Frequency comb generation via synchronous pumped χ(3) resonator on thin-film lithium niobate.

Resonator-based optical frequency comb generation is an enabling technology for a myriad of applications ranging from communications to precision spectroscopy. These frequency combs can be generated in nonlinear resonators driven using either continuous-wave (CW) light, which requires alignment of the pump frequency with the cavity resonance, or pulsed light, which also mandates that the pulse repetition rate and cavity free spectral range (FSR) are carefully matched. Advancements in nanophotonics have ignited interest in chip-scale optical frequency combs. However, realizing pulse-driven on-chip Kerr combs remains challenging, as microresonator cavities have limited tuning range in their FSR and resonance frequency. Here, we take steps to overcome this limitation and demonstrate broadband frequency comb generation using a χ(3) resonator synchronously pumped by a tunable femtosecond pulse generator with on-chip amplitude and phase modulators. Notably, employing pulsed pumping overcomes limitations in Kerr comb generation typically seen in crystalline resonators from stimulated Raman scattering.

Plasma metabolomics reveals risk factors for lung adenocarcinoma.

Background: Metabolic reprogramming plays a significant role in the advancement of lung adenocarcinoma (LUAD), yet the precise metabolic changes remain incompletely understood. This study aims to uncover metabolic indicators associated with the progression of LUAD. Methods: A total of 1083 subjects were recruited, including 670 LUAD, 135 benign lung nodules (BLN) and 278 healthy controls (HC). Gas chromatography-mass spectrometry (GC/MS) was used to identify and quantify plasma metabolites. Odds ratios (ORs) were calculated to determine LUAD risk factors, and machine learning algorithms were utilized to differentiate LUAD from BLN. Results: High levels of oxalate, glycolate, glycine, glyceric acid, aminomalonic acid, and creatinine were identified as risk factors for LUAD (adjusted ORs>1.2, P<0.03). Remarkably, oxalate emerged as a distinctive metabolic risk factor exhibiting a strong correlation with the progression of LUAD (adjusted OR=5.107, P<0.001; advanced-stage vs. early-stage). The Random Forest (RF) model demonstrated a high degree of efficacy in distinguishing between LUAD and BLN (accuracy = 1.00 and 0.73, F1-score= 1.00 and 0.79, and AUC = 1.00 and 0.76 in the training and validation sets, respectively). TCGA and GTEx gene expression data have shown that lactate dehydrogenase A (LDHA), a crucial enzyme involved in oxalate metabolism, is increasingly expressed in the progression of LUAD. High LDHA expression levels in LUAD patients are also linked to poor prognoses (HR=1.66, 95% CI=1.34-2.07, P<0.001). Conclusions: This study reveals risk factors associated with LUAD.

Ghost fishing efficiency in swimming crab (Portunus trituberculatus) pot fishery.

Abandoned, lost, or otherwise discarded fishing gear (ALDFG) is a global challenge that negatively affects marine environment through plastic pollution and continued capture of marine animals, so-called "ghost fishing". In different pot fisheries, ghost fishing related to ALDFG is of concern, including pot fishery targeting swimming crab (Portunus trituberculatus). This study quantified the ghost fishing efficiency by comparing it to the catch efficiency of actively fished pots of the commercial fishery. The results showed that the ghost fishing affects both target and bycatch species. On average, the ghost fishing pots captured 12.53 % (confidence intervals: 10.45 %-15.00 %) undersized crab and 15.70 % (confidence intervals: 12.08 %-20.74 %) legal-sized crab compared to the actively fished pots. Few individuals of several bycatch species were also captured by ghost fishing pots. The results of this study emphasized the need to develop new management strategies for reducing marine pollution by ALDFG and associated negative effects in this pot fishery.

Lysozyme promotes renal fibrosis through the JAK/STAT3 signal pathway in diabetic nephropathy.

Introduction: Diabetic nephropathy (DN) is a leading cause of kidney failure. Lysozyme (LYZ) is an essential component of innate immunity and exhibits antibacterial properties. However, LYZ has been reported to induce nephropathy, implying a possible association between impaired renal function and lysozyme expression. Material and methods: Bioinformatics analysis was used to predict the hub gene associated with DN, and the differential expression of the hub gene was confirmed using a mouse model. A mouse model of streptozotocin (STZ)-induced diabetic nephropathy was established to investigate the correlation between DN and LYZ expression, and the functionality of LYZ was verified through knockdown and overexpression experiments conducted in vivo. Immunohistochemistry (IHC) was utilized to assess fibrosis-related markers and cytokines, while Masson staining was performed to assess renal fibrosis. Fibroblast proliferation was assessed using the Cell Counting Kit-8 (CCK-8) assay. The role of the JAK pathway was confirmed using the JAK inhibitor AG490, and Western blot was used to investigate the underlying mechanisms. Results: Mechanistically, 25 mM glucose promotes the expression of LYZ in fibroblastic cells, and LYZ may in turn promote the proliferation of renal interstitial fibroblasts. Western blot shows that glucose can activate STAT3 in an LYZ-dependent manner, and the JAK inhibitor AG490 can partially suppress LYZ-induced STAT3 activation. Furthermore, in vivo observations have revealed that overexpression of LYZ is associated with the senescent phenotype of renal tubular epithelial cells (RTECs). Conclusions: Lysozyme promotes kidney fibrosis via the JAK/STAT3 signaling pathway in diabetic nephropathy, and glucose may promote fibroblast proliferation by promoting LYZ auto-secretion.

Effect of gillnet mesh size on the capture probability and capture patterns in the Asian paddle crab (Charybdis japonica) fishery.

In the Asian paddle crab (Charybdis japonica) gillnet fishery in the Yellow Sea, China, the minimum mesh size (MMS) regulation has been of a major importance due to high bycatch rates of undersized crabs. In this study, we evaluated how gillnet mesh size can affect the capture probability of C. japonica and capture patterns in this fishery by comparing the performance of gillnets with four different mesh sizes (60, 70, 80, and 90 mm). Our results showed that changes in gillnet mesh size significantly affect the capture probability of different sizes of crabs. Specifically, increased mesh size decreased the capture probability of undersized crabs and their fraction in the catches decreased from 64 % to 24 % when mesh size was increased from 60 mm to 90 mm. In contrast, gillnets with larger mesh sizes significantly improved the capture probability of legal-sized crabs. Moreover, no significant differences were observed for the species catch composition between gillnets of different mesh sizes. Based on these results, we recommend 90 mm as the MMS in gillnets to improve sustainability in C. japonica fishery.

Glymphatic system dysfunction in middle-aged and elderly chronic insomnia patients with cognitive impairment evidenced by diffusion tensor imaging along the perivascular space (DTI-ALPS).

BACKGROUND: Chronic insomnia impairs the glymphatic system and may lead to cognitive impairment and dementia in elderly population. The diffusion tensor image analysis along the perivascular space (DTI-ALPS) has been proposed as a non-invasive method to measure the activity of human brain glymphatic. We aim to explore whether glymphatic function is impaired in middle-aged and elderly chronic insomnia individuals and to identify the relationships between glymphatic dysfunction and cognitive impairment. METHODS: A total of 33 chronic insomnia patients (57.36 ± 5.44 years, 30 females) and 20 age- and sex-matched healthy controls (57.95 ± 5.78 years, 16 females) were prospectively enrolled between May 2022 and January 2023. All participants completed MRI screening, cognition and sleep assessments, and DTI-ALPS index analysis. RESULTS: Our findings revealed that the DTI-ALPS index was significantly difference among the chronic insomnia patients with impaired cognition group (1.32 ± 0.14), with normal cognition group (1.46 ± 0.09), and healthy controls (1.61 ± 0.16) (p = 0.0012, p < 0.0001, p = 0.0008, respectively). Mini-Mental State Examination (MMSE) scores of chronic insomnia patients with cognitive impairment were positively correlated with the DTI-ALPS index (Partial correlation analyses after correction for age, sex, education level and duration of chronic insomnia: r = 0.78, p = 0.002). DTI-ALPS had moderate accuracy in distinguishing chronic insomnia patients with cognitive impairment from those with normal cognition. DATA CONCLUSION: The glymphatic system dysfunction is involved in chronic insomnia among middle-aged and elderly individuals, and it has been found to be correlated with cognitive decline.

Effects of trichlorobisphenol A on the expression of proteins and genes associated with puberty initiation in GT1-7 cells and the relevant molecular mechanism.

This study evaluated the effects of Cl3BPA on kisspeptin-G-protein coupled receptor 54 (GPR54)/gonadotropin-releasing hormone (GnRH) (KGG) signals and analyzed the roles of estrogen receptor alpha (ERɑ) and G-protein coupled estrogen receptor 1 (GPER1) in regulating KGG signals. The results showed that Cl3BPA at 50 µM increased the levels of intracellular reactive oxygen species (ROS) and GnRH, upregulated the protein levels of kisspeptin and the expression of fshr, lhr and gnrh1 genes related to KGG in GT1-7 cells. In addition, 50 µM Cl3BPA significantly upregulated the phosphorylation of extracellular regulated protein kinases 1/2 (Erk1/2), the protein levels of GPER1 and the expression of the gper1 as well as the most target genes associated with mitogen-activated protein kinase (MAPK)/Erk1/2 pathways. Specific signal inhibitor experiments found that Cl3BPA activated KGG signals by activating the GPER1-mediated MAPK/Erk1/2 signaling pathway at the mRNA level. A docking test further confirmed the interactions between Cl3BPA and GPER1. The findings suggest that Cl3BPA might induce precocious puberty by increasing GnRH secretion together with KGG signaling upregulation, which is driven by GPER1-mediated signaling pathway. By comparison, ClxBPAs with fewer chlorine atoms had more obvious effects on the expression of proteins and partial genes related to KGG signals in GT1-7 cells.

Amino acids analysis reveals serum methionine contributes to diagnosis of the Kawasaki disease in mice and children.

BACKGROUND: Kawasaki disease (KD) patients often lack early and definitive diagnosis due to insufficient clinical criteria, whereas biomarkers might accelerate the diagnostic process and treatment. METHODS: The KD mouse models were established and thirteen amino acids were determined. A total of 551 serum samples were collected including KD patients (n = 134), HCs (n = 223) and KD patients after intravascular immunoglobulin therapy (IVIG, n = 194). A paired analysis of pre- and post-IVIG was employed in 10 KD patients. RESULTS: The pathological alterations of the aorta, myocardial interstitium and coronary artery vessel were observed in KD mice; the serum levels of methionine in KD mice (n = 40) were markedly altered and negatively correlated with the C-reactive protein levels. Consistent with the mouse model, serum methionine were significantly decreased in KD children, with the relative variation ratio of KD with HCs above 30% and AUROC value of 0.845. Serum methionine were correlated with Z-Score and significantly restored to the normal ranges after KD patient IVIG treatment. Another case-control study with 10 KD patients with IVIG sensitivity and 20 healthy controls validated serum methionine as a biomarker for KD patients with AUROC of 0.86. Elevation of serum DNMT1 activities, but no differences of DNMT3a and DNMT3b, were observed in KD patients when comparing with those in the HCs. CONCLUSIONS: Our study validated that serum methionine was a potential biomarker for KD, the alteration of which is associated with the activation of DNMT1 in KD patients.

Artificial intelligence differentiates abdominal Henoch-Schönlein purpura from acute appendicitis in children.

OBJECTIVE: This study aims to construct an artificial intelligence (AI) model capable of effectively discriminating between abdominal Henoch-Schönlein purpura (AHSP) and acute appendicitis (AA) in pediatric patients. METHODS: A total of 6965 participants, comprising 2201 individuals with AHSP and 4764 patients with AA, were enrolled in the study. Additionally, 53 laboratory indicators were taken into consideration. Five distinct artificial intelligence (AI) models were developed employing machine learning algorithms, namely XGBoost, AdaBoost, Gaussian Naïve Bayes (GNB), MLPClassifier (MLP), and support vector machine (SVM). The performance of these prediction models was assessed through receiver operating characteristic (ROC) curve analysis, calibration curve assessment, and decision curve analysis (DCA). RESULTS: We identified 32 discriminative indicators (p < .05) between AHSP and AA. Five indicators, namely the lymphocyte ratio (LYMPH ratio), eosinophil ratio (EO ratio), eosinophil count (EO count), neutrophil ratio (NEUT ratio), and C-reactive protein (CRP), exhibited strong performance in distinguishing AHSP from AA (AUC ≥ 0.80). Among the various prediction models, the XGBoost model displayed superior performance evidenced by the highest AUC (XGBoost = 0.895, other models < 0.89), accuracy (XGBoost = 0.824, other models < 0.81), and Kappa value (XGBoost = 0.621, other models < 0.60) in the validation set. After optimization, the XGBoost model demonstrated remarkable diagnostic performance for AHSP and AA (AUC > 0.95). Both the calibration curve and decision curve analysis suggested the promising clinical utility and net benefits of the XGBoost model. CONCLUSION: The AI-based machine learning model exhibits high prediction accuracy and can differentiate AHSP and AA from a data-driven perspective.

Comparison of physical properties and fishing performance between biodegradable PLA and conventional PA trammel nets in grey mullet (Mugil cephalus) and red-lip mullet (Liza haematocheila) fishery.

Marine plastic pollution and continuous capture of marine animals, so-called "ghost fishing", by abandoned, lost, or otherwise discarded fishing gear (ALDFG) are global concerns. This study investigated whether biodegradable polylactic acid (PLA) monofilaments can be used to replace conventionally used non-biodegradable polyamide (PA) in trammel net fishery for limiting ALDFG associated effects. It evaluated the physical properties of PLA and PA monofilaments and compared fishing performance of PLA and PA trammel nets in a commercial mullet fishery in the Yellow Sea, China. Although PA monofilament exhibited superior physical properties, no significant differences in catch efficiency between PA and PLA trammel nets were observed. Fish of both species were mainly captured by pocketing which can further explain observed similar catch efficiency. These initial results suggest a potential for applying biodegradable materials in trammel net fisheries. Therefore, further long-term testing is encouraged to investigate whether this promising performance is persistent over long-term.

Serum metabolomics detected by LDI-TOF-MS can be used to distinguish between diabetic patients with and without diabetic kidney disease.

Diabetic kidney disease (DKD) is an important cause of end-stage renal disease with changes in metabolic characteristics. The objective of this study was to study changes in serum metabolic characteristics in patients with DKD and to examine metabolite panels to distinguish DKD from diabetes with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). We recruited 40 type II diabetes mellitus (T2DM) patients with or without DKD from a single center for a cross-sectional study. Serum metabolic profiling was performed with MALDI-TOF-MS using a vertical silicon nanowire array. Differential metabolites between DKD and diabetes patients were selected, and their relevance to the clinical parameters of DKD was analyzed. We applied machine learning methods to the differential metabolite panels to distinguish DKD patients from diabetes patients. Twenty-four differential serum metabolites between DKD patients and diabetes patients were identified, which were mainly enriched in butyrate metabolism, TCA cycle, and alanine, aspartate, and glutamate metabolism. Among the metabolites, l-kynurenine was positively correlated with urinary microalbumin, urinary microalbumin/creatinine ratio (UACR), creatinine, and urea nitrogen content. l-Serine, pimelic acid, 5-methylfuran-2-carboxylic acid, 4-methylbenzaldehyde, and dihydrouracil were associated with the estimated glomerular filtration rate (eGFR). The panel of differential metabolites could be used to distinguish between DKD and diabetes patients with an AUC value reaching 0.9899-0.9949. Among the differential metabolites, l-kynurenine was related to the progression of DKD. The differential metabolites exhibited excellent performance at distinguishing between DKD and diabetes. This study provides a novel direction for metabolomics-based clinical detection of DKD.

Preparation of Fe/Ni-MOFs for the Adsorption of Ciprofloxacin from Wastewater.

This work studies the use of Fe/Ni-MOFs for the removal of ciprofloxacin (CIP) in wastewater. Fe/Ni-MOFs are prepared by the solvothermal method and characterized by X-ray diffraction (XRD), a scanning electron microscope (SEM), Fourier transform infrared spectroscopy (FT-IR), and a thermal gravimetric analyzer (TG). Under the conditions of the concentration of 50 ppm, a mass of 30 mg, and a temperature of 30 °C, the maximum adsorption capacity of ciprofloxacin removal within 5 h was 232.1 mg/g. The maximum removal rate was 94.8% when 40 mg of the Fe/Ni-MOFs was added to the solution of 10 ppm ciprofloxacin. According to the pseudo-second-order (PSO) kinetic model, the R2 values were all greater than 0.99, which proved that the adsorption theory of ciprofloxacin by Fe/Ni-MOFs was consistent with the practice. The adsorption results were mainly affected by solution pH and static electricity, as well as other factors. The Freundlich isotherm model characterized the adsorption of ciprofloxacin by Fe/Ni-MOFs as multilayer adsorption. The above results indicated that Fe/Ni-MOFs were effective in the practical application of ciprofloxacin removal.

Identification of potential serum biomarkers for congenital heart disease children with pulmonary arterial hypertension by metabonomics.

BACKGROUND: Pulmonary arterial hypertension is a common complication in patients with congenital heart disease. In the absence of early diagnosis and treatment, pediatric patients with PAH has a poor survival rate. Here, we explore serum biomarkers for distinguishing children with pulmonary arterial hypertension associated with congenital heart disease (PAH-CHD) from CHD. METHODS: Samples were analyzed by nuclear magnetic resonance spectroscopy-based metabolomics and 22 metabolites were further quantified by ultra-high-performance liquid chromatography-tandem mass spectroscopy. RESULTS: Serum levels of betaine, choline, S-Adenosyl methionine (SAM), acetylcholine, xanthosine, guanosine, inosine and guanine were significantly altered between CHD and PAH-CHD. Logistic regression analysis showed that combination of serum SAM, guanine and N-terminal pro-brain natriuretic peptide (NT-proBNP), yielded the predictive accuracy of 157 cases was 92.70% with area under the curve of the receiver operating characteristic curve value of 0.9455. CONCLUSION: We demonstrated that a panel of serum SAM, guanine and NT-proBNP is potential serum biomarkers for screening PAH-CHD from CHD.

STING agonist-loaded mesoporous manganese-silica nanoparticles for vaccine applications.

Cyclic dinucleotides (CDNs), as one type of Stimulator of Interferon Genes (STING) pathway agonist, have shown promising results for eliciting immune responses against cancer and viral infection. However, the suboptimal drug-like properties of conventional CDNs, including their short in vivo half-life and poor cellular permeability, compromise their therapeutic efficacy. In this study, we have developed a manganese-silica nanoplatform (MnOx@HMSN) that enhances the adjuvant effects of CDN by achieving synergy with Mn2+ for vaccination against cancer and SARS-CoV-2. MnOx@HMSN with large mesopores were efficiently co-loaded with CDN and peptide/protein antigens. MnOx@HMSN(CDA) amplified the activation of the STING pathway and enhanced the production of type-I interferons and other proinflammatory cytokines from dendritic cells. MnOx@HMSN(CDA) carrying cancer neoantigens elicited robust antitumor T-cell immunity with therapeutic efficacy in two different murine tumor models. Furthermore, MnOx@HMSN(CDA) loaded with SARS-CoV-2 antigen achieved strong and durable (up to one year) humoral immune responses with neutralizing capability. These results demonstrate that MnOx@HMSN(CDA) is a versatile nanoplatform for vaccine applications.

Lithium niobate photonics: Unlocking the electromagnetic spectrum.

Lithium niobate (LN), first synthesized 70 years ago, has been widely used in diverse applications ranging from communications to quantum optics. These high-volume commercial applications have provided the economic means to establish a mature manufacturing and processing industry for high-quality LN crystals and wafers. Breakthrough science demonstrations to commercial products have been achieved owing to the ability of LN to generate and manipulate electromagnetic waves across a broad spectrum, from microwave to ultraviolet frequencies. Here, we provide a high-level Review of the history of LN as an optical material, its different photonic platforms, engineering concepts, spectral coverage, and essential applications before providing an outlook for the future of LN.

Tetrachlorobisphenol A and bisphenol AF induced cell migration by activating PI3K/Akt signaling pathway via G protein-coupled estrogen receptor 1 in SK-BR-3 cells.

Different subtypes of breast cancer express positively G protein-coupled estrogen receptor 1 (GPER1). Our previous studies found that tetrachlorobisphenol A (TCBPA) and bisphenol AF (BPAF) significantly promoted SK-BR-3 cell proliferation by activating GPER1-regulated signals. The present study further investigated the effects of TCBPA and BPAF on the migration of SK-BR-3 cells and examined the role of phosphatidylinositol 3-kinase-protein kinase B (PI3K/Akt) and its downstream signal targets in this process. We found that low-concentration BPAF and TCBPA markedly accelerated the migration of SK-BR-3 cells and elevated the mRNA levels of target genes associated with PI3K/Akt and mitogen-activated protein kinase (MAPK) signals. TCBPA- and BPAF-induced upregulation of target genes was significantly reduced by GPER1 inhibitor G15, the PI3K/Akt inhibitor wortmannin (WM), and the epidermal growth factor receptor (EGFR) inhibitor ZD1839 (ZD). G15 and WM also decreased cell migration induced by TCBPA and BPAF. The findings revealed that TCBPA and BPAF promoted SK-BR-3 cell migration ability by activating PI3K/Akt signaling pathway via GPER1-EGFR.

Identification of Hub Genes in the Remodeling of Non-Infarcted Myocardium Following Acute Myocardial Infarction.

(1) Background: There are few diagnostic and therapeutic targets for myocardial remodeling in the salvageable non-infarcted myocardium. (2) Methods: Hub genes were identified through comprehensive bioinformatics analysis (GSE775, GSE19322, and GSE110209 from the gene expression omnibus (GEO) database) and the biological functions of hub genes were examined by gene ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Furthermore, the differential expression of hub genes in various cell populations between the acute myocardial infarction (AMI) and sham-operation groups was analyzed by processing scRNA data (E-MTAB-7376 from the ArrayExpress database) and RNA-seq data (GSE183168). (3) Results: Ten strongly interlinked hub genes (Timp1, Sparc, Spp1, Tgfb1, Decr1, Vim, Serpine1, Serpina3n, Thbs2, and Vcan) were identified by the construction of a protein-protein interaction network from 135 differentially expressed genes identified through comprehensive bioinformatics analysis and their reliability was verified using GSE119857. In addition, the 10 hub genes were found to influence the ventricular remodeling of non-infarcted tissue by modulating the extracellular matrix (ECM)-mediated myocardial fibrosis, macrophage-driven inflammation, and fatty acid metabolism. (4) Conclusions: Ten hub genes were identified, which may provide novel potential targets for the improvement and treatment of AMI and its complications.

Bisphenol AF Promoted the Growth of Uterus and Activated Estrogen Signaling Related Targets in Various Tissues of Nude Mice with SK-BR-3 Xenograft Tumor.

Environmental estrogens can promote the growth, migration, and invasion of breast cancer. However, few studies evaluate adverse health impacts of environmental estrogens on other organs of breast cancer patients. Therefore, the present study investigated the effects of environmental estrogen bisphenol AF (BPAF) on the main organs of female Balb/cA nude mice with SK-BR-3 xenograft tumor by detecting the organ development and gene expression of targets associated with G protein-coupled estrogen receptor 1 (GPER1)-mediated phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) and mitogen-activated protein kinase (MAPK) signaling pathways in hypothalamus, ovary, uterus, liver, and kidney. The results showed that BPAF at 20 mg/kg bw/day markedly increased the uterine weight and the uterine coefficient of nude mice compared to SK-BR-3 bearing tumor control, indicating that BPAF promoted the growth of uterus due to its estrogenic activity. Additionally, BPAF significantly up-regulated the mRNA relative expression of most targets related to nuclear estrogen receptor alpha (ERα) and GPER1-mediated signaling pathways in the hypothalamus, followed by the ovary and uterus, and the least in the liver and kidney, indicating that BPAF activated different estrogen activity related targets in different tissues. In addition, BPAF markedly up-regulated the mRNA expression of GPER1 in all tested tissues, and the molecular docking showed that BPAF could dock into GPER1. Because gene change is an early event of toxicity response, these findings suggested that BPAF might aggravate the condition of breast cancer patients through exerting its estrogenic activity via the GPER1 pathway in various organs.

Spectral control of nonclassical light pulses using an integrated thin-film lithium niobate modulator.

Manipulating the frequency and bandwidth of nonclassical light is essential for implementing frequency-encoded/multiplexed quantum computation, communication, and networking protocols, and for bridging spectral mismatch among various quantum systems. However, quantum spectral control requires a strong nonlinearity mediated by light, microwave, or acoustics, which is challenging to realize with high efficiency, low noise, and on an integrated chip. Here, we demonstrate both frequency shifting and bandwidth compression of heralded single-photon pulses using an integrated thin-film lithium niobate (TFLN) phase modulator. We achieve record-high electro-optic frequency shearing of telecom single photons over terahertz range (±641 GHz or ±5.2 nm), enabling high visibility quantum interference between frequency-nondegenerate photon pairs. We further operate the modulator as a time lens and demonstrate over eighteen-fold (6.55 nm to 0.35 nm) bandwidth compression of single photons. Our results showcase the viability and promise of on-chip quantum spectral control for scalable photonic quantum information processing.

Integrated femtosecond pulse generator on thin-film lithium niobate.

Integrated femtosecond pulse and frequency comb sources are critical components for a wide range of applications, including optical atomic clocks1, microwave photonics2, spectroscopy3, optical wave synthesis4, frequency conversion5, communications6, lidar7, optical computing8 and astronomy9. The leading approaches for on-chip pulse generation rely on mode-locking inside microresonators with either third-order nonlinearity10 or with semiconductor gain11,12. These approaches, however, are limited in noise performance, wavelength and repetition rate tunability 10,13. Alternatively, subpicosecond pulses can be synthesized without mode-locking, by modulating a continuous-wave single-frequency laser using electro-optic modulators1,14-17. Here we demonstrate a chip-scale femtosecond pulse source implemented on an integrated lithium niobate photonic platform18, using cascaded low-loss electro-optic amplitude and phase modulators and chirped Bragg grating, forming a time-lens system19. The device is driven by a continuous-wave distributed feedback laser chip and controlled by a single continuous-wave microwave source without the need for any stabilization or locking. We measure femtosecond pulse trains (520-femtosecond duration) with a 30-gigahertz repetition rate, flat-top optical spectra with a 10-decibel optical bandwidth of 12.6 nanometres, individual comb-line powers above 0.1 milliwatts, and pulse energies of 0.54 picojoules. Our results represent a tunable, robust and low-cost integrated pulsed light source with continuous-wave-to-pulse conversion efficiencies an order of magnitude higher than those achieved with previous integrated sources. Our pulse generator may find applications in fields such as ultrafast optical measurement19,20 or networks of distributed quantum computers21,22.