Gapr for large-scale collaborative single-neuron reconstruction.

Whole-brain analysis of single-neuron morphology is crucial for unraveling the complex structure of the brain. However, large-scale neuron reconstruction from terabyte and even petabyte data of mammalian brains generated by state-of-the-art light microscopy is a daunting task. Here, we developed 'Gapr' (Gapr accelerates projectome reconstruction) that streamlines deep learning-based automatic reconstruction, 'automatic proofreading' that reduces human workloads at high-confidence sites, and high-throughput collaborative proofreading by crowd users through the Internet. Furthermore, Gapr offers a seamless user interface that ensures high proofreading speed per annotator, on-demand conversion for handling large datasets, flexible workflows tailored to diverse datasets and rigorous error tracking for quality control. Finally, we demonstrated Gapr's efficacy by reconstructing over 4,000 neurons in mouse brains, revealing the morphological diversity in cortical interneurons and hypothalamic neurons. Here, we present Gapr as a solution for large-scale single-neuron reconstruction projects.

BESST: a novel LncRNA knockout strategy with less genome perturbance.

Long noncoding RNAs (lncRNAs) are >200 nt RNA transcripts without protein-coding potential. LncRNAs can be categorized into intergenic, intronic, bidirectional, sense, and antisense lncRNAs based on the genomic localization to nearby protein-coding genes. The current CRISPR-based lncRNA knockout strategy works efficiently for lncRNAs distant from the protein-coding gene, whereas it causes genomic perturbance inevitably due to technical limitations. In this study, we introduce a novel lncRNA knockout strategy, BESST, by deleting the genomic DNA fragment from the branch point to the 3' splicing site in the last intron of the target lncRNA. The BESST knockout exhibited comparable or superior repressive efficiency to RNA silencing or conventional promoter-exon1 deletion. Significantly, the BESST knockout strategy minimized the intervention of adjacent/overlap protein-coding genes by removing an average of ∼130 bp from genomic DNA. Our data also found that the BESST knockout strategy causes lncRNA nuclear retention, resulting in decapping and deadenylation of the lncRNA poly(A) tail. Further study revealed that PABPN1 is essential for the BESST-mediated decay and subsequent poly(A) deadenylation and decapping. Together, the BESST knockout strategy provides a versatile tool for investigating gene function by generating knockout cells or animals with high specificity and efficiency.

Thermal stability of triple-junction gallium arsenide cells.

Laser wireless power transmission (LWPT) systems have significant applications in the field of wireless energy transmission, including spacecraft sensor networks, satellite-to-satellite communication, and remote power supply. However, continuous laser exposure increases the temperature of the photovoltaic (PV) cells in the LWPT system, thus decreasing the electrical output performance. This work, which we believe is a new approach, is on the basis of a notch film designed by a combined merit function proposed to maintain the electrical output performance while under 1064-nm continuous laser irradiation. Moreover, the thermal stability of PV cells under laser irradiation was investigated, which revealed the recoverability of the open-circuit voltage (Voc) of the cells at different temperatures, and the thermal damage to cells was a gradual process. This process began with the vaporization of the encapsulation adhesive, followed by a decline in, but still recoverable and functional, electrical performance, and finally, the cell was completely damaged. The thermal stability of the PV cells coated with the notch film increased ten-fold compared to those without it. Furthermore, the correlation between the minimum Voc and maximum temperature of the cells with notch films of different performances was established. These investigations serve as references for further optimization of LWPT.

Development and first-in-human study of PSMA-targeted PET tracers with improved pharmacokinetic properties.

PURPOSE: A series of new 68Ga-labeled tracers based on [68Ga]Ga-PSMA-617 were developed to augment the tumor-to-kidney ratio and reduce the activity accumulation in bladder, ultimately minimize radiation toxicity to the urinary system. METHODS: We introduced quinoline group, phenylalanine and decanoic acid into different tracers to enhance their lipophilicity, strategically limiting their metabolic pathway through the urinary system. Their binding affinity onto LNCaP cells was determined through in vitro saturation assays and competition binding assays. In vivo metabolic study, PET imaging and biodistribution experiment were performed in LNCaP tumor-bearing B-NSG male mice. The most promising tracer was selected for first-in-human study. RESULTS: Four radiotracers were synthesized with radiochemical purity (RCP) > 95% and molar activity in a range of 20.0-25.5 GBq/µmol. The binding affinities (Ki) of TWS01, TWS02 to PSMA were in the low nanomolar range (< 10 nM), while TWS03 and TWS04 exhibited binding affinities with Ki > 20 nM (59.42 nM for TWS03 and 37.14 nM for TWS04). All radiotracers exhibited high stability in vivo except [68Ga]Ga-TWS03. Micro PET/CT imaging and biodistribution analysis revealed that [68Ga]Ga-TWS02 enabled clear tumor visualization in PET images at 1.5 h post-injection, with higher tumor-to-kidney ratio (T/K, 0.93) and tumor-to-muscle ratio (T/M, 107.62) compared with [68Ga]Ga-PSMA-617 (T/K: 0.39, T/M: 15.01) and [68Ga]Ga-PSMA-11 (T/K: 0.15, T/M: 24.00). In first-in-human study, [68Ga]Ga-TWS02 effectively detected PCa-associated lesions including primary and metastatic lesions, with lower accumulation in urinary system, suggesting that [68Ga]Ga-TWS02 might be applied in the detection of bladder invasion, with minimized radiation toxicity to the urinary system. CONCLUSION: Introduction of quinoline group, phenylalanine and decanoic acid into different tracers can modulate the binding affinity and pharmacokinetics of PSMA in vivo. [68Ga]Ga-TWS02 showed high binding affinity to PSMA, excellent pharmacokinetic properties and clear imaging of PCa-associated lesions, making it a promising radiotracer for the clinical diagnosis of PCa. Moreover, TWS02 with a chelator DOTA could also label 177Lu and 225Ac, which could be used for PCa treatment without significant side effects. TRIAL REGISTRATION: The clinical evaluation of this study was registered On October 30, 2021 at https://www.chictr.org.cn/ (No: ChiCTR2100052545).

Diabetic kidney disease screening status and related factors: a cross-sectional study of patients with type 2 diabetes in six provinces in China.

OBJECTIVE: To understand the awareness and practice of diabetic kidney disease (DKD) or nephropathy screening among community-based patients with type 2 diabetes in six provinces and cities in China, and to analyse the related factors affecting screening practices. METHODS: From December 2021 to March 2022, a cross-sectional survey was conducted using a structured questionnaire in 6230 patients with type 2 diabetes aged 18 years and older. The content of the questionnaire includes three parts: the general situation of diabetic patients (gender, age, ethnicity, marriage, education, occupation, etc.), DKD screening practices, and the evaluation of DKD screening services. RESULTS: 89.70% of the patients had their fasting blood glucose measured every six months, 21.12% of the patients had their glycosylated hemoglobin measured every six months, and only 13.11% and 9.34% of the patients had a urine protein-creatinine ratio test and estimated glomerular filtration rate test every 12 months. The proportions of glycosylated hemoglobin, urine protein-creatinine ratio, and estimated glomerular filtration rate were relatively high in young, northern, highly educated, and long-duration type 2 diabetic patients. CONCLUSION: The results of this survey found that the proportion of urine protein-creatinine ratio testing, estimated glomerular filtration rate testing, and glycosylated hemoglobin testing in Chinese patients with type 2 diabetes was very low. Patients with type 2 diabetes in rural areas, southern areas, with low education level, and short course of disease have lower detection rates for DKD, and hence lower rates of prevention and treatment.

Highly sensitive electrochemical quantification of carbendazim via synergistic enhancement of ring-opening metathesis polymerization and polyethyleneimine modified graphene oxide.

A novel aptamer-based sensor was developed using the signal amplification strategy of ring-opening metathesis polymerization (ROMP) and polyethyleneimine modified graphene oxide to achieve trace detection of carbendazim (CBZ). The dual identification of aptamer and antibody was used to avoid false positive results and improve the selectivity. Polyethyleneimine modified graphene oxide (GO-PEI), as a substrate material with excellent conductivity, was modified on the surface of a glassy carbon electrode (GCE) to increase the grafting amount of aptamer on the electrode surface. Moreover, a large number of cyclopentenyl ferrocene (CFc) was aggregated to form long polymer chains through ring-opening metathesis polymerization (ROMP), so as to significantly improve the detection sensitivity of the biosensor. The linear range of this sensor was 1 pg/mL-100 ng/mL with a detection limit as low as 7.80 fg/mL. The sensor exhibited excellent reproducibility and stability, and also achieved satisfactory results in actual sample detection. The design principle of such a sensor could provide innovative ideas for sensors in the detection of other types of targets.

DCFNet: Infrared and Visible Image Fusion Network Based on Discrete Wavelet Transform and Convolutional Neural Network.

Aiming to address the issues of missing detailed information, the blurring of significant target information, and poor visual effects in current image fusion algorithms, this paper proposes an infrared and visible-light image fusion algorithm based on discrete wavelet transform and convolutional neural networks. Our backbone network is an autoencoder. A DWT layer is embedded in the encoder to optimize frequency-domain feature extraction and prevent information loss, and a bottleneck residual block and a coordinate attention mechanism are introduced to enhance the ability to capture and characterize the low- and high-frequency feature information; an IDWT layer is embedded in the decoder to achieve the feature reconstruction of the fused frequencies; the fusion strategy adopts the l1-norm fusion strategy to integrate the encoder's output frequency mapping features; a weighted loss containing pixel loss, gradient loss, and structural loss is constructed for optimizing network training. DWT decomposes the image into sub-bands at different scales, including low-frequency sub-bands and high-frequency sub-bands. The low-frequency sub-bands contain the structural information of the image, which corresponds to the important target information, while the high-frequency sub-bands contain the detail information, such as edge and texture information. Through IDWT, the low-frequency sub-bands that contain important target information are synthesized with the high-frequency sub-bands that enhance the details, ensuring that the important target information and texture details are clearly visible in the reconstructed image. The whole process is able to reconstruct the information of different frequency sub-bands back into the image non-destructively, so that the fused image appears natural and harmonious visually. Experimental results on public datasets show that the fusion algorithm performs well according to both subjective and objective evaluation criteria and that the fused image is clearer and contains more scene information, which verifies the effectiveness of the algorithm, and the results of the generalization experiments also show that our network has good generalization ability.

Anchoring Fe Species on the Highly Curved Surface of S and N Co-Doped Carbonaceous Nanosprings for Oxygen Electrocatalysis and a Flexible Zinc-Air Battery.

Oxygen reduction reaction (ORR) is of critical significance in the advancement of fuel cells and zinc-air batteries. The iron-nitrogen (Fe-Nx ) sites exhibited exceptional reactivity towards ORR. However, the task of designing and controlling the local structure of Fe species for high ORR activity and stability remains a challenge. Herein, we have achieved successful immobilization of Fe species onto the highly curved surface of S, N co-doped carbonaceous nanosprings (denoted as FeNS/Fe3 C@CNS). The induction of this twisted configuration within FeNS/Fe3 C@CNS arose from the assembly of chiral templates. For electrocatalytic ORR tests, FeNS/Fe3 C@CNS exhibits a half-wave potential (E1/2 ) of 0.91 V in alkaline medium and a E1/2 of 0.78 V in acidic medium. The Fe single atoms and Fe3 C nanoparticles are coexistent and play as active centers within FeNS/Fe3 C@CNS. The highly curved surface, coupled with S substitution in the coordination layer, served to reduce the energy barrier for ORR, thereby enhancing the intrinsic catalytic activity of the Fe single-atom sites. We also assembled a wearable flexible Zn-air battery using FeNS/Fe3 C@CNS as electrocatalysts. This work provides new insights into the construction of highly curved surfaces within carbon materials, offering high electrocatalytic efficacy and remarkable performance for flexible energy conversion devices.

Design, production, and characterization of a pair of positive and negative high dispersive mirrors for chirped pulse amplification systems.

We report a novel modified Gires-Tournois interferometer (MGTI) starting design for high-dispersive mirrors (HDMs). The MGTI structure combines multi-G-T and conjugate cavities and introduces a large amount of dispersion while covering a wide bandwidth. With this MGTI starting design, a pair of positive (PHDM) and negative highly dispersive mirrors (NHDM) providing group delay dispersions of +1000 fs2 and -1000 fs2 in the spectral range of 750 nm to 850 nm is developed. The pulse stretching and compression capabilities of both HDMs are studied theoretically by simulating the pulse envelopes reflected from the HDMs. A near Fourier Transform Limited pulse is obtained after 50 bounces on each positive and negative HDM, which verifies the excellent matching between the PHDM and NHDM. Moreover, the laser-induced damage properties of the HDMs are studied using laser pulses of 800 nm and 40 fs. The damage thresholds of the PHDM and NHDM are approximately 0.22 J/cm2 and 0.11 J/cm2, respectively. The laser-induced blister structure of the HDMs is observed, the formation and evolution processes of the blister are evaluated.

Ultra-broad bandwidth low-dispersion mirror with smooth dispersion and high laser damage resistance.

Low-dispersion mirrors (LDMs), which require a broad bandwidth, low dispersion, and high damage threshold, are essential optics in ultra-intense and ultra-short laser devices. Bragg mirrors and chirped LDMs do not satisfy these requirements simultaneously. We propose a novel LDM (NLDM) based on the hump-like structure and quarter wavelength optical thickness (QWOT) structure to achieve a broad bandwidth, smooth dispersion, and high robustness. The spectral and dispersion characteristics of the two structures compensate for each other, which makes up for the deficiency that the dispersion bandwidth of the sinusoidal modulation structure cannot be broadened. Based on this structure, the LDM can achieve a design bandwidth of 240 nm and support the transmission of sub-11-fs pulses. The accuracy of the NLDM is experimentally evaluated. The structure shows the potential for broad-spectrum laser damage performance due to the low electric field intensity. The NLDM improves the mirror performance and paves the way for a new generation of ultra-intense and ultra-short laser devices.

Systematic review and meta-analysis of individual serum lipids and analysis of lipid ratios in ankylosing spondylitis and healthy control cohorts: significantly lower mean HDL-cholesterol level in ankylosing spondylitis cohorts.

OBJECTIVES: Ankylosing spondylitis (AS) is suspected to have increased risk of atherosclerosis and cardiovascular disease (CVD) mortality. This systematic review and meta-analysis aims to critically study serum lipids and lipoprotein ratios in AS compared to healthy control (HC) subjects and determine any significant difference. METHODS: English-language articles were systematically searched in PubMed, Ovid Medline, Embase (Medline records removed), and Scopus databases from 1970 to 2021. Random-effects model was used to pool results expressed as standardised mean difference (SMD) in the lipid outcomes. Lipid ratios of total ÷ HDL-C and the log10 (TG/HDL-C), i.e. atherogenic index of plasma (AIP), were analysed by histograms of differences in weighted means and weighted SDs between AS and HC exposure cohorts. RESULTS: The meta-analysis included a total of 68 articles, 47 from database search and 21 from reference reviews. Pooled Hedges' g effect size revealed no difference in mean total cholesterol, mean triglycerides, and mean LDL-C between AS and HC subjects. However, mean HDL-C was significantly (p<0.001) lower in AS than HC subjects, with pooled Hedges' g (SE) for HDL-C of -0.484 (0.092), with 95% mean CIs [-0.664, -0.305]. In comparing differencesin AS minus HC weighted means of total HDL-C ratios, 8 values in HC were below the lowest ratio in AS. CONCLUSIONS: Highly significantly lower HDL-C levels occurred in AS versus HC subjects. The lower HDL-C levels in AS than HC populations deserve further study and may be attributable to uninvestigated demographic, exercise capacity, or clinical manifestations.

Five new compounds from Zingiberis Rhizoma Recens and their anti-apoptotic activity.

Five new compounds, named gingerol A (1a and 1b), gingerol B (2), diphenylheptane glycoside A (3) and diphenylheptane glycoside B (4), were isolated from the acetone extract of Zingiberis Rhizoma Recens. The structures of new compounds were elucidated on the basis of spectroscopic methods including UV, IR, 1D NMR, 2D NMR and HR-ESI-MS. Compounds 2-4 could significantly decrease the apoptosis rate and increase the survival rate of human normal lung epithelial cells (BEAS-2B) at the concentration of 10 µM.

Ordered Mesoporous Intermetallic Ga-Pt Nanoparticles: Phase-Controlled Synthesis and Performance in Oxygen Reduction Electrocatalysis.

The intermetallic phase control is a promising strategy to optimize the physicochemical properties of ordered intermetallic compounds and engineer their performance in various (electro)catalytic reactions. However, the intermetallic phase-dependent catalytic performance is still rarely reported because of the difficulty in synthesizing ordered intermetallics with precisely controlled phase structures at atomic level, especially having ordered mesoscopic structure/morphology. Here, we successfully reported a precise synthesis of two phase-pure mesoporous intermetallic gallium-platinum (meso-i-Ga-Pt) nanoparticles, including meso-i-Ga3 Pt5 with an orthorhombic space group and meso-i-Ga1 Pt1 with a non-symmorphic chiral cubic space group. The intermetallic phase control of ordered meso-i-Ga-Pt nanoparticles was realized by carefully tuning the induced Ga salts with different anions that optimized the free energies during the synthesis. The intermetallic phase-dependent catalytic performance of ordered meso-i-Ga-Pt was systematically evaluated for oxygen reduction reaction (ORR) electrocatalysis, with completely opposite catalytic performance in alkaline media. Interestingly, ordered meso-i-Ga1 Pt1 catalyst with chiral atomic arrangements disclosed unexpected high ORR activity and stability with 5.9 and 3.2 enhancement factors in mass activity compared to those of meso-i-Ga3 Pt5 and commercial Pt/C.

FPIA: A database for gene fusion profiling and interactive analyses.

As one of the hallmarks of cancer, gene fusions play an important role in tumorigenesis, and have been established as biomarkers and therapeutic targets. Although recent years have witnessed the development of gene fusion databases, a tool with interactive analytic functions remains lacking. Here, we introduce fusion profiling interactive analysis (FPIA), a web server to perform interactive and customizable analysis on fusion genes. With this platform, researchers can easily explore fusion-associated biological and molecular differences including gene expression, tumor purity and ploidy, mutation, copy number variations, protein expression, immune cell infiltration, stemness, telomere length, microsatellite instability, survival and novel peptides based on 33 cancer types from The Cancer Genome Atlas (TCGA) data. Currently, it contains 31 633 fusion events from 6910 patients. FPIA complements the existing gene fusion annotation databases with its multiomics analytic capacity, integrated analysis features, customized analysis selection and user-friendly design. The comprehensive data analyses by FPIA will greatly facilitate data mining, hypothesis generation and therapeutic target discovery. FPIA is available at http://bioinfo-sysu.com/fpia.

The Role of Surface Curvature in Electrocatalysts.

Excessive consumption of fossil fuels has caused unavoidable environmental problems. The development of renewable and clean alternatives is essential for the sustainable and green development of human society. Electrocatalysts are most important parts in these energy-related devices. Recently, scientists found that the surface curvature of electrocatalysts could play an important role for the improvement of catalytic performance and the optimization of intrinsic catalytic activity during electrocatalytic process. The role of surface curvature in electrocatalysts is still under investigating. In this minireview, we summarized the latest progress of electrocatalysts with different surface curvatures and their applications in energy-related applications. This review mainly involves the strategies for preparation of electrocatalysts with different surface curvatures, three typical electrocatalysts with different surface curvatures (curled surface, onion-like structure, and spiral structure), and the potential mechanisms that surface curvature in electrocatalysts affects activities.

Impact of Patient Engagement and Social Determinants of Health on Care of Eosinophilic Gastrointestinal Disorders Patients.

ABSTRACT: The purpose of this study was to identify factors that influence eosinophilic gastrointestinal disorders (EGID) patients to switch gastroenterologists, assess the prevalence of social determinants of health (SDoH) in EGID patients, and the impact of SDoH on provider switching. 191 patients/caregivers participated in this cross-sectional, online study distributed through Patient Advocacy Groups. The 35-question survey took about 20 minutes to complete and was divided into three sections: demographics; 10 questions about provider switching; and nine-domain SDoH screen.Patients with EGIDs often switch providers, most commonly due to dissatisfaction with engagement in decision making. Additionally, these patients commonly have SDoH, some of which are associated with increased provider switching. Our results highlight the need to mindfully engage patients in decision-making and disease management. Providers also need to look beyond the "clinic space" and into SDoH. These low-cost/high-impact changes in provider behavior can promote continuity of care and patient engagement.

[Mechanism of Cyathulae Radix in treatment of knee osteoarthritis based on metabolomics].

Metabolomics based on ultra-high performance liquid chromatography-tandem quadrupole time-of-flight mass spectrometry(UHPLC-Q-TOF-MS) was employed to analyze the effect of Cyathulae Radix on serum and urine in rats with knee osteoarthritis, and to decipher the mechanism of Cyathulae Radix in the treatment of knee osteoarthritis. SD rats were randomized into a normal group, a model group, a positive drug group, and a Cyathulae Radix group. The knee osteoarthritis model was established by injecting 2% pa-pain and 0.03 mol·L~(-1) cysteine, and the serum levels of tumor necrosis factor-α(TNF-α) and matrix metalloproteinase-3(MMP-3) in the model group was measured to preliminarily evaluate the therapeutic effect of Cyathulae Radix on knee osteoarthritis. UHPLC-Q-TOF-MS was employed to establish the metabolic profile of endogenous small molecule metabolites in the four groups. Potential biomarkers were screened out by multivariate analysis methods such as partial least squares discriminant analysis(PLS-DA) and orthogonal partial least squares discriminant analysis(OPLS-DA) in combination with t-test, variable importance for projection(VIP), and fold-change. The related metabolic pathways were enriched with the help of MetaboAnalyst 5.0. The results showed that Cyathulae Radix alleviated the general signs of rats with knee osteoarthritis, and reduced the levels of TNF-α and MMP-3 in the rat serum. Twenty-eight differential metabolites that might be associated with the therapeutic effect of Cyathulae Radix were screened out from serum and urine. They were mainly involved in arginine biosynthesis, nicotinate and nicotinamide metabolism, tricarboxylic acid cycle, alanine, aspartate and glutamate metabolism, riboflavin metabolism, glyoxylate and dicarboxylate metabolism, and pyrimidine metabolism. Through metabonomics analysis, this study predicted the possible mechanism of Cyathulae Radix in the treatment of knee osteoarthritis, which laid a foundation for further research.

Plant U-box E3 ligases PUB25 and PUB26 control organ growth in Arabidopsis.

Plant organs often grow into a genetically determined size and shape. How organ growth is finely regulated to achieve a well defined pattern is a fascinating, but largely unresolved, question in plant research. We utilised the Arabidopsis petal to study the genetic control of plant organ growth, and identify two closely related U-box E3 ligases PUB25 and PUB26 as important growth regulators by screening the targets of the petal-specific growth-promoting transcription factor RABBIT EARS (RBE). We showed that PUB25 is directly controlled by RBE in petal development in a spatial- and temporal-specific manner and acts as a major target to mediate RBE's function in petal growth. We also showed that PUB25 and PUB26 repress petal growth by restricting the period of cell proliferation, and their regulation appears to be independent of other plant E3 ligase genes implicated in growth control. PUB25 and PUB26 are among the first U-box E3 ligases shown to function in plant growth control. Furthermore, as they were also found to play a vital role in plant stress responses, PUB25 and PUB26 may act as a key hub to integrate developmental and environmental signals for balancing growth and defence in plants.

Effect of the interface on femtosecond laser damage of a metal-dielectric low dispersion mirror.

Metal-dielectric low dispersion mirrors (MLDM) have a promising application prospect in petawatt (PW) laser systems. We studied the damage characteristics of MLDM and found that the damage source of MLDM (Ag + Al2O3+SiO2) is located at the metal-dielectric interface. We present the effect of the interface on the femtosecond laser damage of MLDM. Finite element analysis shows that thermal stress is distributed at the interface, causing stress damage which is consistent with the damage morphology. After enhancing the interface adhesion and reducing the residual stress, the damage source transfers from the interface to a surface SiO2 layer, and the damage threshold can be increased from 0.60 J/cm2 to 0.73 J/cm2. This work contributes to the search for new techniques to improve the damage threshold of MLDM used in PW laser systems.

Low-dispersion mirror with a broad bandwidth and high laser damage resistance.

A low-dispersion mirror (LDM), an important component in ultrafast laser systems, requires both a broad low-dispersion laser-induced damage threshold (LIDT). It is difficult for a traditional quarter-wavelength-based dielectric LDM to achieve these characteristics at the same time. We propose a novel, to the best of our knowledge, low-dispersion mirror (NLDM) that combines periodic chirped layers at the top and alternating quarter-wavelength layers at the bottom. Low dispersion is achieved by introducing a large same group delay (GD) for different wavelengths, so the bandwidth is broadened greatly. In addition, owing to the staggered electric field intensity peak effect in the structure, the NLDM shows the potential for high laser damage resistance. The experiments demonstrated that the NLDM doubles the low-dispersion bandwidth, while the LIDT is also increased compared with the LDM. This novel concept results in improved performance and paves the way toward a new generation of the LDM for ultrafast bandwidth and a high laser applications.