Anti-Tumor Potential of Post-Translational Modifications of PD-1.

Programmed cell death protein-1 (PD-1) is a vital immune checkpoint molecule. The location, stability, and protein-protein interaction of PD-1 are significantly influenced by post-translational modification (PTM) of proteins. The biological information of PD-1, including its gene and protein structures and the PD-1/PD-L1 signaling pathway, was briefly reviewed in this review. Additionally, recent research on PD-1 post-translational modification, including the study of ubiquitination, glycosylation, phosphorylation, and palmitoylation, was summarized, and research strategies for PD-1 PTM drugs were concluded. At present, only a part of PD-1/PD-L1 treated patients (35-45%) are benefited from immunotherapies, and novel strategies targeting PTM of PD-1/PD-L1 may be important for anti-PD-1/PD-L1 non-responders (poor responders).

In Situ Constructing Ultrastable Mechanical Integrity of Single-Crystalline LiNi0.9 Co0.05 Mn0.05 O2 Cathode by Interior and Exterior Decoration Strategy.

Planar gliding along with anisotropic lattice strain of single-crystalline nickel-rich cathodes (SCNRC) at highly delithiated states will induce severe delamination cracking that seriously deteriorates LIBs' cyclability. To address these issues, a novel lattice-matched MgTiO3 (MTO) layer, which exhibits same lattice structure as Ni-rich cathodes, is rationally constructed on single-crystalline LiNi0.9 Co0.05 Mn0.05 O2 (SC90) for ultrastable mechanical integrity. Intensive in/ex situ characterizations combined with theoretical calculations and finite element analysis suggest that the uniform MTO coating layer prevents direct contact between SC90 and organic electrolytes and enables rapid Li-ion diffusion with depressed Li-deficiency, thereby stabilizing the interfacial structure and accommodating the mechanical stress of SC90. More importantly, a superstructure is simultaneously formed in SC90, which can effectively alleviate the anisotropic lattice changes and decrease cation mobility during successive high-voltage de/intercalation processes. Therefore, the as-acquired MTO-modified SC90 cathode displays desirable capacity retention and high-voltage stability. When paired with commercial graphite anodes, the pouch-type cells with the MTO-modified SC90 can deliver a high capacity of 175.2 mAh g-1 with 89.8% capacity retention after 500 cycles. This lattice-matching coating strategy demonstrate a highly effective pathway to maintain the structural and interfacial stability in electrode materials, which can be a pioneering breakthrough in commercialization of Ni-rich cathodes.

2 × 4†kW near-single-mode laser output assisted by an optimized bidirectional oscillating-amplifying integrated fiber laser configuration.

Bidirectional output oscillating-amplifying integrated fiber laser (B-OAIFL) can achieve the two-ports laser amplification based on a single cavity, showcasing a promising prospect. In order to improve both the laser power and beam quality, we first simulate and optimize the stimulated Raman scattering (SRS) effect in the B-OAIFL. The simulation results show the SRS effect can be suppressed by optimizing the diameter as well as the length of the active fiber at different locations. With the guidance of theoretical and experimental analysis for the combined suppression of SRS and transverse mode instability (TMI), a near-single-mode B-OAIFL with 2 × 4 kW was demonstrated. Based on this foundation, we further devoted ourselves to the pursuit of the optimization of the structure and performance. The necessity of the configuration of side pump, which was initially introduced for its exceptional performance in stabilizing temporal chaos, was reevaluated in detail. With its negative impacts on efficiency improvement and SRS suppression were analyzed and verified, we removed this configuration and finally demonstrated a more simplified design with superior performance. A total bidirectional output of 8105 W was achieved, with an O-O efficiency of 79.6% and a near-single-mode beam quality of M A 2∼1.36,M B 2∼1.63. No signs of TMI were observed, and the signal-to-SRS suppression ratio was over 38 dB. The results still demonstrate a promising potential for power scaling based on this configuration and parameters.

Selection principle of seed power in high-power narrow linewidth fiber amplifier seeded by a FBGs-based fiber oscillator.

Here, we have experimentally demonstrated the selection principle of the seed power in a narrow linewidth fiber amplifier seeded by fiber oscillator based on a pair of fiber Bragg gratings. During the study on the selection of seed power, the spectral instability of the amplifier is found when a low power seed with bad temporal characteristics is amplified. This phenomenon is thoroughly analyzed from seed itself and the influence of the amplifier. Increasing the seed power or isolating the backward light of amplifier could effectively eliminate the spectral instability. Based on this point, we optimize the seed power and utilize a band pass filter circulator to isolate the backward light and filter the Raman noise. Finally, a 4.2 kW narrow linewidth output power is achieved with signal to noise ratio of 35 dB, which has exceeded the value under the highest output power reported in this type of narrow linewidth fiber amplifiers. This work provides a solution for high power and high signal to noise ratio narrow-linewidth fiber amplifiers seeded by FBGs-based fiber oscillator.

Origin of SRS-induced beam quality distortion under TMI threshold.

In high power fiber lasers, the degradation of beam quality caused by Raman effect has attracted more and more attention in recent years, but its physical mechanism is still unclear. We're going to differentiate between heat effect and nonlinear effect by duty cycle operation. The evolution of beam quality at different pump duty cycles has been studied based on a quasi-continuous wave (QCW) fiber laser. It is found that even if the Stokes intensity is only -6 dB (energy proportion: 26%) lower than that of the signal light intensity, the beam quality has no obvious change with the duty cycle of 5%; on the contrary, when the duty cycle gradually approaches 100% (CW-pumped scheme), the beam quality distortion changes faster and faster with the increase of Stokes intensity. The experimental results are contrary to core-pumped Raman effect theory [IEEE Photon. Technol. Lett.34, 215 (2022)10.1109/LPT.2022.3148999], and further analysis confirms that the heat accumulation in the process of Stokes frequency shift should be responsible for this phenomenon. That is the first time, to the best of our knowledge, for intuitive reveal of the origin of stimulated Raman scattering (SRS)-induced beam quality distortion under transverse mode instability (TMI) threshold in an experiment.

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.

Towards a tapered Yb-doped fiber-based narrow linewidth single-mode fiber laser with a high signal to Raman ratio.

We demonstrate an all-fiber high-power narrow-linewidth fiber laser based on a homemade tapered Yb-doped fiber (T-YDF). The laser performance is investigated and systematically compared with different seed powers and pump manners. The experimental results reveal that the injected seed power requires a trade-off designed to take into account the impact of spectral broadening, nonlinear effects, and transverse mode instability (TMI). Compared with the co-pump manner, the counter-pump manner performs well in inhibiting nonlinearities, spectral broadening, and improving the TMI threshold. Under the counter-pump manner, this narrow-linewidth T-YDF amplifier realized a 2.09 kW output power with a 3 dB spectral linewidth of ∼0.34 nm, a beam quality of M2∼1.28 and a high Raman suppression ratio over 53.5 dB, the highest reported power for such a T-YDF-based narrow-linewidth single-mode laser, to the best of our knowledge. This work provides a promising pathway towards implementing monolithic high-power narrow-linewidth single-mode fiber lasers.

Demonstration of 3kW × 2 ports bidirectional output oscillating-amplifying integrated fiber laser employing chirped and tilted fiber Bragg gratings for co-SRS suppression.

Bidirectional output oscillating-amplifying integrated fiber laser (B-OAIFL) is a newly developed configuration with many advantages like compactness and good reliability. In this work, a B-OAIFL with a low time-stabilized threshold was constructed by employing a pair of side pump/signal combiner in the oscillating section, which demonstrates smooth temporal characteristics with no pulse detected by the photodetector at the output power level of only a few of tens Watts. We investigated the effect of side pumping on the Raman Stokes light and verified its contribution to mitigating the temporal-chaos-induced stimulated Raman scattering (SRS). The phenomenon of co-SRS caused by the mutual excitation of backward Stokes light from two amplifying sections under bidirectional pumping was first reported and studied. A pair of chirped and tilted fiber Bragg gratings (CTFBGs) were applied between the oscillating and amplifying sections to suppress the co-SRS, and the effect of the number of CTFBGs on the suppression of co-SRS was studied in detail experimentally. Finally, we successfully suppressed the co-SRS, and achieved a 3kW × 2 ports laser output, with a near-single-mode beam quality of M A 2∼1.3,M B 2∼1.4. In contrast, without the use of CTFBG, only a 2 kW-level output was obtained from each port, limited by co-SRS (with an SRS suppression ratio of less than 15 dB). The maximum output power of end A and end B is 3133 W and 3213 W, with the SRS suppression ratio of about 27.6 dB and 28.1 dB, respectively. No TMI features were observed under bidirectional pumping. The results demonstrate a significant potential for further power scaling based on this configuration. To the best of our knowledge, it is the highest output power achieved based on the B-OAIFL.

10 kW tandem pumping fiber amplifier with good beam quality based on tapered ytterbium-doped fiber.

In this paper, we established a high power tandem pumped fiber amplifier based on tapered ytterbium-doped fiber (TYDF). The TYDF is developed in-house with a core/inner cladding diameter of 30/250 µm at the small-core region and 48/400 µm at the large-core region. The key parameters of the amplifier in a co-pumped and counter-pumped configuration are experimentally investigated, such as slope efficiency, stimulated Raman scattering (SRS) threshold, and beam quality evolution. Up to 10.28 kW laser free of SRS or transverse mode instability is obtained from the counter-pumped amplifier, and the beam quality factor M2 is 2.29, which is significantly improved compared with the 48/400 µm uniform YDF. To the best of our knowledge, this is the highest average output power achieved so far based on the TYDF. This work could provide a solution for balancing the SRS suppression and high order modes control in high power tandem pumped YDF 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.

Demonstration of constant-cladding tapered-core Yb-doped fiber for mitigating thermally-induced mode instability in high-power monolithic fiber amplifiers.

In this work, a large-mode-area (LMA) step-index constant-cladding tapered-core (CCTC) Yb-doped fiber with a cladding diameter of ∼600 µm is successfully fabricated. The CCTC fiber has a small-core region (diameter of ∼20 µm) at both ends and a large-core region (diameter of ∼36 µm) in the middle. To prove the laser performance of the CCTC fiber, a detailed comparison experiment with conventional uniform fiber with the same effective core diameter is carried out in a multi-kW all-fiber MOPA configuration. The experimental results show that employing the CCTC fiber can effectively mitigate the thermally-induced transverse mode instability (TMI) in both co-pump and counter-pump schemes, and realize high slope efficiency and single-mode beam quality (M2∼1.30). Under the counter-pump scheme, the TMI threshold of the CCTC fiber is observed at ∼2.49 kW with a slope efficiency of 86.2%, while the uniform fiber amplifier exhibits a TMI threshold of ∼2.05 kW. The theoretical analysis based on a semi-analytical model indicates this CCTC fiber can effectively improve the TMI threshold owing to a stronger gain saturation. Our results verify the great potential of such an LMA CCTC fiber to mitigate thermal-induced TMI effect and achieve single-mode operation without sacrifice of laser efficiency in high power monolithic fiber lasers, and the further power scaling is expected by optimizing the fiber design.

2 × 2†kW near-single-mode bidirectional high-power output from a single-cavity monolithic fiber laser.

Traditional monolithic fiber lasers can only achieve unidirectional high-power laser output. In this Letter, a novel high-power linear cavity fiber laser that can achieve bidirectional high-power output is proposed and demonstrated. In an ordinary laser resonant cavity, we replace the high-reflectivity fiber Bragg grating with a low-reflectivity fiber Bragg grating to realize bidirectional laser output. In our experiment, the laser cavity was composed of two fiber Bragg gratings with a reflectivity of about 10%. The pump power provided by the 976 nm laser diodes was injected into a double-clad Yb-doped fiber with core/cladding diameters of 20/400 µm. At the maximum pump power, the bidirectional output powers were 2025 W and 1948 W, respectively, and the output laser beam quality (M2 factor) at both ends was about 1.5. For the first time, to the best of our knowledge, the feasibility of a bidirectional output fiber laser that can achieve double high (2-kW-level) power was verified. Compared with a traditional unidirectional output laser, this type of bidirectional output laser can achieve a double high-power laser by employing a laser resonant cavity. Thus, the average cost and structure size can be further reduced in mass production.

Kilowatt random Raman fiber laser with full-open cavity.

Random Raman fiber laser (RRFL) has been widely studied in high-power laser generation due to its special lasing characteristics. However, all previous high-power results are based on the half-open cavity. In this letter, we demonstrate an applicable high-power RRFL with the simplest structure, that is, a full-open cavity. The lasing dynamic and output characteristics are theoretically and experimentally studied. Laser source with multi-longitudinal modes can result in the random laser output from one side even in the full-open cavity. The ratio of the backward output power is mainly determined by the reflectivity of fiber ends. The experimental results show that such a simple structure can easily generate kilowatts of random laser power and is a promising setup to achieve higher output power, which is also an important platform to study the laser dynamic in high-power full-open cavity without any point-action or regular distributed reflectors.

Tapered Yb-doped fiber enabled a 4†kW near-single-mode monolithic fiber amplifier.

In this Letter, we demonstrate a monolithic high-power master oscillator power amplifier by using a home-made double-clad tapered Yb-doped fiber (T-YDF) with an input end of ∼20/400 µm and an output end of ∼30/600 µm. Thanks to perfect core/cladding matching with the fiber components at both ends of the T-YDF, the laser is pumped bidirectionally and an output power of over 4 kW with a high slope efficiency of 84.1% and excellent beam quality M2 ∼ 1.46 is achieved. In contrast to previous work on common fiber lasers, experimental results also reveal that the co-pump scheme has a higher transverse mode instability (TMI) threshold and power-boosting capability than that of a counter-pump scheme. To the best of our knowledge, this is the highest output power demonstrated to date from such a T-YDF with excellent beam quality. This work indicates the great potential of the T-YDF to realize further power scaling, high laser efficiency, and excellent beam quality in high-power fiber lasers.

Simple method for high average power supercontinuum generation based on Raman mode locking in a quasi-CW fiber laser oscillator.

A simple generation method for a supercontinuum (SC) based on Raman mode locking (RML) in a quasi-continuous wave (QCW) fiber laser oscillator is demonstrated experimentally and analyzed in this paper. The power of the SC is adjustable by changing the pump repetition rate and duty cycle. Under the pump repetition rate of 1 kHz and duty cycle of 11.5%, an SC output with a spectral range of 1000-1500 nm is obtained at a maximum output power of 791 W. The RML is fully analyzed in terms of the spectral and temporal dynamics. RML plays a major role in this process and further enriches the generation of the SC. To the best of the authors' knowledge, this is the first report on directly generating a high and adjustable average power SC using a large-mode-area (LMA)-based oscillator, which provides a proof-of-concept experiment for achieving a high average power SC source and greatly improves the potential application value of the SC source.

Molecular Networking-Based Screening Led to the Discovery of a Cyclic Heptadepsipeptide from an Endolichenic Xylaria sp.

MS/MS-based molecular networking strain prioritization led to the discovery of a group of cyclic depsipeptides from an endolichenic Xylaria sp. The main component, xylaroamide A (1), was obtained by LC-MS-guided isolation. The planar structure of compound 1 was elucidated via 1D and 2D NMR, as well as MS/MS data. The configurations were fully determined by the combination of advanced Marfey's analysis, partial hydrolysis, Mosher's reaction, and GIAO NMR calculation based on a restricted conformational search. A plausible biosynthetic pathway for xylaroamide A (1) involving a rare trans-acting N-methyltransferase is proposed based on bioinformatics analysis. Xylaroamide A (1) exhibited inhibitory activity against cancer cell lines BT-549 and RKO with IC50 values of 2.5 and 9.5 µM, respectively.

High-peak-power pump-modulated quasi-CW fiber laser.

Quasi-continuous wave (CW) laser output with high peak power and high energy is preferred in some industrial applications. Due to the non-linear effects and transverse mode instability, such high-peak-power laser output is difficult to achieve via monolithic fiber lasers in CW mode. For diode-pumped monolithic fiber lasers, by applying overshoot pulse modulation to the pumping diodes, we obtain a pulse laser output with a peak power much higher than that in CW mode. In this paper, it has been theoretically studied that stable pulses with the width of µs level can be generated with quasi-CW operation without distortion according to our simulation. We also experimentally demonstrate a bi-directional pumped quasi-CW monolithic fiber laser operating in CW and pulse modes. In quasi-CW mode, by applying overshoot pulse modulation to the diodes, with a frequency of 1 kHz and a pulse width of 100 µs, the peak power of the output laser reached 9713 W with an average power of 898 W and M2 of 2.4 and 2.3 in the two orthogonal directions, respectively. To the best of our knowledge, this is the very first quasi-CW fiber laser of a 10-kW level with the M2 level of 2.

Leakage channels enabled multi-resonant all-solid photonic bandgap fiber for effective single-mode propagation.

All-solid photonic bandgap fiber (AS-PBGF) has been fully demonstrated to be a promising candidate of large-mode-area fiber for its mode-dependent selectivity and spectral filtering mechanism. In the present work, the concepts of multiple-resonant coupling and leakage channels are taken into consideration simultaneously for mode area scaling of AS-PBGF. The single-mode performance and bending resistance of a modified structure, called leakage channels enabled multi-resonant AS-PBGF (LC-PBGF), are evaluated numerically. Robust single-mode transmission is guaranteed by a specially designed microstructure cladding with only four layers of germanium-doped rods. Multi-resonant cores in the inner layers and leakage channels in the outermost layer, resulting from missing rods in the microstructure cladding, are employed to generate modal dissipation of high-order modes under bent configuration. The missing germanium-doped rods in each layer are properly designed to eliminate the dependence on bending direction, leading to differential bending loss between fundamental mode and high-order-modes with high loss ratio. In addition, some typical derivative structures based on the LC-PBGF concept have also been proved to have great potential for effective single-mode operation.

6 kW single mode monolithic fiber laser enabled by effective mitigation of the transverse mode instability.

The transverse mode instability (TMI) has been one of the main limitations for the power scaling of single mode fiber lasers. In this work, we report a 6 kW single mode monolithic fiber laser enabled by effective mitigation of the TMI. The fiber laser employs a custom-made wavelength-stabilized 981 nm pump source, which remarkably enhanced the TMI threshold compared with the wavelength of 976 nm. With appropriately distributing bidirectional pump power, the monolithic fiber laser is scaled to 6 kW with single mode beam quality (M2<1.3). The stability is verified in a continuous operation for over 2 hours with power fluctuation below 1%.

Numerical investigation for the mode transmission characteristics of a large mode area optical fiber with heterogeneous helical claddings designed for 2.0 µm.

Large mode area (LMA) fibers are widely used in high-power fiber lasers to solve the nonlinear problems. In this Letter, a novel LMA fiber with heterogeneous helical claddings (HHCs) is proposed. A coordinate transformation simulation technique is adopted to analyze the fiber mode transmission characteristics. The effects of the fiber parameters such as θ,Λ,r,n0,n1,n2,n3, and λ on the mode transmission characteristics include loss coefficient L and effective mode area Aeff. When θ=14∘, Λ=22mm, n0=n2=1.439, and n1=n3=1.438 are adopted. The loss coefficients are L01=0.093dB/m, L11=9.47dB/m, and L21=23.36dB/m; the single-mode fiber diameter 2r is at least 60 µm; and the corresponding effective mode field area Aeff is 2025µm2. As the helix pitch is a centimeter order of magnitude and the fiber is all solid state, the HHC fiber is relatively easy to fabricate and convenient for cutting, splicing, etc., and will be well applied in the field of high-power fiber lasers.