Design and development of a soluble PDA-Emodin-PVP-MN patch and its anti-obesity effect in rats.

Emodin has been proven to have weight-reducing and lipid-lowering effects. In order to make emodin play a better anti-obesity role, we designed and developed an emodin loaded dissolving microneedle patch, in which emodin existed in the form of emodin-polyvinylpyrrolidone co-precipitate (Emodin-PVP). Meanwhile, polydopamine (PDA) was added to the microneedle patch (PDA-Emodin-PVP-MN) for photothermal-enhanced chemotherapy of obesity. The average weight of the patch was 0.1 ± 0.05 g and the drug loading was 0.37 ± 0.031 mg. After 5 min of NIR irradiation (808 nm, 0.6 W/cm2), the rat abdominal temperature could reach 48 ℃, and the cumulative release of emodin reached 96.25%. The diffusion coefficient of emodin in the in vitro agar diffusion experiment was 249.27 mm2 h-1. No obvious toxicity was observed in hemolysis test, CCK-8 assay and microscopic histopathological analysis. The patch significantly reduced the percent of body weight ( P < 0.01), lipid-body ratio ( P < 0.001), serum FFAs ( P < 0.01) and the cell volume of peritesticular adipose tissue in the high-fat diet induced obese rats, indicating the patch had good anti-obesity effect. The mechanism of action may be related to the up-regulation of HSL and LPL protein levels in rat peritesticular adipose tissue.

Versatile triblock peptides mimicking ABC-type heterotrimeric collagen with stabilizing salt bridges.

Type IV collagen, a principal constituent of basement membranes, consists of six distinct α chains that assemble into both ABC and AAB-type heterotrimers. While collagen-like peptides have been investigated for heterotrimer formation, the construction of ABC-type heterotrimeric collagen mimetic peptides remains a formidable challenge, primarily due to the intricate composition and arrangement of the chains. We have herein for the first time reported the development of a versatile triblock peptide system to mimic ABC-type heterotrimeric collagen stabilized by salt bridges. The triblock peptides A, B, and C incorporate functional natural type IV collagen sequences in the center, along with charged amino acids at their N and C-terminals. By leveraging electrostatic repulsion at these charged termini, the formation of homotrimers is effectively inhibited, while stable ABC-type heterotrimers are generated through the establishment of salt bridges between oppositely charged terminals. Circular dichroism (CD) spectroscopy demonstrated that peptides A, B, and C existed as individual monomers, while they effectively formed stable ABC-type heterotrimers upon being mixed at a molar ratio of 1:1:1. Additionally, fluorescence quenching results indicated that fluorescence-labeled peptides A', B', and C' formed ABC-type heterotrimer, exhibiting comparable thermal stability as determined by CD spectroscopy. Molecular dynamics simulations elucidated the role of salt bridges between arginine and aspartic acid residues at N- and C-terminals in maintaining a unique chain register in the ABC-type heterotrimers. These triblock peptides offer a robust approach for replicating the structural and functional characteristics of type IV collagen, with promising applications in elucidating the biological roles and pathologies associated with heterotrimeric collagen.

Cholesterol-lowering effects of rhubarb free anthraquinones and their mechanism of action.

Rhubarb free anthraquinones (RhA) have significant lipid-regulating activity. However, whether RhA monomers have a role in lipid-regulating and their mechanism of action remains unclear. Based on the cholesterol accumulated HepG2 cell model, the cholesterol-regulating effect of RhA monomers and their combinations was investigated. The expression of sterol-regulatory element binding protein 2 (SREBP2), 3-hydroxy-3-methyl glutaryl coenzyme A reductase (HMGCR) and squalene monooxygenase (SQLE) of the model cells was analyzed to preliminarily explore the mechanism of action. After that, the liposomes of each active RhA monomer were separately prepared with the same lipid materials and the same preparation method so that each monomer has similar or equal bioavailability after oral administration to rats. Finally, the hypercholesterolemic rat model was established, and the effect of active RhA monomers loaded liposomes as well as their combinations on cholesterol-regulating was investigated and their mechanism of action was analyzed. The results showed that aloe-emodin, rhein and emodin were the main cholesterol-regulating components of RhA, and the combination of rhein and emodin showed significant cholesterol-lowering effect, which may be related to the expression of SREBP2, HMGCR and SQLE in the rat liver.

Recombinant Collagen-Templated Biomineralized Synthesis of Biocompatible pH-Responsive Porous Calcium Carbonate Nanospheres.

The synthesis of calcium carbonate with controlled morphology is crucial for its biomedical applications. In this study, we synthesized well-ordered porous calcium carbonate nanospheres using recombinant collagen as a biomineralization template. Porous collagen-calcium carbonate was created by incubating calcium chloride and sodium carbonate with collagen biotemplates at room temperature. Our results show that the recombinant collagen-calcium carbonate nanomaterials underwent a morphological transition from solid nanospheres to more porous nanospheres and a phase transformation from vaterite to a mixture of calcite and vaterite. This study highlights the crucial role of recombinant collagen in modulating the morphology and crystallinity of calcium carbonate nanoparticles. Importantly, the highly porous recombinant collagen-calcium carbonate hybrid nanospheres demonstrated superior loading efficacy for the model drug cefoperazone. Furthermore, the drug loading and releasing results suggest that hybrid nanospheres have the potential to be robust and biocompatible pH-responsive drug carriers. Our findings suggest that recombinant collagen's unique amino acid content and rodlike structure make it a superior template for biomineralized synthesis. This study provides a promising avenue for the production of novel organic-inorganic nanostructures, with potential applications in biomedical fields such as drug delivery.

Biocompatible and bioactive hydrogels of recombinant fusion elastin with low transition temperature for improved healing of UV-irradiated skin.

Prolonged exposure to UV radiation can cause severe photodamage to the skin, leading to abnormal fragmentation of elastin fibers. As one of the main protein components of the dermal extracellular matrix, elastin plays a critical role in the mechanical behavior and physiological function of the skin. Animal-derived elastin has attracted extensive attention in tissue engineering, however it suffers from severe drawbacks such as a risk of virus transmission, ready degradation, and challenging quality control. Herein, we have for the first time developed a novel recombinant fusion elastin (RFE) and its cross-linked hydrogel for improved healing efficacy for UV-irradiated skin. RFE showed temperature-sensitive aggregation behavior similar to natural elastin. Compared with recombinant elastin without the fusion V-foldon domain, RFE showed a much more ordered secondary structure and lower transition temperature. Furthermore, Native-PAGE results indicated that the addition of the V-foldon domain triggered the formation of remarkable oligomers in RFE, which may result in a more ordered conformation. Tetrakis Hydroxymethyl Phosphonium Chloride (THPC) cross-linking of RFE led to the production of a fibrous hydrogel with uniform three-dimensional porous nanostructures and excellent mechanical strength. The RFE hydrogel showed superior cellular activity, significantly promoting the survival and proliferation of human foreskin fibroblast-1 (HFF-1). Studies of mice models of UV-irradiated skin demonstrated that the RFE hydrogel pronouncedly accelerated their healing process by inhibiting epidermal hyperplasia as well as boosting the regeneration of collagen and elastin fibers. The highly biocompatible and bioactive recombinant fusion elastin and its cross-linked hydrogel provide a potent treatment for photodamaged skin, which may have promising applications in dermatology and tissue engineering.

Multifunctional Fluorinated Lubricant-Infused Poly(4-Hydroxybutyrate) (P4HB) Membranes for Full-Thickness Abdominal Wall Defect Repair.

Abdominal wall defect caused by surgical trauma, congenital rupture, or tumor resection may result in hernia formation or even death. Tension-free abdominal wall defect repair by using patches is the gold standard to solve such problems. However, adhesions following patch implantation remain one of the most challenging issues in surgical practice. The development of new kinds of barriers is key to addressing peritoneal adhesions and repairing abdominal wall defects. It is already well recognized that ideal barrier materials need to have good resistance to nonspecific protein adsorption, cell adhesion, and bacterial colonization for preventing the initial development of adhesion. Herein, electrospun poly(4-hydroxybutyrate) (P4HB) membranes infused with perfluorocarbon oil are used as physical barriers. The oil-infused P4HB membranes can greatly prevent protein attachment and reduce blood cell adhesion in vitro. It is further shown that the perfluorocarbon oil-infused P4HB membranes can reduce bacterial colonization. The in vivo study reveals that perfluoro(decahydronaphthalene)-infused P4HB membranes can significantly prevent peritoneal adhesions in the classic abdominal wall defects' model and accelerate defect repair, as evidenced by gross examination and histological evaluation. This work provides a safe fluorinated lubricant-impregnated P4HB physical barrier to inhibit the formation of postoperative peritoneal adhesions and efficiently repair soft-tissue defects.

Peptide-triggered self-assembly of collagen mimetic peptides into nanospheres by electrostatic interaction and π-π stacking.

Collagen is the most abundant protein in various connective tissues, providing mechanical integrity as well as regulating cellular activities. Self-assembled peptides have been extensively explored to develop collagen mimetic materials, due to their attractive features such as easy synthesis, selective sequences and low immunogenicity. Metal ion-triggered self-assembly of collagen mimetic peptides has recently received increasing interests, since the addition of external stimuli offers programmable control of the self-assembly process. We have for the first time reported a peptide-stimulated self-assembly of collagen mimetic peptides into nanospheres by electrostatic interaction and π-π stacking. We have accidentally discovered that FAM-modified positively-charged triple helical peptide FAM-PRG was highly soluble, while the addition of a single-stranded negatively-charged peptide EOG-10 efficiently drove its self-assembly into well-ordered spherical nanomaterials. Peptide EOG-10 has been shown to mediate similar self-assembly of TPE-modified triple-helical peptide TPE-PRG into luminescent exquisite nanospheres, consistently demonstrating the robustness of this peptide-triggered strategy. Fluorescence monitoring of the interaction of EOG-10 and TPE-PRG at different ratios indicated that EOG-10 specifically binds to TPE-PRG to form a 3 : 1 complex. High salt concentration was shown to inhibit the self-assembly of TPE-PRG with EOG-10, suggesting that their self-assembly was controlled by electrostatic interaction. The self-assembly of TPE-PRG with EOG-10 has been further revealed to require the exact lengths of both peptides as well as complementary sequences without mutations, indicating a pairwise "side-by-side" binding mode. Notably, the identity of the N-terminal residues of X-PRG has been found to play a determinant role in the self-assembly, while non-aromatic residues lost the self-assembling capability, suggesting that π-π stacking and electrostatic interactions collectively modulate the self-assembly of X-PRG and EOG-10. To conclude, we have developed a highly biocompatible and programmably controlled peptide-triggered self-assembly approach to create novel collagen mimetic nanomaterials, which may have great potential in advanced functional materials.

Concentration-mediated Folding and Unfolding of Collagen Triple Helix.

BACKGROUND: Collagen has been widely utilized in tissue engineering, regenerative medicine and cosmetics. Collagen of low concentrations is frequently applied to reduce the production cost, while it may result in the loss of triple helical structure and bioactivity. CD and NMR techniques have enhanced our understanding of collagen triple helix, while they require high concentrations of collagen samples. OBJECTIVE: We have systematically investigated the folding and unfolding features of collagen mimetic peptides at a broad variety of concentrations in order to decipher the role of the concentration in the triple helical stability. METHODS: Peptide FAM-G(POG)10 was synthesized by the solid phase synthesis method. Fluorescence spectra of peptide FAM-G(POG)10 at different concentrations were recorded. The unfolding and folding profiles of peptide FAM-G(POG)10 with concentrations varying from 1 nM to 100 µM were examined. The effect of concentration on the folding and unfolding capability of peptide FAMG( POG)10 was investigated. RESULTS: Fluorescence characterization of peptide FAM-G(POG)10 under widely varying concentrations from 1 nM to 100 µM has revealed that concentration played a critical role in the stability of collagen peptides. The two-phase pattern of the concentration-dependent folding and unfolding curves has for the first time demonstrated the presence of a critical concentration for the collagen peptide to trigger the complete folding of the triple helix and to maintain the triple helix structure. It is noteworthy that the triple helix structure of collagen peptides was very stable at µM-level concentrations from both the folding and unfolding perspectives. CONCLUSION: It has significantly contributed to our understanding of collagen triple helix stability at low and ultra-low concentrations, and provided valuable and practical guidelines for the preparation of collagen-based products.

Calcium and Sodium-mediated Dynamic Assembly of Intermediate Filament-like Protein FilP.

BACKGROUND: Cytoskeletal elements play key roles in cell morphology, cell division, cell mobility, and DNA partitioning in all domains of life. The IF-like protein FilP was discovered in Streptomyces coelicolor, and it was found to perform a structurally important cytoskeletal role by providing direct mechanical support for the cells. OBJECTIVE: This work investigated the factors influencing FilP polymerization under a variety of conditions. METHODS: DLS technique was applied to real-time monitor the in vitro assembly process of Streptomyces coelicolor FilP. RESULTS: The presence of small amounts of divalent cations, such as CaCl2 or MgCl2, enhanced the polymerization of FilP, while higher amounts suppressed its polymerization. Moreover, high concentrations of NaCl, KCl, NH4Cl, and KNO3 both suppressed the polymerization of FilP. EDTA was found to have a very prohibitive effect on FilP polymerization, and even the following addition of Ca2+ could not initiate the assembly of FilP. FilP polymerized under a range of pHs ranging from pH 6 to pH 8, while the polymerization degree was sensitive to pH. FilP formed network-like, striated filaments at neutral pH, while the filaments became more disordered or loosely packed at pH 8 and pH 6, respectively. CONCLUSION: FilP assembly is calcium-mediated. Ca2+ is not only required for FilP polymerization, but also required for FilP to maintain the higher-order polymer structure. The accelerative effect of Ca2+ and the suppressive effect of Na+ persisted under a wide range of conditions, suggesting that FilP might use calcium and sodium ions as a general mechanism to mediate its polymerization process.

Bioactive Poly(4-hydroxybutyrate)/Poly(ethylene glycol) Fibrous Dressings Incorporated with Zinc Oxide Nanoparticles for Efficient Antibacterial Therapy and Rapid Clotting.

Antibacterial and hemostatic properties are of great importance to wound dressing in treating trauma. Poly(4-hydroxybutyrate) (P4HB), an U.S. Food and Drug Administration (FDA)-approved bioabsorbable polyester, is used as dermal substitutes to prevent sever wound contraction and improve wound healing. However, P4HB fibrous mats are not efficient in halting bleeding and preventing bacterial associated infection. Here the authors prepare a new kind of wound dressing by incorporating poly(ethylene glycol) (PEG) and zinc oxide (ZnO) nanoparticles into the P4HB matrix by using electrospinning method. The in vitro results reveal that the P4HB/PEG/ZnO dressings can synergistically help blood clotting, prevent bacteria adhesion, and kill bacteria efficiently. It's found that the bactericidal activity of the bioactive P4HB/PEG/ZnO dressings is related to the release of Zn2+ ions rather than reactive oxygen species (ROS) under dark condition. The in vivo antibacterial evaluation indicates that the bioactive P4HB/PEG/ZnO dressings can successfully prevent wound infections in Sprague-Dawley (SD) rats' skin defect model. The in vivo hemostatic experiments evaluated in the rabbit ear injury model further confirm that the bioactive P4HB/PEG/ZnO dressings have excellent hemostatic performance. Hence, this study demonstrates that the bioactive P4HB/PEG/ZnO dressings with hemostatic and bactericidal properties have great potential in possible clinical applications.

Distributed adaptive specified-time synchronization tracking of multiple 6-DOF fixed-wing UAVs with guaranteed performances.

Different from the finite/fixed-time control methodologies on longitudinal/attitude synchronization or 2-D motion of UAVs, this article attempts to propose a distributed adaptive specified-time control scheme for synchronization tracking of networked 6-degree-of-freedom (DOF) UAVs. To be specific, the novel specified-time performance functions (STPFs) are designed in such a way that the desired performance bounds can be imposed on velocity and attitude tracking errors. Based on the transformed errors, by utilizing the barrier Lyapunov functions (BLFs), a distributed specified-time control scheme is constructed with adaptive robustifying terms to enhance the fault-tolerant ability and compensate the modeling uncertainties. By means of Lyapunov stability theory, it is proved that the resulting control scheme can guarantee the boundedness of all closed-loop state variables, and preserve the guaranteed performance bounds for synchronization tracking errors of velocity and attitude at the same time. Theoretical results are confirmed by experiment and simulation validations.

Slippery 3-dimensional porous bioabsorbable membranes with anti-adhesion and bactericidal properties as substitute for vaseline gauze.

Vaseline gauze is a common type of wound dressing that consist of absorbent gauze impregnated with white petrolatum. It has excellent anti-adhesive property which can reduce trauma during dressing changes. However, this kind of wound dressing doesn't have bacterial killing property. Thus, a new kind of wound dressing that has anti-adhesive and bactericidal properties is needed urgently. Creating slippery liquid-impregnated porous surfaces (SLIPS) that insensitive to the structure of porous solid are generally viewed as a new anti-adhesion strategy. To expand the potential utility of SLIPS as substitute for vaseline gauze, dual-functional slippery membranes with anti-adhesion and bactericidal properties by using triclosan, vegetable oils and polylactic acid (PLA) were prepared. It's demonstrated that the triclosan-loaded/vegetable oils-infused PLA membranes (T/V-PM) has good cytocompatibility in vitro. Notably, the T/V-PM can gradually release biocide molecule into surrounding aqueous media. Moreover, the T/V-PM can kill planktonic bacterial cells without loss of their antifouling property. The in vivo study revealed that the T/V-PM can prevent the secondary injuries during wound dressing changes. This simple and low-cost strategy can be applied to inhibit blood and bacterial adhesion, and prevent tissue adhesion at the wound site. It's confirmed that the T/V-PM have great potential as substitute for vaseline gauze.

Bioabsorbable poly(4-hydroxybutyrate) (P4HB) fibrous membranes as a potential dermal substitute.

Dermal substitutes are indispensable for repairing large full-thickness skin defects. Only a few biomaterials for dermal substitution have been put into clinical practice. Therefore, novel artificial dermal substitutes that can meet clinical requirements are in urgent need. Biodegradable poly(4-hydroxybutyrate) (P4HB), which has been approved by the U.S. FDA, can be considered as a possible alternative biomaterial to construct dermal substitutes. In this work, three-dimensional P4HB fibrous membranes were constructed by an electrospinning technique. These P4HB fibrous membranes showed excellent air-permeability, and better water uptake capacity compared to P4HB strip and polycaprolactone (PCL) fibrous membrane controls. The in vitro hemocompatibility and cytotoxicity of P4HB fibrous membranes were investigated. In vivo Sprague-Dawley (SD) rat model studies revealed that P4HB fibrous membranes can be used as artificial dermis to improve wound healing for full-thickness skin defects.

Ln3+-Triggered self-assembly of a heterotrimer collagen mimetic peptide into luminescent nanofibers.

Type I collagen, the most abundant and arguably the most complex molecule in the human body, is an ABB heterotrimer that self-assembles to form well-defined nanofibers. We herein for the first time report the construction of peptides that could simultaneously mimic the heterotrimer composition and the self-assembly features of Type I collagen.

A graphene oxide-aided triple helical aggregation-induced emission biosensor for highly specific detection of charged collagen peptides.

Aggregation-induced emission (AIE) probes have emerged as promising "turn-on" sensing tools for DNA and proteins, and the AIE biosensors conjugated with graphene oxide (GO) have shown improved selectivity. Collagen is an essential structural protein in the human body, and its degraded products are involved in a plethora of severe diseases. Collagen has a high content of charged amino acids, while EOG represents one of the most abundant charged triplets in Type I collagen. We, herein, for the first time report the construction of a GO-aided AIE biosensor for the detection of charged collagen peptides. We have shown that an AIE fluorophore TPE conjugated with a triple helical peptide TPE-PRG possesses strong fluorescence due to the restriction of intramolecular rotation of TPE in the trimer state. The adsorption of the probe TPE-PRG by GO leads to efficient fluorescence quenching, while the addition of target collagen peptide EOG releases the probe peptide from the GO surface and recovers its fluorescence. We have demonstrated that the TPE-PRG/GO complex provides a highly specific "turn-on" sensing platform for the target collagen peptide with a typical charged amino acid-rich sequence. The assay has shown little interference from other biomolecules, and it can also effectively distinguish the target charged collagen peptide from its single amino acid mutant type. The development of robust analytical assays for charged collagen peptides could pronouncedly extend our capability to investigate the pathology of collagen diseases, showing great potential for their molecular diagnosis.

Expression of Serum PTTG1 in Laryngeal Carcinoma and Its Correlation to Prognosis.

OBJECTIVES: The purpose of this study was to investigate serum pituitary tumor transforming gene (PTTG1) expression in laryngeal carcinoma and its relationship with the clinical pathological characteristics and prognosis. METHODS: Expression of serum PTTG1 was measured by enzyme-linked immunosorbent assay in 110 patients with laryngeal carcinoma and 60 patients with vocal cord polyps. Expression of the serum PTTG1 levels relationship with the clinicopathological characteristics and prognosis were analyzed. RESULTS: In laryngeal carcinoma patients' serum, the PTTG1 median concentration was 141.43 pg/mL (interquartile range [IQR], 111.387 to 160.837 pg/mL), significantly higher than that of the vocal cord polyp group of 94.01 pg/mL (IQR, 81.26 to 108.59 pg/mL), and the difference was statistically significant (z=-6.715, P<0.001). PTTG1 expression with lymph node metastasis, clinical stage, and patients with laryngeal carcinoma was significantly correlated with the tumor differentiation degree (P<0.05). The total survival rate of the PTTG1 high expression group was significantly lower than the low expression group, and the difference of total survival time of the two groups was statistically significant (P<0.001). CONCLUSION: The PTTG1 expression level can be used as an index for evaluating prognosis of laryngeal cancer. High PTTG1 expression is one of the factors of poor prognosis of laryngeal carcinoma patients.

Luminescent Biofunctional Collagen Mimetic Nanofibers.

Collagen has long been one of the top targets for biomimetic design due to its superior structural and functional properties. Significant progress has been achieved to construct self-assembling peptides to mimic the fibrous nanostructure of native collagen, while it is still very demanding to fabricate peptide assemblies that can recapitulate both structural and biofunctional features of collagen. Herein, collagen-like peptides have been synthesized to contain negatively charged amino acids as the binding groups of lanthanide ions and the integrin-binding motif GFOGER. The simultaneous inclusion of negatively charged amino acids in the middle as well as at both terminals drives the peptides to self-assemble to form well-ordered nanofibers with distinct periodic banding patterns specifically mediated by lanthanide ions. The aggregation tendency and the morphology of the final assembled materials for the peptides are modulated in a pH-cooperative manner, which well mimics the pH-dependent fibrillogenesis of Type I collagen. The utilization of lanthanide ions in the system not only offers a convenient external stimulus but also functionalizes assembled materials with excellent luminescent features. Most notably, the lanthanide-triggered peptide assembled nanomaterials possess good cell adhesion properties, which resemble the biological function of collagen. This peptide-Ln3+ system provides a facile and potent strategy to generate nanofibers that mimic both the structural and functional properties of natural collagen. These novel pH-responsive, luminescent, and biofunctional collagen mimetic nanofibers open fascinating opportunities in the development of improved functional biomaterials in tissue engineering, drug delivery, and medical diagnostics.

Detection of target collagen peptides with single amino acid mutation using two fluorescent peptide probes.

Collagen with a single amino acid substitution is the main cause of a plethora of heritable disorders such as Osteogenesis Imperfecta and Ehlers-Danlos syndrome. Though significant advances have been achieved in the development of protein assays, it remains very challenging to distinguish a protein with a single amino acid mutation from the wild-type protein. A novel fluorescent self-quenching assay has been constructed to detect target collagen peptides with a single amino acid mutation using two probe peptides. The hybridization of the probe peptide and the natural target collagen peptide results in a complete heterotrimer and strong fluorescence, whereas the mixture of the probe peptide and the mutation collagen sequences leads to a partial homotrimer and pronounced fluorescence self-quenching. The extent of fluorescence quenching is dependent on the identity of the residue replacing Gly following the order of Ala < Ser < Arg, while the Gly-Ala mutation causes the mildest fluorescence loss. The probe peptide-based fluorescence self-quenching assay facilitates specific detection of the target collagen sequence with a single Gly mutation at the nM level. The simultaneous utilization of both probe peptides enables efficient discrimination between different mutation peptides. To our knowledge, our work may be the first report of a robust analytical assay that can identify collagen fragments with single amino acid mutation, which will greatly contribute to deciphering the molecular mechanism of Osteogenesis Imperfecta as well as developing novel diagnostic strategies.

Serum IRS-1 acts as a novel biomarker for diagnosis in patients with nasopharyngeal carcinoma.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a major head and neck cancer with high occurrence in Southeast Asia and southern China. Insulin receptor substrate 1 (IRS-1) plays an important role in the development, progression, invasion and metastasis of tumors. The purpose of this study was to evaluate whether IRS-1 could be used as biomarkers for the diagnosis of NPC through measuring their expression and assess their relationship with clinical pathological factors. METHODS: Quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR) and Western blot were used to analyze the expression of IRS-1 in 133 NPC patients and 104 healthy controls. The relationship between IRS-1 expression and clinicopathological characteristics in NPC was estimated through chi-square test. We calculated diagnostic values of serum IRS-1 expression by receiver operating characteristic (ROC) curve. RESULTS: This study reports that IRS-1 protein was weakly expressed in NPC specimens, but highly in healthy controls. Serum IRS-1 were up-regulation in NPC patients compared with healthy controls. Their up-regulation was significantly correlated with lymph node status (P=0.029). Furthermore, the value of the area under the receiver-operating characteristic curve (AUC-ROC) was 0.907. The optimal cutoff value was 2.255, providing a sensitivity of 88.0% and a specificity of 77.9% in differentiating NPC patients from healthy controls. CONCLUSION: Our data indicates that serum IRS-1 might increase the sensitivity and accuracy in diagnosis of NPC, and may be a potential target for diagnosis and gene therapy.

WS2 and MoS2 biosensing platforms using peptides as probe biomolecules.

Biosensors based on the two-dimensional layered nanomaterials transition metal dichalcogenides such as WS2 and MoS2 have shown broad applications, while they largely rely on the utilization of single stranded DNA as probe biomolecules. Herein we have constructed novel WS2- and MoS2- based biosensing platforms using peptides as probe biomolecules. We have revealed for the first time that the WS2 and MoS2 nanosheets display a distinct adsorption for Arg amino acid and particularly, Arg-rich peptdies. We have demonstrated that the WS2 and MoS2 dramatically quench the fluorescence of our constructed Arg-rich probe peptide, while the hybridization of the probe peptide with its target collagen sequence leads to the fluorescence recovery. The WS2-based platform provides a sensitive fluorescence-enhanced assay that is highly specific to the target collagen peptide with little interferences from other proteins. This assay can be applied for quantitative detection of collagen biomarkers in complex biological fluids. The successful development of WS2- and MoS2- based biosensors using non-ssDNA probes opens great opportunities for the construction of novel multifunctional biosensing platforms, which may have great potential in a wide range of biomedical field.