Erbium-ytterbium codoped thin-film lithium niobate integrated waveguide amplifier with a 27†dB internal net gain.

A photonic integrated waveguide amplifier fabricated on erbium-ytterbium (Er-Yb) codoped thin-film lithium niobate (TFLN) has been investigated in this work. A small-signal internal net gain of 27 dB is achieved at a signal wavelength of 1532 nm in the fabricated Er-Yb TFLN waveguide amplifier pumped by a diode laser at ≈980 nm. Experimental characterizations reveal the suitability of waveguide fabrication by the photolithography-assisted chemo-mechanical etching (PLACE) technique and also the gain in an Yb-sensitized-Er material. The demonstrated high-gain chip-scale TFLN amplifier is promising for interfacing with established lithium niobate integrated devices, greatly extending the spectrum of TFLN photonic applications.

Electro-optically tunable optical delay line with a continuous tuning range of ∼220 fs in thin-film lithium niobate.

We demonstrate fabrication of a 30-cm-long thin-film lithium niobate (TFLN) optical delay line (ODL) incorporated with segmented microelectrodes of 24-cm total length using the femtosecond laser lithography technique. The transmission spectra of the unbalanced Mach-Zehnder interferometers (MZIs) reveal an ultra-low propagation loss of 0.025 dB/cm. The device exhibits a low half-wave voltage of 0.45 V, corresponding to a voltage-length product of 10.8 V·cm, which is equivalent to 5.4 V·cm in the push-pull configuration. We also demonstrate a high electro-optic (EO) tuning efficiency of 3.146 fs/V and a continuous tuning range of 220 fs in the fabricated ODL.

On-chip single-mode thin-film lithium niobate Fabry-Perot resonator laser based on Sagnac loop reflectors.

We demonstrate an on-chip single-mode Er3+-doped thin-film lithium niobate (Er:TFLN) laser which consists of a Fabry-Perot (FP) resonator based on Sagnac loop reflectors (SLRs). The fabricated Er:TFLN laser has a footprint of 6.5 mm × 1.5 mm with a loaded quality (Q) factor of 1.6 × 105 and a free spectral range (FSR) of 63 pm. We generate the single-mode laser at 1544 nm wavelength with a maximum output power of 44.7 µW and a slope efficiency of 0.18%.

Clinical Application of a Modified Local Transposition Flap (Parallelogram Flap) Surgery in Repairing Fingertip Defects.

OBJECTIVE: Parallelogram flap was performed for transverse finger amputation with the loss of distal pulp, nails, and bone. This study aimed to compare the clinical effects of parallelogram flap, antegrade homodigital island flaps, and reverse digital artery island flaps in fingertip reconstruction. PATIENTS AND METHODS: From January 2017 to January 2021, clinical patient data with parallelogram flaps (78 cases), antegrade homodigital island flaps (78 cases), and reverse digital artery island flaps (78 cases) to repair fingertip defects were collected and analyzed. Two hundred thirty-four cases (234 fingers) were included in our study. All operations were performed by one surgical team. The operation time, 2-point discrimination, total active movement, and the Michigan Hand Questionnaire (MHQ) of the injured fingers were recorded to evaluate the therapeutic effect. RESULTS: Parallelogram flaps (group A), antegrade homodigital island flaps (group B), and reverse digital artery island flaps (group C) had survived postoperatively. The operative duration of group A is the shortest (A < B < C, P < 0.05). At the last 6-month follow-up, there was no difference with the 2-point discrimination of the palmar part of the flaps in group A and group B but better than group C (P < 0.05). There was no difference with the total active movement of injured figures in 3 groups (P > 0.05). The MHQ summary scores in group A were much higher than those in group B and group C (P < 0.05). Evaluation of the MHQ subscale performance showed that the overall hand function, activities of daily living, work performance, and pain score had no differences (P > 0.05), but aesthetics and satisfaction score was the highest in group A (A > B > C, P < 0.05). CONCLUSIONS: The reconstruction of transverse finger amputation using parallelogram flaps can achieve a shorter operation time, a more satisfying appearance. Parallelogram flaps and antegrade homodigital island flaps can both achieve a better sensory recovery. Parallelogram flaps is a better choice for reconstruction of transverse finger amputation with the loss of distal pulp, nails, and bone.

TUDCA protects against tunicamycin-induced apoptosis of dorsal root ganglion neurons by suppressing activation of ER stress.

The existence of endoplasmic reticulum (ER) stress in neurodegenerative diseases has been well established. Tauroursodeoxycholic acid (TUDCA) is a bile acid taurine conjugate derived from ursodeoxycholic acid, which has been reported to exert cytoprotective effects on several types of cells by inhibiting ER stress. The present study explored the effects of TUDCA on primary cultured rat dorsal root ganglion (DRG) neurons. Cell viability and apoptosis of DRG neurons treated with TUDCA and tunicamycin were detected by CellTiter-Blue assay and TUNEL staining, respectively. The protein levels and phosphorylation of apoptosis and ERS-related signaling pathway molecules were detected by western blot, and the mRNA levels of related genes were assessed by reverse transcription-quantitative PCR. Notably, TUDCA had no significant cytotoxic effect on DRG neurons at concentrations ≤250 µM. In addition, the apoptosis induced by tunicamycin exposure was markedly suppressed by TUDCA, as indicated by the percentage of TUNEL-positive cells, the activities of caspases and the changes in expression levels of critical apoptosis factors. Furthermore, the cytotoxicity of tunicamycin in DRG neurons was accompanied by an increase in malondialdehyde (MDA) content, reactive oxygen species (ROS) and lactate dehydrogenase (LDH) production, and a decrease in glutathione (GSH) levels. The changes in oxidative stress-related factors (ROS, LDH, MDA and GSH) were reversed by TUDCA. Furthermore, as determined by western blotting, the increase in C/EBP homologous protein, glucose-regulated protein 78 and cleaved caspase-12 expression following tunicamycin treatment suggested the activation of ER stress. Downregulation of ER stress components and unfolded protein response sensors by TUDCA confirmed the implication of ER stress in the effects of TUDCA on DRG neurons. In conclusion, the present study indicated that TUDCA may protect against tunicamycin-induced DRG apoptosis by suppressing the activation of ER stress. The protective effect and the therapeutic value of TUDCA in nervous system injury require further study in animal models.

Parallelogram flap versus homodigital island flap in the treatment of fingertip defects with bone exposure: a prospective controlled study.

PURPOSE: A modified local transposition flap (we call it "parallelogram flap") surgery was performed for fingertip injuries. This study aimed to compare the clinical effects of parallelogram flap and homodigital island flaps in fingertip reconstruction. METHODS: The study collected patients who underwent parallelogram transposition flaps and homodigital island flaps to repair fingertip defects from 2019 to 2021. 150 cases (150 fingers) were included in our study. All operations were performed by one surgical team. Record the operation time, two-point discrimination (2PD), Total Active Movement (TAM) and the MHQ (Michigan Hand Questionnaire) of the injured fingers to evaluate the therapeutic effect. RESULTS: All parallelogram (Group A) and homodigital island flap (Group B) had survived postoperatively. The operative duration of Group A (31.2 ± 3.3 min) is shorter than Group B (97.8 ± 6.1 min) (P < 0.05). At the 6-month follow-up, there was no difference with the two-point discrimination (2PD) of the palmar part of the flaps and the Total Active Movement (TAM) of injured figures in Group A and Group B. The MHQ summary scores in Group A (94.29 ± 3.14) were much higher than in Group B (91.73 ± 3.41) (P < 0.05). Evaluation of the MHQ subscale performance showed that the overall hand function, activities of daily living, work performance and pain score had no differences(P > 0.05), but aesthetics (92.15 ± 7.16) and satisfaction (92.45 ± 5.61) score in Group A was higher than aesthetics (86.56 ± 5.60) and satisfaction (86.72 ± 8.21) score in Group B (P < 0.05 for both). CONCLUSIONS: The reconstruction using parallelogram flaps is a easier and more versatile treatment with better functions, less morbidity and better aesthetics. This method is a better choice for reconstruction of fingertip injury.

High-Production-Rate Fabrication of Low-Loss Lithium Niobate Electro-Optic Modulators Using Photolithography Assisted Chemo-Mechanical Etching (PLACE).

Integrated thin-film lithium niobate (LN) electro-optic (EO) modulators of broad bandwidth, low insertion loss, low cost and high production rate are essential elements in contemporary interconnection industries and disruptive applications. Here, we demonstrated the design and fabrication of a high performance thin-film LN EO modulator using photolithography assisted chemo-mechanical etching (PLACE) technology. Our device shows a 3-dB bandwidth over 50 GHz, along with a comparable low half wave voltage-length product of 2.16 Vcm and a fiber-to-fiber insertion loss of 2.6 dB. The PLACE technology supports large footprint, high fabrication uniformity, competitive production rate and extreme low device optical loss simultaneously, our result shows promising potential for developing high-performance large-scale low-loss photonic integrated devices.

Laser diode-pumped compact hybrid lithium niobate microring laser.

We demonstrate a compact hybrid lithium niobate microring laser by butt coupling a commercial 980-nm pump laser diode chip with a high-quality Er3+-doped lithium niobate microring chip. Single-mode lasing emission at 1531-nm wavelength from the Er3+-doped lithium niobate microring can be observed with the integrated 980-nm laser pumping. The compact hybrid lithium niobate microring laser occupies the chip size of 3 mm × 4 mm × 0.5 mm. The threshold pumping laser power is 6 mW and the threshold current is 0.5 A (operating voltage 1.64 V) at atmospheric temperature. The spectrum featuring single-mode lasing with small linewidth of 0.05 nm is observed. This work explores a robust hybrid lithium niobate microring laser source which has potential applications in coherent optical communication and precision metrology.

On-chip microdisk laser on Yb3+-doped thin-film lithium niobate.

We demonstrate an on-chip Yb3+-doped lithium niobate (LN) microdisk laser. The intrinsic quality factors of the fabricated Yb3+-doped LN microdisk resonator are measured up to 3.79×105 at a 976 nm wavelength and 1.1×106 at a 1514 nm wavelength. The multi-mode laser emissions are obtained in a band from 1020 to 1070 nm pumped by a 984 nm laser and with the low threshold of 103µW, resulting in a slope efficiency of 0.53% at room temperature. Furthermore, both the second-harmonic frequency of pump light and the sum frequency of the pump light and laser emissions are generated in the on-chip Yb3+-doped LN microdisk, benefiting from the strong χ(2) nonlinearity of LN. These microdisk lasers are expected to contribute to the high-density integration of a lithium niobate on insulator-based photonic chip.

Electro-optically tunable microring laser monolithically integrated on lithium niobate on insulator.

We demonstrate monolithic integration of an electro-optically (EO) tunable microring laser on lithium niobate on insulator (LNOI) platform. The device is fabricated by photolithography assisted chemo-mechanical etching, and the pump laser is evanescently coupled into the erbium (${\rm{E}}{{\rm{r}}^{3 +}}$)-doped lithium niobate (LN) microring laser using an undoped LN waveguide mounted above the microring. The quality factor of the LN microring resonator is measured as high as ${1.54} \times {{1}}{{{0}}^5}$ at the wavelength of 1542 nm. Lasing action can be observed at a pump power threshold below 3.5 mW using a 980 nm continuous-wave pump laser. Finally, tuning of the laser wavelength is achieved by varying the electric voltage on the microelectrodes fabricated in the vicinity of a microring waveguide, showing an EO coefficient of 0.33 pm/V.

An Ultra-High-Q Lithium Niobate Microresonator Integrated with a Silicon Nitride Waveguide in the Vertical Configuration for Evanescent Light Coupling.

We demonstrate the hybrid integration of a lithium niobate microring resonator with a silicon nitride waveguide in the vertical configuration to achieve efficient light coupling. The microring resonator is fabricated on a lithium niobate on insulator (LNOI) substrate using photolithography assisted chemo-mechanical etching (PLACE). A fused silica cladding layer is deposited on the LNOI ring resonator. The silicon nitride waveguide is further produced on the fused silica cladding layer by first fabricating a trench in the fused silica while using focused ion beam (FIB) etching for facilitating the evanescent coupling, followed by the formation of the silicon nitride waveguide on the bottom of the trench. The FIB etching ensures the required high positioning accuracy between the waveguide and ring resonator. We achieve Q-factors as high as 1.4 × 107 with the vertically integrated device.

On-chip tunable microdisk laser fabricated on Er3+-doped lithium niobate on insulator.

We demonstrate a C-band wavelength-tunable microlaser with an Er3+-doped high quality (∼1.8×106) lithium niobate microdisk resonator. With a 976 nm continuous-wave pump laser, lasing action can be observed at a pump power threshold lower than 400 µW at room temperature. Furthermore, the microdisk laser wavelength can be tuned by varying the pump laser power, showing a tuning efficiency of ∼-17.03pm/mW at low pump power below 13 mW, and 10.58 pm/mW at high pump power above 13 mW.

LncRNA HOTTIP leads to osteoarthritis progression via regulating miR-663a/ Fyn-related kinase axis.

BACKGROUND: Long non-coding RNA (lncRNA) has been implicated in the progression of osteoarthritis (OA). This study was aimed to explore the role and molecular mechanism of lncRNA HOXA terminal transcriptional RNA (HOTTIP) in the development of OA. METHODS: The expression of HOTTIP, miR-663a and Fyn-related kinase (FRK) in the OA articular cartilage and OA chondrocyte model induced by IL-1ß was determined by qRT-PCR. CCK-8, colony formation and flow cytometry were used to determine the cell proliferation and apoptosis of OA chondrocytes. The specific molecular mechanism of HOTTIP in OA chondrocytes was determined by dual luciferase reporter assay, qRT-PCR, western blotting and RNA pull-down. RESULTS: The expression of HOTTIP and FRK were up-regulated, while miR-663a was down-regulated in OA cartilage tissues. Knockdown of HOTTIP decreased the proliferation and induced the apoptosis of OA cartilage model cells, while overexpression of HOTTIP increased the proliferation and reduced the apoptosis of OA cartilage model cells. Moreover, HOTTIP could bind to miR-663a as competitive endogenous RNA. Inhibition of miR-663a expression could alleviate the effect of HOTTIP knockdown on the proliferation and apoptosis of OA cartilage model cells. Furthermore, FRK was found to be a direct target of miR-663a, which could markedly down-regulate the expression of FRK in OA chondrocytes, while HOTTIP could remarkably up-regulate the expression of FRK. In addition, miR-663a inhibition increased the proliferation and reduced the apoptosis of OA cells, while FRK knockdown reversed the effect of miR-663a inhibition on the proliferation and apoptosis of OA cells. Meanwhile, overexpression of miR-663a decreased the proliferation and induced the apoptosis of OA cells, while overexpression of FRK reversed the effect of miR-663a overexpression on the proliferation and apoptosis of OA cells. CONCLUSION: HOTTIP was involved in the proliferation and apoptosis of OA chondrocytes via miR-663a/ FRK axis, and HOTTIP/miR-663a/FRK might be a potential target for the treatment of OA.

Polygon Coherent Modes in a Weakly Perturbed Whispering Gallery Microresonator for Efficient Second Harmonic, Optomechanical, and Frequency Comb Generations.

We observe high optical quality factor (Q) polygonal and star coherent optical modes in a lithium niobate microdisk. In contrast to the previous polygon modes achieved by deformed microcavities at lower mechanical and optical Q, we adopt weak perturbation from a tapered fiber for the polygon mode formation. The resulting high intracavity optical power of the polygon modes triggers second harmonic generation at high efficiency. With the combined advantages of a high mechanical Q cavity, we observe optomechanical oscillation in polygon modes for the first time. Finally, we observe frequency microcomb generation from the polygon modes with an ultrastable taper-on-disk coupling mechanism.

Phase-separated condensate-aided enrichment of biomolecular interactions for high-throughput drug screening in test tubes.

Modification-dependent and -independent biomolecular interactions, including protein-protein, protein-DNA/RNA, protein-sugar, and protein-lipid interactions, play crucial roles in all cellular processes. Dysregulation of these biomolecular interactions or malfunction of the associated enzymes results in various diseases; therefore, these interactions and enzymes are attractive targets for therapies. High-throughput screening can greatly facilitate the discovery of drugs for these targets. Here, we describe a biomolecular interaction detection method, called phase-separated condensate-aided enrichment of biomolecular interactions in test tubes (CEBIT). The readout of CEBIT is the selective recruitment of biomolecules into phase-separated condensates harboring their cognate binding partners. We tailored CEBIT to detect various biomolecular interactions and activities of biomolecule-modifying enzymes. Using CEBIT-based high-throughput screening assays, we identified known inhibitors of the p53/MDM2 (MDM2) interaction and of the histone methyltransferase, suppressor of variegation 3-9 homolog 1 (SUV39H1), from a compound library. CEBIT is simple and versatile, and is likely to become a powerful tool for drug discovery and basic biomedical research.

Phase Separation in Regulation of Aggrephagy.

The selective degradation of protein aggregates is called aggrephagy. Misfolded proteins are thought to form aggregates, which are then surrounded by selective autophagy receptors and targeted to autophagosomes for degradation. Recent studies of p62 bodies, PGL granules, and stress granules indicate that proteins targeted for aggrephagy are not simple protein aggregates but rather form liquid-like protein condensates through liquid-liquid phase separation. The liquid-like properties of the condensates and hardening to a gel-like state may be crucial in the initiation of aggrephagy. Dysregulation of phase separation may cause human diseases. Here we review the potential roles of liquid-liquid phase separation in the process of aggrephagy.

Fabrication of a multifunctional photonic integrated chip on lithium niobate on insulator using femtosecond laser-assisted chemomechanical polish.

We report fabrication of a multifunctional photonic integrated chip on lithium niobate on insulator, which is achieved by femtosecond laser-assisted chemomechanical polish. We demonstrate a high-extinction-ratio beam splitter, a 1×6 optical switch, and a balanced 3×3 interferometer on the fabricated chip by reconfiguring the microelectrode array integrated with the multifunctional photonic circuit.

High-Precision Propagation-Loss Measurement of Single-Mode Optical Waveguides on Lithium Niobate on Insulator.

We demonstrate the fabrication of single-mode optical waveguides on lithium niobate on an insulator (LNOI) by optical patterning combined with chemomechanical polishing. The fabricated LNOI waveguides had a nearly symmetric mode profile of ~2.5 µm mode field size (full-width at half-maximum). We developed a high-precision measurement approach by which single-mode waveguides were characterized to have propagation loss of ~0.042 dB/cm.

Fabrication of Crystalline Microresonators of High Quality Factors with a Controllable Wedge Angle on Lithium Niobate on Insulator.

We report the fabrication of crystalline microresonators of high quality (Q) factors with a controllable wedge angle on lithium niobate on insulator (LNOI). Our technique relies on a femtosecond laser assisted chemo-mechanical polish, which allows us to achieve ultrahigh surface smoothness as critically demanded by high Q microresonator applications. We show that by refining the polish parameters, Q factors as high as 4.7 × 107 can be obtained and the wedge angle of the LNOI can be continuously tuned from 9° to 51°.

Broadband Quasi-Phase-Matched Harmonic Generation in an On-Chip Monocrystalline Lithium Niobate Microdisk Resonator.

We reveal a unique broadband natural quasi-phase-matching (QPM) mechanism underlying an observation of highly efficient second- and third-order harmonic generation at multiple wavelengths in an x-cut lithium niobate (LN) microdisk resonator. For light waves in the transverse-electric mode propagating along the circumference of the microdisk, the effective nonlinear optical coefficients naturally oscillate periodically to change both the sign and magnitude, facilitating QPM without the necessity of domain engineering in the micrometer-scale LN disk. The second-harmonic and cascaded third-harmonic waves are simultaneously generated with normalized conversion efficiencies as high as 9.9%/mW and 1.05%/mW^{2}, respectively, thanks to the utilization of the highest nonlinear coefficient d_{33} of LN. The high efficiency achieved with the microdisk of a diameter of ∼30 µm is beneficial for realizing high-density integration of nonlinear photonic devices such as wavelength convertors and entangled photon sources.