An ULK1/2-PXN mechanotransduction pathway suppresses breast cancer cell migration.

The remodeling and stiffening of the extracellular matrix (ECM) is a well-recognized modulator of breast cancer progression. How changes in the mechanical properties of the ECM are converted into biochemical signals that direct tumor cell migration and metastasis remain poorly characterized. Here, we describe a new role for the autophagy-inducing serine/threonine kinases ULK1 and ULK2 in mechanotransduction. We show that ULK1/2 activity inhibits the assembly of actin stress fibers and focal adhesions (FAs) and as a consequence impedes cell contraction and migration, independent of its role in autophagy. Mechanistically, we identify PXN/paxillin, a key component of the mechanotransducing machinery, as a direct binding partner and substrate of ULK1/2. ULK-mediated phosphorylation of PXN at S32 and S119 weakens homotypic interactions and liquid-liquid phase separation of PXN, impairing FA assembly, which in turn alters the mechanical properties of breast cancer cells and their response to mechanical stimuli. ULK1/2 and the well-characterized PXN regulator, FAK/Src, have opposing functions on mechanotransduction and compete for phosphorylation of adjacent serine and tyrosine residues. Taken together, our study reveals ULK1/2 as important regulator of PXN-dependent mechanotransduction.

Gradient-descent noise whitening techniques for short-reach IM-DD optical interconnects with severe bandwidth limitation.

Bandwidth limitation in optoelectrical components and the chromatic dispersion-induced power fading phenomenon cause severe inter-symbol interference (ISI) in high-speed intensity modulation and direct detection (IM-DD) optical interconnects. While the equalizer implemented in the receiver's digital signal processing procedure can mitigate ISI, it also inevitably enhances the noise located in the decayed frequency region, known as equalization-enhanced colored noise (EECN). Additionally, the nonlinear impairments of the modulator and photodetector also deteriorate the performance of the IM-DD system, especially for high-order modulation formats. In this work, we propose a gradient-descent noise whitening (GD-NW) algorithm to address EECN and extend it by introducing nonlinear kernels to simultaneously mitigate EECN and nonlinear impairments. The proposed algorithms are compared with conventional counterparts in terms of the achievable baud rate and the receiver optical power sensitivity. As a proof-of-concept experiment, we validate the principles of the proposed algorithms by successfully transmitting 360-GBd on-off-keying (OOK) and 180-GBd 4-level pulse-amplitude-modulation (PAM-4) signals in the back-to-back case under a 62-GHz brick-wall bandwidth limitation. 280-GBd OOK and 150-GBd PAM-4 transmissions are also demonstrated over 1-km standard single-mode fiber with a bit error rate below 7% hard-decision forward error correction aided by the proposed approach.

Impact of non-Gaussian noise on GMI and LDPC performance in neural network equalized systems.

In this Letter, the impact of non-Gaussian noise caused by a nonlinear equalizer on low-density parity-check code (LDPC) performance is investigated in a 25-km 50-Gb/s pulse amplitude modulation4 (PAM4) direct detection system. The lookup table (LUT)-based log-likelihood ratio (LLR) calculation method is proposed to enhance the LDPC performance for the non-Gaussian noise case. Compared to the conventional LLR calculation method based on Gaussian distribution, the proposed method can improve 0.6-dB sensitivity in artificial neural network (ANN) equalizer systems. In addition, the conventional generalized mutual information (GMI) is proven to be an imperfect predictor of LDPC performance after nonlinear equalizers, such as decision feedback equalization (DFE) and ANN equalizer.

Weight-adaptive joint mixed-precision quantization and pruning for neural network-based equalization in short-reach direct detection links.

Neural network (NN)-based equalizers have been widely applied for dealing with nonlinear impairments in intensity-modulated direct detection (IM/DD) systems due to their excellent performance. However, the computational complexity (CC) is a major concern that limits the real-time application of NN-based receivers. In this Letter, we propose, to our knowledge, a novel weight-adaptive joint mixed-precision quantization and pruning approach to reduce the CC of NN-based equalizers, where only integer arithmetic is taken into account instead of floating-point operations. The NN connections are either directly cutoff or represented by a proper number of quantization bits by weight partitioning, leading to a hybrid compressed sparse network that computes much faster and consumes less hardware resources. The proposed approach is verified in a 50-Gb/s 25-km pulse amplitude modulation (PAM)-4 IM/DD link using a directly modulated laser (DML) in the C-band. Compared with the traditional fully connected NN-based equalizer operated with standard floating-point arithmetic, about 80% memory can be saved at a minimum network size without degrading the system performance. Quantization is also shown to be more suitable to over-parameterized NN-based equalizers compared with NNs selected at a minimum size.

112-GBaud mode-division-multiplexing IM-DD transmission beyond net 6.4†Tb/s over weakly coupled FMF for optical interconnections.

Weakly coupled mode-division-multiplexing (MDM) systems based on intensity modulation and direct detection (IM-DD) are a good candidate for further improving the capacity of short-reach optical interconnections. However, restrained by the modal crosstalk of the transmission link and the reception of degenerate mode groups (DMGs) utilizing bandwidth-limited multimode photodetectors (PDs), high-speed MDM IM-DD has encountered a capacity bottleneck. In this Letter, we investigate a high-speed weakly coupled MDM IM-DD transmission system utilizing a degenerate mode diversity receiver scheme adopting high-bandwidth single-mode PDs over a multiple-ring-core (MRC) few-mode fiber (FMF) and a low-crosstalk mode multiplexer/demultiplexer (MUX/DMUX). An MDM IM-DD transmission with four DMGs and eight wavelengths is experimentally demonstrated with 112-GBaud four-level pulse-amplitude modulation (PAM4) and probabilistically shaped PAM8 per lane over 200-m weakly coupled MRC-FMF. To the best of our knowledge, this is the first experimental demonstration of the MDM IM-DD transmission system with up to 112-GBaud baud rate and beyond 6.4-Tb/s net rate. Meanwhile, the experimental results show that the proposed MDM IM-DD transmission link has a superior performance only adopting a low-complexity feedforward equalizer, making it a promising candidate for high-speed optical interconnections.

Low-latency 100†Gb/s PAM-4 PON with a 42.5†dB power budget over the 20†km anti-resonant hollow-core fiber.

The surging growth in data traffic has necessitated the development of higher-speed, lower-latency intensity modulation and direct detection (IM/DD) passive optical networks (PONs) with higher power budgets. To address the inherent limitations of traditional silica-based solid-core fibers, anti-resonant hollow-core fibers have garnered significant attention from both academia and industry. In this Letter, we present an experimental demonstration of 100 Gb/s PAM-4 IM/DD PON transmission over a 20 km anti-resonant hollow-core fiber in the C band, utilizing low-complexity digital signal processing (DSP). The result achieves a record high power budget of 42.5 dB, facilitated by a 3-tap weighted lookup table (LUT) at the optical line terminal (OLT) side and a semiconductor optical amplifier used as a preamplifier at the optical network unit (ONU) side. This represents the highest power budget reported for IM/DD PON to date, to the best of our knowledge, and offers a promising alternative for the future evolution of PON systems.

Mode-division-multiplexing self-homodyne coherent transmission over a weakly coupled few-mode fiber for optical interconnections.

Self-homodyne coherent transmission has recently received extensive investigation as a coherent lite candidate for high-speed short-reach optical networks. In this Letter, we propose a weakly coupled mode-division-multiplexing (MDM) self-homodyne coherent scheme using a multiple-ring-core few-mode fiber, in which one of the modes transmits a self-homodyne local oscillator (LO) and the rest are utilized for carrying signals. Multiple rings of index perturbations in the fiber core are applied to achieve low modal crosstalk, allowing the signals and the remote LO to be transmitted independently. We experimentally demonstrate a 7.2-Tb/s (5.64-Tb/s net rate) self-homodyne coherent transmission with an 800-Gb/s data rate for each of the nine information-bearing modes formatted in 80-GBaud probabilistic constellation-shaped 64-quadrature-amplitude modulation. To the best of our knowledge, this is the first experimental demonstration of an MDM self-homodyne coherent transmission with up to 10 spatial modes. The proposed scheme may pave the way for future high-capacity data center interconnections.

Multiplication-free and hardware-efficient baud-rate timing error detector for Nyquist and faster than Nyquist optical IM/DD systems.

Clock recovery (CR) algorithms that support higher baud rates and advanced modulation formats are crucial for short-distance optical interconnections, and it is desirable to push CR to operate at baud rate with minimal computing resources and power. In this Letter, we proposed a hardware-efficient and multiplication operation-free baud-rate timing error detector (TED) as a solution to meet these demands. Our approach involves employing both the absolute value of samples and the nonlinear sign operation to emphasize the clock tone, which is deteriorated by severe bandwidth limitation in Nyquist and faster than Nyquist (FTN) systems. Through experimental investigations based on a transceiver system with a 3 dB bandwidth of 30 GHz, the proposed baud-rate TED exhibits excellent performance. The proposed scheme successfully achieves clock synchronization of the received signals with the transmitted signals, including 50 GBaud PAM4/8, 80 GBaud PAM4, and up to 120 GBaud PAM4 FTN signals. To the best of our knowledge, the CR based on the proposed baud-rate TED is the most optimal solution for ultrahigh-speed short-reach IM/DD transmission, comprehensively considering the timing jitter, bit error rate (BER), and implementation complexity.

Calcineurin controls proximodistal blastema polarity in zebrafish fin regeneration.

Planarian flatworms regenerate their heads and tails from anterior or posterior wounds and this regenerative blastema polarity is controlled by Wnt/ß-catenin signaling. It is well known that a regeneration blastema of appendages of vertebrates such as fish and amphibians grows distally. However, it remains unclear whether a regeneration blastema in vertebrate appendages can grow proximally. Here, we show that a regeneration blastema in zebrafish fins can grow proximally along the proximodistal axis by calcineurin inhibition. We used fin excavation in adult zebrafish to observe unidirectional regeneration from the anterior cut edge (ACE) to the posterior cut edge (PCE) of the cavity and this unidirectional regeneration polarity occurs as the PCE fails to build blastemas. Furthermore, we found that calcineurin activities in the ACE were greater than in the PCE. Calcineurin inhibition induced PCE blastemas, and calcineurin hyperactivation suppressed fin regeneration. Collectively, these findings identify calcineurin as a molecular switch to specify the PCE blastema of the proximodistal axis and regeneration polarity in zebrafish fin.

A novel n-UV convertible colour-tunable emitting oxynitride phosphor: Realization based on Ce3+ -Tb3+ energy transfer.

In the present work, a novel n-UV convertible colour-tunable emitting phosphor was obtained based on the efficient Ce3+ -Tb3+ energy transfer in the Y10 Al2 Si3 O18 N4 host. By properly controlling the ratio of Ce3+ /Tb3+ , the colour hue of the obtained powder covered the blue and green regions, under excitation of 365 nm. The steady-state and dynamic-state luminescence measurement was performed to shed light on the related mechanism, which was justified by the electronic dipole-quadrupole dominating the related energy transfer process. Preliminary studies showed that Y10 Al2 Si3 O18 N4 :Ce3+ ,Tb3+ can be promising as an inorganic phosphor for white LED applications.

12.7 W intra-cavity pumped Ho:YAG laser with near-diffraction-limited beam quality.

We demonstrated a compact and efficient Ho:YAG slab laser intra-cavity pumped by a Tm:YLF slab laser for the first time. In the Tm:YLF laser operation, the maximum power of 32.1 W with optical-to-optical efficiency of 52.8% was obtained. In the intra-cavity pumped Ho:YAG laser operation, the output power of 12.7 W at 2122 nm was obtained. The beam quality factors M2 in the vertical and horizontal directions were 1.22 and 1.11, respectively. The RMS instability was measured to be lower than 0.1%. To the best of our knowledge, this was the maximum power for the Tm-doped laser intra-cavity pumped Ho-doped laser with near-diffraction-limited beam quality.

Fast polarization state tracking for dual-polarization direct detection with Jones-space field recovery.

Direct detection system is expected to possess the phase and polarization diversity in order to achieve high spectral efficiency and fiber impairment compensation such as chromatic dispersion and polarization rotation. In this Letter, we theoretically extend the concept of the proposed Jones-space field recovery (JSFR) to include a dynamic polarization rotation matrix and experimentally demonstrate the rapid polarization state tracking ability of the JSFR receiver based on a 3 × 3 optical coupler. Under a rotation of the state of polarization at a rate of 1 Mrad/s, we successfully transmit 59-GBd dual-polarization 16-ary quadrature-amplitude-modulation signals over an 80-km standard single-mode fiber based on a decision-directed least mean square (DD-LMS) or a recursive least square (DD-RLS), with a bit-error rate below the 14% hard-decision forward error correction threshold of 1 × 10-2. The experimental results indicate that the legacy polarization tracking algorithms designed for coherent optical communication are also applicable for this direct detection scheme. To our best knowledge, this work demonstrates the first polarization rotation-tolerant direct detection system with phase and polarization diversity, providing a low-cost and high-speed solution for short-reach communications.

Effect of Solvents on the Color Recovery Responses of Swollen Structural-Color Epoxy Films Based on Inverse Opal Photonic Crystals.

Photonic crystal (PC) films have been widely applied in color displays and the anticounterfeiting field due to their facile fabrication process and easily tunable properties. However, the method for improving the reusability of the color-changed swollen PC films is still a challenge. In this paper, we report the color recovery behavior of epoxy resin inverse opal photonic crystal (EP-IOPC) films, which show different responses after being infiltrated with ethanol, acetone, and dimethyl sulfoxide (DMSO) based on the swelling and deswelling process. DMSO achieved the best effect on the color recovery of the swollen EP-IOPC films compared to ethanol and acetone, and the reflection spectrum blue-shifted in a small range and finally stabilized at a 60 nm deviation from the original spectrum after 10 times recovery. This strategy of color recovery not only solved the problem that the swollen EP-IOPC film's color changes to a certain extent but also showed promising potential in the color display and anticounterfeiting field.

Nitazoxanide induced myocardial injury in zebrafish embryos by activating oxidative stress response.

Nitazoxanide (NTZ) is a broad-spectrum antiparasitic and antiviral drug (thiazole). However, although NTZ has been extensively used, there are no reports concerning its toxicology in vertebrates. This study used the zebrafish as a vertebrate model to evaluate the safety of NTZ and to analyse the related molecular mechanisms. The experimental results showed that zebrafish embryos exposed to NTZ had cardiac malformation and dysfunction. NTZ also significantly inhibited proliferation and promoted apoptosis in cardiomyocytes. Transcriptomic analysis used compared gene expression levels between zebrafish embryos in the NTZ treatment and the control groups identified 200 upregulated genes and 232 downregulated genes. Analysis by Kyoto encyclopaedia of genes and genomes (KEGG) and gene ontology (GO) showed that signal pathways on cardiomyocyte development were inhibited while the oxidative stress pathways were activated. Further experiments showed that NTZ increased the content of reactive oxygen species (ROS) in the hearts of zebrafish. Antioxidant gadofullerene nanoparticles (GFNPs) significantly alleviated the developmental toxicity to the heart, indicating that NTZ activated the oxidative stress response to cause embryonic cardiomyocyte injury in zebrafish. This study provides evidence that NTZ causes developmental abnormalities in the cardiovascular system of zebrafish.

High-efficiency Ho:YLF slab laser with 125 W continuous-wave output power.

We demonstrate a compact and efficient Ho:YLF slab laser that is pumped by a self-made Tm:YAP slab laser. The maximum output power of 125 W at 2064 nm was obtained with the incident pump power of 245 W. To the best of our knowledge, this is the first report for an Ho:YLF laser oscillator to reach hundred-watts-level output power. The slope efficiency with respect to the incident pump power was 62.5%, and the optical-to-optical conversion efficiency was 51%. The RMS instability of the maximum output power was measured to be 0.24% in 30 min. The beam quality factors M2 were 475 and 1.59 in the x and y directions, respectively.

Cardiac toxicity assessment of pendimethalin in zebrafish embryos.

Pendimethalin (PND) is one of the best sellers of selective herbicide in the world and has been frequently detected in the water. However, little is known about its effects on cardiac development. In this study, we used zebrafish to investigate the developmental and cardiac toxicity of PND. We exposed the zebrafish embryos with a serial of concentrations at 3, 4, and 5 mg/L at 5.5-72 h post-fertilization (hpf). We found that PND exposure can reduce the heart rate, survival rate, and body length of zebrafish embryos. Furthermore, we identified many malformations including pericardial and yolk sac edema, spinal deformity, and cardiac looping abnormality. In addition, PND increased the expression of reactive oxygen species and malondialdehyde and reduced the activity of superoxide dismutase (Antioxidant enzymes); We examined the expression of cardiac development-related genes and the apoptosis markers, and found changes of the following marker: vmhc, nppa, tbx5a, nkx2.5, gata4, tbx2b and FoxO1, bax, bcl-2, p53, casp-9, casp-3. Our data showed that activation of Wnt pathway can rescue the cardiac abnormalities caused by PND. Our results provided new evidence for the toxicity of PND and suggested that the PND residual should be treated as a hazard in the environment.

Effects of sulfometuron-methyl on zebrafish at early developmental stages.

Sulfometuron methyl (SM) is a widely used herbicide and thus leading to accumulation in the environment. The toxicity assessments of SM in model organisms are currently rare. In the present study, zebrafish were utilized for evaluating the detrimental effects of SM in aquatic vertebrates. Zebrafish embryos were exposed to 0, 10, 20, and 40 mg/L SM from 5.5 to 72 h post-fertilization (hpf), respectively. Consequently, SM exposure resulted in increasing the mortality rate and reducing hatching rate in larval zebrafish at 10, 20, and 40 mg/L SM-treated groups. The reduced numbers of immune cells (neutrophils and macrophages) were observed after SM exposure by a dose-dependent manner. The inflammatory responses (TLR4, MYD88, IL-1ß, IL-6, IL-8, IFN-γ, IL-10, and TGF-ß) were measured to estimate immune responses. Anti-inflammatory factors (IL-10 and TGF-ß) were down-regulated in all the treated groups and significantly altered at 40 mg/L exposure group. Additionally, behavioral tests suggested that SM treatment significantly increased the total distance, average speed, and maximum acceleration of larval zebrafish during light-dark transition and subsequently enzymology test displayed the same trend to locomotor behaviors. The content significantly increased in oxidative stress, as reflected in ROS level in all the treated groups. The numbers of cell apoptosis were significantly increased at 20, and 40 mg/L and the highest concentration group induced the substantial increment (P < 0.001) of apoptosis-related genes including p53, Bax/Bcl-2, caspase-9, and caspase-3. In summary, our results demonstrated that exposure to SM caused toxicity of development, immune system, locomotor behavior, oxidative stress, and cell apoptosis at the early developmental stages of zebrafish.

Cascade recurrent neural network-assisted nonlinear equalization for a 100 Gb/s PAM4 short-reach direct detection system.

We propose a novel, to the best of our knowledge, cascade recurrent neural network (RNN)-based nonlinear equalizer for a pulse amplitude modulation (PAM)4 short-reach direct detection system. A 100 Gb/s PAM4 link is experimentally demonstrated over 15 km standard single-mode fiber (SSMF), using a 16 GHz directly modulated laser (DML) in C-band. The link suffers from strong nonlinear impairments which is mainly induced by the mixture of linear channel effects with square-law detection, the DML frequency chirp, and the device nonlinearity. Experimental results show that the proposed cascade RNN-based equalizer outperforms other feedforward or non-cascade neural network (NN)-based equalizers owing to both its cascade and recurrent structure, showing the great potential to effectively tackle the nonlinear signal distortion. With the aid of a cascade RNN-based equalizer, a bit-error rate (BER) lower than the 7% hard-decision forward error correction (FEC) threshold can be achieved when the receiver power is larger than 5 dBm. Compared with traditional non-cascade NN-based equalizers, the training time could also be reduced by half with the help of the cascade structure.

Yolk-Shell Fe3 O4 @Void@N-Carbon Nanostructures Based on One-Step Deposition of SiO2 and Resorcinol-3-Aminophenol-Formaldehyde (R-APF) Cocondensed Resin Dual Layers onto Fe3 O4 Nanoclusters.

Yolk-shell magnetic nanoparticles@nitrogen-enriched Carbon nanostructures with a magnetic core and a hollow nitrogen-enriched carbon shell exhibit considerable promise in various applications, such as drug delivery, heterogenous catalysts, removal of metal ions and organic pollutants, and screening of biomolecules, due to their strong magnetic response, unique cavities, and the selective absorption ability of nitrogen-enriched groups. However, their complicated synthesis always involves possible surface modification, layer-by-layer deposition of a sacrificial middle layer and an outer nitrogen-enriched layer on magnetic nanoparticles, subsequent carbonization, and final removal of the sacrificial middle layer. Herein, yolk-shell Fe3 O4 @nitrogen-enriched carbon nanostructures are constructed based on NH4 + ion-induced one-step deposition of SiO2 and Resorcinol-3-aminophenol-formaldehyde cocondensed resin (R-APF) dual layers onto poly acrylic acid-modified Fe3 O4 nanoclusters without any extra surface modification. The N-Carbon shell thickness of the yolk-shell Fe3 O4 @Void@N-Carbon nanostructure can be finely tailored though tailoring the feeding amount of aminophenol and resorcinol to tune the thickness of the outer R-APF resin shell onto Fe3 O4 @SiO2 intermediate particles. This NH4 + ion-induced one-pot deposition of double layers can effectively promote synthesis efficiency of this kind of yolk-shell nanostructure.

Famoxadone-cymoxanil induced cardiotoxicity in zebrafish embryos.

Famoxadone-cymoxanil is a new protective and therapeutic fungicide, but little research has been done on it or its toxicity in aquatic organisms. In this study, we used zebrafish to investigate the cardiotoxicity of famoxadone-cymoxanil and the potential mechanisms involved. Zebrafish embryos were exposed to different concentrations of famoxadone-cymoxanil until 72 h post-fertilization (hpf), then changes of heart morphology in zebrafish embryos were observed. We also detected the levels of oxidative stress, myocardial-cell proliferation and apoptosis, ATPase activity, and the expression of genes related to the cardiac development and calcium-signaling pathway. After famoxadone-cymoxanil exposure, pericardial edema, cardiac linearization, and reductions in the heart rate and cardiac output positively correlated with concentration. Although myocardial-cell apoptosis was not detected, proliferation of the cells was severely reduced and ATPase activity significantly decreased, resulting in a severe deficiency in heart function. In addition, indicators of oxidative stress changed significantly after exposure of the embryos to the fungicide. To better understand the possible molecular mechanisms of cardiovascular toxicity in zebrafish, we studied the transcriptional levels of cardiac development, calcium-signaling pathways, and genes associated with myocardial contractility. The mRNA expression levels of key genes in heart development were significantly down-regulated, while the expression of genes related to the calcium-signaling pathway (ATPase [atp2a1], cardiac troponin C [tnnc1a], and calcium channel [cacna1a]) was significantly inhibited. Expression of klf2a, a major endocardial flow-responsive gene, was also significantly inhibited. Mechanistically, famoxadone-cymoxanil toxicity might be due to the downregulation of genes associated with the calcium-signaling pathway and cardiac muscle contraction. Our results found that famoxadone-cymoxanil exposure causes cardiac developmental toxicity and severe energy deficiency in zebrafish.