Catalytic Atroposelective Synthesis of N-N Axially Chiral Indolylamides.

The catalytic atroposelective synthesis of N-N axially chiral indolylamides was established via dynamic kinetic resolution, which makes use of chiral Lewis base-catalyzed asymmetric acylation of N-acylaminoindoles as a new type of platform molecule with anhydrides. By this strategy, a series of N-N axially chiral indolylamides were synthesized in overall good yields (up to 98%) with excellent enantioselectivities (up to 99% ee). Moreover, some of these N-N axially chiral indolylamides display some extent of anticancer activity, which demonstrates their potential application in medicinal chemistry. Therefore, this work has not only provided a new strategy for the synthesis of N-N axially chiral monoaryl indoles but also offered a new member of N-N axially chiral monoaryl indoles with configurational stability and promising application, thereby solving the challenges in atroposelective synthesis and application of N-N axially chiral monoaryl indoles.

Glucagon-like peptide-1 receptor agonist liraglutide therapy for psoriasis patients with type 2 diabetes: a randomized-controlled trial.

OBJECTIVE: There were some clinical studies on GLP-1R agonist liraglutide therapy for psoriasis patients with type 2 diabetes, but there is a lack of randomized controlled trials and the mechanism of which remains unclear. METHOD: A total of 25 psoriasis patients with type 2 diabetes were randomized 1: 1 divided into the control group (n = 13) or liraglutide group (n = 12) for 12 weeks. We determined the PASI, the DLQI, histopathology of psoriasis skin, and the expression of IL-17, IL-23, and TNF-α in the psoriasis skin. RESULTS: After 12 weeks of treatment, the mean DLQI of the treatment group decreased from 22.00 ± 5.85 to 3.82 ± 3.60 (p < .05). Compared to week 12, the change in the baseline value of PASI and DLQI in the treatment group showed a significant difference compared with the control group (p < .05). The pathological changes of psoriasis skin and the expression of IL-17, IL-23, TNF-α in the psoriasis skin were improved in the treatment group. No serious adverse events occurred. CONCLUSION: The skin lesions in psoriasis patients with type 2 diabetes were significantly improved after treatment with liraglutide, which may be related to the inhibition of the expression of inflammatory factors such as IL-23, IL-17, and TNF-α.

[Preliminary report on partial pressure changes of oxygen and carbon dioxide in umbilical artery and vein before and after the first breath in Chinese neonates II-The personalized analysis of partial pressure of oxygen and carbon dioxide difference between umbilical artery and vein at same time in same newborn].

Objective: In order to explore the mechanism of neonatal spontaneous breathing, the difference of oxygen and carbon dioxide between umbilical cord arteries and veins before the start of spontaneous breathing after birth has been analyzed among people. In this part, the related information is analyzed individually. Methods: After all fetal parents signed the informed consent before birth, and before the newborn was born and did not breathe, the umbilical cord was exposed as quickly as possible, and the heparinized arterial indwelling needle was inserted into the umbilical artery and umbilical vein in the direction of newborn and placenta, and then blood was taken continuously. Although dozens of mothers were selected,but only 3 cases were collected from Pua and Puv blood samplers at the same time for blood gas analysis and determination, and the differences and dynamic changes of umbilical vein and umbilical artery were calculated and analyzed. Results: In all 3 none spontaneous breathing newborns,PuvO2 was significantly higher than PuaO2 at the same time (P<0.01), with an average difference of (24.17±7.09) mmHg; while PuvCO2 was significantly lower than PuaCO2 (all P<0.01), with an average difference of (-7.67±3.70) mmHg.The difference of Puv-uaO2 was significantly higher than those of Puv-uaCO2 (P<0.05). Conclusion: PuaO2 decreases gradually with time (heartbeat frequency) before spontaneous breathing after the delivered fetus as a newborn, and it induces the first inhalation to start spontaneous breathing when it reaches the threshold of triggering breathing.

[Preliminary report on partial pressure changes of oxygen and carbon dioxide in umbilical artery and vein before and after the first breath in Chinese neonates I-The group difference of partial pressure of oxygen and carbon dioxide between umbilical artery and vein in newborns].

Objective: The fetus has no actual respiration, and the newborn begins to breathe after birth. We assume that the first breath dominantly generated by hypoxia. In this study, the changes and lowest limit of blood oxygen partial pressureof umbilical artery (PuaO2) after chemoreceptor were analyzed to explore the mechanism of neonatal spontaneous breathing. Methods: With signed consent form by all fetal parents before birth, 14 newborns successfully completed the umbilical artery or vein catheterization and drawn blood according to the heartbeat. All blood samples analyzed by blood gas analyzer,calculated and analyzed the similarities and differences between umbilical vein(Puv) and umbilical artery(Pua). Results: Although we completed 14 newborns, there were only 9 cases of umbilical artery samples and 8 cases of umbilical vein samples were collected. Only 3 cases collected both Pua and Puv blood samples at the same time (see serial paper II). PuaO2 in gradually decreased with time (heartbeat frequency), until Pua contracted after spontaneous breathing produced about 8~10 heartbeats, and then could not get enough blood samples. Only 3 newborns were able to take blood samples after spontaneous breathing for 8~10 heartbeats, and their PuaO2 were jumped to 186.0, 137.0 and 93.8 mmHg respectively. The mean value of PuaO2 was (25.94±6.79, 18.04~37.51)mmHg, the highest value was (29.11±6.46, 23.00~45.90)mmHg, and the lowest value was (21.34±5.54, 14.00~33.60)mmHg. Although PuvO2 decreased gradually with time (heartbeat) too, most of them also showed the tendency of alternately rising and falling with the regularity of mother's respiration. The mean value of PuvO2 was (53.35±21.35, 32.56~100.73)mmHg, the highest value was (90.38±48.44, 43.40~153.00)mmHg, and the lowest value was (36.96±14.90, 24.80~73.80)mmHg. Although there were large individual differences, the mean, highest and lowest values of PuvO2 were significantly higher than those of PuaO2 (P<0.05); although PuvCO2 slightly lower than PuaCO2, it was no significant difference (P>0.05). Conclusion: PuaO2 decreases gradually with time before spontaneous breathing after the delivered fetus as a newborn, and it induces the first inhalation to start spontaneous breathing when it reaches the threshold of triggering breathing.

Liraglutide improved inflammation via mediating IL-23/Th-17 pathway in obese diabetic mice with psoriasiform skin.

OBJECTIVES: The purpose of this study was to investigate the effect of liraglutide on obesity diabetic mice with psoriasiform skin inflammation. METHODS: Wild-type mice and db/db mice were randomly divided into five groups (n = 6): including the control group which received Vaseline, the imiquimod (IMQ)-induction group and the liraglutide-treatment group. The advanced treatment with liraglutide (0.3 mg/kg/d) for 4 weeks before IMQ induced psoriatic skin inflammation in the db/db + IMQ + Lira group. Basic parameters of diabetes, PASI, histopathology of skin, the expression of IL-17A, IL-23, IL-22, and TNF-α in the skin of back were measured. RESULTS: After IMQ induction, the psoriatic skin inflammation and pathological changes in the db/db + IMQ group were more serious than those in the WT + IMQ group. The glucose metabolism and insulin resistance of in the db/db + IMQ + Lira group were significantly improved, Psoriasis Area and Severity Index (PASI) was significantly reduced, and the protein and mRNA expressions of IL-23, IL-17, IL-22, and TNF-α in the back skin tissues were decreased. CONCLUSIONS: Liraglutide can improve psoriasis skin lesions of obese diabetic mice, and the mechanism may be related to the inhibition of the expression of IL-23, IL-17, IL-22, and TNF-α through the IL-23/Th-17 pathway.

Hundred-watt level linearly polarized visible supercontinuum generation.

An all-fiber linearly polarized supercontinuum (SC) laser source with 93 W average output power and spectrum ranging from 520 nm to 2300 nm is experimentally demonstrated. The linearly-polarized SC is generated in a piece of 2.6 m long polarization-maintaining photonic crystal fiber (PM-PCF), pumped by a polarization-maintaining picosecond Yb-doped master oscillator power amplifier (PM-MOPA). The source exhibits a flat spectrum from 600 nm to 1880 nm at -10 dB level except for the residual pump peak. A new method is proposed to measure the polarization extinction ratio (PER) of each single wavelength of the broadband supercontinuum at a high-power level, resulting in larger than 16 dB PER from 900 nm to 1600 nm and larger than 15 dB PER from 540 nm to 650 nm. To our knowledge, this is the first demonstration of hundred-watt level linearly polarized visible SC and the first demonstration of PER measurement of each single wavelength within such a wide spectrum range.

Treatment with liraglutide, a glucagon-like peptide-1 analogue, improves effectively the skin lesions of psoriasis patients with type 2 diabetes: A prospective cohort study.

BACKGROUND: It has been reported that GLP-1 analogue can improve the skin lesions of psoriasis. However further research is needed to confirm that finding. OBJECTIVE: The study can provide further data regarding the efficacy and safety of GLP-1 analogue liraglutide in the treatment of psoriasis patients with type 2 diabetes. METHODS: We recruit 7 psoriasis patients with type 2 diabetes, and use hypodermic injection with liraglutide1.8 mg. In 12 weeks of treatment, we estimate the difference of before and after respectively, likeBMI, waist circumference, fasting blood glucose, fasting C-peptide, HbA1c, blood lipid levels, CRP, PASI, DLQI, skin tissue and pathological analysis of psoriasis. RESULTS: After 12 weeks of treatment, the mean value of PASI decreased from 15.7 ±â€¯11.8 to 2.2 ±â€¯3.0 (P = 0.03), while the DLQI decreased from 21.8 ±â€¯6 to 4.1 ±â€¯3.9 (P = 0.001). HbA1c was significantly improved after 12 weeks of treatment, decreased to 6.4 ±â€¯0.8% (P = 0.04), the BMI decreased to 21 ±â€¯3 kg m-2 (P < 0.01), and the waist circumference was also significantly improved to 83 ±â€¯1 cm (P < 0.05). And 12 weeks after, the fasting C-peptide levels increased to 1.9 ±â€¯0.5 ng/ml (P = 0.006), HOMA - IR fell to 1.6 ±â€¯0.6 (P = 0.03). Histological analysis showed a reduction in epidermal thickness after treatment. The mean PASI decreased from 15.7 (1.5-31.3) to 2.0 (0.3-8.7) (P = 0.03), the DLQI decreased from 22 (8-27) to 4 (0-10) (P = 0.001). CONCLUSION: GLP-1 analogueliraglutide can improve the skin lesions of psoriasis patients with type 2 diabetes effectively, especially for extremely severe psoriasis patients. Its therapeutic effect may be related to anti-inflammatory, hypoglycemic and reducing weight.

High power LP11 mode supercontinuum generation from an all-fiber MOPA.

High power LP11 mode supercontinuum is generated from 25/250 large mode area (LMA) fiber. A mechanical long period grating (LPG) is utilized to control the transverse modes in the LMA fiber to realize the LP11 mode supercontinuum generation in a master oscillator power amplifier (MOPA) configuration. The generated LP11 mode supercontinuum covers the spectral range from ~900 nm to ~2100 nm with a -30-dB spectral width of ~1200 nm and 50% optical to optical conversion efficiency. The seed laser produces picosecond pulses with 1 MHz repetition rate at the wavelength of 1060 nm. After multi-stage amplification in ytterbium-doped fibers, the average output power is scaled to 54.51 W and 56.79 W respectively for LP11 and LP01 mode, accompanying supercontinuum generation. Obvious difference of supercontinuum generation between the LP01 and LP11 modes is experimentally observed due to the different dispersion characters.

Hyperspectral imaging for the spectral measurement of far-field beam divergence angle and beam uniformity of a supercontinuum laser.

A new novel method, hyperspectral imaging (HSI), is presented in this work to measure the beam divergence angle and beam profile uniformity of supercontinuum lasers. The obtained results of divergence angles are consistent with theoretically calculated values. The uniformity of different-size projected Gaussian beams was measured through referencing the data sets provided by HSI camera under the wavelength variation. HSI, compared with traditional methods, is much faster and capable of providing critical reference to supercontinuum output parameters measurements and practical application in far-field situation.

High-power visible-enhanced all-fiber supercontinuum generation in a seven-core photonic crystal fiber pumped at 1016 nm.

An 80 W 350-2400 nm monolithic supercontinuum (SC) source is reported. The high-power SC is generated in a uniform multi-core photonic crystal fiber (PCF) pumped by a 1016 nm pulsed fiber laser. The specially designed PCF has seven 4.5 µm diameter cores, a 0.85 air-filling fraction, and a zero dispersion wavelength (ZDW) of 991 nm. The 1016 nm pulsed laser delivers up to 114 W average power, which is believed to be the highest currently reported for picosecond fiber lasers working below 1020 nm. In order to ensure a robust and compact all-fiber structure, the pump laser is fusion spliced to the PCF using a selective air-hole collapse technique, achieving an ultra-low splicing loss of 0.2 dB despite the severe mode field mismatch. The proximity of the pump wavelength to the ZDW of PCF leads to enhanced visible generation. The output SC has a high spectral density of up to 108 mW/nm (at 580 nm) and over 50 mW/nm across the entire visible waveband. The achieved short-wavelength edge and high-spectral-power density in the visible region, to the best of our knowledge, are the best results reported for high-power visible SC sources.

Ultraviolet-enhanced supercontinuum generation with a mode-locked Yb-doped fiber laser operating in dissipative-soliton-resonance region.

We experimentally demonstrate an all-fiber, ultraviolet-enhanced, supercontinuum generation in a specifically designed seven-core photonic crystal fiber pumped by a picosecond Yb-doped master oscillator power amplifier (MOPA). The MOPA source is seeded by a giant-chirped Yb-doped mode-locked fiber laser operating in the dissipative-soliton-resonance (DSR) region. The DSR is achieved by using a nonlinear optical loop mirror (NOLM) with a fundamental repetition rate of 4.5 MHz and a central wavelength of 1035 nm. An extremely wide optical spectrum spanning from 350 nm to 2400 nm is obtained with a total output power of 6.86 W.

State distributions in two-dimensional parameter spaces of a nonlinear optical loop mirror-based, mode-locked, all-normal-dispersion fiber laser.

We present the results of numerical simulations of dissipative soliton generation using nonlinear Schrödinger equations in an all-normal-dispersion (ANDi) mode-locked fiber laser based on a nonlinear optical loop mirror (NOLM). Firstly, systematic and computationally intensive analysis of the pulse state distributions in two-dimensional parameter spaces of an ANDi fiber laser was conducted. In addition, we determined that unstable non-vanishing regions including pulsation and noise-like pulses are directly related to the saturable absorptions of NOLMs and that two critical filter bandwidths separate those regions from stable ones. Finally, we found that the multi-pulsing power threshold can be maximized by using an optimal optical filter bandwidth.

High-power transverse-mode-switchable all-fiber picosecond MOPA.

A high-power transverse-mode-switchable all-fiber picosecond laser in a master-oscillator power-amplifier (MOPA) configuration is demonstrated. The master oscillator is a gain-switched laser diode delivering picosecond pulses with 25 MHz repetition rate at the wavelength of 1.06 µm. After multi-stage amplification in ytterbium-doped fibers, the average output power is scaled to 117 W. A mechanical long-period grating is employed as a fiber mode convertor to achieve controllable conversion from the fundamental (LP01) to the second-order (LP11) mode. Efficient mode conversion is demonstrated and the output characteristics for both modes are investigated. It is shown that LP01 and LP11 modes have nearly identical optical-to-optical conversion efficiency during amplification, but the nonlinear spectral degradation is significantly alleviated for LP11 mode operation. Owing to the compact all-fiber architecture, this high-power transverse-mode-switchable fiber laser is reliable during long-term operation and thus promising for many practical applications, e.g. high-resolution laser micro-processing.

Selective transverse mode operation of an all-fiber laser with a mode-selective fiber Bragg grating pair.

We propose a novel approach for achieving selective transverse mode operation of few-mode all-fiber lasers. Lasing in a specific transverse mode is enabled by employing a pair of few-mode fiber Bragg gratings as an efficient transverse mode selector. As a proof-of-principle, we have implemented a ytterbium-doped all-fiber laser operating in the second-order (LP11) transverse mode. The achieved output power is 81 mW, and the slope efficiency is as high as 54%. This simple and compact all-fiber laser is also capable of delivering cylindrical vector beams through appropriate polarization control. Furthermore, the approach has great scalability and can be applied to other working modes and spectral regimes.

Mode-locked all-fiber dumbbell-shaped laser based on a nonlinear amplifying optical loop mirror.

We report a hybrid passively mode-locked dumbbell-shaped fiber laser based on a nonlinear optical loop mirror and a nonlinear amplifying optical fiber-loop mirror. The laser produced noise-like pulses with repetition rate of 8.85 MHz and pulse energy of 16.2 and 26.4 nJ from the two output ports, respectively. Several interesting phenomena are observed and briefly discussed in the paper.

Ultrahigh-brightness, spectrally-flat, short-wave infrared supercontinuum source for long-range atmospheric applications.

Fiber based supercontinuum (SC) sources with output spectra covering the infrared atmospheric window are very useful in long-range atmospheric applications. It is proven that silica fibers can support the generation of broadband SC sources ranging from the visible to the short-wave infrared region. In this paper, we present the generation of an ultrahigh-brightness spectrally-flat 2-2.5 µm SC source in a cladding pumped thulium-doped fiber amplifier (TDFA) numerically and experimentally. The underlying physical mechanisms behind the SC generation process are investigated firstly with a numerical model which includes the fiber gain and loss, the dispersive and nonlinear effects. Simulation results show that abundant soliton pulses are generated in the TDFA, and they are shifted towards the long wavelength side very quickly with the nonlinearity of Raman soliton self-frequency shift (SSFS), and eventually the Raman SSFS process is halted due to the silica fiber's infrared loss. A spectrally-flat 2-2.5 µm SC source could be generated as the result of the spectral superposition of these abundant soliton pulses. These simulation results correspond qualitatively well to the following experimental results. Then, in the experiment, a cladding pumped large-mode-area TDFA is built for pursuing a high-power 2-2.5 µm SC source. By enhancing the pump strength, the output SC spectrum broadens to the long wavelength side gradually. At the highest pump power, the obtained SC source has a maximum average power of 203.4 W with a power conversion efficiency of 38.7%. It has a 3 dB spectral bandwidth of 545 nm ranging from 1990 to 2535 nm, indicating a power spectral density in excess of 370 mW/nm. Meanwhile, the output SC source has a good beam profile. This SC source, to the best of our knowledge, is the brightest spectrally-flat 2-2.5 µm light source ever reported. It will be highly desirable in a lot of long-range atmospheric applications, such as broad-spectrum LIDAR, free space communication and hyper-spectral imaging.

80 nJ ultrafast dissipative soliton generation in dumbbell-shaped mode-locked fiber laser.

A novel all-fiberized dumbbell-shaped mode-locked fiber laser was developed to directly generate 80 nJ dissipative solitons, which can be linearly compressed from 85 to 1.2 ps externally with a diffraction grating pair. The pulse peak power reached 42 kW after compression. With the most available pump power, stable dissipative soliton bundles with up to 628 nJ bundle energy were obtained. The corresponding average output power reached 2.2 W. The employment of dual-nonlinear-optical-loop mirrors and large-mode-area fibers in the cavity played an essential role in improving structural compactness and producing high-energy ultrafast pulses. To the best of our knowledge, these are the most energetic compressible dissipative solitons generated from a strictly all-fiber cavity.

1016nm all fiber picosecond MOPA laser with 50W output.

This paper presents an all fiber high power picosecond laser at 1016 nm in master oscillator power amplifier (MOPA) configuration. A direct amplification of this seed source encounters obvious gain competition with amplified spontaneous emission (ASE) at ~1030 nm, leading to a seriously reduced amplification efficiency. To suppress the ASE and improve the amplification efficiency, we experimentally investigate the influence of the gain fiber length and the residual ASE on the perforemance of the 1016 nm amplifier. The optimized 1016 nm MOPA laser exhibits an average power of 50 W and an optical conversion efficiency of 53%.

Diversified pulse generation from frequency shifted feedback Tm-doped fibre lasers.

Pulsed fibre lasers operating in the eye-safe 2 µm spectral region have numerous potential applications in areas such as remote sensing, medicine, mid-infrared frequency conversion, and free-space communication. Here, for the first time, we demonstrate versatile 2 µm ps-ns pulses generation from Tm-based fibre lasers based on frequency shifted feedback and provide a comprehensive report of their special behaviors. The lasers are featured with elegant construction and the unparalleled capacity of generating versatile pulses. The self-starting mode-locking is initiated by an intra-cavity acousto-optical frequency shifter. Diversified mode-locked pulse dynamics were observed by altering the pump power, intra-cavity polarization state and cavity structure, including as short as 8 ps single pulse sequence, pulse bundle state and up to 12 nJ, 3 ns nanosecond rectangular pulse. A reflective nonlinear optical loop mirror was introduced to successfully shorten the pulses from 24 ps to 8 ps. Beside the mode-locking operation, flexible Q-switching and Q-switched mode-locking operation can also be readily achieved in the same cavity. Up to 78 µJ high energy nanosecond pulse can be generated in this regime. Several intriguing pulse dynamics are characterized and discussed.