Single-cell RNA-sequencing reveals the transcriptional landscape of lacrimal gland in GVHD mouse model.

PURPOSE: To investigate the global transcriptional landscape of lacrimal gland cell populations in the GVHD mouse model. METHODS: Single-cell RNA sequencing and further bioinformatic analysis of dissociated lacrimal gland (LG) cells from the mouse model were performed. Parts of transcriptional results were confirmed by immunofluorescence staining. RESULTS: We identified 23 cell populations belonging to 11 cell types. In GVHD LG, the proportion of acinar cells, myoepithelial cells, and endothelial cells was remarkably decreased, while T cells and macrophages were significantly expanded. Gene expression analysis indicated decreased secretion function, extracellular matrix (ECM) synthesis, and increased chemokines of myoepithelial cells. A newly described epithelial population named Lrg1high epithelial cells, expressing distinct gene signatures, was exclusively identified in GVHD LG. The fibroblasts exhibited an inflammation gene pattern. The gene pattern of endothelial cells suggested an increased ability to recruit immune cells and damaged cell-cell junctions. T cells were mainly comprised of Th2 cells and effective memory CD8+ T cells. GVHD macrophages exhibited a Th2 cell-linked pattern. CONCLUSIONS: This single-cell atlas uncovered alterations of proportion and gene expression patterns of cell populations and constructed cell-cell communication networks of GVHD LG. These data may provide some new insight into understanding the development of ocular GVHD.

CXXC5 drove inflammation and ovarian cancer proliferation via transcriptional activation of ZNF143 and EGR1.

CXXC5, a zinc-finger protein, is known for its role in epigenetic regulation via binding to unmethylated CpG islands in gene promoters. As a transcription factor and epigenetic regulator, CXXC5 modulates various signaling processes and acts as a key coordinator. Altered expression or activity of CXXC5 has been linked to various pathological conditions, including tumorigenesis. Despite its known role in cancer, CXXC5's function and mechanism in ovarian cancer are unclear. We analyzed multiple public databases and found that CXXC5 is highly expressed in ovarian cancer, with high expression correlating with poor patient prognosis. We show that CXXC5 expression is regulated by oxygen concentration and is a direct target of HIF1A. CXXC5 is critical for maintaining the proliferative potential of ovarian cancer cells, with knockdown decreasing and overexpression increasing cell proliferation. Loss of CXXC5 led to inactivation of multiple inflammatory signaling pathways, while overexpression activated these pathways. Through in vitro and in vivo experiments, we confirmed ZNF143 and EGR1 as downstream transcription factors of CXXC5, mediating its proliferative potential in ovarian cancer. Our findings suggest that the CXXC5-ZNF143/EGR1 axis forms a network driving ovarian cell proliferation and tumorigenesis, and highlight CXXC5 as a potential therapeutic target for ovarian cancer treatment.

All-solid-state ultrafast 2 µm laser with 1.83 W output power.

In this paper, a high-power all-solid-state ultrafast 2 µm mode-locked laser is investigated. The particularity of this laser is the simultaneous utilization of two Tm:YAP crystals in the same resonant cavity, independently pumped by two laser diodes. Using a 20% output coupler, pulses with output power as high as 1.83 W are achieved at a wavelength of 1938 nm with a pulse duration of 1.97 ps and a pulse repetition frequency of 100 MHz. To our knowledge, this mode-locked laser achieves the highest output power of any mode-locked Tm:YAP ultrafast laser reported to date. In addition, this paper provides a new approach to solve the problem of low output power due to multi-mode low-brightness laser diode pumping.

A novel homozygous nonsense variant of AK7 is associated with multiple morphological abnormalities of the sperm flagella.

RESEARCH QUESTION: Is the novel homozygous nonsense variant of AK7 associated with multiple morphological abnormalities of the sperm flagella (MMAF), a specific type of oligoasthenoteratozoospermia leading to male infertility? DESIGN: Whole-exome sequencing and Sanger sequencing were performed to identify potential gene variants. Immunoblotting and immunofluorescence were applied to confirm the relationship between mutated genes and disease phenotypes. The concentration of reactive oxygen species and the rate of apoptosis were measured to evaluate the mitochondrial function of spermatozoa. Transmission electron microscopy and scanning electron microscopy were employed to observe sperm ultrastructure. RESULTS: A novel homozygous nonsense variant of AK7, c.1153A>T (p. Lys385*), was identified in two infertile siblings with asthenoteratozoospermia through whole-exome sequencing. Both immunoblotting and immunofluorescence assays showed practically complete absence of AK7 in the patient's spermatozoa. Additionally, the individual with the novel AK7 variant exhibited a phenotype characterized by severe oxidative stress and apoptosis caused by mitochondrial metabolic dysfunction of spermatozoa. Notably, remarkable flagellar defects with multiple axonemes in uniflagellate spermatozoa, accompanied by mitochondrial vacuolization, were observed; this has not been reported previously in patients with other AK7 variants. CONCLUSIONS: This study found that a novel identified homozygous nonsense variant of AK7 may be associated with MMAF-related asthenoteratozoospermia. The observed functional associations between mitochondria and sperm flagellar assembly provide evidence for potential mutual regulation between AK7 and flagella-associated proteins during spermatogenesis.

Sub-50-fs Kerr-lens mode-locked Yb-doped fluoride laser with 44% optical efficiency.

Yb-doped fluoride has been demonstrated to be potential crystals for application in efficient ultrafast lasers. However, the trade-off between the shorter pulses with higher efficiencies is a challenge. In this work, using Y b,G d:C a S r F 2 crystal, we report on a sub-50-fs Kerr-lens mode-locked oscillator with an optical efficiency up to 44%. Pumped by a 976-nm diffraction-limited fiber laser and using chirped mirrors combined with prism pairs for the dispersion compensation, a pulse as short as 46 fs was obtained with 620-mW output power, corresponding to an optical efficiency more than 40%. Stable Kerr-lens mode-locking with RMS of output power lower than 0.3% and beam quality factors M 2<1.14 were achieved. Moreover, a maximum output power of 780 mW was obtained in continuous-wave operation with 55.3% optical efficiency. To the best of our knowledge, the results in this work represent the shortest pulses generated from Yb-doped fluoride lasers as well as the highest optical efficiencies ever reported in sub-100 fs Yb bulk lasers.

FBXO5-mediated RNF183 degradation prevents endoplasmic reticulum stress-induced apoptosis and promotes colon cancer progression.

Endoplasmic reticulum (ER) stress induces the unfolded protein response (UPR), and prolonged ER stress leads to cell apoptosis. Despite increasing research in this area, the underlying molecular mechanisms remain unclear. Here, we discover that ER stress upregulates the UPR signaling pathway while downregulating E2F target gene expression and inhibiting the G2/M phase transition. Prolonged ER stress decreases the mRNA levels of E2F2, which specifically regulates the expression of F-Box Protein 5(FBXO5), an F-box protein that functions as an inhibitor of the anaphase-promoting complex/cyclosome (APC/C) ubiquitin ligase complex. Depletion of FBXO5 results in increased ER stress-induced apoptosis and decreased expression of proteins related to PERK/IRE1α/ATF6 signaling. Overexpression of FBXO5 wild-type (not its ΔF-box mutant) alleviates apoptosis and the expression of the C/EBP Homologous Protein (CHOP)/ATF. Mechanistically, we find that FBXO5 directly binds to and promotes the ubiquitin-dependent degradation of RNF183, which acts as a ubiquitin E3 ligase in regulating ER stress-induced apoptosis. Reversal of the apoptosis defects caused by FBXO5 deficiency in colorectal cancer cells can be achieved by knocking down RNF183 in FBXO5-deficient cells. Functionally, we observed significant upregulation of FBXO5 in colon cancer tissues, and its silencing suppresses tumor occurrence in vivo. Therefore, our study highlights the critical role of the FBXO5/RNF183 axis in ER stress regulation and identifies a potential therapeutic target for colon cancer treatment.

Sub-100-fs Kerr-lens mode-locked Yb:Lu2O3 laser with more than 60% optical efficiency.

Yb-doped sesquioxides represent one of the most excellent laser crystals applying for high-power ultrafast lasers owing to their very high thermal conductivities and broadband emission spectra. Pumped by a high-brightness Yb-fiber laser at 976 nm, the Yb:Lu2O3 laser delivers a maximum output power that amounts to 3.55 W in the continuous-wave regime with an optical efficiency of 75%. In the mode-locked regime, 90-fs pulses were generated via soft-aperture Kerr-lens mode-locking at 1080.6 nm with an average output power of 2.85 W, which corresponds to an optical efficiency of 60.3% and a slope efficiency of 68.8%. Average output power of the mode-locked Yb:Lu2O3 laser can be further scaled to 3.05 W at the expense of the pulse duration (178 fs), which corresponds to an optical efficiency as high as 64.5%. To the best of our knowledge, it is the highest optical efficiency ever reported from any solid-state Kerr-lens mode-locked Yb lasers.

67†mJ, 137†ns narrow bandwidth 355†nm UV laser.

A high-efficiency, high-energy, narrow bandwidth, hundred-nanosecond pulse width 355 nm ultraviolet (UV) laser was realized. A high-energy single-frequency 1064 nm fundamental laser was demonstrated firstly with multistage end-pumped preamplifiers and side-pumped main amplifiers. The corresponding pulse energy, repetition rate, pulse duration, bandwidth, and beam quality factor M2 were determined to be 221 mJ, 100 Hz, 156 ns, 2.25 MHz, and 1.23, respectively. By using type-I phase-matching LBO crystal for second harmonic generation (SHG) and type-II phase-matching LBO crystal for the sum frequency generation of the third harmonic, 67 mJ, a narrow bandwidth 355 nm UV laser was obtained with a pulse width of 137 ns and an energy stability of RMS < 1.2%@2 h. The fundamental to UV optical conversion efficiency was 30.3%. Our results provided a new way for generating high-energy, narrow bandwidth hundred-nanosecond 355 nm UV lasers used for direct-detection Doppler wind lidar (DWL) system.

Advances in swept-source optical coherence tomography and optical coherence tomography angiography.

Background: The fast development of swept-source optical coherence tomography (SS-OCT) and swept-source optical coherence tomography angiography (SS-OCTA) enables both anterior and posterior imaging of the eye. These techniques have evolved from a research tool to an essential clinical imaging modality. Main text: The longer wavelength and faster speed of SS-OCT and SS-OCTA facilitate better visualization of structure and vasculature below pigmented tissue with a larger field of view of the posterior segment and 360-degree visualization of the anterior segment. In the past 10 years, algorithms dealing with OCT and OCTA data also vastly improved the image quality and enabled the automated quantification of OCT- and OCTA-derived metrics. This technology has enriched our current understanding of healthy and diseased eyes. Even though the high cost of the systems currently limited the widespread use of SS-OCT and SS-OCTA at the first beginning, the gap between research and clinic practice got obviously shortened in the past few years. Conclusions: SS-OCT and SS-OCTA will continue to evolve rapidly, contributing to a paradigm shift toward more widespread adoption of new imaging technology in clinical practice.

Rapid flattening of massive hemorrhagic retinal pigment epithelial detachment secondary to polypoidal choroidal vasculopathy after surgery.

Purpose: To report 2 polypoidal choroidal vasculopathy (PCV) patients whose massive hemorrhagic pigment epithelial detachments (PEDs) were flattened within a short period after surgery. Observations: Two PCV patients who presented with submacular hemorrhage and massive hemorrhagic PEDs with sizes of more than 50 disc areas underwent pars plana vitrectomy combined with subretinal injection of tissue plasminogen activator (tPA), intravitreous injection of anti-vascular endothelial growth factor medicine, and perfluoropropane tamponade. The massive hemorrhagic PEDs were flattened within a short period after both surgeries, and both patients experienced improved visual acuity. Conclusions: These findings suggest that subretinal injection of tPA together with perfluoropropane tamponade promotes the rapid clearance of hemorrhage under RPE.

Evaluation of a new Q-switched Nd:YAG laser on premacular hemorrhage.

BACKGROUND: Premacular hemorrhage is among the causes of sudden deterioration of visual acuity. This study aimed to investigate the therapeutic outcomes of a new Q-switched Nd:YAG laser on premacular hemorrhage. METHODS: Retrospective, case series study of 16 eyes from 16 patients diagnosed with premacular hemorrhage, including 3 cases of Valsalva retinopathy, 8 cases of retinal macroaneurysm, 3 cases of diabetic retinopathy, 1 case of trauma-related hemorrhage and 1 case with leukemia. A 1064nm Q-switched Nd:YAG laser was performed to puncture the posterior hyaloid and inner limiting membrane to drain the hemorrhage. RESULTS: The success rate of 16 patients with premacular hemorrhage drainage was 100% in this study. Improved visual acuity was observed in each patient. CONCLUSIONS: In this case series of 16 patients, the new Q-switched Nd:YAG laser was successful in draining premacular hemorrhage with no serious complications.

A Modified Technique for Preventing Lens-Iris Diaphragm Retropulsion Syndrome in Vitrectomized Eyes during Phacoemulsification.

BACKGROUND: Lens-iris diaphragm retropulsion syndrome (LIDRS) is common in vitrectomized or high myopic eyes during phacoemulsification. We evaluated the results of a modified technique for cataract treatment using phacoemulsification in vitrectomized eyes. METHODS: In this retrospective study, we enrolled thirty-four vitrectomized eyes treated with modified phacoemulsification (Modified Group) and nineteen vitrectomized eyes treated with routine phacoemulsification (Control Group). The modified technique comprised irrigation with a balanced salt solution underneath the pupil before phacoemulsification instrument entry, lens implantation and stromal hydration to stabilize the anterior chamber and equilibrate the pressure between the anterior chamber and posterior cavity. RESULTS: We compared the incidences of intra and postoperative complications and visual outcomes between modified and routine phacoemulsification. Pain, LIDRS and difficulty in stromal hydration were significantly more common in the Control Group than in the Modified Group (p < 0.05). There were no significant differences in the rates of posterior capsular rupture, iris trauma, lens dislocation, or posterior capsular opacification between the Modified and Control Groups (p > 0.05). However, there was no significant difference in visual acuity between the groups (p > 0.05). Complications such as loss of nuclear fragments into the vitreous cavity, cystoid macular edema, retina redetachment, suprachoroidal hemorrhage and vitreous hemorrhage did not occur either intra or postoperatively in any of our patients. CONCLUSIONS: Our modified technique prevents LIDRS and complications arising during cataract surgery in vitrectomized eyes. Aside from this, the results of modified and routine phacoemulsification are similar in vitrectomized eyes.

Self-Q-switched Er:Lu2O3 laser at 2.74 µm.

A diode-pumped self-Q-switched 2.74 µm Er:Lu2O3 crystal solid-state laser has been experimentally and theoretically studied. Without any additional modulation elements, stable self-Q-switched pulses with a pulse width of 145.3 ns, a repetition rate of 227.8 kHz, and an average output power of 877 mW were generated. Considering the excited-state absorption on the laser photons of the Er:Lu2O3 crystal, we have simulated the dynamic process of self-pulsed generation by solving the rate equations numerically. The simulation results are consistent with the typical characteristics of a Q-switched laser.

Passively Q-switched single crystal fiber pulsed laser at 1.05†µm with T3C2Tx as the saturable absorber.

In this paper, Ti3C2Tx MXene prepared by LiF/HCl etching method was spin-coated on glass substrate and sapphire substrate as the saturable absorber (SA), and the MXene SA is combined with Yb: LuAG single crystal fiber (SCF) for the first time to achieve a 1.05 µm passively Q-switched pulsed laser output with the average power, pulse width, and repetition frequency of 1.989 W, 149.6 ns, and 365.44 kHz, respectively, which is the highest average power ever reported for passively Q-switched SCF pulsed lasers. This work enriches the research on SCF pulsed lasers and provides a feasible approach for achieving high-power all-solid-state pulsed lasers.

Direct generation of continuous-wave and passively Q-switched visible vortex beams from a doughnut-shaped diode-pumped Pr: YLF laser.

We demonstrate the direct generation of visible vortex beams (LG01 mode) from a doughnut-shaped diode-pumped Pr:YLF laser. In continuous-wave mode, the maximum vortex output power was 36 mW at 523 nm, 354 mW at 607 nm, 838 mW at 639 nm, 722 mW at 721 nm, respectively. Moreover, based on this operation, the orange and red passively Q-switched vortex lasers were also achieved by inserting a Co:MgAl2O4 crystal into the laser cavity as a saturable absorber. The shortest pulse width of Q-switched vortex laser was 58 ns for 607 nm, and 34 ns for 639 nm, respectively. Our work provides a reliable and efficient method for the direct generation of visible vortex lasers for potential applications.

High output mode-locked laser empowered by defect regulation in 2D Bi2O2Se saturable absorber.

Atomically thin Bi2O2Se has emerged as a novel two-dimensional (2D) material with an ultrabroadband nonlinear optical response, high carrier mobility and excellent air stability, showing great potential for the realization of optical modulators. Here, we demonstrate a femtosecond solid-state laser at 1.0 µm with Bi2O2Se nanoplates as a saturable absorber (SA). Upon further defect regulation in 2D Bi2O2Se, the average power of the mode-locked laser is improved from 421 mW to 665 mW, while the pulse width is decreased from 587 fs to 266 fs. Moderate Ar+ plasma treatments are employed to precisely regulate the O and Se defect states in Bi2O2Se nanoplates. Nondegenerate pump-probe measurements show that defect engineering effectively accelerates the trapping rate and defect-assisted Auger recombination rate of photocarriers. The saturation intensity is improved from 3.6 ± 0.2 to 12.8 ± 0.6 MW cm-2 after the optimized defect regulation. The enhanced saturable absorption and ultrafast carrier lifetime endow the high-performance mode-locked laser with both large output power and short pulse duration.

OCT biomarkers related to subthreshold micropulse laser treatment effect in central serous chorioretinopathy.

BACKGROUND: To identify the OCT biomarkers related to the anatomical outcomes in eyes with central serous chorioretinopathy (CSCR) after subthreshold micropulse laser (SML) treatment. METHODS: Patients with CSCR underwent SML were enrolled in this retrospective study. Only patients who underwent enhanced depth imaging optical coherence tomography (EDI-OCT) examination before and after SML were selected. Patients were divided into two groups based on whether subretinal fluid (SRF) absorbed or not after SML. Group 1 was the SRF resolved group, and Group 2 was the SRF non-resolved group. Factors including age and gender, duration of symptoms, CSCR history, the height of SRF at baseline, retinal pigment epithelium (RPE) /inner choroid alterations, as well as subfoveal choroidal thickness (SFCT) of the affected eye and the fellow eye before and after SML were recorded and compared between two groups. Longitudinal change of SFCT of a subgroup of patients were analyzed. RESULTS: A total of 58 eyes of 58 patients were involved in this study. SRF of 31 eyes got completely absorbed, and SRF of 27 eyes was retained after SML. Logistic regression analysis revealed baseline SFCT of the affected eye (OR = 1.007, 95% CI: 1.001-1.012, P = 0.019) and RPE/inner choroid alterations (OR = 25.229, 95% CI: 2.890-220.281, P = 0.004) were correlated with SML efficacy. Thirty-three eyes of 33 patients were enrolled in the subgroup analysis. A significant difference of SFCT changes between two groups were demonstrated (P = 0.001). The difference of SFCT between baseline and three months after SML was also related to SRF resolution (OR = 0.952, 95% CI: 0.915-0.990, P = 0.014). CONCLUSION: Baseline SFCT, change of SFCT at 3-month after treatment, and RPE/inner choroid alterations were the OCT biomarkers related to SRF resolution after SML treatment.

Modified Frantz-Nodvik equation and numerical simulation of a high-power Innoslab picosecond laser amplifier.

A modified Frantz-Nodvik (F-N) equation and a simple one-dimensional unfolded slicing model for numerically simulating high-power Innoslab picosecond amplifier are developed for the first time. The anisotropic stimulated emission cross-section of laser crystal, the influence of the tilted optical path, the spatial overlap of the seed and pump laser, as well as the pump absorption saturation effect are considered. Based on the as-developed model, 4-, 6- and 8-pass schemes high-power Nd:YVO4 Innoslab picosecond amplifiers are designed with output powers of 76.2 W, 81.4 W, and 85.5 W, respectively. The experimental results agree well with that of numerical simulation, indicating that our model is a powerful tool and paves a new way for designing and optimizing high-power Innoslab picosecond laser amplifier.

Clinical Study on the Treatment of Benign Prostatic Hyperplasia by Embolization of Prostate Artery Based on Embosphere Microspheres and Gelatin Sponge Granules.

Prostatic hyperplasia can cause dysuria, such as frequent urination, urgency of urination, increased nocturia, poor urination, and other symptoms, which seriously affect the quality of life of old men. We aim to compare and analyze the safety and clinical effect of embolization of the target blood vessels of ruptured prostatic hyperplasia with gelatin sponge particles and embosphere microspheres. Methods. The transcatheter MRI was performed in 422 patients. Among them, 198 patients were treated with gelfoam particles and 224 patients were treated with embosphere microspheres. The clinical effect and adverse reactions were observed and analyzed by biochemical and imaging examination. Four hundred and twenty two cases were hemostasis. In the gelatin sponge group, 34 patients had recurrent bleeding 24-36 hours after embolization, 122 patients had different degrees of elevation of prostatic hyperplasia transaminase (31 cases increased to more than 1000 U/L), 198 patients had different degrees of elevation of bilirubin; in the microsphere group, there was no significant difference in prostatic hyperplasia function indexes between the two groups. Conclusion. Compared with the gelfoam embolic agent, the embosphere embolic microsphere has a good efficacy and safety in the treatment of prostatic hyperplasia rupture and hemorrhage, with a light adverse reaction, a low probability of recanalization, and little damage to the postoperative prostatic hyperplasia function, which is conducive to the benign recovery of perioperative patients and is worthy of clinical application.