High-average-power single-frequency pulse optical parametric oscillator based on pulse-integrated seed-injection automatic locking.

Near-infrared nanosecond (ns) single-longitudinal-mode (SLM) pulse light generated from an optical parametric oscillator (OPO) is an important source in nonlinear optics and high-precision spectral analysis. In this Letter, a stable SLM near-infrared ns pulse light source generated from the OPO is presented, which is achieved by developing a seed-injection automatic locking technique based on a pulse-integrated photodetector (PIPD). Depending on the PIPD, the peak power of the pulse light detected by the photodiode is converted to the average power by integrating several pulses. As a result, the detector saturation is thoroughly eliminated, and the interference signal including the resonance point between seed and pulse lights can easily be attained by scanning the resonator length. On this basis, a microcontroller unit (MCU) is employed to realize automatic locking by looking for the minimum value of the interference signal. Finally, a SLM 824 nm pulse light source with an output power of 20.5 W and a linewidth of 51.42 MHz is obtained. The presented method can pave the way to implement a low-cost and compact high-average-power SLM pulse OPO.

A novel reverse perilesional home phototherapy can promote the repigmentation of vitiligo patches with complete leukotrichia: A 12-week, open-label, double-arm, multicenter, randomized clinical trial.

BACKGROUND/PURPOSE: Existing phototherapies are ineffective for treating patients with vitiligo with complete leukotrichia. We compared the efficacy of reverse perilesional irradiation, during which only the lesional areas are covered, with conventional narrowband ultraviolet B (NB-UVB) home phototherapy for repigmentation of non-segmental vitiligo in patients with complete leukotrichia. METHODS: This was a 12-week, open-label, double-arm, multicenter clinical trial, with a total of 121 patients with non-segmental vitiligo who were randomly divided into two groups (both received topical tacrolimus): the conventional NB-UVB irradiation (CI) and reverse perilesional NB-UVB irradiation (RI) groups. RESULTS: A statistically significant difference in improvement from baseline was observed in the RI group compared with the findings in the CI group (-30.8% ± 11.8% vs. -25.5% ± 11.05%, respectively [p = .010]; pair-wise comparison p = .900 at week 4, p = .104 at week 8, and p = .010 at week 12). At week 12, the average percentage change from baseline of leukotrichia in the irradiation area significantly decreased from 100% to 82.2% ± 13.65% in the RI group, and from 100% to 88.7% ± 9.64% in the CI group (p = .027). Adverse events were minor, including desquamation, dryness, erythema, and blisters. No severe or lasting side effects were observed during the study. CONCLUSION: RI mediated better repigmentation of vitiligo with complete leukotrichia than CI.

Efficacy and safety of Ruxolitinib, Crisaborole, and Tapinarof for mild-to-moderate atopic dermatitis: a Bayesian network analysis of RCTs.

Given the lack of head-to-head studies of novel non-steroidal molecule topical therapies in mild-to-moderate atopic dermatitis (AD), network meta-analyses (NMAs) can provide comparative efficacy and safety data for clinical decision-making. In this NMA, we performed a literature search until 01 March 2023 for eligible studies written in English using databases, including PubMed, EMBASE, Cochrane Library, and ClinicalTrials.gov. Only double-blind randomized clinical trials (RCTs) with topical Ruxolitinib, Crisaborole, or Tapinarof versus vehicle for patients with mild-to-moderate AD were included. Baseline and follow-up data were extracted. Efficacy was evaluated using Investigator's Global Assessment (IGA) achieving "clear" or "almost clear," with 2 points or more improvement from baseline at the end of treatment, referred to as "IGA success." For binary outcomes, we analyzed in random-effects Bayesian NMA consistency models to compare the efficacy of these 3 topical therapies by odds ratio (OR) with 95% credibility interval (CrI). Overall, 10 phase 2 or phase 3 RCTs were identified, which included 4010 patients with mild to moderate AD. Compared with the topical vehicle control, all these 3 treatments had higher response rate of "IGA success" at the end of trial (Ruxolitinib 1.5% b.i.d: OR, 11.94; 95%CrI, 6.28-23.15; Crisaborole 2% b.i.d: OR, 2.08; 95%CrI, 1.46-3.52; Tapinarof 1% b.i.d: OR, 2.64; 95%CrI, 0.75-9.70). Notably, Ruxolitinib 1.5% b.i.d. had the highest probability of achieving "IGA success" in ranking analysis (Rank 1, SUCRA = 0.75) and lower risk of AE (Rank 8, SUCRA = 0.22). Besides, there was no difference in treatment-related adverse events between 3 therapies. Heterogeneity was not significant across studies.

Identification of Shared Biomarkers and Immune Infiltration Signatures between Vitiligo and Hashimoto's Thyroiditis.

Background: Vitiligo and Hashimoto's thyroiditis (HT) are concomitant autoimmune diseases characterized by the destruction of melanocytes or thyrocytes. We aimed to explore the immunological mechanism of this comorbidity and screen their potential biomarkers. Methods: We downloaded the microarray datasets from the GEO database. Differentially expressed genes (DEGs) and immune-related genes (IRGs) were selected. The immune-related differentially expressed genes (IRDEGs) were obtained by taking the intersection. Candidate biomarkers were elected by Cytoscape software. CIBERSORT was used to depict immune cell infiltration prospects. Correlation analysis was conducted between infiltrating cells and several indicators. The results were validated by real-time quantitative PCR (RT-qPCR). Results: Three datasets and 60 IRDEGs were obtained in total. Pathway enrichment analysis showed that the T cell receptor signaling pathway, IL-17 signaling pathway, receptor-ligand activity, and signaling receptor activator activity were significantly enriched. We screened out four hub genes, including IFNG, STAT1, IL1B, and CXCL10. The ROC curve indicated the highest diagnostic value of CXCL10 in both vitiligo and HT. Immuno-infiltration analysis revealed significant changes in T cell subsets and macrophage subtypes, which were correlated with four hub genes, melanocyte markers, and thyroid-specific antigens. qPCR validated the hub genes in peripheral blood mononuclear cells from patients with comorbidity. Conclusion: IFNG, STAT1, IL1B, and CXCL10, were the key IRDEGs to vitiligo and HT. These genes may participate in the comorbidity by remodeling the immune cell infiltration pattern, and cross-expressed antigens may mediate the common damage of melanocytes and thyroid tissues.

High-average-power single-longitudinal-mode pulse laser based on a pulse saturation seed-injection locking OPO.

A high-average-power and narrow-linewidth nanosecond (ns) pulse 824 nm laser is a crucial source for the generation of deep-ultraviolet (DUV) 248 nm laser by means of the sum-frequency process with the 354.5 nm laser. To this purpose, in this Letter, we present a seed-injection-locked high-average-power ns pulse single-longitudinal-mode (SLM) 824 nm laser. By developing a novel, to the best of our knowledge, pulse-saturated seed-injection locking method, disturbance of the pulse laser on the locking of the injected seed laser is successfully eliminated. As a result, the output power of 824 nm laser is up to 21.2 W at the incident pump power of 48.1 W, and the pulse width is 15 ns. Especially, the signal-to-noise ratio of the detected modulated sideband signal exceeds 28 dB, which ensures that the achieved linewidth of the 824 nm laser is as narrow as 38.8 MHz. These results demonstrate the potential of the proposed pulse saturation seed-injection locking OPO cavity for high-power and narrow-linewidth laser applications.

Nomograms for predicting the prognosis of patients with penoscrotal extramammary Paget's disease: A retrospective study in the SEER database and two medical centers.

Background: Extramammary Paget' s disease (EMPD) is a rare cutaneous malignant tumor, and the prognostic factors associated with penoscrotal EMPD remains unclear. The purpose of this study is to investigate prognostic factors and construct nomograms to predict the outcome of patients with EMPD located in the penis or scrotum. Methods: From the Surveillance, Epidemiology and End Results (SEER) database, we extracted 95 patients with primary EMPD located in the penis or scrotum as the training cohort. Forty-nine penoscrotal EMPD patients were included from two medical centers as the external validation cohort. Univariate and multivariate Cox regression model were applied to investigating risk factors of cancer-specific survival (CSS) and overall survival (OS). Based on the results of multivariate Cox regression analysis, the nomograms were constructed for predicting CSS and OS of patients with penoscrotal EMPD. The concordance index (C-index), receiver operating characteristic (ROC) curves and calibration curves were applied to evaluate the practicability and accuracy of the nomograms. Results: In the training cohort, multivariate Cox regression analysis showed that marital status and tumor stage were independent factors of CSS, and marital status, tumor stage and surgery are associated with OS independently in patients with penoscrotal EMPD. Based on these results, we developed nomograms to predict CSS and OS respectively. The C-index values were 0.778 for CSS, and 0.668 for OS in the training set, which displayed the good discriminations. In the external validation set, the C-index values were 0.945 for CSS, and 0.703 for OS. The areas under the curve (AUC) values of nomogram predicting 1-, 3-, and 5-year CSS were 0.815, 0.833, and 0.861 respectively, and 0.839, 0.654, and 0.667 for nomogram predicting 1-, 3-, and 5-year OS respectively. In the validation set, the AUC values of nomogram predicting 1-, 3-, and 5-year CSS were 0.944, 0.896, and 0.896 respectively, and 0.777, 0.762 and 0.692 for nomogram predicting 1-, 3-, and 5-year OS respectively. Additionally, the internal calibration curves also proved that our nomograms have good accuracy. Conclusions: By incorporating marital status, tumor stage and/or surgery, our nomograms can efficiently predict CSS and OS of patients with penoscrotal EMPD.

The Identification and Validation of a Robust Immune-Associated Gene Signature in Cutaneous Melanoma.

BACKGROUND: Cutaneous melanoma is defined as one of the most aggressive skin tumors in the world. An increasing body of evidence suggested an indispensable association between immune-associated gene (IAG) signature and melanoma. This article is aimed at formulating an IAG signature to estimate prognosis of melanoma. METHODS: 434 melanoma patients were extracted from The Cancer Genome Atlas (TCGA) database, and 1811 IAGs were downloaded from the ImmPort database in our retrospective study. The Cox regression analysis and LASSO regression analysis were utilized to establish a prognostic IAG signature. The Kaplan-Meier (KM) survival analysis was performed, and the time-dependent receiver operating characteristic curve (ROC) analysis was further applied to assess the predictive value. Besides, the propensity score algorithm was utilized to balance the confounding clinical factors between the high- and low-risk groups. RESULTS: A total of six prognostic IAGs comprising of INHA, NDRG1, IFITM1, LHB, GBP2, and CCL8 were eventually filtered out. According to the KM survival analysis, the results displayed a shorter overall survival (OS) in the high-risk group compared to the low-risk group. In the multivariate Cox model, the gene signature was testified as a remarkable prognostic factor (HR = 45.423, P < 0.001). Additionally, the ROC curve analyses were performed which demonstrated our IAG signature was superior to four known biomarkers mentioned in the study. Moreover, the IAG signature was significantly related to immunotherapy-related biomarkers. CONCLUSION: Our study demonstrated that the six IAG signature played a critical role in the prognosis and immunotherapy of melanoma, which might help clinicians predict patients' survival and provide individualized treatment.

Diving angle optimization of BRF in a single-frequency continuous-wave wideband tunable titanium:sapphire laser.

In this study, the optimal condition of a multi-plate birefringent filter (BRF) used in a single-frequency continuous-wave (CW) tunable laser is theoretically and experimentally investigated. The dependence of the optimal condition on the diving angle of the BRF optical axis is first deduced. Based on the proposed optimal condition, the diving angle of the BRF optical axis is optimized to 29.1°. Subsequently, a novel off-axis multi-plate BRF with a thickness ratio of 1:2:5:9 and the thinnest plate of 0.5 mm is designed and utilized in a tunable titanium:sapphire (Ti:S) laser. As a result, the operating wavelength of the Ti:S laser is successfully tuned from 691.48 to 995.55 nm by rotating the BRF 18°. The obtained tuning slope efficiency and maximum tuning range are 16.9 nm/° and 304.07 nm, respectively. The experimental results agree well with the theoretical analysis results, which provide a feasible approach for designing BRFs to satisfy the requirements of other single-frequency CW wideband tunable lasers.

Realization of compact Watt-level single-frequency continuous-wave self-tuning titanium: sapphire laser.

Here, we present a compact Watt-level single-frequency continuous-wave (CW) self-tuning titanium:sapphire (Ti:S) laser, which is implemented using a three-plate Ti:S crystal as both a gain medium and frequency-tuning element. The thickness ratio of the three-plate Ti:S crystal is 1:2:4, of which the thinnest plate measured 1 mm. The optical axes lie on their own surfaces and parallel to each other. Based on the presented self-tuning crystal, a ring resonator is designed and built. The maximum wavelength tuning range of the single-frequency self-tuning Ti:S laser is 108.84 nm, as demonstrated experimentally by rotating the three-plate Ti:S crystal, indicating good agreement with theoretical prediction. To the best of our knowledge, this is the first study to report a single-frequency CW self-tuning Ti:S laser, which can provide a feasible approach for achieving a compact all-solid-state single-frequency CW-tunable Ti:S laser.

Highly efficient synthesis of phytosterol linolenate in the presence of Bronsted acidic ionic liquid.

Phytosterols are effective in reducing plasma cholesterol. However, phytosterols in a free form have some disadvantages because they have a high melting point and a poor oil solubility, thereby limiting their practical application in foods. The present study was to establish a green and highly efficient method to synthesize phytosterol linolenate for the first time by employing Bronsted acidic ionic liquid (IL) as a catalyst in order to improve its oil solubility. The product was separated, analyzed and subsequently characterized using thin layer chromatography, fourier transform infrared spectroscopy and mass spectroscopy. The conversion of phytosterols could reach above 96% in a very short time (30 min) under the following optimum conditions: 3% 1-butylsulfonate-3-methylimidazolium trifluoromethanesulfonate ([BSO3HMim]OTf) as a catalyst, 110 °C and 1:1.75 M ratio of phytosterols to ethyl linolenate. The present method demonstrated that [BSO3HMim]OTf would be a potential catalyst for phytosterol ester synthesis. Most importantly was that the oil solubility of phytosterol linolenate was much greater than its corresponding free phytosterols.