OAM mode-division multiplexing IM/DD transmission at 4.32†Tbit/s with a low-complexity adaptive-network-based fuzzy inference system nonlinear equalizer.

Stochastic nonlinear impairment is the primary factor that limits the transmission performance of high-speed orbital angular momentum (OAM) mode-division multiplexing (MDM) optical fiber communication systems. This Letter presents a low-complexity adaptive-network-based fuzzy inference system (LANFIS) nonlinear equalizer for OAM-MDM intensity-modulation direct-detection (IM/DD) transmission with three OAM modes and 15 wavelength division multiplex (WDM) channels. The LANFIS equalizer could adjust the probability distribution functions (PDFs) of the distorted pulse amplitude modulation (PAM) symbols to fit the statistical characteristics of the WDM-OAM-MDM transmission channel. Therefore, although the transmission symbols in the WDM-OAM-MDM system are subjected to a stochastic nonlinear impairment, the proposed LANFIS equalizer can effectively compensate the distorted signals. The proposed equalizer outperforms the Volterra equalizer with improvements in receiver sensitivity of 2, 1.5, and 1.3 dB for three OAM modes at a wavelength of 1550.12 nm, respectively. It also outperforms a CNN equalizer, with improvements in receiver sensitivity of 1, 0.5, and 0.3 dB, respectively. Moreover, complexity reductions of 67%, 74%, and 99.9% are achieved for the LANFIS equalizer compared with the Volterra, CNN, and ANFIS equalizers, respectively. The proposed equalizer has high performance and low complexity, making it a promising candidate for a high-speed WDM-OAM-MDM system.

Emerging Roles of Microfluidics in Brain Research: From Cerebral Fluids Manipulation to Brain-on-a-Chip and Neuroelectronic Devices Engineering.

Remarkable progress made in the past few decades in brain research enables the manipulation of neuronal activity in single neurons and neural circuits and thus allows the decipherment of relations between nervous systems and behavior. The discovery of glymphatic and lymphatic systems in the brain and the recently unveiled tight relations between the gastrointestinal (GI) tract and the central nervous system (CNS) further revolutionize our understanding of brain structures and functions. Fundamental questions about how neurons conduct two-way communications with the gut to establish the gut-brain axis (GBA) and interact with essential brain components such as glial cells and blood vessels to regulate cerebral blood flow (CBF) and cerebrospinal fluid (CSF) in health and disease, however, remain. Microfluidics with unparalleled advantages in the control of fluids at microscale has emerged recently as an effective approach to address these critical questions in brain research. The dynamics of cerebral fluids (i.e., blood and CSF) and novel in vitro brain-on-a-chip models and microfluidic-integrated multifunctional neuroelectronic devices, for example, have been investigated. This review starts with a critical discussion of the current understanding of several key topics in brain research such as neurovascular coupling (NVC), glymphatic pathway, and GBA and then interrogates a wide range of microfluidic-based approaches that have been developed or can be improved to advance our fundamental understanding of brain functions. Last, emerging technologies for structuring microfluidic devices and their implications and future directions in brain research are discussed.

DACNN-aided nonlinear equalizer for a probabilistic shaping coherent optical communication system.

The probabilistic shaping (PS) technique is a key technology for fiber optic communication systems to further approach the Shannon limit. To solve the problem that nonlinear equalizers are ineffective for probabilistic shaping optical communication systems with non-uniform distribution, a distribution alignment convolutional neural network (DACNN)-aided nonlinear equalizer is proposed. The approach calibrates the equalizer using the probabilistic shaping prior distribution, which reduces the training complexity and improves the performance of the equalizer simultaneously. Experimental results show nonlinear equalization of 120 Gb/s PS 64QAM signals in a 375 km transmission scenario. The proposed DACNN equalizer improves the receiver sensitivity by 2.6 dB and 1.1 dB over the Volterra equalizer and convolutional neural network (CNN) equalizer, respectively. Meanwhile, DACNN converges with fewer training epochs than CNN, which provides great potential for mitigating the nonlinear distortion of PS signals in fiber optic communication systems.

400 Gbit/s 4 mode transmission for IM/DD OAM mode division multiplexing optical fiber communication with a few-shot learning-based AffinityNet nonlinear equalizer.

Nonlinear impairment in a high-speed orbital angular momentum (OAM) mode-division multiplexing (MDM) optical fiber communication system presents high complexity and strong stochasticity due to the massive optoelectronic devices. In this paper, we propose an Affinity Network (AffinityNet) nonlinear equalizer for an OAM-MDM intensity-modulation direct-detection (IM/DD) transmission with four OAM modes. The labeled training and testing signals from the OAM-MDM system can be regarded as "small sample" and "large target", respectively. AffinityNet can be used to build an accurate nonlinear model using "small sample" based on few-shot learning and can predict the stochastic characteristic nonlinearity of OAM-MDM with a high level of generalization. As a result, the AffinityNet nonlinear equalizer can effectively compensate the stochastic nonlinearity in the OAM-MDM system, despite the large difference between the training and testing signals due to the stochastic nonlinear impairment. An experiment was conducted on a 400 Gbit/s transmission with four OAM modes using a pulse amplitude modulation-8 (PAM-8) signal over a 2 km ring-core fiber (RCF). Our experimental results show that the proposed nonlinear equalizer outperformed the conventional Volterra equalizer with improvements in receiver sensitivity of 1.7, 1.8, 3, and 3.3 dB for the four OAM modes at the 15% forward error correction (FEC) threshold, respectively. In addition, the proposed equalizer outperformed a convolutional neural network (CNN) equalizer with improvements in receiver sensitivity of 0.8, 0.5, 0.9, and 1.4 dB for the four OAM modes at the 15% FEC threshold. In the experiment, a complexity reduction of 37% and 83% of the AffinityNet equalizer is taken compared to the conventional Volterra equalizer and CNN equalizer, respectively. The proposed equalizer is a promising candidate for a high-speed OAM-MDM optical fiber communication system.

Hidden conditional random field-based equalizer for the 3D-CAP-64 transmission of OAM mode-division multiplexed ring-core fiber communication.

As a key technique for achieving ultra-high capacity optical fiber communications, orbital angular momentum (OAM) mode-division multiplexing (MDM) is affected by severe nonlinear impairments, including modulation related nonlinearities, square-law nonlinearity and mode-coupling-induced nonlinearity. In this paper, an equalizer based on a hidden conditional random field (HCRF) is proposed for the nonlinear mitigation of OAM-MDM optical fiber communication systems with 20 GBaud three-dimensional carrierless amplitude and phase modulation-64 (3D-CAP-64) signals. The HCRF equalizer extracts the stochastic nonlinear feature of the OAM-MDM 3D-CAP-64 signals by estimating the conditional probabilities of the hidden variables, thereby enabling the signals to be classified into subclasses of constellation points. The nonlinear impairment can then be mitigated based on the statistical probability distribution of the hidden variables of the OAM-MDM transmission channel in the HCRF equalizer. Our experimental results show that compared with a convolutional neural network (CNN)-based equalizer, the proposed HCRF equalizer improves the receiver sensitivity by 2 dB and 1 dB for the two OAM modes used here, with l = + 2 and l = + 3, respectively, at the 7% forward error correction (FEC) threshold. When compared with a Volterra nonlinear equalizer (VNE) and CNN-based equalizer, the computational complexity of the proposed HCRF equalizer was found to be reduced by 30% and 41%, respectively. The bit error ratio (BER) performance and reduction in computational complexity indicate that the proposed HCRF equalizer has great potential to mitigate nonlinear distortions in high-speed OAM-MDM fiber communication systems.

Adaptive Bayesian neural networks nonlinear equalizer in a 300-Gbit/s PAM8 transmission for IM/DD OAM mode division multiplexing.

The strong stochastic nonlinear impairment induced by random mode coupling appears to be a long-standing performance-limiting problem in the orbital angular momentum (OAM) mode division multiplexing (MDM) of intensity modulation direct detection (IM/DD) transmission systems. In this Letter, we propose a Bayesian neural network (BNN) nonlinear equalizer for an OAM-MDM IM/DD transmission with three modes. Unlike conventional Volterra and convolutional neural network (CNN) equalizers with fixed weight coefficients, the weights and biases of the BNN nonlinear equalizer are regarded as probability distributions, which can accurately match the stochastic nonlinear model of the OAM-MDM. The BNN nonlinear equalizer is capable of adaptively updating its weights and biases sample-by-sample, according to the probability distribution. An experiment was conducted on a 300-Gbit/s PAM8 signal with three modes over a 2.6-km OAM-MDM RCF transmission. The experimental results demonstrate that the proposed BNN nonlinear equalizer exhibits promising solutions to effectively mitigate nonlinear distortions, which outperforms conventional Volterra and CNN equalizers with receiver sensitivity improvements of 1.0 dBm and 2.5 dBm, respectively, under hard-decision forward error correction (HD-FEC) thresholds. Moreover, compared with the Volterra and CNN equalizers, the complexity of the OAM-MDM is significantly improved through the BNN nonlinear equalizer. The proposed BNN nonlinear equalizer is a promising candidate for the high capacity inter-data center interconnects.

Identification and verification of ferroptosis-related genes in diabetic foot using bioinformatics analysis.

Ferroptosis is a novel form of cell death that plays a key role in several diseases, including inflammation and tumours; however, the role of ferroptosis-related genes in diabetic foot remains unclear. Herein, diabetic foot-related genes were downloaded from the Gene Expression Omnibus and the ferroptosis database (FerrDb). The least absolute shrinkage and selection operator regression algorithm was used to construct a related risk model, and differentially expressed genes were analysed through immune infiltration. Finally, we identified relevant core genes through a protein-protein interaction network, subsequently verified using immunohistochemistry. Comprehensive analysis showed 198 genes that were differentially expressed during ferroptosis. Based on functional enrichment analysis, these genes were primarily involved in cell response, chemical stimulation, and autophagy. Using the CIBERSORT algorithm, we calculated the immune infiltration of 22 different types of immune cells in diabetic foot and normal tissues. The protein-protein interaction network identified the hub gene TP53, and according to immunohistochemistry, the expression of TP53 was high in diabetic foot tissues but low in normal tissues. Accordingly, we identified the ferroptosis-related gene TP53 in the diabetic foot, which may play a key role in the pathogenesis of diabetic foot and could be used as a potential biomarker.

Bioinformatics analysis and verification of m6A related genes based on the construction of keloid diagnostic model.

Keloids are formed due to abnormal hyperplasia of the skin connective tissue. We explored the relationship between N6-methyladenosine (m6A)-related genes and keloids. The transcriptomic datasets (GSE44270 and GSE185309) of keloid and normal skin tissues samples were obtained from the Gene Expression Omnibus database. We constructed the m6A landscape and verified the corresponding genes using immunohistochemistry. We extracted hub genes for unsupervised clustering analysis using protein-protein interaction (PPI) network; gene ontology enrichment analysis was performed to determine the biological processes or functions affected by the differentially expressed genes (DEGs). We performed immune infiltration analysis to determine the relationship between keloids and the immune microenvironment using single-sample gene set enrichment analysis and CIBERSORT. Differential expression of several m6A genes was observed between the two groups; insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) was significantly upregulated in keloid patients. PPI analysis elucidated six genes with significant differences between the two keloid sample groups. Enrichment analysis revealed that the DEGs were mainly enriched in cell division, proliferation, and metabolism. Moreover, significant differences in immunity-related pathways were observed. Therefore, the results of this study will provide a reference for the elucidation of the pathogenesis and therapeutic targets of keloids.

Tunable and anisotropic perfect absorber using graphene-black phosphorus nanoblock.

Two-dimensional (2D) materials, which have attracted attention due to intriguing optical properties, form a promising building block in optical and photonic devices. This paper numerically investigates a tunable and anisotropic perfect absorber in a graphene-black phosphorus (BP) nanoblock array structure. The suggested structure exhibits polarization-dependent anisotropic absorption in the mid-infrared, with maximum absorption of 99.73% for x-polarization and 53.47% for y-polarization, as determined by finite-difference time-domain FDTD analysis. Moreover, geometrical parameters and graphene and BP doping amounts are possibly employed to tailor the absorption spectra of the structures. Hence, our results have the potential in the design of polarization-selective and tunable high-performance devices in the mid-infrared, such as polarizers, modulators, and photodetectors.

Modified low CSPR Kramer-Kronig receivers based on a signal-signal beat interference estimation.

Due to their simple structures and high robustness to fibre dispersion, single-sideband transmission systems using Kramer-Kronig (KK) receivers are an attractive solution for 80 km data centre interconnects. However, a major problem with KK receivers is that the optimal carrier signal power ratio (CSPR) needs to be large, due to the existence of signal-signal beat interference (SSBI), but this results in low receiver sensitivity. We propose two modified KK receivers that can estimate and eliminate SSBI and allow for signal detection when the CSPR is less than 0 dB. After transmission over an 80 km optical fibre, our modified KK receivers were able to increase the receiver sensitivity by 3 dB compared with a traditional KK receiver while the CSPR was reduced by 6 dB, and improvements of 1.16 and 1.60 dB in the OSNR were achieved with a reduction in the CSPR of 8 dB. Our improved KK receivers can greatly reduce the carrier power and CSPR necessary for the system, and thus reduce the cost of the system transmitter.

Probabilistic neural network equalizer for nonlinear mitigation in OAM mode division multiplexed optical fiber communication.

Orbital angular momentum (OAM) mode-division multiplexing (MDM) is a key technique to achieve ultra-high-capacity optical fiber communications. However, the high nonlinear impairment from optoelectronic devices, such as spatial light modulators, modulators, and photodiodes, is a long-standing challenge for OAM-MDM. In this paper, an equalizer based on a probabilistic neural network (PNN) is presented to mitigate the nonlinear impairment for an OAM-MDM fiber communication system with 32 GBaud Nyquist pulse amplitude modulation-8 (PAM8) intensity-modulation direct-detection (IM-DD) signals. PNN equalizer can calculate the distribution of the nonlinearity using Bayesian decision theory and thus mitigate the stochastic nonlinear impairment of the received signal. Experimental results show that compared with the convolutional neural network (CNN) equalizer, the PNN equalizer improves the receiver sensitivity by 0.6dB and 2dB for two OAM modes with l = + 3 and l = + 4 at the 20% FEC limit, respectively. Moreover, compared with Volterra or CNN equalizers, the PNN equalizer can reduce the computation complexity significantly, which has great potential to mitigate the nonlinear signal distortions in high-speed IM-DD OAM-MDM fiber communication systems.

Fiber optofluidic Coriolis flowmeter based on a dual-antiresonant reflecting optical waveguide.

A microfiber optofluidic flowmeter based on the Coriolis principle and a dual-antiresonant reflecting optical waveguide (ARROW) is proposed and experimentally demonstrated. A hollow hole in a hollow-core fiber is fabricated as an optofluidic channel to move the liquid sample, which forms a dual-ARROW in the hollow-core fiber. Two sides of the hollow-core fiber are used as two adjacent Fabry-Perot resonators based on the refractive index modulation of a CO2 laser, which is used to investigate the vibration signals of the two resonators. The flow rate can be measured based on the Coriolis force by calculating the phase difference between the two ARROWs. The experimental results show that a flow rate sensitivity of 8.04 deg/(µl/s) can be achieved for ethanol solution. The proposed micro Coriolis fiber optic flowmeter can be used in various fields, such as food production, medicine, bioanalysis, etc.

Protective role of selenium on ammonia-mediated nephrotoxicity via PI3K/AKT/mTOR pathway: Crosstalk between autophagy and cytokine release.

Ammonia (NH3) is a hazardous substance to human and animal health. Selenium (Se) is an essential micronutrient with multiple health benefits. The present study aimed to verify whether and how Se supplementation has a protective role against NH3 mediated-nephrotoxicity in pigs. A Se-NH3 interaction model was established in pigs and the kidney samples were collected after a 30-day treatment period. The results showed that NH3 exposure inhibited the PI3K/AKT/mTOR pathway and enhanced the secretion of inflammatory cytokines to induce autophagy and inflammation. Se can regulate the PI3K/AKT/mTOR pathway and attenuate the secretion of inflammatory cytokines altered by NH3 to reduce autophagy and inflammation. In addition, Se co-treatment inhibited ROS production, elevated the activities of antioxidant systems, and increased the expression of 13 selenoproteins in pig kidneys caused by NH3 exposure. These results implied that L-selenomethionine can moderate NH3-induced nephrotoxicity in pigs. Our study gives new ideas for the specific mechanism of NH3 nephrotoxicity and provides a reference for comparative medicine and clinical medication.

Evaluation of potential cardiotoxicity of ammonia: l-selenomethionine inhibits ammonia-induced cardiac autophagy by activating the PI3K/AKT/mTOR signaling pathway.

Ammonia is a major harmful gas in the environment of livestock and poultry. Studies have shown that excessive ammonia inhalation has adverse effects in pig heart. However, the mechanism of ammonia-induced cardiac toxicity in pigs has not been reported. L-selenomethionine is a kind of organic selenium (Se) which is easily absorbed by the body. Therefore, in this study, twenty-four 125-day-old pigs were randomly divided into 4 groups: C (control) group, A (ammonia) group, Se group (Se content: 0.5 mg kg-1), and A (ammonia) + Se group. The mechanism of ammonia-induced cardiotoxicity and the alleviating effect of L-selenomethionine were examined. The results in the A group showed as follows: a large number of myocardial fiber edema and cytoplasmic bleakness were observed in the heart; a large number of mitochondrial autophagy were observed; ATP content, ATPase activities and hematological parameters decreased significantly; Endoplasmic reticulum stress (ERS) markers (GRP78, IRE1α, ATF4, ATF6, and CHOP) were significantly induced in the mRNA and protein levels; PI3K/AKT/mTOR signaling pathway was activated; and autophagy key genes and proteins (Beclin-1, LC3, ATG3, and ATG5) were significantly up-regulated. The results of comparison between the A + Se group and the A group were as follows: the degree of edema of cardiac muscle fiber in the A + Se group was somewhat relieved; the level of mitochondrial autophagy decreased; ATP content and ATPase activities increased significantly; the mRNA and protein levels of ERS markers were significantly down-regulated; the expression level of PI3K/AKT/mTOR signaling pathway was decreased; and the mRNA and protein levels of key autophagy genes were decreased. However, the changes of these indexes in the A + Se group were still significantly different from those in the C group. Our results indicated that L-selenomethionine supplementation inhibited ammonia-induced cardiac autophagy by activating the PI3K/AKT/mTOR signaling pathway, which confirmed that L-selenomethionine could alleviate the cardiac injury caused by excessive ammonia inhalation to a certain extent. This study aims to enrich the toxicological mechanism of ammonia and provide valuable reference for future intervention of ammonia toxicity.

The use of selenomethionine to reduce ammonia toxicity in porcine spleen by inhibiting endoplasmic reticulum stress and autophagy mediated by oxidative stress.

Ammonia (NH3) is a typical pollutant in the atmosphere and is well known for its harmful effects on plants, animals as well as human health. Previous studies have shown that NH3 exposure can cause damage to immune organs and impaired immune function in animals. Selenomethionine is a kind of organic selenium, which can not only promote the growth and development of the body, but also inhibit the generation of intracellular reactive oxygen species (ROS), and effectively improve the immune function of the body. Therefore, this study evaluated the toxic effect of NH3 exposure on spleen from a new perspective and investigated the protective effect of selenomethionine on ammonia-induced immunotoxicity. Twenty-four Large White*Duroc*Min pigs were randomly assigned to 4 groups: control group, NH3 group, selenium group, and NH3 + selenium group. Our results showed that NH3 inhalation caused autophagy in the pig spleen, a decrease in lymphocytes, and an increase in autophagic vesicles. Also, NH3 exposure led to a decrease in the activity of some antioxidant enzymes (decreased by about 50%) and a significant increase in the expression of genes related to oxidative stress and endoplasmic reticulum stress (ERS). Our results indicated that selenomethionine mitigated ammonia toxicity in pigs (alleviated about 20-55%). In summary, our findings should be of value in providing a theoretical basis for revealing the toxicity of the high-risk gas NH3, and providing a new perspective on the mechanism of Se against toxic substances.

Cadmium induces testosterone synthesis disorder by testicular cell damage via TLR4/MAPK/NF-κB signaling pathway leading to reduced sexual behavior in piglets.

Cadmium (Cd) is a highly toxic metal pollutant that can endanger the life and health of animals. Toll-like receptor 4 (TLR4) can result in testicular cell damage by positively regulating mitogen-activated protein kinase (MAPK)/nuclear factor-kappaB (NF-κB) signaling pathway. Meanwhile, Testosterone (T) synthesis disorder can affect sexual behavior. However, the harmful influence of Cd on animal sexual behavior during its growth and development and the role of TLR4/MAPK/NF-κB signaling pathway in testicular cell damage and testosterone production remained poorly understood. Forty-two-day-old male piglets were fed with diets that contained CdCl2 (20 mg Cd/kg) for 40 days to explore the toxic effects of Cd on sexual behavior. The results showed that Cd activated TLR4, promoted MAPK (p-ERK, p-JNK, and p-p38)/NF-κB expression, induced apoptosis (Caspase-3, Cleaved Caspase3, Bax, Cyt-c, and Caspase-9 expression increased, but Bcl-2 expression decreased) and necroptosis (MLKL, RIPK1, and RIPK3 expression increased) in piglet testis. In addition, Cd exposure decreased mRNA expression of STAR, CYP11A1, 3ß-HSD, CYP17A1, and 17ß-HSD of testis and the concentrations of T and thyroid-stimulating hormone (TSH). Both the mRNA and protein expression levels of the major genes in TLR4/MAPK/NF-κB signaling pathway, apoptosis signaling pathway, and necroptosis signaling pathway increased significantly and the expression levels of testosterone decreased gradually in pig Leydig cells cultured in vitro after being treated with different concentrations of Cd. Moreover, Cd reduced sexual behavior (the parameters of sniffing, chin resting, and mounting decreased) in piglets. In conclusion, Cd induced testicular cell damage via TLR4/MAPK/NF-κB signaling pathway leading to testosterone synthesis disorder and sexual behavior reduction in piglets.

Identification of a novel tumour microenvironment-based prognostic biomarker in skin cutaneous melanoma.

Skin cutaneous melanoma (SKCM) is one of the most destructive skin malignancies and has attracted worldwide attention. However, there is a lack of prognostic biomarkers, especially tumour microenvironment (TME)-based prognostic biomarkers. Therefore, there is an urgent need to investigate the TME in SKCM, as well as to identify efficient biomarkers for the diagnosis and treatment of SKCM patients. A comprehensive analysis was performed using SKCM samples from The Cancer Genome Atlas and normal samples from Genotype-Tissue Expression. TME scores were calculated using the ESTIMATE algorithm, and differential TME scores and differentially expressed prognostic genes were successively identified. We further identified more reliable prognostic genes via least absolute shrinkage and selection operator regression analysis and constructed a prognostic prediction model to predict overall survival. Receiver operating characteristic analysis was used to evaluate the diagnostic efficacy, and Cox regression analysis was applied to explore the relationship with clinicopathological characteristics. Finally, we identified a novel prognostic biomarker and conducted a functional enrichment analysis. After considering ESTIMATEScore and tumour purity as differential TME scores, we identified 34 differentially expressed prognostic genes. Using least absolute shrinkage and selection operator regression, we identified seven potential prognostic biomarkers (SLC13A5, RBM24, IGHV3OR16-15, PRSS35, SLC7A10, IGHV1-69D and IGHV2-26). Combined with receiver operating characteristic and regression analyses, we determined PRSS35 as a novel TME-based prognostic biomarker in SKCM, and functional analysis enriched immune-related cells, functions and signalling pathways. Our study indicated that PRSS35 could act as a potential prognostic biomarker in SKCM by investigating the TME, so as to provide new ideas and insights for the clinical diagnosis and treatment of SKCM.

Data-defined naïve Bayes (DNB) based decision scheme for the nonlinear mitigation for OAM mode division multiplexed optical fiber communication.

In this manuscript, a data-defined naïve Bayes (DNB)-based decision scheme for nonlinear mitigation is presented for an orbital angular momentum (OAM) mode-division multiplexed optical fiber communication system. Due to the inherent nonlinearity characteristic of opto-electronic devices, the strong nonlinear impairments are deemed inevitable in OAM mode-division multiplexed transmission, leading to severely nonlinear effects. A DNB algorithm based on the prior probability distribution is adopted to mitigate the strong device nonlinearity of the OAM communication system, which is hard to solve using the conventional approaches due to the complex theoretical model of opto-electronic devices. An experiment using eight-mode OAM with a 32GBaud Nyquist QPSK signal optical fiber communication system is carried out with ring core fiber (RCF) transmission over 10 km to verify the effectiveness of the proposed scheme. The experimental results demonstrate that the nonlinear effects on OAM transmission can be effectively mitigated using a DNB-based decision with a bit error rate (BER) reduction of at most 66%. Moreover, compared with other nonlinear decision algorithms based on machine learning, such as support vector machine (SVM) or k-nearest neighbors (KNN), the digital signal processing complexity of the DNB algorithm is significantly reduced.

UTRN inhibits melanoma growth by suppressing p38 and JNK/c-Jun signaling pathways.

BACKGROUND: Utrophin (UTRN), as a tumor suppressor gene, is involved in various cancer progression. The function of UTRN in the melanoma process and the related molecular mechanisms are still unclear. Herein, we studied the function of UTRN in melanoma growth and the relevant molecular mechanisms. METHODS: Using the GEO database and UCSC Xena project, we compared the expression of UTRN in non-cancerous and melanoma tissues. Immunohistochemistry (IHC) staining, qRT-PCR and Western Blot (WB) were performed to evaluate UTRN expression in clinical samples. A total of 447 cases with UTRN expression data, patient characteristics and survival data were extracted from TCGA database and analyzed. After stable transduction and single cell cloning, the proliferation ability of A375 human melanoma cells was analyzed by Cell Counting Kit­8 (CCK) and 5­ethynyl­2'­deoxyuridine (EdU) incorporation assays. GSEA was performed to predict the mechanism by which UTRN regulated melanoma growth. Then WB analysis was used to assess the protein expression levels of pathway signaling in overexpression (EXP) melanoma cells. Epac activator 8-pCPT-2'-O-Me-cAMP was then used to evaluate the proliferation ability by activation of p38 and JNK/c-Jun signaling pathways. RESULTS: Data from GEO and UCSC Xena project indicated that UTRN expression was decreased in melanoma. Experiment on clinical samples further confirmed our finding. TCGA results showed that a reduced expression of UTRN in 447 melanoma samples was associated with advanced clinical characteristics (T stage, Clark level, ulceration), shorter survival time and poorer prognosis. In addition, up-regulated UTRN expression inhibited melanoma cell proliferation when compared to control group. MAPK signaling pathway was presented in both KEGG and BioCarta databases by using GSEA tool. WB results confirmed the down-regulated expression of p38, JNK1 and c-Jun in EXP group when compared to control group. Epac activator 8-pCPT-2'-O-Me-cAMP treatment could partially rescue proliferation of tumor cells. CONCLUSION: We have demonstrated that reduced UTRN predicted poorer prognosis and UTRN inhibited melanoma growth via p38 and JNK1/c-Jun pathways. Therefore, UTRN could serve as a tumor suppressor and novel prognostic biomarker for melanoma patients.

Myosin IIA interacts with the spectrin-actin membrane skeleton to control red blood cell membrane curvature and deformability.

The biconcave disk shape and deformability of mammalian RBCs rely on the membrane skeleton, a viscoelastic network of short, membrane-associated actin filaments (F-actin) cross-linked by long, flexible spectrin tetramers. Nonmuscle myosin II (NMII) motors exert force on diverse F-actin networks to control cell shapes, but a function for NMII contractility in the 2D spectrin-F-actin network of RBCs has not been tested. Here, we show that RBCs contain membrane skeleton-associated NMIIA puncta, identified as bipolar filaments by superresolution fluorescence microscopy. MgATP disrupts NMIIA association with the membrane skeleton, consistent with NMIIA motor domains binding to membrane skeleton F-actin and contributing to membrane mechanical properties. In addition, the phosphorylation of the RBC NMIIA heavy and light chains in vivo indicates active regulation of NMIIA motor activity and filament assembly, while reduced heavy chain phosphorylation of membrane skeleton-associated NMIIA indicates assembly of stable filaments at the membrane. Treatment of RBCs with blebbistatin, an inhibitor of NMII motor activity, decreases the number of NMIIA filaments associated with the membrane and enhances local, nanoscale membrane oscillations, suggesting decreased membrane tension. Blebbistatin-treated RBCs also exhibit elongated shapes, loss of membrane curvature, and enhanced deformability, indicating a role for NMIIA contractility in promoting membrane stiffness and maintaining RBC biconcave disk cell shape. As structures similar to the RBC membrane skeleton exist in many metazoan cell types, these data demonstrate a general function for NMII in controlling specialized membrane morphology and mechanical properties through contractile interactions with short F-actin in spectrin-F-actin networks.