Femtosecond laser direct writing large-area fiber Bragg grating based on diaphragm shaping.

We propose and demonstrate a new method of direct writing large-area fiber Bragg grating by femtosecond laser through the coating. By adding an adjustable diaphragm before the focusing objective, we can precisely control the length of the refractive index modulation line along the femtosecond laser incident direction up to 29.1 µm. In combination with femtosecond laser scanning fabrication technology, a uniform refractive index modulation plane can be inscribed in the fiber in a single scanning. Based on the plane-by-plane inscription method, we have fabricated a high-quality high-reflectivity fiber Bragg grating and a chirped fiber Bragg grating on 20/400 double-clad fiber core. The reflectivity of both gratings is greater than 99%, and the insertion loss is as low as 0.165 dB and 0.162 dB, respectively. The thermal slope of chirped fiber Bragg grating without any refrigeration is 0.088 °C/W and there is no obvious temperature increase when using the water cooling. Therefore, the fabrication method of large-area fiber Bragg grating based on diaphragm shaping can efficiently fabricate high-quality fiber Bragg grating in the large core diameter fiber, which has an important application prospect in high-power all-fiber oscillators, especially all-fiber oscillators in special wavebands.

Effects of electroacupuncture on the PI3K/Akt/CREB signaling pathway and hippocampal neuronal apoptosis in diabetic cognitive impairment rats. / ç”µé’ˆå¯¹ç³–å°¿ç— è®¤çŸ¥åŠŸèƒ½éšœç¢å¤§é¼ PI3K/Akt/CREBä¿¡å·é€šè·¯å’Œæµ·é©¬ç¥žç»å ƒå‡‹äº¡çš„å½±å“.

OBJECTIVES: To observe the effects of electroacupuncture (EA) on the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt)/cAMP response element binding protein (CREB) signaling pathway-related proteins and hippocampal neuron apoptosis in diabetic cognitive impairment (DCI) rats, and to explore the mechanisms of EA in treating DCI. METHODS: Adult male SD rats were randomly divided into normal, model, and EA groups, with 12 rats in each group. The animal model of DCI was replicated using a high-fat, high-sugar diet combined with low-dose streptozotocin. The EA group received EA stimulation at "Yishu" (EX-B6), "Zusanli" (ST36), "Baihui" (GV20), and "Dazhui" (GV14). Blood glucose contents of the rats in each group were measured. The Morris water maze test was used to assess the learning and memory abilities of rats. Transmission electron microscopy was used to observe the ultrastructure of hippocampal CA1 neurons. Nissl staining was used to observe the pathological changes in hippocampal CA1 neurons. TUNEL staining was used to detect the apoptosis in hippocampal CA1 neurons. Western blot was used to detect the protein expression levels of p-PI3K/PI3K and p-Akt/Akt, as well as CREB, p-CREB, cysteine aspartate pro-tease (Caspase)-3, B-cell lymphoma-2 (Bcl-2), and Bcl-2 related X protein (Bax) in the hippocampal tissue of rats. RESULTS: Compared with the normal group, the rats' random blood glucose contents were significantly increased (P<0.01), the escape latency prolonged (P<0.01), and the original platform crossing counts reduced (P<0.01) in the model group. Significant damage to hippocampal CA1 neurons, a significantly increased neuronal apoptosis index (P<0.01), decreased ratio of p-PI3K/PI3K and p-Akt/Akt and expression of CREB, p-CREB and Bcl-2 proteins, increased expression of Caspase-3 and Bax proteins (P<0.01) were observed in the hippocampal tissue of rats in the model group. Compared with the model group, the rats in the EA group showed decreased random blood glucose content (P<0.01), shortened escape latency (P<0.01), increased original platform crossing counts (P<0.01), improved quantity and pathological morphology and ultrastructure of hippocampal CA1 neurons, reduced neuronal apoptosis index (P<0.01), increased ratio of p-PI3K/PI3K and p-Akt/Akt, and expression of CREB, p-CREB and Bcl-2 proteins (P<0.05, P<0.01) in the hippocampal tissue, and decreased expression of Caspase-3 and Bax proteins (P<0.01). CONCLUSIONS: EA can improve the learning and memory abilities of rats with DCI, and the mechanism may be related to the regulation of the expression of PI3K/Akt/CREB signaling pathway-related proteins, which attenuates the neuronal apoptosis in the hippocampus of rats, and improves the neural function.

Integrating Olefin Carboamination and Hofmann-Löffler-Freytag Reaction by Radical Deconstruction of Hydrazonyl N-N Bond.

As a type of elementary organic compounds containing N-N single bond, hydrazone involved chemical conversions are extremely extensive, but they are mainly limited to N2-retention and N2-removal modes. We report herein an unprecedented protocol for the realization of division utilization of the N2-moiety of hydrazone by a radical facilitated N-N bond deconstruction strategy. This new conversion mode enables the successful combination of alkene carboamination and Hofmann-Löffler-Freytag reaction by the reaction of N-homoallyl mesitylenesulfonyl hydrazones with ethyl difluoroiodoacetate under photocatalytic redox neutral conditions. Mechanism studies reveal that the reaction undergoes a radical relay involving addition, crucial remote imino-N migration and H-atom transfer. Consequently, a series of structurally significant ϵ-N-sulphonamide-α,α-difluoro-γ-amino acid esters are efficiently produced via continuous C-C bond and dual C-N bonds forging.

Covalently Cross-Linked Chemistry of a Three-Dimensional Network Binder at Limited Dosage Enables Practical Si/C Composite Electrode Applications.

Currently, Si (or SiOx, 1 < x < 2) and graphite composite (Si/C) electrodes (e.g., Si/C450 and Si/C600 with specific capacities of 450 and 600 mAh g-1 at 0.1 C, respectively) have become the most promising alternative to traditional graphite anodes toward high-energy lithium-ion battery (LIB) applications by virtue of their higher specific capacity compared to graphite ones and improved cycle performance compared to Si (or SiOx) ones. However, such composite electrodes remain challenging to practical for implementation owing to electrode structure disintegration and interfacial instability caused by a large volume change of inner Si-based particles. Herein, we develop a covalent-bond cross-linking network binder for Si/C450 and Si/C600 electrodes via reversible addition-fragmentation chain transfer (RAFT) polymerization. The as-developed binder with a 3 mol % cross-linker of other monomers [termed P(SH-BA3%)] achieves improved mechanical and adhesive properties and decreased Si/C anode volume expansion, compared to the linear binder counterpart. Impressively, the P(SH-BA3%) binder at only 3 wt % dosage enables 83.56% capacity retention after 600 cycles at 0.5 C in Si/C450 anode based half-cells and retains 86.42% capacity retention at 0.3 C after 200 cycles and 80.95% capacity retention at 0.5 C after 300 cycles in LiNi0.8Co0.1Mn0.1O2 cathode (15 mg cm-2) based homemade soft package full cells. This work provides insight into binder cross-linking chemistry under limited dosage and enlightens cross-linking binder design toward practical Si/C electrode applications.

Raman suppression in high-power fiber oscillators by femtosecond-written chirped and tilted fiber Bragg gratings.

Realizing stimulated Raman scattering (SRS) suppression is a key topic for high-power fiber lasers. Here, we report an effective and simple strategy for SRS suppression using chirped and tilted fiber Bragg gratings (CTFBGs) in high-power fiber oscillators while maintaining the compactness and stability of the system. The CTFBG is inserted on the side of a cavity mirror FBG without cutting the gain fiber. To improve power handling capability, the CTFBG and cavity mirror FBGs are inscribed by femtosecond (fs) lasers. The optimal SRS suppression effect can be realized when the CTFBG is inserted into the resonant cavity and on the side of the output coupler FBG. The SRS threshold is increased by approximately 11% with an SRS suppression ratio of nearly 14 dB. Moreover, the output power of the fiber oscillator is improved to 3.5 kW, which is the maximum power achieved in fiber oscillators with SRS suppression using CTFBGs, to the best of our knowledge. The temperature of the air-cooled CTFBG is 50.2 °C, which has the potential to handle higher power. This work provides new insights for suppressing SRS in fiber oscillators, promoting the application of CTFBGs in high-power lasers.

Robust femtosecond-written chirped and tilted fiber Bragg gratings for Raman filtering in multi-kW fiber lasers.

We present a robust chirped and tilted fiber Bragg grating (CTFBG) in a large-mode-area double-cladding fiber (LMA-DCF) written by a femtosecond (fs) laser. By implementing the fs-CTFBG into the output end of a high-power fiber laser for Raman filtering, a power handling capability of 4 kW is achieved with a Raman filtering ratio of ∼13 dB. To the best of our knowledge, this is the maximum handling power of a CTFBG for Raman filtering. The signal loss of the fs-CTFBG is 0.03 dB, which has little effect on the output laser beam quality. The air-cooled fs-CTFBG has a minimum temperature slope of 7.8°C/kW due to a self-annealing effect. This work proves the excellent performance of the fs-CTFBG, promoting the development of high-power CTFBGs.

Femtosecond laser fabrication of chirped and tilted fiber Bragg gratings for stimulated Raman scattering suppression in kilowatt-level fiber lasers.

Chirped and tilted fiber Bragg gratings (CTFBGs) are important all-fiber filtering components in high-power fiber lasers for stimulated Raman scattering (SRS) suppression. The fabrication of CTFBGs in large-mode-area double-cladding fibers (LMA-DCFs) by femtosecond (fs) laser is reported for the first time to the best of our knowledge. The chirped and tilted grating structure is obtained by scanning the fiber obliquely and moving the fs-laser beam relative to the chirped phase mask at the same time. By this method, the CTFBGs with different chirp rates, grating lengths, and tilted angles are fabricated, and the maximum rejection depth and bandwidth are ∼25 dB and ∼12 nm, respectively. To test the performance of the fabricated CTFBGs, one is inserted between the seed laser and the amplifier stage of a 2.7 kW fiber amplifier, and an SRS suppression ratio of ∼4 dB is achieved with no reduction in laser efficiency and degradation in beam quality. This work provides a highly fast and flexible method to fabricate large-core CTFBGs, which is of great significance to the development of high-power fiber laser systems.

Lactoferrin-containing immunocomplex mediates antitumor effects by resetting tumor-associated macrophages to M1 phenotype.

BACKGROUND: Tumor-associated macrophages (TAMs) resemble M2-polarized cells with potent immunosuppressive activity and play a pivotal role in tumor growth and progression. Converting TAMs to proinflammatory M1-like phenotype is thus an attractive strategy for antitumor immunotherapy. METHODS: A mouse IgG1 (kappa) monoclonal Ab, M-860, specific to human lactoferrin (LTF) was generated by using the traditional hybridoma cell fusion technology. TAMs were generated by culturing human and mouse CD14+ monocytes in tumor-conditioned media containing a cytokine cocktail containing recombinant interleukin-4 (IL-4), interleukin-10 (IL-10) and macrophage colony stimulating factor (M-CSF). TAMs after treatment with immunocomplex (IC) between human LTF and M860 (LTF-IC) were phenotypically and functionally characterized by flow cytometry (FACS), ELISA, Q-PCR and killing assays. The antitumor effects of LTF-IC were further analyzed using in vivo experiments employing tumor-bearing human FcγRIIa-transgenic mouse models. RESULTS: Through coligation of membrane-bound CD14 and FcγRIIa, LTF-IC rendered TAMs not only M2 to M1 conversion, evidenced by increased tumor necrosis factor α production, down-regulated M2-specific markers (CD206, arginase-1 and vascular endothelial growth factor) and upregulated M1-specific markers (CD86 and HLA-DR) expression, but also potent tumoricidal activity in vitro. LTF-IC administration conferred antitumor protective efficacy and prolonged animal survival in FcγRIIa-transgenic mice, accompanied by accumulation of M1-like macrophages as well as significantly reduced infiltration of immunosuppressive myeloid-derived suppressor cells and regulatory T cells in solid tumor tissues. CONCLUSIONS: LTF-IC is a promising cancer therapeutic agent capable of converting TAMs into tumoricidal M1-like cells.

Author Correction: Extraordinarily potent proinflammatory properties of lactoferrin-containing immunocomplexes against human monocytes and macrophages.

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Lactoferrin-Containing Immunocomplexes Drive the Conversion of Human Macrophages from M2- into M1-like Phenotype.

Macrophages are multifunctional cells that perform diverse roles in health and disease and considered the main source of inflammatory cytokines in affected joints of patients with rheumatoid arthritis (RA). M2 macrophages are well known as anti-inflammation and wound-healing cells; however, recent evidence suggests that they can also promote inflammation in RA, although the underlying mechanism remains to be clarified. Based upon our recent finding that lactoferrin (LTF)-containing IgG immunocomplex (LTF-IC), found elevated in RA sera, potent activators of human monocytes/macrophages, we herein demonstrate that LTF-IC was able to elicit immediate proinflammatory cytokine production by M2-polarized human macrophages through coligation with CD14/toll-like receptor (TLR) 4 and FcγRIIa (CD32a). The LTF-IC-treated M2 cells adopted surface maker expression profile similar to that of M1 phenotype and became functionally hyperactive to subsequent stimuli such as lipopolysaccharide, zymosan and IL-1ß, which could provide a positive feedback signal to promote excessive inflammation in RA. They also acquired the ability to facilitate activation of Th17 cells that are known to play critical roles in RA pathology. We propose that IgG ICs containing TLR agonizing autoantigens are able to directly switch human macrophages from M2 into M1-like phenotype, thereby promoting excessive inflammation in autoimmune diseases such as RA.

Extraordinarily potent proinflammatory properties of lactoferrin-containing immunocomplexes against human monocytes and macrophages.

Lactoferrin (LTF), an important first line defense molecule against infection, is a common target for humoral autoimmune reactions in humans. Since LTF is a multifunctional protein capable of activating innate immune cells via various surface receptors, we hypothesized that LTF-containing immune complexes (ICs) (LTF-ICs), likely formed in patients with high titer anti-LTF autoantibodies, could possess unique monocyte/macrophage-activating properties compared with other ICs. ELISA analysis on serum samples from rheumatoid arthritis (RA) patients (n = 80) and healthy controls (n = 35) for anti-LTF autoantibodies confirmed a positive correlation between circulating LTF-specific IgG and RA. ICs between human LTF and LTF-specific IgG purified from patient sera or immunized rabbits and mice, but not control ICs, LTF or Abs alone, elicited strong production of TNF-α and IL-1ß by freshly fractionated human peripheral blood monocytes and monocytes-derived macrophages. Furthermore, LTF-ICs utilized both membrane-anchored CD14 and CD32a (FcγRIIa) to trigger monocyte activation in an internalization-, Toll-like receptor (TLR)4- and TLR9-dependent manner, and also that LTF-IC-induced cytokine production was blocked by specific inhibitors of caspase-1, NF-κB and MAPK. These results uncover a possible pathway for LTF-ICs perpetuating local inflammation and contributing to the pathogenesis of autoimmune diseases by triggering activation of infiltrating monocytes or tissue macrophages in vivo.

Expression, purification, and breast cancer cell inhibiting effect of recombinant human lactoferrin C-lobe.

Lactoferrin (LTF), a multifunctional glycoprotein of the transferrin family mainly found in exotic secretions in mammals, is an important defense molecule against not only microbial invasion but also tumors. It folds into two globular domains (N- and C-lobes) each containing an iron-binding site. The cationic antimicrobial peptide in N-lobe is known to exert anti-tumor effect via a non-receptor-mediated pathway. However, whether LTF C-lobe also contributes to its anti-tumor activity remains to be investigated. In this study, a human LTF fragment (amino acid residues 343-682) covering the C-lobe was expressed with a histidine tag in E. coli and the purified polypeptide refolded through a series of buffer changing procedure. The resultant recombinant protein caused significant growth arrest of breast carcinoma cells MDA-MB-231 in a dose- and time-dependent manner, evidently via induction of apoptosis of the cell. Our data suggest a positive role for the C-lobe of human LTF in controlling tumors in vitro.