U-fiber-based biosensor for temperature-compensated acetylcholine-specific measurement.

This paper presents a U-fiber-based biosensor to achieve temperature-compensated acetylcholine-specific measurement. The surface plasmon resonance (SPR) and multimode interference (MMI) effects are simultaneously realized in a U-shaped fiber structure for the first time, to the best of our knowledge. The experimental results show refractive index (RI) sensitivities of 3042 and 2958 nm/RIU and temperature sensitivities of -0.47 and -0.40 nm/°C for the MMI and SPR, which are greatly improved compared with the traditional structure. Simultaneously, a sensitivity matrix for detecting two parameters is introduced to solve the problem of temperature interference of biosensors based on RI changes. Label-free detection of acetylcholine (ACh) was achieved by immobilizing acetylcholinesterase (AChE) on optical fibers. The experimental results show that the sensor can realize the specific detection of acetylcholine and has good stability and selectivity, and the detection limit of the sensor is 30 nM. The sensor has the advantages of simple structure, high sensitivity, convenient operation, direct insertion into small spaces, temperature compensation, etc., which provide an important supplement to traditional fiber-optic SPR biosensors.

ADGRA1 negatively regulates energy expenditure and thermogenesis through both sympathetic nervous system and hypothalamus-pituitary-thyroid axis in male mice.

Adhesion G protein-coupled receptor A1 (ADGRA1, also known as GPR123) belongs to the G protein-coupled receptors (GPCRs) family and is well conserved in the vertebrate lineage. However, the structure of ADGRA1 is unique and its physiological function remains unknown. Previous studies have shown that Adgra1 is predominantly expressed in the central nervous system (CNS), indicating its important role in the transduction of neural signals. The aim of this study is to investigate the central function of Adgra1 in vivo and clarify its physiological significance by establishing an Adgra1-deficient mouse (Adgra1-/-) model. The results show that Adgra1-/- male mice exhibit decreased body weight with normal food intake and locomotion, shrinkage of body mass, increased lipolysis, and hypermetabolic activity. Meanwhile, mutant male mice present elevated core temperature coupled with resistance to hypothermia upon cold stimulus. Further studies show that tyrosine hydroxylase (TH) and ß3-adrenergic receptor (ß3-AR), indicators of sympathetic nerve excitability, are activated as well as their downstream molecules including uncoupling protein 1 (UCP1), coactivator 1 alpha (PGC1-α) in brown adipose tissue (BAT), and hormone-sensitive lipase (HSL) in white adipose tissue (WAT). In addition, mutant male mice have higher levels of serum T3, T4, accompanied by increased mRNAs of hypothalamus-pituitary-thyroid axis. Finally, Adgra1-/- male mice present abnormal activation of PI3K/AKT/GSK3ß and MEK/ERK pathways in hypothalamus. Overexpression of ADGRA1 in Neuro2A cell line appears to suppress these two signaling pathways. In contrast, Adgra1-/- female mice show comparable body weight along with normal metabolic process to their sex-matched controls. Collectively, ADGRA1 is a negative regulator of sympathetic nervous system (SNS) and hypothalamus-pituitary-thyroid axis by regulating PI3K/AKT/GSK3ß and MEK/ERK pathways in hypothalamus of male mice, suggesting an important role of ADGRA1 in maintaining metabolic homeostasis including energy expenditure and thermogenic balance.

Amplified Photoacoustic Signal and Enhanced Photothermal Conversion of Polydopamine-Coated Gold Nanobipyramids for Phototheranostics and Synergistic Chemotherapy.

Light-responsive nanoprobes were suffering from the threat of high-dose laser irradiation, and it was important for constructing new nanoprobes for safe and efficient phototheranostics. Here, polydopamine (PDA)-coated gold nanobipyramids (AuNBPs@PDA) were synthesized for amplified photoacoustic (PA) signal and enhanced photothermal conversion with low-dose laser irradiation and then doxorubicin (DOX)-loaded AuNBPs@PDA-DOX nanoprobes were constructed for PA imaging-guided synergistic photothermal therapy (PTT) and chemotherapy. The AuNBPs@PDA nanoparticles possessed higher photothermal conversion efficiency (42.07%) and stronger PA signal than those of AuNBP nanoparticles, and the AuNBPs@PDA-DOX nanoprobes showed dual-responsive DOX release of pH and photothermal stimulation. With low-dose laser irradiation (1.0 W/cm2) and low-concentration AuNBPs@PDA-DOX (60 µg/mL), the 4T1 cell viability was reduced to about 5%, owing to the combination of PTT and chemotherapy, compared with 42.3% of single chemotherapy and 25.3% of single PTT. Moreover, by modeling 4T1 tumor-bearing nude mice, in vivo PA imaging was achieved and the tumors were completely inhibited, demonstrating the excellent synergistic effect of PTT/chemotherapy. Therefore, the developed AuNBPs@PDA-DOX nanoprobes can be used for phototheranostics and synergistic chemotherapy, achieving low-dose laser irradiation and high-efficient visualized theranostics.

OncoKB: A Precision Oncology Knowledge Base.

PURPOSE: With prospective clinical sequencing of tumors emerging as a mainstay in cancer care, there is an urgent need for a clinical support tool that distills the clinical implications associated with specific mutation events into a standardized and easily interpretable format. To this end, we developed OncoKB, an expert-guided precision oncology knowledge base. METHODS: OncoKB annotates the biological and oncogenic effect and the prognostic and predictive significance of somatic molecular alterations. Potential treatment implications are stratified by the level of evidence that a specific molecular alteration is predictive of drug response based on US Food and Drug Administration (FDA) labeling, National Comprehensive Cancer Network (NCCN) guidelines, disease-focused expert group recommendations and the scientific literature. RESULTS: To date, over 3000 unique mutations, fusions, and copy number alterations in 418 cancer-associated genes have been annotated. To test the utility of OncoKB, we annotated all genomic events in 5983 primary tumor samples in 19 cancer types. Forty-one percent of samples harbored at least one potentially actionable alteration, of which 7.5% were predictive of clinical benefit from a standard treatment. OncoKB annotations are available through a public web resource (http://oncokb.org/) and are also incorporated into the cBioPortal for Cancer Genomics to facilitate the interpretation of genomic alterations by physicians and researchers. CONCLUSION: OncoKB, a comprehensive and curated precision oncology knowledge base, offers oncologists detailed, evidence-based information about individual somatic mutations and structural alterations present in patient tumors with the goal of supporting optimal treatment decisions.

[Quantitative study of meridian topology model based on acupoint-symptom relationship].

Meridian theory plays an important role in the guidance of clinical practice of acupuncture and moxibustion. Since the publication of Zhenjiu Jiayi Jing (A-B Classic of Acupuncture and Moxibustion), the meridian theory has been developed. In the paper, in view of complex science, the topological properties of acupoint-symptom network were analyzed quantitatively by taking acupoint as node and indication as the connection, such as high clustering coefficient and the small world effect. It was the first time to give the abstraction for the topological proof of the high efficiency information transmission property of acupoint-symptom network meridian system at different times. Its quantitative and digitalized significance was analyzed on the development of meridian theory under the complex scientific background so as to provide a new thought and method for the study of meridian theory and acupuncture modernization.

Heated lipiodol as an embolization agent for transhepatic arterial embolization in VX2 rabbit liver cancer model.

PURPOSE: To evaluate the therapeutic effect of heated (60 degrees C) lipiodol via hepatic artery administration in a rabbit model of VX2 liver cancer. MATERIALS AND METHODS: Thirty male New Zealand white rabbits were randomly divided into three groups with 10 rabbits assigned to each group. VX2 carcinoma cells were surgically implanted into the left hepatic lobe. The tumors were allowed to grow for 2 weeks, and studies were performed until the diameter of the tumors detected by ultrasonograph reached 2-3cm. Under anesthesia, trans-catheter hepatic arterial embolization was performed and doxorubicin-lipiodol (37 degrees C) (1mL), lipiodol (60 degrees C) (1mL) or control (physiological saline (37 degrees C) (1mL)) solution was injected into the hepatic arteries of animals in the three groups. One week later, the volume of the tumor was measured by ultrasonograph again. The serum of all rabbits was collected before injection and at 4 and 7 days after injection, and the level of aspartate aminotransferase (AST) was checked. The survival period of the three groups of rabbits after treatment was also recorded. During the last course of their disease, the rabbits were given analgesics to relieve suffering. RESULTS: The tumor growth rate in the lipiodol (60 degrees C) group (0.92+/-0.21, tumor volume from 1811+/-435 to 1670+/-564mm(3)) was significantly lower than that in the control group (3.48+/-1.17, tumor volume from 1808+/-756 to 5747+/-1341mm(3)) (P<0.05) and in the doxorubicin-lipiodol (37 degrees C) group (1.69+/-0.26, tumor volume from 1881+/-641 to 2428+/-752mm(3)) (P<0.05). Consequently, the survival period of the animals in the lipiodol (60 degrees C) group (41.0+/-3.0 days) was significantly greater than that in the doxorubicin-lipiodol (37 degrees C) group (38.0+/-2.5 days) (P<0.05). On the other hand, there was no statistically significant difference in serum AST levels between the lipiodol (60 degrees C) group (148.2+/-11.3UL(-1)) and the doxorubicin-lipiodol (37 degrees C) group (139.7+/-12.3UL(-1)) (P>0.05). However, the serum AST level in the lipiodol (60 degrees C) group was significantly higher at 4 days after injection (P<0.05) than in the control group (68.6+/-6.6UL(-1)). CONCLUSIONS: Treatment with lipiodol (60 degrees C) resulted in an effect on serum AST levels similar to that caused by treatment with doxorubicin-lipiodol (37 degrees C). Thus, lipiodol (60 degrees C) treatment could greatly prolong the survival period of rabbits with VX2 cancer by inhibiting tumor growth.

Immune responses to foot-and-mouth disease DNA vaccines can be enhanced by coinjection with the Isatis indigotica extract.

The Isatis indigotica extract is widely used in clinical practice for the treatment of influenza, epidemic hepatitis, epidemic encephalitis B etc. The goal of this study was to investigate whether coinjection of the Isatis indigotica extract with foot-and-mouth disease virus (FMDV) DNA vaccine could increase the protective immune response. Mice were vaccinated twice with either FMDV DNA vaccine plus the Isatis indigotica extract or DNA vaccine alone. Compared with the group of DNA vaccine alone, in the group that received DNA vaccine plus the Isatis indigotica extract was observed a significant increase in not only FMDV-specific antibody response but also T cell proliferation assay. All swine immunized with either FMDV DNA vaccine plus the Isatis indigotica extract or DNA vaccine alone were partially protected from FMDV challenge, but the signs of DNA vaccine plus the Isatis indigotica extract group were less severe than that of DNA vaccine alone. Coinjection of the Isatis indigotica extract with DNA vaccine has adjuvant effect on the immune response against viral pathogens and its application provides an effective strategy to improve the efficacy of DNA vaccines.

[Adriamycin thermotherapy through hepatic artery for model of VX2 carcinoma in rabbit liver].

BACKGROUND & OBJECTIVE: It was reported that heating can enhance sensitivity of rabbit VX2 cell to adriamycin and increase intracellular concentration of adriamycin. This study was designed to evaluate the anti-tumor effects of interventional hyperthermia and interventional chemotheramotherapy on VX2 carcinoma in rabbit liver. METHODS: VX2 carcinoma cells were surgically implanted into the right liver lobe of 60 male New Zealand white rabbits, which were randomly divided into 4 groups(15 rabbits per group). To inject physiological saline(37 degrees C), adriamycin (37 degrees C), physiological saline(60 degrees C), and adriamycin (60 degrees C) in different groups via hepatic artery of the rabbits with liver cancer. One week later, to observe the volume of tumor, the serum level of aspartate transaminase(AST), and observe the survival period of VX2 rabbits. RESULTS: In group of ADM(60 degrees C), the tumor growth rate (0.53 +/- 0.21)% was significantly lower than group 2(1.09 +/- 0.26)%, group 3(3.32 +/- 1.28)%, and group 4(3.48 +/- 1.17)% (P < 0.05, P < 0.05, P < 0.01, respectively). The survival period of adriamycin (60 degrees C) group (50.0 +/- 2.0)d was significantly higher than the untreated control group (40.5 +/- 3.0)d, (P < 0.05). The serum level of AST of TNP-470 with lipiodol group was not higher than the other treated groups(P > 0.05), but being significantly higher than the untreated control group after treated(P < 0.05). CONCLUSION: Adriamycin (60 degrees C) greatly decreases the tumour growth rate, and prolongs the survival period.

[Effect of interventional chemothermotherapy on vascular permeability of tumor liver tissue and normal liver tissue in VX-2 tumor-bearing rabbits].

BACKGROUND & OBJECTIVE: It was reported that heating could enhance the sensitivity of chemotherapy with Adriamycin and increase the intracellular content of Adriamycin. The aim of this study was to investigate the effect of interventional chemothermotherapy on vascular permeability of tumor liver tissue and normal liver tissue in VX-2 tumor-bearing rabbits. METHODS: Thirty rabbits used as implanted hepatocarcinoma model were randomly divided into 3 groups: non-perfusion group (injected only with 1% Evans blue after catheterization), normothermic perfusion group (the perfusion fluid was 25 degrees C normal solution), and hyperthermic perfusion group(the perfusion fluid was 60 degrees C normal solution). The contents of Evans blue in the tissues of three groups, which were used as the indices of vascular permeability, were calculated by the standard curve and spectrophotometry. RESULTS: The Evans blue contents in tumor liver tissue and normal liver tissue is statistically different (P < 0.05). There was no over difference of the Evans blue contents in two kinds of tissue between normal perfusion group and non-perfusion group. There was overt difference of the Evans blue contents in two kinds of tissue between hyperthermic perfusion group and normothermic perfusion group. CONCLUSION: Interventional chemothermotherapy could increase the vascular permeability of normal liver tissue and tumor liver tissue.