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.

Electro-Optical Comb Envelope Engineering Based on Mode Crossing.

Resonator-enhanced electro-optical (EO) combs could generate a series of comb lines with high coherence and stability. Recently, EO comb based on thin-film lithium niobate (TFLN) has begun to show great potential thanks to the high second-order nonlinearity coefficient of lithium niobate crystal. Here we demonstrate that EO comb envelope engineering based on mode crossing induced a quality factor reduction in the TFLN racetrack microcavity both in the numerical simulation and experiment. Our method paves the way for the generation of EO combs with an arbitrary envelope.

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.

Prevalent landscape of tumor genomic alterations of luminal B1 breast cancers using a comprehensive genomic profiling assay in Taiwan.

BACKGROUND: The human epidermal growth factor receptor 2 (HER2) negative luminal B1 subtype of breast cancer has been reported with a poorer outcome than luminal A in recent studies. This study aimed to investigate the molecular alterations and identify potential therapeutic targets by analyzing the genetic profiling from a cohort of luminal B1 breast cancer in Taiwan. METHODS: We enrolled patients with luminal B1 breast cancer in our study. They were classified as patients who received curative surgery and adjuvant or neoadjuvant chemotherapy as the low-risk group, and who had advanced or metastatic disease or early relapse during the follow-up time as the high-risk group. Using targeted sequencing, we evaluated genomic alterations, interpreting variants with the ESMO Scale of clinical actionability of molecular targets (ESCAT). RESULTS: A total of 305 luminal B1 breast cancer patients underwent targeted sequencing analyses. The high-risk patients reported more actionable genes and called variants than the low-risk group (P < 0.05). PIK3CA (42%), FGFR1 (25%), and BRCA1/2 (10.5%) were the most prevalent ESCAT actionable alterations in luminal B1 breast cancer. There was no difference in the prevalence of actionable mutations between these two groups, except for ERBB2 oncogenic mutations, which were more prevalent among the high-risk than the low-risk group (P < 0.05). Alterations in PTEN, ERBB2, and BRCA1/2 were associated with disease relapse events in luminal B1 breast cancer. CONCLUSIONS: PIK3CA, FGFR1, and BRCA1/2 were the most prevalent actionable alterations among Taiwanese luminal B1 breast cancer. Moreover, PTEN and BRCA1/2 was significantly associated with disease relapse.

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.

Comparative Proteomic Analysis of Irradiation-Induced Radioresistant Breast Cancer Cells Using Label-Free Quantitation.

BACKGROUND: Breast cancer poses severe threats to human health as radioresistance becomes increasingly prevalent. The mechanisms of radioresistance are hard to expound completely. This study aims to explore proteomic changes of radioresistance, which will help elucidate the potential mechanisms responsible for breast cancer radioresistance and explore potential therapeutic targets. METHODS: A radioresistant breast cancer cell line was established by repeated irradiation. Liquid Chromatograph Mass Spectrometer (LC-MS) was used to quantify protein expression. Proteomic changes associated with radioresistance were evaluated by proteomic analysis. Further, cell radioresistance and several identified proteins were verified in in vitro experiments. RESULTS: In the study, more than 3000 proteins were detected, 243 of which were identified as up-regulated proteins and another 633 as down-regulated proteins. Gene Ontology (GO) enrichment analysis indicated that these proteins were mainly expressed in the lysosome and ribosome, associated with coenzyme binding and the structural constituent of the ribosome, involved in mitotic cytokinesis and ribonucleoprotein complex biogenesis. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that many biological processes were extensively altered, particularly spliceosome and thermogenesis. It is worth noting that the functions and pathways related to ribosomes were significantly enriched, therefore ribosomal proteins (RPL6 and RPS13) were identified through western blot and highly expressed in relatively radiosensitive cells. Additionally, several identified proteins, including S100A4, RanBP9, and ISG15, were also verified to be differentially expressed in different radiosensitive cells. CONCLUSIONS: Our results provide a framework for further studies into the mechanisms of radioresistance and serve as a basis to construct a predictive model of radioresistance in breast cancer. Ribosome may participate in the radioresistance of breast cancer, which provides new insights into the proteomic characteristics of the mechanisms of radioresistance.

Concordance of Targeted Sequencing from Circulating Tumor DNA and Paired Tumor Tissue for Early Breast Cancer.

In this study, we evaluated the concordance of targeted sequencing between paired ctDNA and matched tumor samples from early breast cancers treated with curative intention. Molecular profiling was performed using the Oncomine Comprehensive Assay v3 and the Oncomine Breast cfDNA Assay v2. The liquid biopsy detection rate was 39% (all-stage breast cancers, n = 612). Among 246 early-stage patients assayed for both ctDNA and matched tumor, the cfDNA assay detected 73 (29.6%) and the comprehensive assay detected 201 (81.7%) breast cancers with at least one alteration (χ2 test, p = 0.001). In total, 67 (25.6%) cases tested positive on both platforms, while the cfDNA and comprehensive assays detected an additional 10 (4%) and 138 (56%) cases, respectively. The most prevalent mutant genes were TP53 (68.3%) and KRAS (53.5%), while the PIK3CA (39.4%), AKT1 (45.9%), and ERBB2 (17.1%) mutations constituted biomarkers for FDA-approved therapeutics. Our study showed that tumor tissue should be the source of actionable mutation detection for early breast cancers, considering that the concordance rate between tumor and liquid biopsy was only one-quarter.

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.

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.

Age-specific cardiovascular disease-related mortality among patients with major gastrointestinal cancers: A SEER population-based study.

BACKGROUND: Studies have reported age as a risk factor for cardiovascular disease (CVD)-related mortality; however, only a few studies have focused on the relationship between age and CVD-related mortality, especially among major gastrointestinal cancers. METHOD: The present retrospective cohort enrolled patients with colorectal, pancreatic, hepatocellular, gastric, and esophageal cancer between 2000 to 2015 from the Surveillance, Epidemiology and End Results Registry (SEER). Standardized mortality ratio (SMR), competing risk regression, and restricted cubic spline (RCS) analyses were used in our study. RESULTS: We analyzed 576,713 patients with major gastrointestinal cancers (327,800 patients with colorectal cancer, 93,310 with pancreatic cancer, 69,757 with hepatocellular cancer, 52,024 with gastric cancer, and 33,822 with esophageal cancer). Overall, CVD-related mortality gradually decreased every year, and the majority were older patients. All cancer patients had a higher CVD-related mortality rate than the general U.S. POPULATION: The adjusted sub-hazard ratios for middle-aged with colorectal cancer, pancreatic cancer, hepatocellular cancer, gastric cancer, and esophageal cancer were 2.55 (95% CI: 2.15-3.03), 1.77 (95% CI: 1.06-2.97), 2.64 (95% CI: 1.60-4.36), 2.15 (95% CI: 1.32-3.51), and 2.28 (95% CI: 1.17-4.44), respectively. The adjusted sub-hazard ratios for older patients with colorectal cancer, pancreatic cancer, hepatocellular cancer, gastric cancer, and esophageal cancer were 11.23 (95% CI: 9.50-13.27), 4.05 (95% CI: 2.46-6.66), 4.47 (95% CI: 2.72-7.35), 7.16 (95% CI: 4.49-11.41), and 4.40 (95% CI: 2.28-8.48), respectively. A non-linear relationship between age at diagnosis and CVD-related mortality was found in colorectal cancer, pancreatic cancer, and esophageal cancer; their reference ages were 67, 69, and 66 years old, respectively. CONCLUSION: This study demonstrated that age was a risk factor for CVD-related mortality among major gastrointestinal cancers.

Characterizing the remobilization flux of cadmium from pre-anthesis vegetative pools in rice during grain filling using an improved stable isotope labeling method.

A clear understanding of the allocation of Cd to grains is essential to manage the level of Cd in cereal diets effectively. Yet, debate remains over whether and how the pre-anthesis pools contribute to grain Cd accumulation, resulting in uncertainty regarding the need to control plant Cd uptake during vegetative growth. To this end, rice seedlings were exposed to 111Cd labeled solution until tillering, transplanted to unlabeled soils, and grown under open-air conditions. The remobilization of Cd derived from pre-anthesis vegetative pools was studied through the fluxes of 111Cd-enriched label among organs during grain filling. The 111Cd label was continuously allocated to the grain after anthesis. The lower leaves remobilized the Cd label during the earlier stage of grain development, which was allocated almost equally to the grains and husks + rachis. During the final stage, the Cd label was strongly remobilized from the roots and, less importantly, the internodes, which was strongly allocated to the nodes and, to a less extent, the grains. The results show that the pre-anthesis vegetative pools are an important source of Cd in rice grains. The lower leaves, internodes, and roots are the source organs, whereas the husks + rachis and nodes are the sinks competing with the grain for the remobilized Cd. This study provides insight into understanding the ecophysiological mechanism of Cd remobilization and setting agronomic measures for lowering grain Cd levels.

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.

First report of haemosporidia and associated risk factors in red junglefowl (Gallus gallus) in China.

BACKGROUND: Avian haemosporidia infect both domestic and wild birds, causing anemia, acute tissue degeneration, and depopulation in wild birds. Poultry and wild birds have been reported as common reservoirs of haemosporidia, but limited information is available for red junglefowl (Gallus gallus) in China. The present study investigated the prevalence and molecular characterization of haemosporidia in red junglefowl. METHODS: Blood samples were collected from 234 red junglefowl from Jinghong City of Yunnan Province, and genomic DNA was extracted from these samples. The prevalence of haemosporidia was determined by nested PCR targeting the mitochondrial cytochrome b (cytb) gene. Molecular characterization was investigated based on phylogenetic analysis of cytb sequences, and associated risk factors were analyzed using the Chi-square (χ2) test. RESULTS: The overall prevalence of haemosporidia was 74.8% (175/234), and three species were identified, namely Haemoproteus enucleator, Leucocytozoon californicus, and Plasmodium juxtanucleare. The prevalence of haemosporidia in adult fowl (81.1%, 107/132) was significantly higher (χ2 = 6.32, df = 1, P = 0.012) than that in juveniles (66.7%, 68/102). Three novel haemosporidian lineages were revealed. CONCLUSIONS: This study examined the prevalence and identified species of avian haemosporidians in red junglefowl, providing new information on the molecular epidemiology and geographical distribution of haemosporidian parasites. Our results indicated high prevalence and diverse species distribution of these haemosporidians in red junglefowl. To the best of our knowledge, this is the first record of haemosporidian infection in red junglefowl in China.

Simulating the Dicke lattice model and quantum phase transitions using an array of coupled resonators.

A proposal for simulating the Dicke-Lattice model in a mechanics-controlled hybrid quantum system is studied here. An array of coupled mechanical resonators (MRs) can homogeneously interact with a group of trapped Bose-Einstein condensates (BECs) via the gradient magnetic field induced by the oscillating resonators. Assisted by the classical dichromatic radio-wave fields, each subsystem with the BEC-MR interaction can mimic the Dicke type spin-phonon interaction, and the whole system is therefore extended to a lattice of Dicke models with the additional adjacent phonon-phonon hopping couplings. In view of this lattice model with theZ2symmetry, its quantum phase transitions behavior can be controlled by this periodic phonon-phonon interactions in the momentum space. This investigation may be considered as a fresh attempt on manipulating the critical behaviors of the collective spins through the external mechanical method.

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.