Downregulation of the (pro)renin receptor alleviates ferroptosis-associated cardiac pathological changes via the NCOA 4-mediated ferritinophagy pathway in diabetic cardiomyopathy.

Ferroptosis, characterized by the accumulation of reactive oxygen species and lipid peroxidation, is involved in various cardiovascular diseases. (Pro)renin receptor (PRR) in performs as ligands in the autophagic process, and its function in diabetic cardiomyopathy (DCM) is not fully understood. We investigated whether PRR promotes ferroptosis through the nuclear receptor coactivator 4 (NCOA 4)-mediated ferritinophagy pathway and thus contributes to DCM. We first established a mouse model of DCM with downregulated and upregulated PRR expression and used a ferroptosis inhibitor. Myocardial inflammation and fibrosis levels were then measured, cardiac function and ferroptosis-related indices were assessed. In vitro, neonatal rat ventricular primary cardiomyocytes were cultured with high glucose and transfected with recombinant adenoviruses knocking down or overexpressing the PRR, along with a ferroptosis inhibitor and small interfering RNA for the ferritinophagy receptor, NCOA4. Ferroptosis levels were measured in vitro. The results showed that the knockdown of PRR not only alleviated cardiomyocyte ferroptosis in vivo but also mitigated the HG-induced ferroptosis in vitro. Moreover, administration of Fer-1 can inhibit HG-induced ferroptosis. NCOA4 knockdown blocked the effect of PRR on ferroptosis and improved cell survival. Our result indicated that inhibition of PRR and NCOA4 expression provides a new therapeutic strategy for the treatment of DCM. The effect of PRR on the pathological process of DCM in mice may be in promoting cardiomyocyte ferroptosis through the NCOA 4-mediated ferritinophagy pathway.

Incarvine C and its analogues inhibit the formation of cell cytoskeleton by targeting Rac1.

Ras-related C3 botulinum toxin substrate 1 (Rac1) has emerged as a key regulator in the treatment of cancer metastasis because of its involvement in the formation of cell plate pseudopods and effects on cell migration. In this study, we found that incarvine C, a natural product isolated from Incarvillea sinensis, and its seven analogues exhibited antitumour activity by inhibiting cell cytoskeleton formation, with moderate cytotoxicity. Accordingly, these compounds inhibited the cytoskeleton-mediated migration and invasion of MDA-MB-231 cells, with inhibition rates ranging from 37.30 % to 69.72 % and 51.27 % to 70.90 % in vitro, respectively. Moreover, they induced G2/M phase cell cycle arrest in MDA-MB-231 cells. A pull-down assay revealed that the interaction between Rac1 and its downstream effector protein PAK1 was inhibited by these compounds and that the compound Ano-6 exhibited substantial activity, with an inhibition rate of more than 90 %. Molecular docking showed that incarvine C and its analogues could bind to the nucleotide-binding pocket of Rac1, maintaining high levels of inactivated Rac1. As Ano-6 exhibited significant activity in vitro, its anti-cancer activity was tested in vivo. Four weeks of oral treatment with Ano-6 was well-tolerated in mice, and it induced a potential anti-tumour response in xenografts of MDA-MB-231 cells. Further studies demonstrated that Ano-6 was enriched in tumour tissues after 2 h of administration and induced an increase in the number of dead tumour cells. In summary, these findings not only reveal the mechanism of incarvine C but also provide a new molecular template for Rac1 inhibitors and identify a promising candidate for breast cancer treatment.

A simple and accurate method to quantify real-time contraction of vascular smooth muscle cell in vitro.

Vascular smooth muscle cells (VSMCs) constitute the medial layer of the blood vessel wall. Their contractile state regulates blood flow in physiological and pathological conditions. Current methods for assessing the contractility of VSMCs are not amenable to the high-throughput screening of pharmaceutical compounds. This study aimed to develop a method to address this shortcoming in the field. Real-time contraction was visualized in living VSMCs using the exogenous expression of green fluorescent protein (GFP). Image-Pro Plus software (IPPS) was used to measure various morphological cell indices. In phenylephrine-treated VSMCs, GFP fluorescence imaging was more accurate than brightfield imaging or phalloidin staining in representing VSMC morphology, as measured using IPPS. Among the multiple indices of VSMC shape, area and mean-diameter were more sensitive than length in reflecting the morphological changes in VSMC. We developed a new index, compound length, by combining the mean-diameter and length to differentiate contracted and uncontracted VSMCs. Based on the compound length, we further generated a contraction index to define a single-VSMC contractile status as single-VSMC contraction-index (SVCI). Finally, compound length and SVCI were validated to effectively assess cell contraction in VSMCs challenged with U46619 and KCl. In conclusion, GFP-based indices of compound length and SVCI can accurately quantify the real-time contraction of VSMCs. In future, the new method will be applied to high-throughput drug screening or basic cardiovascular research.

Using a Gene Network of Pyroptosis to Quantify the Responses to Immunotherapy and Prognosis for Neuroblastoma Patients.

Background: Pyroptosis, as an inflammatory form of cell death, is involved in many physiological and pathological processes. Neuroblastoma is the most common extra-cranial solid tumor in children. In this study, the relationship between pyroptosis and tumor microenvironment in neuroblastoma was systematically studied. Methods: We integrated four datasets of neuroblastomas. Through robust clustering of the mRNA expression profiles of 24 pyroptosis-related genes, a total of three pyroptosis patterns were identified. We then constructed a novel scoring method named as pyroscore to quantify the level of pyroptosis in neuroblastoma. Multi-omics data and single-cell RNA sequencing were used to accurately and comprehensively evaluate the effectiveness of pyroscore. Clinical data sets were used to evaluate the use of pyroscore to predict the responsiveness of immune checkpoint treatment. Results: High pyroscore was associated with good prognosis, immune activation, and increased response to checkpoint blockade immunotherapy. Multivariate Cox analysis revealed that the pyroscore was an independent prognostic biomarker and could increase the accuracy of clinical prediction models. Etoposide, a drug picked up by our analysis, could increase the sensitivity of neuroblastoma cells to pyroptosis. External verification using four cohorts of patients who had received immunotherapy showed that high pyroscore was significantly associated with immunotherapy treatment benefit. Conclusions: Taken together, this study revealed that pyroptosis-related gene network could quantify the response of neuroblastoma to immune checkpoint blockade therapy and prognosis, and it may be helpful for clinical practitioners to choose treatment strategies for neuroblastoma patients.

Lysosome-Targeted Biosensor for the Super-Resolution Imaging of Lysosome-Mitochondrion Interaction.

Background: The interaction between lysosomes and mitochondria includes not only mitophagy but also mitochondrion-lysosome contact (MLC) that enables the two organelles to exchange materials and information. In our study, we synthesised a biosensor with fluorescence characteristics that can image lysosomes for structured illumination microscopy and, in turn, examined morphological changes in mitochondria and the phenomenon of MLC under pathological conditions. Methods: After designing and synthesising the biosensor, dubbed CNN, we performed an assay with a Cell Counting Kit-8 to detect CNN's toxicity in relation to H9C2 cardiomyocytes. We next analysed the co-localisation of CNN and the commercial lysosomal probe LTG in cells, qualitatively analysed the imaging characteristics of CNN in different cells (i.e. H9C2, HeLa and HepG2 cells) via structured illumination microscopy and observed how CNN entered cells at different temperatures and levels of endocytosis. Last, we treated the H9C2 cells with mannitol or glucose to observe the morphological changes of mitochondria and their positions relative to lysosomes. Results: After we endocytosed CNN, a lysosome-targeted biosensor with a wide, stable pH response range, into cells in an energy-dependent manner. SIM also revealed that conditions in high glucose induced stress in lysosomes and changed the morphology of mitochondria from elongated strips to round spheres. Conclusion: CNN is a new tool for tracking lysosomes in living cells, both physiologically and pathologically, and showcases new options for the design of similar biosensors.

ATP6AP2 knockdown in cardiomyocyte deteriorates heart function via compromising autophagic flux and NLRP3 inflammasome activation.

Moderate autophagy can remove damaged proteins and organelles. In some inflammatory diseases, autophagy plays a protective role by inhibiting the NOD-like receptor family pyrin domain containing 3(NLRP3). (Pro)renin receptor (PRR, or ATP6AP2) is a critical component of the V-ATPase required for autophagy. It remains controversial about ATP6AP2 in the pathological process. The impact of ATP6AP2 on NLRP3 inflammasome and autophagic flux remains unknown under pressure overload stress. This research explores the potential link between ATP6AP2, autophagic flux, and NLRP3. There was upregulation of ATP6AP2 from 5-day post-TAC, and this expression remained at a high level until 8-weeks post-TAC in wild mice. Meanwhile, autophagic flux switched from early compensatory activation to blocking in the heart failure phase. NLRP3 activation can be seen at 8-week post-TAC. Adenovirus-mediated knockdown of ATP6AP2(shR-ATP6AP2) accelerated the progress of heart failure. After TAC was induced, shR-ATP6AP2 significantly deteriorated heart function and fibrosis compared with the shR-Scr group. Meanwhile, there was an elevated expression of NLRP3 and autophagic flux blockage. A transgenic mouse(Tg) with cardio-restricted ATP6AP2/(P)RR overexpression was constructed. Although high expression in cardiac tissue, there were no spontaneous functional abnormalities under the basal state. Cardiac function, fibrosis, hypertrophy remained identical to the control TAC group. However, SQSTM1/P62 was reduced, which indicated the relief of autophagic flux blockage. Further, Neonatal rat ventricular myocyte (NRVMs) transfected with shR-ATP6AP2 showed more susceptibility than sh-Scr NRVMs to phenylephrine-induced cell death. More reactive oxygen species (ROS) or mito-ROS accumulated in the shR-ATP6AP2 group when phenylephrine stimulation. Blocking NLRP3 activation in vivo partly rescued cardiac dysfunction and fibrosis. In conclusion, ATP6AP2 upregulation is a compensatory response to pressure overload. If not effectively compensated, it compromises autophagic flux, leads to dysfunctional mitochondria accumulation, further produces ROS to activate NLRP3, eventually accelerates heart failure.

Anlotinib Induces a T Cell-Inflamed Tumor Microenvironment by Facilitating Vessel Normalization and Enhances the Efficacy of PD-1 Checkpoint Blockade in Neuroblastoma.

PURPOSE: Anlotinib has achieved good results in clinical trials of a variety of cancers. However, the effects of anlotinib on the tumor microenvironment (TME) and systemic immunity have not been reported. There is an urgent need to identify the underlying mechanism to reveal new opportunities for its application in neuroblastoma (NB) and other cancers. Understanding the mechanism will hopefully achieve the goal of using the same method to treat different cancers. EXPERIMENTAL DESIGN: This study used bioinformatics, NB syngeneic mouse models, flow cytometry, RNA-seq, and immunofluorescence staining to explore the mechanisms of anlotinib on the TME, and further explored anlotinib-containing combination treatment strategies. RESULTS: We proved that anlotinib facilitates tumor vessel normalization at least partially through CD4+ T cells, reprograms the immunosuppressive TME into an immunostimulatory TME, significantly inhibits tumor growth, and effectively prevents systemic immunosuppression. Moreover, the combination of anlotinib with a PD-1 checkpoint inhibitor counteracts the immunosuppression caused by the upregulation of PD-L1 after monotherapy, extends the period of vascular normalization, and finally induces NB regression. CONCLUSIONS: To our knowledge, this study is the first to dynamically evaluate the effect of a multitarget antiangiogenic tyrosine kinase inhibitor on the TME. These findings have very important clinical value in guiding the testing of related drugs in NB and other cancers. Based on these findings, we are conducting a phase II clinical study (NCT04842526) on the efficacy and safety of anlotinib, irinotecan, and temozolomide in the treatment of refractory or relapsed NB, and hopefully we will observe patient benefit.

EZH2 identifies the precursors of human natural killer cells with trained immunity.

OBJECTIVE: Trained immunity of natural killer (NK) cells has shown great potential in the treatment of cancers by eliciting enhanced effector responses to restimulation by cytokines or cancer cells for long time periods after preactivation. However, the human NK cells responsible for the generation and maintenance of trained immunity are largely unknown. We hypothesized that heterogeneous human NK cells would respond differentially to stimulation with a combination of IL-12, IL-15, and IL-18, and that an NK cell subset might exist that is mainly responsible for the induction of trained immunity. On the basis of our hypothesis, we aimed to identify the subset from which cytokine-trained human NK cells originate and to explore possible regulatory targets for drug intervention. METHODS: Flow cytometry assays were performed to analyze the functions of cytokine-trained NK cells and examine cell division and protein expression in NK cell subsets. Single-cell RNA sequencing (scRNA-seq) plus TotalSeq™ technology was used to track the heterogeneity of NK cells during the induction of trained immunity. RESULTS: Traditional developmental markers for peripheral NK cells were unable to identify the precursors of human NK cells with trained immunity. Therefore, we used scRNA-seq plus TotalSeq™ technology to track the heterogeneity of NK cells during the induction of trained immunity and identified a unique cluster of CD57-NKG2A+EZH2+IFNG+MKI67+IL12R+IL15R+IL18R+ NK cells. Enrichment and pseudotime trajectory analyses suggested that this cluster of NK cells contained the precursor of trained NK cells. We then used flow cytometry to further investigate the role of EZH2 in trained NK precursors and found that CD57-NKG2A+EZH2+ NK cells had faster cell cycles and an enhanced trained phenotype, and EZH2 inhibition significantly impaired the induction of trained immunity in NK cells. These results suggested that EZH2 is a unique epigenetic marker of precursors of human NK cells with trained immunity. CONCLUSIONS: Our work revealed human NK heterogeneity in the induction of trained immunity, identified the precursor subset for trained NK cells, and demonstrated the critical role of EZH2 in the induction of trained immunity in human NK cells.

Dual-channel fiber surface plasmon resonance sensor based on a metallized core.

We propose a novel dual-channel fiber surface plasmon resonance (SPR) sensor based on a metalized core. Using a polymer, the cladding and coating layer of the sensor coated with a metal sensing film are restored. The parameters of the sensor are determined after studying the influence of different polymers and sensing films on the dynamic range and sensing sensitivity. A silver film coated with UV-curable adhesive and a gold film coated with polydimethylsiloxane (PDMS) with respective sensing sensitivities of up to 1.39 and 1.48 nm/°C are selected after optimization to construct the dual-channel sensor. A dual-channel fiber SPR temperature compensation refractive index sensor with improved accuracy is then constructed with a 20-nm gold film for the refractive index sensing unit and a 50-nm gold film coated with PDMS for the temperature sensing unit. Owing to its complete fiber structure, the SPR sensor has good mechanical properties and high practical value, and it can be easily applied to real-time temperature measurements and temperature compensation in various fields.

Durable efficacy of anlotinib in a patient with advanced thymic squamous cell carcinoma after multiline chemotherapy and apatinib: A case report and literature review.

Thymic carcinoma is a rare and highly aggressive mediastinal tumor. Most patients are diagnosed at surgically unresectable stages. Current prospective and retrospective studies have indicated that platinum and anthracycline-based chemotherapy are the first choice drugs of first-line therapy for advanced thymic carcinoma. However, there is no optimal treatment after progression for patients who have undergone first-line and subsequent chemotherapy. Anlotinib, a novel small molecule tyrosine kinase multitarget inhibitor, was approved by the China Food and Drug Administration as a third-line treatment for advanced non-small cell lung cancer (NSCLC) in May 2018. Herein we report a case of an advanced thymic squamous cell carcinoma patient harboring EGFR exon 20 insertion who had previously received multiline therapy, including chemotherapy, radiotherapy as well as antiangiogenic therapy. Also as an angiogenesis inhibitor, anotinib had controlled his mediastinal mass after failure of the apatinib treatment. To date, over 23 months of progression-free survival (PFS) and six years of overall survival (OS) have been achieved. Compared with apatinib, the adverse reactions have been mild and tolerable and the patient's quality of life has improved. To our knowledge, this is the first report where anlotinib has been effective in controlling the progression of thymic carcinoma. In the multiline treatment of advanced thymic carcinoma, anlotinib appears to show great potential when utilized as a salvage treatment.

Fiber SPR refractive index sensor with the variable core refractive index.

In this paper, a refractive index sensor based on the control of the fiber core refractive index is proposed. By employing ultraviolet curable adhesive with the different refractive index and hollow capillary fiber, the special fiber with a variable core refractive index is fabricated. Using the special fiber, a novel, to the best of our knowledge, refractive index surface plasmon resonance (SPR) sensor with a controllable detecting range of refractive index is realized. Functional testing of the sensing probes with the core refractive indices of 1.590, 1.516, and 1.454 is performed respectively, indicating that their sensitivities are 1580 nm/RIU, 2220 nm/RIU, and 3467 nm/RIU, respectively, and their detecting ranges of refractive index are 1.385-1.435 RIU, 1.365-1.415 RIU, and 1.335-1.385 RIU, respectively. Furthermore, in order to explore the detection effect of the sensing probe with the higher-core refractive index, we conducted theoretical calculation using the Kretchmann model. The experimental and simulating results indicates that, with the increase of the core refractive index, the magnitude of refractive index that can be detected increases. This study provides a new method for the detection of high refractive index solutions and a new idea for the fabrication of wavelength-division multiplexing distributed SPR sensors.

Optical Fiber Cladding SPR Sensor Based on Core-Shift Welding Technology.

The typical structure of an optical fiber surface plasmon resonance (SPR) sensor, which has been widely investigated, is to produce the SPR phenomenon by the transmission of light in a fiber core. The traditional method is to peel off the fiber cladding by complex methods such as corrosion, polishing, and grinding. In this paper, the transmitted light of a single-mode fiber is injected into three kinds of fiber cladding by core-shift welding technology to obtain the evanescent field directly between the cladding and the air interface and to build the Kretschmann structure by plating with a 50-nm gold film. The SPR sensing phenomenon is realized in three kinds of fiber cladding of a single-mode fiber, a graded-index multimode fiber, and a step-index multimode fiber. For the step-index multimode fiber cladding SPR sensor, all the light field energy is coupled to the cladding, leading to no light field in the fiber core, the deepest resonance valley, and the narrowest full width at half maximum. The single-mode fiber cladding SPR sensor has the highest sensitivity, and the mean sensitivity of the probe reaches 2538 nm/RIU (refractive index unit) after parameter optimization.

Distribution of ALK Fusion Variants and Correlation with Clinical Outcomes in Chinese Patients with Non-Small Cell Lung Cancer Treated with Crizotinib.

BACKGROUND: ALK-rearranged non-small cell lung cancer (NSCLC) represents a molecular subgroup with high sensitivity to ALK inhibitors. Crizotinib, a US Food and Drug Administration (FDA)-approved tyrosine kinase inhibitor for treating ALK-rearranged NSCLC, has shown remarkable response in ALK-positive NSCLC. However, heterogeneity of clinical responses exists among different ALK fusion partners. Several small studies have investigated the correlation between fusion partners and efficacy, but not yielded consistent results. OBJECTIVE: We investigated the prevalence of ALK rearrangements in a Chinese NSCLC population, and correlated clinical outcomes of crizotinib with different ALK partners/variants. PATIENTS AND METHODS: We retrospectively reviewed genomic profiling and clinical data of 110 ALK-rearranged NSCLC patients from five centers. The clinical response to crizotinib and survival data in ALK-positive patients was retrospectively analyzed. RESULTS: A total of 134 ALK rearrangements with 39 partners were identified in 110 patients (5.6%) among a cohort of 1971 NSCLC patients. The most frequently occurring ALK fusion partner was EML4, which was identified in 71.6% (96/134) of all of the rearrangements in 87.3% (96/110) patients, and with variant 3 (41/96, 42.7%) as the main variant type. No statistically significant differences in terms of progression-free survival (PFS) and overall survival (OS) were found between EML4-ALK and non-EML4-ALK NSCLC patients in our cohort (PFS, p = 0.207; OS, p = 0.678). Outcomes did not differ significantly between patients above and below 40 years of age (PFS, p = 0.427; OS, p = 0.686), nor between patients treated with crizotinib in different lines of therapy (PFS, p = 0.171; OS, p = 0.922). For EML4-ALK-positive NSCLC (n = 96), patients harboring variant 3 or variant 5 displayed significantly lower PFS and OS than those with other variants (PFS, 8.6 vs. 11.3 months, p = 0.046; OS, 31.0 vs. 37.6 months, p = 0.026). In addition, patients with a single EML4-ALK rearrangement event displayed favorable PFS (10.0 vs. 7.2 months, p = 0.040) and OS (36.0 vs. 20.0 months, p = 0.029) compared to those harboring multiple ALK rearrangements. CONCLUSIONS: This study illustrates the patterns of ALK fusion variants present in Chinese NSCLC patients and might help explain heterogeneous clinical outcomes to crizotinib treatment according to different ALK fusion variants.

Surface-Plasmon-Resonance-Based Optical Fiber Curvature Sensor with Temperature Compensation by Means of Dual Modulation Method.

Curvature measurement plays an important role in many fields. Aiming to overcome shortcomings of the existing optical fiber curvature sensors, such as complicated structure and difficulty in eliminating temperature noise, we proposed and demonstrated a simple optical fiber curvature sensor based on surface plasmon resonance. By etching cladding of the step-index multimode fiber and plating gold film on the bare core, the typical Kretschmann configuration is implemented on fiber, which is used as the bending-sensitive region. With increases in the curvature of the optical fiber, the resonance wavelength of the SPR (Surface Plasmon Resonance) dip linear red-shifts while the transmittance decreases linearly. In the curvature range between 0 and 9.17 m-1, the wavelength sensitivity reached 1.50 nm/m-1 and the intensity sensitivity reached -3.66%/m-1. In addition, with increases in the ambient temperature, the resonance wavelength of the SPR dips linearly blueshifts while the transmittance increases linearly. In the temperature range between 20 and 60 °C, the wavelength sensitivity is -0.255 nm/°C and the intensity sensitivity is 0.099%/°C. The sensing matrix is built up by combining the aforementioned four sensitivities. By means of the dual modulation method, the cross-interference caused by temperature change is eliminated. Additionally, simultaneous measurement of curvature and temperature is realized.

[A Case Report of Advanced Lung Adenocarcinoma Harboring KRAS Mutation 
Treated with Anlotinib].

In recent years, the number of advanced non-small cell lung cancer (NSCLC) patients has gradually increased, and the treatment methods have also been significantly increased. However, there are no standard treatment plans at home and abroad for third-line and above patients who are refractory to targeted therapy epidermal growth factor receptor (EGFR)/anaplastic lymphoma kinase (ALK) or chemotherapy. The clinical treatment effect is also not satisfactory. Anlotinib is a novel TKI targeting the vascular endothelial growth factor receptor (VEGFR), fibroblast growth factor receptor (FGFR), platelet-derived growth factor receptor (PDGFR) and c-Kit. ALTER0303 trail, phase III study has demonstrated that Anlotinib significantly prolonged overall survival (OS) and progression-free survival (PFS) in advanced NSCLC patients as 3rd line treatment.Here we report a case of advanced lung adenocarcinoma harboring KRAS mutation treated with Anlotinib.
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A patient with classic biphasic pulmonary blastoma harboring CD74-ROS1 fusion responds to crizotinib.

Pulmonary blastoma (PB) is a rare aggressive lung malignancy with a poor prognosis. Surgical resection is the treatment of choice for localized disease, and there are no standard treatment guidelines for metastatic PB. Due to its rareness, its molecular profile has not been elucidated. We present the first case of classic biphasic pulmonary blastoma (CBPB) with CD74-ROS1 rearrangement in a 44-year-old Asian female with stage IV disease diagnosed using capture-based ultra-deep targeted sequencing. It has been reported that ROS1 rearranged lung adenocarcinoma and squamous cell carcinoma are sensitive to crizotinib, an ALK/MET/ ROS1 multitargeted tyrosine kinase inhibitor. However, its efficacy has not been reported in CBPB patients harboring ROS1 rearrangement. This CBPB patient was given crizotinib and she achieved partial response after 1 month of treatment. We report the first clinical evidence of efficacy shown by crizotinib for targeting CD74-ROS1 fusion in CBPB.

Two-Channel SPR Sensor Combined Application of Polymer- and Vitreous-Clad Optic Fibers.

By combining a polymer-clad optic fiber and a vitreous-clad optic fiber, we proposed and fabricated a novel optic fiber surface plasmon resonance (SPR) sensor to conduct two-channel sensing at the same detection area. The traditional optic fiber SPR sensor has many disadvantages; for example, removing the cladding requires corrosion, operating it is dangerous, adjusting the dynamic response range is hard, and producing different resonance wavelengths in the sensing area to realize a multi-channel measurement is difficult. Therefore, in this paper, we skillfully used bare fiber grinding technology and reverse symmetry welding technology to remove the cladding in a multi-mode fiber and expose the evanescent field. On the basis of investigating the effect of the grinding angle on the dynamic range change of the SPR resonance valley wavelength and sensitivity, we combined polymer-clad fiber and vitreous-clad fiber by a smart design structure to realize at a single point a two-channel measurement fiber SPR sensor. In this paper, we obtained a beautiful spectral curve from a multi-mode fiber two-channel SPR sensor. In the detection range of the refractive rate between 1.333 RIU and 1.385 RIU, the resonance valley wavelength of channel Ⅰ shifted from 622 nm to 724 nm with a mean average sensitivity of 1961 nm/RIU and the resonance valley wavelength of channel Ⅱ shifted from 741 nm to 976 nm with a mean average sensitivity of 4519 nm/RIU.

Segmented detection SPR sensor based on seven-core fiber.

By using a seven-core fiber (SCF), we propose and demonstrate a novel segmented detection SPR sensor, which solves two bottlenecks about the fiber SPR sensor of low sensitivity and the difficulty in the multichannel detection. The proposed sensor has ultra high sensitivity and wide detection range because of employing the segmented detection technology. Besides that, the proposed sensor employs reflection-type time division multiplexing (TDM) technology in fiber multichannel detection for the first time. We couple light into and out of the six circularly symmetric distributed cores of the seven-core fiber to realize the three channel SPR sensing and testing. This three-channel SPR sensor has the advantages of detecting biochemical or multi analytes reactions and eliminating the distractions due to temperature fluctuations or sample composition variations and adsorption of non-target molecules to the sensor surface. This SPR sensor also has the advantages of online monitoring by inserting into the blood vessel because of its small size. Furthermore, this paper has deeply researched the relationship between the refractive index of the solution to be measured, the grinding angle of the sensing channel, the sensitivity and the detection range. In this paper, we propose a novel segmented detection method which realizes the wide detection range with the wider refractive index range of 1.333~1.395 and the narrower working bandwidth of 250nm compared with the common SPR sensor, the average sensitivity and the maximum sensitivity of the sensor reach 7387.1nm/RIU and 8502.5nm/RIU respectively.