Octave soliton microcombs in lithium niobate microresonators.

Soliton microcombs are regarded as an ideal platform for applications such as optical communications, optical sensing, low-noise microwave sources, optical atomic clocks, and frequency synthesizers. Many of these applications require a broad comb spectrum that covers an octave, essential for implementing the f - 2f self-referencing techniques. In this work, we have successfully generated an octave-spanning soliton microcomb based on a z-cut thin-film lithium niobate (TFLN) microresonator. This achievement is realized under on-chip optical pumping at 340 mW and through extensive research into the broadening of dual dispersive waves (DWs). Furthermore, the repetition rate of the octave soliton microcomb is accurately measured using an electro-optic comb generated by an x-cut TFLN racetrack microresonator. Our results represent a crucial step toward the realization of practical, integrated, and fully stabilized soliton microcomb systems based on TFLN.

Evidence of 3D Topological-Domain Dynamics in KTN:Li Polarization-Supercrystal Formation.

We experimentally and theoretically investigate thermal domain evolution in near-transition KTN:Li. Results allow us to establish how polarization supercrystals form, a hidden 3D topological phase composed of hypervortex defects. These are the result of six converging polarization vortices, each associated to one orientation of the 3D broken inversion symmetry. We also identify rescaling soliton lattices and domain patterns that replicate on different scales. Findings shed light on volume domain self-organization into closed-flux patterns and open up new scenarios for topologically protected noise-resistant ferroelectric memory bits.

Construction of 1,3,4-oxadiazolines bearing CF3-quaternary centers via amino-assisted [3 + 2] cycloadditions.

An amino-assisted [3 + 2] cycloaddition strategy of nitrile imines with o-aminotrifluoroacetophenones has been explored, thus providing functionalized 1,3,4-oxadiazolines bearing CF3-quaternary centers in good to excellent yields in the presence of K2CO3 under mild conditions. The amino groups located at the ortho-position of trifluoroacetophenone might play a crucial role in the present cyclization. The MTT assay shows that the 1,3,4-oxadiazoline derivatives could be potential candidates for the treatment of head and neck cancers.

Association between admission blood pressure and spontaneous reperfusion and long-term prognosis in STEMI patients: an observational and multicenter study.

BACKGROUND: This study aims to assess the associations of admission systolic blood pressure (SBP) level with spontaneous reperfusion (SR) and long-term prognosis in ST-elevation myocardial infarction (STEMI) patients. METHODS: Data from 3809 STEMI patients who underwent primary percutaneous coronary intervention within 24 h, as recorded in the Chinese STEMI PPCI Registry (NCT04996901), were analyzed. The primary endpoint was SR, defined as thrombolysis in myocardial infarction grade 2-3 flow of IRA according to emergency angiography. The second endpoint was 2-year all-cause mortality. The association between admission BP and outcomes was evaluated using Logistic regression or Cox proportional hazards models with restricted cubic splines, adjusting for clinical characteristics. RESULTS: Admission SBP rather than diastolic BP was associated with SR after adjustment. Notably, this relationship exhibits a nonlinear pattern. Below 120mmHg, There existed a significant positive correlation between admission SBP and the incidence of SR (adjusted OR per 10-mmHg decrease for SBP ≤ 120 mm Hg: 0.800; 95% CI: 0.706-0.907; p<0.001); whereas above 120mmHg, no further improvement in SR was observed (adjusted OR per 10-mmHg increase for SBP >120 mm Hg: 1.019; 95% CI: 0.958-1.084, p = 0.552). In the analysis of the endpoint event of mortality, patients admitted with SBP ranging from 121 to 150 mmHg exhibited the lowest mortality compared with those SBP ≤ 120mmHg (adjusted HR: 0.653; 95% CI: 0.495-0.862; p = 0.003). In addition, subgroups analysis with Killip class I-II showed SBP ≤ 120mmHg was still associated with increased risk of mortality. CONCLUSION: The present study revealed admission SBP above 120 mmHg was associated with higher SR,30-d and 2-y survival rate in STEMI patients. The admission SBP could be a marker to provide clinical assessment and treatment. TRIAL REGISTRATION: ClinicalTrials.gov (NCT04996901), 07/27/2021.

Prevalence of BRCA1, BRCA2, and PALB2 genomic alterations among 924 Taiwanese breast cancer assays with tumor-only targeted sequencing: extended data analysis from the VGH-TAYLOR study.

BACKGROUND: The homologous recombination (HR) repair pathway for DNA damage, particularly the BRCA1 and BRCA2 genes, has become a target for cancer therapy, with poly ADP-ribose polymerase (PARP) inhibitors showing significant outcomes in treating germline BRCA1/2 (gBRCA1/2) mutated breast cancer. Recent studies suggest that some patients with somatic BRCA1/2 (sBRCA1/2) mutation or mutations in HR-related genes other than BRCA1/2 may benefit from PARP inhibitors as well, particularly those with PALB2 mutations. The current analysis aims to evaluate the prevalence of genetic alterations specific to BRCA1, BRCA2, and PALB2 in a large cohort of Taiwanese breast cancer patients through tumor-targeted sequencing. METHODS: A total of 924 consecutive assays from 879 Taiwanese breast cancer patients underwent tumor-targeted sequencing (Thermo Fisher Oncomine Comprehensive Assay v3). We evaluated BRCA1, BRCA2, and PALB2 mutational profiles, with variants annotated and curated by the ClinVAR, the Oncomine™ Knowledgebase Reporter, and the OncoKB™. We also conducted reflex germline testing using either whole exome sequencing (WES) or whole genome sequencing (WGS), which is ongoing. RESULTS: Among the 879 patients analyzed (924 assays), 130 had positive mutations in BRCA1 (3.1%), BRCA2 (8.6%), and PALB2 (5.2%), with a total of 14.8% having genetic alterations. Co-occurrence was noted between BRCA1/BRCA2, BRCA1/PALB2, and BRCA2/PALB2 mutations. In BRCA1-mutated samples, only p.K654fs was observed in three patients, while other variants were observed no more than twice. For BRCA2, p.N372H was the most common (26 patients), followed by p.S2186fs, p.V2466A, and p.X159_splice (5 times each). For PALB2, p.I887fs was the most common mutation (30 patients). This study identified 176 amino acid changes; 60.2% (106) were not documented in either ClinVAR or the Oncomine™ Knowledgebase Reporter. Using the OncoKB™ for annotation, 171 (97.2%) were found to have clinical implications. For the result of reflex germline testing, three variants (BRCA1 c.1969_1970del, BRCA1 c.3629_3630del, BRCA2 c.8755-1G > C) were annotated as Pathogenic/Likely pathogenic (P/LP) variants by ClinVar and as likely loss-of-function or likely oncogenic by OncoKB; while one variant (PALB2 c.448C > T) was not found in ClinVar but was annotated as likely loss-of-function or likely oncogenic by OncoKB. CONCLUSION: Our study depicted the mutational patterns of BRCA1, BRCA2, and PALB2 in Taiwanese breast cancer patients through tumor-only sequencing. This highlights the growing importance of BRCA1/2 and PALB2 alterations in breast cancer susceptibility risk and the treatment of index patients. We also emphasized the need to meticulously annotate variants in cancer-driver genes as well as actionable mutations across multiple databases.

Clinical characteristics and treatment outcomes of invasive ductal and lobular carcinoma: analyses of 54,832 taiwan cancer registry index cases.

PURPOSE: Invasive lobular cancer (ILC) is the second most common histology type of breast cancer followed by invasive ductal carcinoma (IDC). This study aimed to investigate the characteristic, treatment strategies, and clinical outcomes of ILC based on a national population-based cancer registry. METHODS: This study recruited 2671 ILC and 52,215 IDC patients diagnosed between 2011 and 2017 using the Taiwan Cancer Registry (TCR). Correlations between ILC and IDC subgroups were assessed using 1:4 propensity score matching and compared using the χ2 test. Disease free survival(DFS) and overall survival(OS) were estimated using the Kaplan-Meier method with the log-rank test. The risk of disease relapse and mortality were assessed using Cox proportional hazards model. RESULTS: ILC patients had larger tumor sizes, more positive axillary lymph node involvement, lower tumor grade, and higher cancer stage than IDC patients. After matching, ILC patients had a significantly higher rate of receiving mastectomy (58.93% and 53.85%) and positive surgical margin regardless of surgery type. ILC exhibited a significantly higher rate of distant metastasis than IDC(3.67% and 2.93%), but no difference in local recurrence rate, DFS or OS between the two groups. Higher cancer stage, higher grade, and mastectomy were risk factors for disease relapse and cancer-specific mortality. The hormone receptor-positive and HER2 over-expression subtypes were found to be associated with a reduced risk of disease relapse, while only PR positivity was associated with a decreased risk of mortality. (all P-values < 0.05). CONCLUSION: ILC patients had a higher mastectomy rate, higher surgical margin rate and distant metastasis rate than IDC patients. There is no significant difference in DFS or OS between ILC and IDC patients. Mastectomy was associated with poor outcomes regardless of ILC or IDC.

Electrically tuned coupling of lithium niobate microresonators.

Microresonators coupled with integrated waveguides operate stably but usually lack tunability for an optimal coupling state. In this Letter, we demonstrate a racetrack resonator with an electrically modulated coupling on an X-cut lithium niobate (LN) platform by introducing a Mach-Zehnder interferometer (MZI) with two balanced directional couplers (DCs) to realize light exchange. This device provides a wide-range coupling regulation, from under-coupling and critical coupling to deep over-coupling. Importantly, it has a fixed resonance frequency when the DC splitting ratio is 3 dB. The measured optical responses of the resonator exhibit a high extinction ratio, exceeding 23 dB, and an effective half-wave voltage length Vπ·L of 0.77 V·cm, suitable for CMOS compatibility. Microresonators with tunable coupling and a stable resonance frequency are expected to find application in nonlinear optical devices on LN-integrated optical platforms.

On-chip ytterbium-doped lithium niobate waveguide amplifiers with high net internal gain.

Integrated optical systems based on lithium niobate on insulator (LNOI) have shown great potential in recent years. However, the LNOI platform is facing a shortage of active devices. Considering the significant progress made in rare-earth-doped LNOI lasers and amplifiers, the fabrication of on-chip ytterbium-doped LNOI waveguide amplifiers based on electron-beam lithography and inductively coupled plasma reactive ion etching was investigated. The signal amplification at lower pump power (<1 mW) was achieved by the fabricated waveguide amplifiers. A net internal gain of ∼18 dB/cm in the 1064 nm band was also achieved in the waveguide amplifiers under a pump power of 10 mW at 974 nm. This work proposes a new, to the best of our knowledge, active device for the LNOI integrated optical system. It may become an important basic component for lithium niobate thin-film integrated photonics in the future.

Second-harmonic and cascaded third-harmonic generation in generalized quasiperiodic poled lithium niobate waveguides.

Lithium niobate (LN) thin film has recently emerged as an important platform for nonlinear optical investigations for its large χ(2) nonlinear coefficients and ability of light localization. In this Letter, we report the first, to the best of our knowledge, fabrication of LN-on-insulator ridge waveguides with generalized quasiperiodic poled superlattices using the electric field polarization technique and microfabrication techniques. Benefiting from the abundant reciprocal vectors, we observed efficient second-harmonic and cascaded third-harmonic signals in the same device, with normalized conversion efficiency of 1735% W-1 cm-2 and 0.41% W-2 cm-4, respectively. This work opens a new direction for nonlinear integrated photonics based on LN thin film.

On-chip erbium-ytterbium-co-doped lithium niobate microdisk laser with an ultralow threshold.

Erbium-ion-doped lithium niobate (LN) microcavity lasers working in the communication band have attracted extensive attention recently. However, their conversion efficiencies and laser thresholds still have significant room to improve. Here, we prepared microdisk cavities based on erbium-ytterbium-co-doped LN thin film by using ultraviolet lithography, argon ion etching, and a chemical-mechanical polishing process. Benefiting from the erbium-ytterbium co-doping-induced gain coefficient improvement, laser emission with an ultralow threshold (∼1 µW) and high conversion efficiency (1.8 × 10-3%) was observed in the fabricated microdisks under a 980-nm-band optical pump. This study provides an effective reference for improving the performance of LN thin-film lasers.

Broadband second-harmonic generation in step-chirped periodically poled lithium niobate waveguides.

Periodically poled lithium niobate (PPLN) structures on a chip enable efficient second-order nonlinear optical effects, benefiting from the tight light confinement and the utilization of d33. Here, we report a broadband second-harmonic (SH) generation in a step-chirped PPLN waveguide on X-cut lithium niobate on insulator (LNOI). The high fidelity of the poling period is demonstrated over the whole length of 7 mm using a non-destructive technique of piezoresponse force microscopy. The SH signal was continuously observed in the step-chirped PPLN waveguides while scanning the wavelength of the pump laser from 1550 nm to 1660 nm. The SH conversion efficiency was measured to be 9.6 % W-1 cm-2 at 1642 nm. This work will benefit wavelength conversions of light sources with wideband spectra.

Integrated ytterbium-doped lithium niobate microring lasers.

Integrated and stable microlasers are indispensable building blocks of micro-photonics. Here, we report the realization of an ytterbium-doped lithium niobate microring laser operating in the 1060-nm band under the pump of a 980-nm-band laser. The monolithic laser has a low threshold of 59.32 µW and relatively high output power of 6.44 µW, a state-of-the-art value for rare-earth ions-doped lithium niobate thin-film lasers. The monolithic laser with desirable performance and attractive scalability may find many applications in lithium niobite photonics.

On-chip ytterbium-doped lithium niobate microdisk lasers with high conversion efficiency.

Integrated optical systems based on lithium niobate on insulator (LNOI) have attracted the interest of researchers. Recently, erbium-doped LNOI lasers have been realized. However, the reported lasers have a relatively lower conversion efficiency and only operate in the 1550 nm band. In this paper, we demonstrate an LNOI laser operating in the 1060 nm band based on a high Q factor ytterbium-doped LNOI microdisk cavity. The threshold and the conversion efficiency of the laser are 21.19 µW and 1.36%, respectively. To our knowledge, the conversion efficiency is the highest among the reported rare-earth-doped LNOI lasers. This research extends the operating band of LNOI lasers and shows the potential in realizing high-power LNOI lasers.

A novel tool for predicting the risk of central lymph node metastasis in patients with papillary thyroid microcarcinoma: a retrospective cohort study.

INTRODUCTION: Central lymph node status in papillary thyroid microcarcinoma (PTMC) plays an important role in treatment decision-making clinically, however, it is not easy to predict central lymph node metastasis (CLNM). The present work focused on finding the more rational alternative for evaluating central lymph node status while identifying influencing factors to construct a model to predict CLNM incidence. METHODS: In this study, we retrospectively analyzed the typical sonographic and clinicopathologic features of 546 PTMC patients who underwent surgery, among which, the data of 382 patients were recruited in the training cohort and that of 164 patients in the validation cohort. Based on the outcome of the training cohort, significant influencing factors were further identified through univariate analysis and were considered as independent variables in multivariable logistic regression analysis and incorporated in and presented with a nomogram. RESULTS: In total, six independent predictors, including the age, sex, tumor size, multifocality, capsular invasion, Hashimotos thyroiditis were entered into the nomogram. Both internal validation and external validation revealed the favorable discrimination of our as-constructed nomogram. Calibration curves exhibited high consistency. As suggested by decision-curve analyses, the as-constructed nomogram might be applied in clinic. Besides, the model also distinguished patients according to risk stratification. CONCLUSIONS: The novel nomogram containing remarkable influencing factors for CLNM cases was established in the present work. The nomogram can assist clinicians in clinical decision-making.

Robust and low cost in-fiber acousto-optic Mach-Zehnder interferometer and its application in a dual-wavelength laser.

A robust in-fiber tunable acousto-optic Mach-Zehnder interferometer with a taper-shaped sandwich-like fiber structure is proposed and characterized experimentally, based on which tunable dual-wavelength lasers are demonstrated. The fiber structure was prepared by two-step etching methods, which could be used to fabricate either a symmetric structure for a continuous tuning dual-wavelength laser or an asymmetric structure for a switchable one. The proposed structure has advantages of low cost, low driving power, and robustness. The method for preparing the fiber structure is agile, which paves the way for its applications.

On-chip erbium-doped lithium niobate microring lasers.

Lithium niobate on insulator (LNOI), regarded as an important candidate platform for optical integration due to its excellent nonlinear, electro-optic, and other physical properties, has become a research hotspot. A light source, as an essential component for an integrated optical system, is urgently needed. In this Letter, we reported the realization of 1550 nm band on-chip LNOI microlasers based on erbium-doped LNOI ring cavities with loaded quality factors higher than 1 million at ∼970nm, which were fabricated by using electron beam lithography and inductively coupled plasma reactive ion etching processes. These microlasers demonstrated a low pump threshold of ∼20µW and stable performance under the pump of a 980 nm band continuous laser. Comb-like laser spectra spanning from 1510 to 1580 nm were observed in a high pump power regime, which lays the foundation of the realization of pulsed laser and frequency combs on a rare-earth ion-doped LNOI platform. This Letter effectively promotes the development of on-chip integrated active LNOI devices.

Anticancer Activity of Lesbicoumestan in Jurkat Cells via Inhibition of Oxidative Stress-Mediated Apoptosis and MALT1 Protease.

This study explores the potential anticancer effects of lesbicoumestan from Lespedeza bicolor against human leukemia cancer cells. Flow cytometry and fluorescence microscopy were used to investigate antiproliferative effects. The degradation of mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) was evaluated using immunoprecipitation, Western blotting, and confocal microscopy. Apoptosis was investigated using three-dimensional (3D) Jurkat cell resistance models. Lesbicoumestan induced potent mitochondrial depolarization on the Jurkat cells via upregulated expression levels of mitochondrial reactive oxygen species. Furthermore, the underlying apoptotic mechanisms of lesbicoumestan through the MALT1/NF-κB pathway were comprehensively elucidated. The analysis showed that lesbicoumestan significantly induced MALT1 degradation, which led to the inhibition of the NF-κB pathway. In addition, molecular docking results illustrate how lesbicoumestan could effectively bind with MALT1 protease at the latter's active pocket. Similar to traditional 2D cultures, apoptosis was markedly induced upon lesbicoumestan treatment in 3D Jurkat cell resistance models. Our data support the hypothesis that lesbicoumestan is a novel inhibitor of MALT1, as it exhibited potent antiapoptotic effects in Jurkat cells.

LncRNA H19 ameliorates myocardial infarction-induced myocardial injury and maladaptive cardiac remodelling by regulating KDM3A.

Myocardial infarction (MI) remains the leading cause of morbidity and mortality worldwide, and novel therapeutic targets still need to be investigated to alleviate myocardial injury and the ensuing maladaptive cardiac remodelling. Accumulating studies have indicated that lncRNA H19 might exert a crucial regulatory effect on cardiovascular disease. In this study, we aimed to explore the biological function and molecular mechanism of H19 in MI. To investigate the biological functions of H19, miRNA-22-3p and KDM3A, gain- and loss-of-function experiments were performed. In addition, bioinformatics analysis, dual-luciferase reporter assays, RNA immunoprecipitation (RIP) assays, RNA pull-down assays, quantitative RT-PCR and Western blot analyses as well as rescue experiments were conducted to reveal an underlying competitive endogenous RNA (ceRNA) mechanism. We found that H19 was significantly down-regulated after MI. Functionally, enforced H19 expression dramatically reduced infarct size, improved cardiac performance and alleviated cardiac fibrosis by mitigating myocardial apoptosis and decreasing inflammation. However, H19 knockdown resulted in the opposite effects. Bioinformatics analysis and dual-luciferase assays revealed that, mechanistically, miR-22-3p was a direct target of H19, which was also confirmed by RIP and RNA pull-down assays in primary cardiomyocytes. In addition, bioinformatics analysis and dual-luciferase reporter assays also demonstrated that miRNA-22-3p directly targeted the KDM3A gene. Moreover, subsequent rescue experiments further verified that H19 regulated the expression of KDM3A to ameliorate MI-induced myocardial injury in a miR-22-3p-dependent manner. The present study revealed the critical role of the lncRNAH19/miR-22-3p/KDM3A pathway in MI. These findings suggest that H19 may act as a potential biomarker and therapeutic target for MI.

Syringic acid mitigates myocardial ischemia reperfusion injury by activating the PI3K/Akt/GSK-3ß signaling pathway.

Syringic acid is an abundant phenolic acid compound that possesses anti-oxidant, anti-microbial, anti-inflammatory, and anti-endotoxic properties. However, the research of pretreatment with syringic acid against myocardial ischemia reperfusion is still limited. Thus, our research revealed the protective effect of syringic acid in the rat model with myocardial ischemia reperfusion injury. Histological analysis was performed by hematoxylin and eosin (H&E). The myocardial systolic function was detected by echocardiographic. Myocardial infarct size was measured by Evans blue and 2,3,5-triphenyltetrazolium chloride (TTC) double staining. The apoptosis index was recorded by Terminal deoxynucleotidyl transferase dUTP nick end labeling staining (TUNEL). The contents of creatine kinase MB (CK-MB) and lactate dehydrogenase (LDH) in the serum were determined by a commercial kit. The expression of the PI3K/Akt/GSK-3ß signaling pathway-related molecules and apoptosis-associated indicators was detected by western blotting or real-time PCR. We found that pretreatment with syringic acid obviously increased the myocardial systolic function (LVEF and LVFS) and decreased the infarct size, the apoptosis index as well as the serum level of CK-MB and LDH. Meanwhile, syringic acid also remarkably augmented the contents of p-PI3K, p-Akt, p-GSK-3ß, Bcl-2 and mitochondria cytochrome c. However, the expression of caspase-3, -9 and Bax significantly reduced. Interestingly, co-treatment with PI3K inhibitor of LY294002 counteracted those effects induced by syringic acid. In conclusion, pretreatment with syringic acid can mitigate myocardial ischemia reperfusion injury by inhibiting mitochondria-induced apoptosis which is regulated by the PI3K/Akt/GSK-3ß signaling pathway.

Tightly focusing terahertz wave using gradient-type slotted grating based on spoof surface plasmons.

The d1-d2-d3-d4-d5 gradient-type spoof surface plasmons (SSP) grating was designed and found to exert an obvious effect on electric field localization. Two gradient-shaped planar ports were added to the bottom of this grating to form a gradient-type slotted SSP grating and achieve tight focusing and local electric field enhancement for a terahertz wave. The size of the focal spot was optimized to 0.01λ. The single-gradient-type slotted SSP grating was considered as a unit and arranged in one and two dimensions to generate a longitudinal focal line and square focal spots array. This did not only improve the resolution of terahertz imaging, but also simultaneously scan multiple focal spots to increase the speed of terahertz imaging. This work makes the manipulation of terahertz wave more flexible and efficient which has great potential in terahertz high-resolution near-field scanning imaging.