LNCHC directly binds and regulates YBX1 stability to ameliorate metabolic dysfunction-associated steatotic liver disease progression.

BACKGROUND AND AIMS: Metabolic dysfunction-associated steatotic liver disease (MASLD) represents the foremost cause of chronic liver disease, yet its underlying mechanisms remain elusive. Our group previously discovered a novel long non-coding RNA (lncRNA) in rats, termed lncHC and its human counterpart, LNCHC. This study aimed to explore the role of LNCHC in the progression of MASLD. METHODS: RNA-binding proteins bound to LNCHC were searched by mass spectrometry. The target genes of LNCHC and Y-Box binding protein 1 (YBX1) were identified by RNA-seq. MASLD animal models were utilised to examine the roles of LNCHC, YBX1 and patatin-like phospholipase domain containing 3 (PNPLA3) in MASLD progression. RESULTS: Here, we identified LNCHC as a native restrainer during MASLD development. Notably, LNCHC directly binds YBX1 and prevents protein ubiquitination. Up-regulation of YBX1 then stabilises PNPLA3 mRNA to alleviate lipid accumulation in hepatocytes. Furthermore, both cell and animal studies demonstrate that LNCHC, YBX1 and PNPLA3 function to improve hepatocyte lipid accumulation and exacerbate metabolic dysfunction-associated steatohepatitis development. CONCLUSIONS: In summary, our findings unveil a novel LNCHC functionality in regulating YBX1 and PNPLA3 mRNA stability during MASLD development, providing new avenues in MASLD treatment.

Integrated Metabolomics and Transcriptomics Analysis of Flavonoid Biosynthesis Pathway in Polygonatum cyrtonema Hua.

Flavonoids, a class of phenolic compounds, are one of the main functional components and have a wide range of molecular structures and biological activities in Polygonatum. A few of them, including homoisoflavonoids, chalcones, isoflavones, and flavones, were identified in Polygonatum and displayed a wide range of powerful biological activities, such as anti-cancer, anti-viral, and blood sugar regulation. However, few studies have systematically been published on the flavonoid biosynthesis pathway in Polygonatum cyrtonema Hua. Therefore, in the present study, a combined transcriptome and metabolome analysis was performed on the leaf, stem, rhizome, and root tissues of P. cyrtonema to uncover the synthesis pathway of flavonoids and to identify key regulatory genes. Flavonoid-targeted metabolomics detected a total of 65 active substances from four different tissues, among which 49 substances were first study to identify in Polygonatum, and 38 substances were flavonoids. A total of 19 differentially accumulated metabolites (DAMs) (five flavonols, three flavones, two dihydrochalcones, two flavanones, one flavanol, five phenylpropanoids, and one coumarin) were finally screened by KEGG enrichment analysis. Transcriptome analysis indicated that a total of 222 unigenes encoding 28 enzymes were annotated into three flavonoid biosynthesis pathways, which were "phenylpropanoid biosynthesis", "flavonoid biosynthesis", and "flavone and flavonol biosynthesis". The combined analysis of the metabolome and transcriptome revealed that 37 differentially expressed genes (DEGs) encoding 11 enzymes (C4H, PAL, 4CL, CHS, CHI, F3H, DFR, LAR, ANR, FNS, FLS) and 19 DAMs were more likely to be regulated in the flavonoid biosynthesis pathway. The expression of 11 DEGs was validated by qRT-PCR, resulting in good agreement with the RNA-Seq. Our studies provide a theoretical basis for further elucidating the flavonoid biosynthesis pathway in Polygonatum.

Optical fiber with homogeneous material by side-array cladding.

Optical fibers are the core elements for various fiber-optic applications in communication, lasers, sensors, tweezers, quantum optics, and bio-photonics. Current optical fibers are based on a core-cladding structure with different refractive indices and are mainly fabricated using the stack-draw method. However, such a traditional fabrication method limits the realization of fibers with various advanced optical materials, thereby restricting the utilization of excellent optical properties offered by these materials. In this study, a novel structure for side-array cladding by laser drilling on the side of the fiber with homogeneous material is proposed. Accordingly, the confinement loss, mode characteristics, birefringence, and dispersion of the side-array cladding fiber are investigated based on the numerical simulation performed via the finite element method. Subsequently, an optimal fiber structure is obtained by taking the crystal material as an example. Essentially, our proposed side-array cladding fiber can eliminate the mismatch problem of core-cladding materials in the current stack-draw fabrication method. Potentially, the proposed approach can serve as a standard design and fabrication method of optical fibers with homogeneous material, by utilizing the rapid development of laser processing. In other words, a large number of advanced optical materials can be fabricated into optical fibers with the proposed technique, thus maximizing their technical advantages for different applications.

Inhibition of miR-188-5p alleviates hepatic fibrosis by significantly reducing the activation and proliferation of HSCs through PTEN/PI3K/AKT pathway.

Persistent hepatic damage and chronic inflammation in liver activate the quiescent hepatic stellate cells (HSCs) and cause hepatic fibrosis (HF). Several microRNAs regulate the activation and proliferation of HSCs, thereby playing a critical role in HF progression. Previous studies have reported that miR-188-5p is dysregulated during the process of HF. However, the role of miR-188-5p in HF remains unclear. This study investigated the potential role of miR-188-5p in HSCs and HF. Firstly, we validated the miR-188-5p expression in primary cells isolated from liver of carbon tetrachloride (CCl4 )-induced mice, TGF-ß1-induced LX-2 cells, livers from 6-month high-fat diet (HFD)-induced rat and 4-month HFD-induced mice NASH models, and human non-alcoholic fatty liver disease (NAFLD) patients. Furthermore, we used miR-188-5p inhibitors to investigate the therapeutic effects of miR-188-5p inhibition in the HFD + CCl4 induced in vivo model and the potential role of miR-188-5p in the activation and proliferation of HSCs. This present study reported that miR-188-5p expression is significantly increased in the human NAFLD, HSCs isolated from liver of CCl4 induced mice, and in vitro and in vivo models of HF. Mimicking the miR-188-5p resulted in the up-regulation of HSC activation and proliferation by directly targeting the phosphatase and tensin homolog (PTEN). Moreover, inhibition of miR-188-5p reduced the activation and proliferation markers of HSCs through PTEN/AKT pathway. Additionally, in vivo inhibition of miR-188-5p suppressed the HF parameters, pro-fibrotic and pro-inflammatory genes, and fibrosis. Collectively, our results uncover the pro-fibrotic role of miR-188-5p. Furthermore, we demonstrated that miR-188-5p inhibition decreases the severity of HF by reducing the activation and proliferation of HSCs through PTEN/AKT pathway.

Promotion of pulse peak power by halving the repetition rate based on a vector soliton.

We report on an all-fiber mode-locked repetition-rate-switch pulse operation in a Yb-doped fiber laser based on a polarization rotation vector soliton. The polarization controller (PC) in a fiber loop and a polarization-dependent isolator at the output port are incorporated into the laser resonator at the switch of the repetition rate. By adjusting the PC in the cavity, the mode locking can be switched between the fundamental repetition rate and half of it with a tiny pulse width change. Also, the halved pulse exhibits unique properties: a huge promotion in energy and peak power. To the best of our knowledge, this is the first all-fiber seed source with a passive switch of the repetition rate based on a vector soliton.

Yb3+ doped gain guided index anti-guided fiber based on the nanoporous silica glass rod.

We report a heavily Yb3+/Al3+/B3+/F- co-doped high silica rod with a negative refractive index relative to pure silica. The high silica rod was fabricated from nanoporous silica rod using glass phase-separation technology. To lower the refractive index, B3+ and F- were simultaneously introduced into the silica rod and the optical properties of the silica rod were investigated. The fiber preform was prepared with the rod-in-tube method by which the Yb3+ doped high silica rod was only used as an active core. The fiber has a core diameter of 80 µm and a cladding diameter of 400 µm. The measurements show that the Yb3+ in the high silica fiber core is 15856 ppm by weight, while the refractive index is 0.0024 lower than that of the inner cladding. The amplification performance of the fiber was investigated. The results indicate that nanoporous silica glass based on the glass phase-separation technology has great potential for gain-guided index anti-guided high silica fiber.

Double negative curvature anti-resonance hollow core fiber.

We report on a double negative curvature anti-resonance hollow core fiber, in which, the cladding is constituted of 6 large tubes and 6 small tubes arranged in a staggered pattern. The simulation shows that the loss of the fiber can reach or even exceed the loss of double-clad negative curvature anti-resonance hollow core fibers in short wavelength band, due to the staggered arrangement of two kind of tubes and the double negative curvature on the core boundary. The best single mode performance with a loss ratio as high as 100,000 between LP11 mode and LP01 mode is obtained due to simultaneously inhibited LP11 modes and LP21 modes in the fiber structure. The reason for loss oscillations in long wavelength band and the fabrication feasibility of proposed fiber are also discussed.

High coupling efficiency technology of large core hollow-core fiber with single mode fiber.

With the research of hollow-core fiber with large core diameter, the coupling efficiency from hollow-core fiber with large core diameter to single-mode fiber is difficult to increase through the traditional technology, we proposed a novel coupling method to improve the coupling efficiency by attaching a pure silica small ball at the front end of single-mode fiber, the coupling efficiency of 50% from hollow-core fiber with a large core diameter of 110 µm to single-mode fiber can be achieved.

532†nm pump induced photo-darkening inhibition and photo-bleaching in high power Yb-doped fiber amplifiers.

A novel method for mitigating photo-darkening and the effective photo-bleaching phenomenon by 532 nm cladding pump in Yb-doped fiber were herein reported. Compared with the pristine fiber, beyond 30% of photo-darkening induced excess loss was suppressed by 532 nm pretreatment. Moreover, the excess loss in the photo-darkened fiber was completely bleached with 532 nm pump. Additionally, the bleached fiber exhibited better photo-darkening resistance. Therefore, for high power application, a 20/400 gamma irradiated fiber was bleached in situ by 532 nm pump and the laser properties were explored. The output power restored to 421W accounting for 82% of the pristine fiber, with the mode instability threshold rising to over 2.6 times and the efficiency increasing from 37% to 63%. The results indicate 532 nm pump has bright prospects for the stable operation of high power fiber lasers.

Mitigation of mode instability in laser oscillators based on deuterium loading.

Ytterbium-doped fiber (YDF) loaded with deuterium is used herein to mitigate mode instability. Experimental results reveal that this method can increase the mode instability threshold in a laser oscillator. Specifically, when the YDF was loaded with deuterium over two- and four-week periods, the mode instability threshold power increased from ∼459 W to ∼533 W (16%) and to ∼622 W (35%), respectively, but the respective laser efficiencies were almost unaffected (71.5% vs. 72.9% and 75.4%). In conclusion, deuterium loading is effective in the mitigation of mode instability. It is envisaged to be applied in the power scaling of high-power fiber lasers.

Numerical investigation of GHz repetition rate fundamentally mode-locked all-fiber lasers.

GHz repetition rate fundamentally mode-locked lasers have attracted great interest for a variety of scientific and practical applications. A passively mode-locked laser in all-fiber format has the advantages of high stability, maintenance-free operation, super compactness, and reliability. In this paper, we present numerical investigation on passive mode-locking of all-fiber lasers operating at repetition rates of 1-20 GHz. Our calculations show that the reflectivity of the output coupler, the small signal gain of the doped fiber, the total net cavity dispersion, and the modulation depth of the saturable absorber are the key parameters for producing stable fundamentally mode-locked pulses at GHz repetition rates in very short all-fiber linear cavities. The instabilities of GHz repetition rate fundamentally mode-locked all-fiber lasers with different parameters were calculated and analyzed. Compared to a regular MHz repetition rate mode-locked all-fiber laser, the pump power range for the mode-locking of a GHz repetition rate all-fiber laser is much larger due to the several orders of magnitude lower accumulated nonlinearity in the fiber cavity. The presented numerical study provides valuable guidance for the design and development of highly stable mode-locked all-fiber lasers operating at GHz repetition rates.

Robust Q-switching based on stimulated Brillouin scattering assisted by Fabry-Perot interference.

Q-switching operation based on stimulated Brillouin scattering (SBS) has been developed for decades due to its inexpensive configuration, high pulse energy output, and the potential to be free from wavelength and material limitations. However, unstable and uncontrollable pulse output affected by SBS's stochastic nature hinders its development. In this work, we demonstrated a unique robust SBS-based Q-switched all-fiber laser. Firstly, a numerical model is developed and a general analysis about the robust Q-switching mechanism is presented. Simulation results show that the spectrum modulation effect such as FP interference is efficient for system to realize steady and controllable output. Secondly, we incorporated a Fabry-Perot (FP) interferometer made of two un-contact end faces of fiber connectors into a SBS-based Q-switched system and demonstrated passively robust Q-switching with simpler and cheaper configuration than most reported ones. Under 600 mW pump power, the SNR was measured to be as high as 62.96 dB, which is the highest SNR obtained from SBS-based Q-switched lasers. To our best knowledge, this is the first demonstration of robust SBS-based Q-switching without any external measures.

Temperature-Insensitive Refractive Index Sensor with Etched Microstructure Fiber.

A Mach-Zehnder interferometer (MZI) based on an etched all-solid microstructure fiber (MOF) has been demonstrated. The MZI works on the basis of interference between the vibrant core and cladding modes in the MOF. The all-solid MOF has a heterostructure cladding composed of Ge-doped rod arrays and pure silica, and thus can support and propagate a vibrant cladding mode with a large mode area. When the outermost cladding of MOF is etched, the cladding mode becomes sensitive to the ambient refractive index (RI). The etched MOF can work as a sensing head for RI sensing. By comparing the interference spectra, the extinction ratio has remained stable at around 20 dB after the MOF was etched. The RI sensing characteristics of the MZI with an etched MOF have also been investigated. The results show that the RI sensitivity can reach up to 2183.6 nm/RIU with a low-temperature coefficient (<10 pm/°C).

Single transverse mode laser in a center-sunken and cladding-trenched Yb-doped fiber.

We report a novel center-sunken and cladding-trenched Yb-doped fiber, which was fabricated by a modified chemical vapor deposition process with a solution-doping technique. The simulation results showed that the fiber with a core diameter of 40 µm and a numerical aperture of 0.043 has a 1217 µm2 effective mode area at 1080 nm. It is also disclosed that the leakage loss can be reduced lower than 0.01 dB/m for the LP01 mode, while over 80 dB/m for the LP11 mode by optimizing the bending radius as 14 cm. A 456 W laser output was observed in a MOPA structure. The laser slope efficiency was measured to be 79% and the M2 was less than 1.1, which confirmed the single mode operation of the large mode area center-sunken cladding-trenched Yb-doped fiber.

Radical passive bleaching of Tm-doped silica fiber with deuterium.

We demonstrate the almost complete 2 µm laser power recovery of the gamma-ray-irradiated thulium (Tm)-doped silica fiber under deuterium loading. The optical-optical slope efficiency and the cladding absorption spectra of the Tm-doped fiber with gamma-ray irradiation and deuterium treatment have been measured for comparison. It was found that the slope efficiency of the irradiated Tm-doped fiber could be recovered to 96.1% of the pristine after deuterium bleaching, which significantly degraded from 60.7% to 25.3% after irradiation. Meanwhile, the additional absorption attenuation of the irradiated Tm-doped with D2 treatment completely vanished. Based on the comprehensive comparison of cladding absorption spectra, the probable mechanism of the deuterium bleaching effect on irradiated Tm-doped fiber has also been discussed.

Confined-doped fiber for effective mode control fabricated by MCVD process.

A confined-doped fiber was fabricated by a modified chemical vapor deposition (MCVD) process based on refractive index matching technology. With theory and experiments, we compared the confined-doped fiber and normal-doped fiber. We found that the confined-doped fiber with a core of 35 µm and 0.07 numerical aperture could achieve single-mode output and improve the beam quality from 2.8 to 1.5 in the fiber laser. Meanwhile, it still possesses high laser efficiency and has good stability of beam quality with the increase in pump power. It suggests that the confined-doped fiber with a MCVD process may be the key material for a high-power fiber laser with excellent beam quality.

Manufacturing a Long-Period Grating with Periodic Thermal Diffusion Technology on High-NA Fiber and Its Application as a High-Temperature Sensor.

We demonstrated a kind of long-period fiber grating (LPFG), which is manufactured with a thermal diffusion treatment. The LPFG was inscribed on an ultrahigh-numerical-aperture (UHNA) fiber, highly doped with Ge and P, which was able to easily diffuse at high temperatures within a few seconds. We analyzed how the elements diffused at a high temperature over 1300 °C in the UHNA fiber. Then we developed a periodically heated technology with a CO2 laser, which was able to cause the diffusion of the elements to constitute the modulations of an LPFG. With this technology, there is little damage to the outer structure of the fiber, which is different from the traditional LPFG, as it is periodically tapered. Since the LPFG itself was manufactured under high temperature, it can withstand higher temperatures than traditional LPFGs. Furthermore, the LPFG presents a higher sensitivity to high temperature due to the large amount of Ge doping, which is approximately 100 pm/°C. In addition, the LPFG shows insensitivity to the changing of the environment’s refractive index and strain.

Mitigation of photodarkening effect in Yb-doped fiber through Na+ ions doping.

In this work, Na+ ions doping into the Yb-doped fiber is proposed to improve the photo-darkening resistance. The results show that the photo-darkening induced excess loss at equilibrium state at 633nm, 702 nm, 810 nm, and 1041 nm is 115.54dB/m, 86.87dB/m, 25.51 dB/m, 2.92 dB/m, respectively, when co-doping with Na+ ions. More than 30% excess loss is reduced comparing to the Yb-doped fiber without Na+ ions. The mechanism of Na+ ions doping to mitigate the PD excess loss is discussed. Besides, we measured the laser efficiency of Yb/Al/Na co-doped fiber to be 76.1%. This result remains almost the same with Yb-doped fiber and proves that the addition of Na+ ions do not deteriorate the fiber slope efficiency. The background loss of the two fibers also stays close. The results indicate this method is promising in high power fiber laser development.

Yb3+ heavily doped photonic crystal fiber lasers prepared by the glass phase-separation technology.

We report a Yb3+ heavily doped photonic crystal fiber with 30 µm core diameter manufactured for the first time by an alternative technique. Silica core rods with a diameter of 3 mm and a length of 280 mm were prepared by the sodium-borosilicate glass phase-separation technology. The measurements show that the fiber has an Yb3+ concentration of 22810 ppm by weight, and a resultant absorption of approximately 8.5 dB/m at 976 nm. The Yb3+ ions are distributed throughout the fiber core with an excellent homogeneity. The laser performance demonstrates a high slope efficiency of 64.5% for laser emission at 1033.4 nm and a low power threshold of 3 W within a short fiber length of 1 m. This novel approach provides an alternative means of preparing large active silica rods with high doping levels and excellent material homogeneity for large mode area fibers with complex designs.

Passively Q-switched Yb-doped all-fiber ring laser based on SBS feedback.

We report on a passively Q-switched Yb-doped all-fiber (YDF) ring laser based on stimulated Brillouin scattering (SBS) feedback in a 20-m single-mode fiber (SMF). The Q-switched pulses are generated from the Stokes pulses of SBS and amplified in the YDF. The 10-ns self-Q-switched pulses with ∼1 kW maximum peak power are obtained. The repetition frequency of the pulse train is tuned from 4 to 12.6 kHz by changing the pump power in the experiment. A bandpass filter inserted in the laser cavity was used to suppress the time jitter of the Q-switched pulses.