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.

On-chip electro-optic frequency shifters and beam splitters.

Efficient frequency shifting and beam splitting are important for a wide range of applications, including atomic physics1,2, microwave photonics3-6, optical communication7,8 and photonic quantum computing9-14. However, realizing gigahertz-scale frequency shifts with high efficiency, low loss and tunability-in particular using a miniature and scalable device-is challenging because it requires efficient and controllable nonlinear processes. Existing approaches based on acousto-optics6,15-17, all-optical wave mixing10,13,18-22 and electro-optics23-27 are either limited to low efficiencies or frequencies, or are bulky. Furthermore, most approaches are not bi-directional, which renders them unsuitable for frequency beam splitters. Here we demonstrate electro-optic frequency shifters that are controlled using only continuous and single-tone microwaves. This is accomplished by engineering the density of states of, and coupling between, optical modes in ultralow-loss waveguides and resonators in lithium niobate nanophotonics28. Our devices, consisting of two coupled ring-resonators, provide frequency shifts as high as 28 gigahertz with an on-chip conversion efficiency of approximately 90 per cent. Importantly, the devices can be reconfigured as tunable frequency-domain beam splitters. We also demonstrate a non-blocking and efficient swap of information between two frequency channels with one of the devices. Finally, we propose and demonstrate a scheme for cascaded frequency shifting that allows shifts of 119.2 gigahertz using a 29.8 gigahertz continuous and single-tone microwave signal. Our devices could become building blocks for future high-speed and large-scale classical information processors7,29 as well as emerging frequency-domain photonic quantum computers9,11,14.

Single-drive electro-optic frequency comb source on a photonic-wire-bonded thin-film lithium niobate platform.

Stable pulse and flat-top frequency comb generation are an indispensable component of many photonic applications, from ranging to communications. Lithium niobate on insulator is an excellent electro-optic (EO) platform, exhibiting high modulation efficiency and low optical loss, making it a fitting candidate for pulse generation through electro-optic modulation of continuous-wave (CW) light, a commonly utilized method for generating ultrashort pulses. Here, we demonstrate an on-chip electro-optic comb generation module on thin-film lithium niobate (TFLN) consisting of a Mach-Zehnder interferometer (MZI) amplitude modulator (AM) and a cascaded phase modulator (PM) system driven by a single-electrode drive. We show that when operated in the correct regime, the lithium niobate chips can generate frequency combs with excellent spectral power flatness. In addition, we optically package one of the pulse generator chips via photonic wire bonding. The pulses generated by the photonic-wire-bonded device are compressed to 840 fs pulse duration using an optical fiber and show extremely stable operation.

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.

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.

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.

Chlorobisphenol A activated kisspeptin/GPR54-GnRH neuroendocrine signals through ERα and GPER pathway in neuronal GT1-7 cells.

Chlorobisphenol A (ClxBPA) is a kind of novel estrogenic compounds. The present study aims to investigate the effects of three ClxBPA compounds on the kisspeptin/G protein-coupled receptor 54 (GPR54, also named KissR1)-gonadotropin-releasing hormone (GnRH) (KGG) system in neuronal GT1-7 cells with mechanistic insights by estrogen receptor signaling pathways. The study demonstrated that low-concentration ClxBPA induced the cell proliferation, promoted GnRH secretion, upregulated the expression of KGG neuroendocrine signal-related proteins (KissR1, GnRH1 and kisspeptin) and genes including Kiss1, GnRH1, KissR1, luteinizing hormone receptor (Lhr) and follicle-stimulating hormone receptor (Fshr) in GT1-7 cells. Additionally, ClxBPA activated nuclear estrogen receptor alpha (ERα) and member estrogen receptor G protein-coupled estrogen receptor (GPER)-regulated phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt) and extracellular signal-regulated kinase (Erk1/2) signaling pathways. Pretreatment of GT1-7 cells with GPER inhibitor G15 and ERα inhibitor ICI reduced the expression of KissR1, GnRH1 and kisspeptin proteins, attenuated mRNA levels of Kiss1, GnRH1, KissR1, Fshr and Lhr genes, and decreased ClxBPA-induced GT1-7 cell proliferation. The results suggested that ClxBPA activated the KGG neuroendocrine signals and induced the proliferation of GT1-7 cells via ERα and GPER signaling pathways. This study provides a new perspective to explore the neuroendocrine toxicity mechanism of ClxBPA. CAPSULE: ClxBPA activated KGG neuroendocrine signaling pathway via ERα and GPER and induced the proliferation of GT1-7 cells.

Detection and verification of coexisting diagnostic markers in plasma and serum of patients with non-small-cell lung cancer.

Aim: To screen and identify the potential biomarkers co-existing in plasma and serum of patients with non-small-cell lung cancer (NSCLC), and establish appropriate diagnostic models. Methods: A cohort of 195 plasma samples and 180 serum samples were obtained from healthy controls (HCs), adenocarcinoma (AdC) and squamous cell carcinoma (SqCC) patients enrolled from the First Affiliated Hospital of Nanjing Medical University. Metabolites in plasma and serum were analyzed by GC-MS. Results: Hypoxanthine was found to have good performance in the differential diagnosis of NSCLC (including AdC and SqCC) and HC (area under the receiver operating characteristic [AUROC] ≥0.85). Combinations of metabolites could be used for differential diagnosis of NSCLC and HC (AUROC >0.93), AdC and HC (AUROC >0.91), SqCC and HC (AUROC >0.95), AdC and SqCC (AUROC >0.72). Conclusions: Metabolomics based on GC-MS can screen and identify the differential metabolites coexisting in plasma and serum of patients with NSCLC, and prediction models established by this method can be used for the differential diagnosis of patients with NSCLC.

Lay abstract Non-small-cell lung cancer (NSCLC) is not easy to diagnose. This study was intended to determine metabolites to differentiate NSCLC and healthy control samples (HC). In this study, we collected plasma and serum of NSCLC and HC. Then we performed a metabolomic analysis on these blood samples. The results showed that some metabolites were co-existing in plasma and serum of NSCLC. These co-existing metabolites (such as hypoxanthine, glyceric acid and aspartate) could differentiate NSCLC and HC.

Nesterov-accelerated adaptive momentum estimation-based wavefront distortion correction algorithm.

In order to improve the wavefront distortion correction performance of the classical stochastic parallel gradient descent (SPGD) algorithm, an optimized algorithm based on Nesterov-accelerated adaptive momentum estimation is proposed. It adopts a modified second-order momentum and a linearly varying gain coefficient to improve iterative stability. It integrates the Nesterov momentum term and the modified Adam optimizer to further improve the convergence speed, correct the direction of gradient descent in a timely fashion, and avoid falling into local extremum. Besides, to demonstrate the algorithm's performance, a wavefront sensorless adaptive optics system model is established using a 6×6 element deformable mirror as wavefront corrector. Simulation results show that, compared with the SPGD algorithm, the proposed algorithm converges faster, and its Strehl ratio after convergence is nearly 6.25 times that of the SPGD algorithm. Also, the effectiveness and superiority of the proposed algorithm are verified by comparing with two existing optimization algorithms.

Integrated microwave acousto-optic frequency shifter on thin-film lithium niobate.

Electrically driven acousto-optic devices that provide beam deflection and optical frequency shifting have broad applications from pulse synthesis to heterodyne detection. Commercially available acousto-optic modulators are based on bulk materials and consume Watts of radio frequency power. Here, we demonstrate an integrated 3-GHz acousto-optic frequency shifter on thin-film lithium niobate, featuring a carrier suppression over 30 dB. Further, we demonstrate a gigahertz-spaced optical frequency comb featuring more than 200 lines over a 0.6-THz optical bandwidth by recirculating the light in an active frequency shifting loop. Our integrated acousto-optic platform leads to the development of on-chip optical routing, isolation, and microwave signal processing.

Elevated temperature shifts soil N cycling from microbial immobilization to enhanced mineralization, nitrification and denitrification across global terrestrial ecosystems.

We assessed the response of soil microbial nitrogen (N) cycling and associated functional genes to elevated temperature at the global scale. A meta-analysis of 1,270 observations from 134 publications indicated that elevated temperature decreased soil microbial biomass N and increased N mineralization rates, both in the presence and absence of plants. These findings infer that elevated temperature drives microbially mediated N cycling processes from dominance by anabolic to catabolic reaction processes. Elevated temperature increased soil nitrification and denitrification rates, leading to an increase in N2 O emissions of up to 227%, whether plants were present or not. Rates of N mineralization, denitrification and N2 O emission demonstrated significant positive relationships with rates of CO2 emissions under elevated temperatures, suggesting that microbial N cycling processes were associated with enhanced microbial carbon (C) metabolism due to soil warming. The response in the abundance of relevant genes to elevated temperature was not always consistent with changes in N cycling processes. While elevated temperature increased the abundances of the nirS gene with plants and nosZ genes without plants, there was no effect on the abundances of the ammonia-oxidizing archaea amoA gene, ammonia-oxidizing bacteria amoA and nirK genes. This study provides the first global-scale assessment demonstrating that elevated temperature shifts N cycling from microbial immobilization to enhanced mineralization, nitrification and denitrification in terrestrial ecosystems. These findings infer that elevated temperatures have a profound impact on global N cycling processes with implications of a positive feedback to global climate and emphasize the close linkage between soil microbial C and N cycling.

Coherent two-octave-spanning supercontinuum generation in lithium-niobate waveguides.

We demonstrate coherent supercontinuum generation (SCG) in a monolithically integrated lithium-niobate waveguide, under the presence of second- and third-order nonlinear effects. We achieve more than two octaves of optical bandwidth in a 0.5-cm-long waveguide with 100-picojoule-level pulses. Dispersion engineering of the waveguide allows for spectral overlap between the SCG and the second harmonic, which enables direct detection of the carrier-envelope offset frequency fCEO using a single waveguide. We measure the fCEO of our femtosecond pump source with a 30-dB signal-to-noise ratio.

Microfluidic mid-infrared spectroscopy via microresonator-based dual-comb source.

Over the past decade, microresonator-based soliton combs based on photonic integration have broadened the scope of applications in sensing, ranging, and imaging. The large comb line spacing on the order of hundreds of gigahertz allows for rapid acquisition of absorption spectra in the condensed matter phase without aliasing via a dual-comb interferometer. We present a proof-of-principle demonstration of high-throughput label-free microresonator-based dual-comb spectroscopy in a microfluidic chip that dynamically probes the linear absorption of liquid acetone in the mid-infrared wavelength regime. We measure the flow dynamics of an acetone droplet with a spectral acquisition rate of 25 kHz (40 µs per spectrum) covering a spectral range from 2900 to 2990 nm. Combining microfluidics and silicon-photonic technology would potentially enable a compact time-resolved spectroscopy system for a wide range of applications such as chemical synthesis, biological cell-sorting, and lab-on-a-chip.

Turn-key, high-efficiency Kerr comb source.

We demonstrate an approach for automated Kerr comb generation in the normal group-velocity dispersion (GVD) regime. Using a coupled-ring geometry in silicon nitride, we precisely control the wavelength location and splitting strength of avoided mode crossings to generate low-noise frequency combs with pump-to-comb conversion efficiencies of up to 41%, which is the highest reported to date for normal-GVD Kerr combs. Our technique enables on-demand generation of a high-power comb source for applications such as wavelength-division multiplexing in optical communications.

Supercontinuum generation in angle-etched diamond waveguides.

We experimentally demonstrate on-chip supercontinuum generation in the visible region in angle-etched diamond waveguides. We measure an output spectrum spanning 670-920 nm in a 5-mm-long waveguide using 100-fs pulses with 187 pJ of incident pulse energy. Our fabrication technique, combined with diamond's broad transparency window, offers a potential route toward broadband supercontinuum generation in the UV domain.

Crowds Replicate Performance of Scientific Experts Scoring Phylogenetic Matrices of Phenotypes.

Scientists building the Tree of Life face an overwhelming challenge to categorize phenotypes (e.g., anatomy, physiology) from millions of living and fossil species. This biodiversity challenge far outstrips the capacities of trained scientific experts. Here we explore whether crowdsourcing can be used to collect matrix data on a large scale with the participation of nonexpert students, or "citizen scientists." Crowdsourcing, or data collection by nonexperts, frequently via the internet, has enabled scientists to tackle some large-scale data collection challenges too massive for individuals or scientific teams alone. The quality of work by nonexpert crowds is, however, often questioned and little data have been collected on how such crowds perform on complex tasks such as phylogenetic character coding. We studied a crowd of over 600 nonexperts and found that they could use images to identify anatomical similarity (hypotheses of homology) with an average accuracy of 82% compared with scores provided by experts in the field. This performance pattern held across the Tree of Life, from protists to vertebrates. We introduce a procedure that predicts the difficulty of each character and that can be used to assign harder characters to experts and easier characters to a nonexpert crowd for scoring. We test this procedure in a controlled experiment comparing crowd scores to those of experts and show that crowds can produce matrices with over 90% of cells scored correctly while reducing the number of cells to be scored by experts by 50%. Preparation time, including image collection and processing, for a crowdsourcing experiment is significant, and does not currently save time of scientific experts overall. However, if innovations in automation or robotics can reduce such effort, then large-scale implementation of our method could greatly increase the collective scientific knowledge of species phenotypes for phylogenetic tree building. For the field of crowdsourcing, we provide a rare study with ground truth, or an experimental control that many studies lack, and contribute new methods on how to coordinate the work of experts and nonexperts. We show that there are important instances in which crowd consensus is not a good proxy for correctness.

Discovery and Validation of Potential Serum Biomarkers for Pediatric Patients with Congenital Heart Diseases by Metabolomics.

To identify and screen serum biomarkers to determine pediatric patients with congenital heart diseases (PCH) from healthy control children (NC), a total of 614 clinically diagnosed subjects from three hospitals, including 491 PCH and 234 NC, were enrolled for nontargeted proton nuclear magnetic resonance spectroscopy (1H NMR)-based and targeted ultra-high-performance liquid chromatography-tandem mass spectroscopy (UPLC-MS/MS)-based metabolomics studies. Nineteen serum metabolites distinguishing PCH from NC were identified by 1H NMR-based metabolomic analysis. The amino acid and choline metabolic pathways were considered to be closely related to PCH. The serum levels of 13 metabolites in these two pathways were further determined by UPLC-MS/MS and observed to be altered significantly in PCH. Taurine, glutamine, and glutamate presented considerable diagnostic value for the diagnosis of PCH (AUROC > 0.80). Logistic regression analysis showed that a combination of four variables, namely, betaine, taurine, glutamine, and phenylalanine, yields a high diagnostic value (AUROC = 0.949) and prediction accuracy (89.1%) for differentiating PCH from the NC, and the sensitivity and specificity were 93.9 and 95.2%, respectively. Further double-blind sample prediction showed that the accuracy of the model was 83.8% for 80 unknown samples. Our results showed that the serum amino acid and choline metabolite levels in PCH were changed considerably. The combination of four metabolites, namely, betaine, taurine, glutamine, and phenylalanine, can be used as potential serum biomarkers in PCH diagnosis, which contributes to the early PCH screening.

Long-term nitrogen fertilization decreases bacterial diversity and favors the growth of Actinobacteria and Proteobacteria in agro-ecosystems across the globe.

Long-term elevated nitrogen (N) input from anthropogenic sources may cause soil acidification and decrease crop yield, yet the response of the belowground microbial community to long-term N input alone or in combination with phosphorus (P) and potassium (K) is poorly understood. We explored the effect of long-term N and NPK fertilization on soil bacterial diversity and community composition using meta-analysis of a global dataset. Nitrogen fertilization decreased soil pH, and increased soil organic carbon (C) and available N contents. Bacterial taxonomic diversity was decreased by N fertilization alone, but was increased by NPK fertilization. The effect of N fertilization on bacterial diversity varied with soil texture and water management, but was independent of crop type or N application rate. Changes in bacterial diversity were positively related to both soil pH and organic C content under N fertilization alone, but only to soil organic C under NPK fertilization. Microbial biomass C decreased with decreasing bacterial diversity under long-term N fertilization. Nitrogen fertilization increased the relative abundance of Proteobacteria and Actinobacteria, but reduced the abundance of Acidobacteria, consistent with the general life history strategy theory for bacteria. The positive correlation between N application rate and the relative abundance of Actinobacteria indicates that increased N availability favored the growth of Actinobacteria. This first global analysis of long-term N and NPK fertilization that differentially affects bacterial diversity and community composition provides a reference for nutrient management strategies for maintaining belowground microbial diversity in agro-ecosystems worldwide.

Carrier envelope offset detection via simultaneous supercontinuum and second-harmonic generation in a silicon nitride waveguide.

We demonstrate a chip-scale f-2f interferometer for carrier-envelope-offset frequency (fCEO) detection. This is enabled by simultaneously producing octave-spanning coherent supercontinuum generation and second-harmonic generation in a single dispersion-engineered silicon nitride waveguide. We measure the fCEO beatnote of an 80 MHz modelocked pump source with a signal-to-noise ratio of 25 dB. Our simple approach for f-2f interferometry enables a straightforward route towards a chip-scale self-referenced frequency comb source that can operate at low pulse energies.

Counter-rotating cavity solitons in a silicon nitride microresonator.

We demonstrate the generation of counter-rotating cavity solitons in a silicon nitride microresonator using a fixed, single-frequency laser. We demonstrate a dual three-soliton state with a difference in the repetition rates of the soliton trains that can be tuned by varying the ratio of pump powers in the two directions. Such a system enables a highly compact, tunable dual comb source that can be used for applications such as spectroscopy and distance ranging.