Genome Atlas (CGGA) and REMBRANDT) to validate this model. In the functional analysis results, the risk signature was associated with almost every step of cancer progression, such as adhesion, proliferation, angiogenesis, drug resistance, and even an immune-suppressed microenvironment. Moreover, we found that IL31RA expression was significantly different between the high-risk and low-risk subgroups. CONCLUSION: The 10 glucose metabolism-related gene risk signatures could serve as an independent prognostic factor for GBM patients and might be valuable for the clinical management of GBM patients. The differential gene IL31RA may be a potential treatment target in GBM.

The 3-O-sulfation of heparan sulfate modulates protein binding and lyase degradation.

Humans express seven heparan sulfate (HS) 3-O-sulfotransferases that differ in substrate specificity and tissue expression. Although genetic studies have indicated that 3-O-sulfated HS modulates many biological processes, ligand requirements for proteins engaging with HS modified by 3-O-sulfate (3-OS) have been difficult to determine. In particular, the context in which the 3-OS group needs to be presented for binding is largely unknown. We describe herein a modular synthetic approach that can provide structurally diverse HS oligosaccharides with and without 3-OS. The methodology was employed to prepare 27 hexasaccharides that were printed as a glycan microarray to examine ligand requirements of a wide range of HS-binding proteins. The binding selectivity of antithrombin-III (AT-III) compared well with anti-Factor Xa activity supporting robustness of the array technology. Many of the other examined HS-binding proteins required an IdoA2S-GlcNS3S6S sequon for binding but exhibited variable dependence for the 2-OS and 6-OS moieties, and a GlcA or IdoA2S residue neighboring the central GlcNS3S. The HS oligosaccharides were also examined as inhibitors of cell entry by herpes simplex virus type 1, which, surprisingly, showed a lack of dependence of 3-OS, indicating that, instead of glycoprotein D (gD), they competitively bind to gB and gC. The compounds were also used to examine substrate specificities of heparin lyases, which are enzymes used for depolymerization of HS/heparin for sequence determination and production of therapeutic heparins. It was found that cleavage by lyase II is influenced by 3-OS, while digestion by lyase I is only affected by 2-OS. Lyase III exhibited sensitivity to both 3-OS and 2-OS.

Extensive Thiol Profiling for Assessment of Intracellular Redox Status in Cultured Cells by HPLC-MS/MS.

Oxidative stress may contribute to the pathology of many diseases, and endogenous thiols, especially glutathione (GSH) and its metabolites, play essential roles in the maintenance of normal redox status. Understanding how these metabolites change in response to oxidative insult can provide key insights into potential methods of prevention and treatment. Most existing methodologies focus only on the GSH/GSH disulfide (GSSG) redox couple, but GSH regulation is highly complex and depends on several pathways with multiple redox-active sulfur-containing species. In order to more fully characterize thiol redox status in response to oxidative insult, a high-performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS) method was developed to simultaneously determine seven sulfur-containing metabolites, generating a panel that systematically examines several pathways involved in thiol metabolism and oxidative stress responses. The sensitivity (LOQ as low as 0.01 ng/mL), accuracy (88-126% spike recovery), and precision (≤12% RSD) were comparable or superior to those of existing methods. Additionally, the method was used to compare the baseline thiol profiles and oxidative stress responses of cell lines derived from different tissues. The results revealed a previously unreported response to oxidative stress in lens epithelial (B3) cells, which may be exploited as a new therapeutic target for oxidative-stress-related ocular diseases. Further application of this method may uncover new pathways involved in oxidative-stress-related diseases and endogenous defense mechanisms.

A flux-adaptable pump-free microfluidics-based self-contained platform for multiplex cancer biomarker detection.

Microfluidics drives technological advancement in point-of-care (POC) bioanalytical diagnostics towards portability, fast response and low cost. In most microfluidic bioanalytical applications, flowing antigen/antibody reacts with immobilized antibody/antigen at a constant flux; it is difficult to reach a compromise to simultaneously realize sufficient time for the antigen-antibody interaction and short time for the entire assay. Here, we present a pump-free microfluidic chip, in which flow is self-initialized by capillary pumping and continued by imbibition of a filter paper. Microfluidic units in teardrop shape ensure that flow passes through the reaction areas at a reduced flux to facilitate the association between antigen and antibody and speeds up after the reaction areas. By spotting different antibodies into the reaction area, four types of biomarkers can be measured simultaneously in one microfluidic chip. Moreover, a small-sized instrument was developed for chemiluminescence detection and signal analysis. The system was validated by testing four biomarkers of colorectal cancer using plasma samples from patients. The assay took about 20 minutes. The limit of detection is 0.89 ng mL-1, 1.72 ng mL-1, 3.62 U mL-1 and 1.05 U mL-1 for the assays of carcinoembryonic antigen, alpha-fetoprotein, carbohydrate antigen 125 and carbohydrate antigen 19-9, respectively. This flux-adaptable and self-contained microfluidic platform is expected to be useful in various POC disease-monitoring applications.

Ultrasensitive and Selective Determination of Carcinoembryonic Antigen Using Multifunctional Ultrathin Amino-Functionalized Ti3C2-MXene Nanosheets.

Herein, we report on a two-dimensional amino-functionalized Ti3C2-MXene (N-Ti3C2-MXene)-based surface plasmon resonance (SPR) biosensor for detecting carcinoembryonic antigen (CEA) utilizing a sandwich format signal amplification strategy. Our biosensor employs an N-Ti3C2-MXene nanosheet-modified sensing platform and a signal enhancer comprising N-Ti3C2-MXene-hollow gold nanoparticles (HGNPs)-staphylococcal protein A (SPA) complexes. Ultrathin Ti3C2-MXene nanosheets were synthesized and functionalized with aminosilane to provide a hydrophilic-biocompatible nanoplatform for covalent immobilization of the monoclonal anti-CEA capture antibody (Ab1). The N-Ti3C2-MXene/HGNPs nanohybrids were synthesized and further decorated with SPA to immobilize the polyclonal anti-CEA detection antibody (Ab2) and serve as signal enhancers. The capture of CEA followed by the formation of the Ab2-conjugated SPA/HGNPs/N-Ti3C2-MXene sandwiched nanocomplex on the SPR chip results in the generation of a response signal. The fabricated N-Ti3C2-MXene-based SPR biosensor exhibited a linear detection range of 0.001-1000 PM with a detection limit of 0.15 fM. The proposed biosensor showed high sensitivity and specificity for CEA in serum samples, which gives it application potential in the early diagnosis and monitoring of cancer. We believe that this work also opens new avenues for development of MXene-based highly sensitive biosensors for determining various biomolecules.

A 2D transition metal carbide MXene-based SPR biosensor for ultrasensitive carcinoembryonic antigen detection.

Surface plasmon resonance (SPR) has become a leading technique for in situ bioaffinity assay of diverse targets without need of fluorescent or enzymatic labeling. Nanomaterials-enhanced SPR sensors have developed rapidly and widened the application scope of SPR sensing technology. In this report we describe an ultrasensitive SPR biosensor for detecting carcinoembryonic antigen (CEA). Our SPR biosensor utilizes a Ti3C2-MXene-based sensing platform and multi-walled carbon nanotube (MWCNTs)-polydopamine (PDA)-Ag nanoparticle (AgNPs) signal enhancer. Ti3C2-MXene, a new class of two-dimensional (2D) transition metal carbides, offers a large hydrophilic-biocompatible surface ideal for SPR biosensing. Ti3C2-MXene/AuNPs composites after synthesis are then decorated with staphylococcal protein A (SPA) to orient and immobilize monoclonal anti-CEA antibody (Ab1) through its Fc region. By introducing MWCNTs-PDA-AgNPs-polyclonal anti-CEA antibody (MWPAg-Ab2) conjugate combined with a sandwich format, the present method provides a dynamic range for CEA determination of 2×10-16 to 2×10-8 M and a detection limit of 0.07 fM. This biosensing approach demonstrates good reproducibility and high specificity for CEA in real serum samples providing a promising method to evaluate CEA in human serum for early diagnosis and monitoring of cancer.