Widespread microRNA degradation elements in target mRNAs can assist the encoded proteins.

Binding of microRNAs (miRNAs) to mRNAs normally results in post-transcriptional repression of gene expression. However, extensive base-pairing between miRNAs and target RNAs can trigger miRNA degradation, a phenomenon called target RNA-directed miRNA degradation (TDMD). Here, we systematically analyzed Argonaute-CLASH (cross-linking, ligation, and sequencing of miRNA-target RNA hybrids) data and identified numerous candidate TDMD triggers, focusing on their ability to induce nontemplated nucleotide addition at the miRNA 3' end. When exogenously expressed in various cell lines, eight triggers induce degradation of corresponding miRNAs. Both the TDMD base-pairing and surrounding sequences are essential for TDMD. CRISPR knockout of endogenous trigger or ZSWIM8, a ubiquitin ligase essential for TDMD, reduced miRNA degradation. Furthermore, degradation of miR-221 and miR-222 by a trigger in BCL2L11, which encodes a proapoptotic protein, enhances apoptosis. Therefore, we uncovered widespread TDMD triggers in target RNAs and demonstrated an example that could functionally cooperate with the encoded protein.

Disruption of Coronin 1 Signaling in T Cells Promotes Allograft Tolerance while Maintaining Anti-Pathogen Immunity.

The ability of the immune system to discriminate self from non-self is essential for eradicating microbial pathogens but is also responsible for allograft rejection. Whether it is possible to selectively suppress alloresponses while maintaining anti-pathogen immunity remains unknown. We found that mice deficient in coronin 1, a regulator of naive T cell homeostasis, fully retained allografts while maintaining T cell-specific responses against microbial pathogens. Mechanistically, coronin 1-deficiency increased cyclic adenosine monophosphate (cAMP) concentrations to suppress allo-specific T cell responses. Costimulation induced on microbe-infected antigen presenting cells was able to overcome cAMP-mediated immunosuppression to maintain anti-pathogen immunity. In vivo pharmacological modulation of this pathway or a prior transfer of coronin 1-deficient T cells actively suppressed allograft rejection. These results define a coronin 1-dependent regulatory axis in T cells important for allograft rejection and suggest that modulation of this pathway may be a promising approach to achieve long-term acceptance of mismatched allografts.

Genetic variation in CCDC93 is associated with elevated central systolic blood pressure, impaired arterial relaxation, and mitochondrial dysfunction.

Genetic studies of blood pressure (BP) traits to date have been performed on conventional measures by brachial cuff sphygmomanometer for systolic BP (SBP) and diastolic BP, integrating several physiologic occurrences. Genetic associations with central SBP (cSBP) have not been well-studied. Genetic discovery studies of BP have been most often performed in European-ancestry samples. Here, we investigated genetic associations with cSBP in a Chinese population and functionally validated the impact of a novel associated coiled-coil domain containing 93 (CCDC93) gene on BP regulation. An exome-wide association study (EWAS) was performed using a mixed linear model of non-invasive cSBP and peripheral BP traits in a Han Chinese population (N = 5,954) from Beijing, China genotyped with a customized Illumina ExomeChip array. We identified four SNP-trait associations with three SNPs, including two novel associations (rs2165468-SBP and rs33975708-cSBP). rs33975708 is a coding variant in the CCDC93 gene, c.535C>T, p.Arg179Cys (MAF = 0.15%), and was associated with increased cSBP (ß = 29.3 mmHg, P = 1.23x10-7). CRISPR/Cas9 genome editing was used to model the effect of Ccdc93 loss in mice. Homozygous Ccdc93 deletion was lethal prior to day 10.5 of embryonic development. Ccdc93+/- heterozygous mice were viable and morphologically normal, with 1.3-fold lower aortic Ccdc93 protein expression (P = 0.0041) and elevated SBP as compared to littermate Ccdc93+/+ controls (110±8 mmHg vs 125±10 mmHg, P = 0.016). Wire myography of Ccdc93+/- aortae showed impaired acetylcholine-induced relaxation and enhanced phenylephrine-induced contraction. RNA-Seq transcriptome analysis of Ccdc93+/- mouse thoracic aortae identified significantly enriched pathways altered in fatty acid metabolism and mitochondrial metabolism. Plasma free fatty acid levels were elevated in Ccdc93+/- mice (96±7mM vs 124±13mM, P = 0.0031) and aortic mitochondrial dysfunction was observed through aberrant Parkin and Nix protein expression. Together, our genetic and functional studies support a novel role of CCDC93 in the regulation of BP through its effects on vascular mitochondrial function and endothelial function.

KDM6A regulates immune response genes in multiple myeloma.

ABSTRACT: The histone H3 at lysine 27 (H3K27) demethylase lysine demethylase 6A (KDM6A) is a tumor suppressor in multiple cancers, including multiple myeloma (MM). We created isogenic MM cells disrupted for KDM6A and tagged the endogenous protein to facilitate genome-wide studies. KDM6A binds genes associated with immune recognition and cytokine signaling. Most importantly, KDM6A binds and activates NLRC5 and CIITA, which encode regulators of major histocompatibility complex genes. Patient data indicate that NLRC5 and CIITA are downregulated in MM with low KDM6A expression. Chromatin analysis shows that KDM6A binds poised and active enhancers and KDM6A loss led to decreased H3K27ac at enhancers, increased H3K27me3 levels in body of genes bound by KDM6A, and decreased gene expression. Reestablishing histone acetylation with an HDAC3 inhibitor leads to upregulation of major histocompatibility complex expression, offering a strategy to restore immunogenicity of KDM6A-deficient tumors. Loss of Kdm6a in Kirsten rat sarcoma virus (K-RAS)-transformed murine fibroblasts led to increased growth in vivo associated with decreased T-cell infiltration.

Recruitment of FBXO22 for targeted degradation of NSD2.

Targeted protein degradation (TPD) is an emerging therapeutic strategy that would benefit from new chemical entities with which to recruit a wider variety of ubiquitin E3 ligases to target proteins for proteasomal degradation. Here we describe a TPD strategy involving the recruitment of FBXO22 to induce degradation of the histone methyltransferase and oncogene NSD2. UNC8732 facilitates FBXO22-mediated degradation of NSD2 in acute lymphoblastic leukemia cells harboring the NSD2 gain-of-function mutation p.E1099K, resulting in growth suppression, apoptosis and reversal of drug resistance. The primary amine of UNC8732 is metabolized to an aldehyde species, which engages C326 of FBXO22 to recruit the SCFFBXO22 Cullin complex. We further demonstrate that a previously reported alkyl amine-containing degrader targeting XIAP is similarly dependent on SCFFBXO22. Overall, we present a potent NSD2 degrader for the exploration of NSD2 disease phenotypes and a new FBXO22-recruitment strategy for TPD.

Targeted blockade of aberrant sodium current in a stem cell-derived neuron model of SCN3A encephalopathy.

Missense variants in SCN3A encoding the voltage-gated sodium (Na+) channel α subunit Nav1.3 are associated with SCN3A-related neurodevelopmental disorder (SCN3A-NDD), a spectrum of disease that includes epilepsy and malformation of cortical development. How genetic variation in SCN3A leads to pathology remains unclear, as prior electrophysiological work on disease-associated variants has been performed exclusively in heterologous cell systems. To further investigate the mechanisms of SCN3A-NDD pathogenesis, we used CRISPR/Cas9 gene editing to modify a control human induced pluripotent stem cell (iPSC) line to express the recurrent de novo missense variant SCN3A c.2624T>C (p.Ile875Thr). With the established Ngn2 rapid induction protocol, we generated glutamatergic forebrain-like neurons (iNeurons), which we showed to express SCN3A mRNA and Nav1.3-mediated Na+ currents. We performed detailed whole-cell patch clamp recordings to determine the effect of the SCN3A-p.Ile875Thr variant on endogenous Na+ currents in, and intrinsic excitability of, human neurons. Compared to control iNeurons, variant-expressing iNeurons exhibit markedly increased slowly-inactivating/persistent Na+ current, abnormal firing patterns with paroxysmal bursting and plateau-like potentials with action potential failure, and a hyperpolarized voltage threshold for action potential generation. We then validated these findings using a separate iPSC line generated from a patient harbouring the SCN3A-p.Ile875Thr variant compared to a corresponding CRISPR-corrected isogenic control line. Finally, we found that application of the Nav1.3-selective blocker ICA-121431 normalizes action potential threshold and aberrant firing patterns in SCN3A-p.Ile1875Thr iNeurons; in contrast, consistent with action as a Na+ channel blocker, ICA-121431 decreases excitability of control iNeurons. Our findings demonstrate that iNeurons can model the effects of genetic variation in SCN3A yet reveal a complex relationship between gain-of-function at the level of the ion channel versus impact on neuronal excitability. Given the transient expression of SCN3A in the developing human nervous system, selective blockade or suppression of Nav1.3-containing Na+ channels could represent a therapeutic approach towards SCN3A-NDD.

HIRA-mediated loading of histone variant H3.3 controls androgen-induced transcription by regulation of AR/BRD4 complex assembly at enhancers.

Incorporation of histone variant H3.3 comprises active territories of chromatin. Exploring the function of H3.3 in prostate cancer (PC), we found that knockout (KO) of H3.3 chaperone HIRA suppresses PC growth in vitro and in xenograft settings, deregulates androgen-induced gene expression and alters androgen receptor (AR) binding within enhancers of target genes. H3.3 affects transcription in multiple ways, including activation of p300 by phosphorylated H3.3 at Ser-31 (H3.3S31Ph), which results in H3K27 acetylation (H3K27Ac) at enhancers. In turn, H3K27Ac recruits bromodomain protein BRD4 for enhancer-promoter interaction and transcription activation. We observed that HIRA KO reduces H3.3 incorporation, diminishes H3.3S31Ph and H3K27Ac, modifies recruitment of BRD4. These results suggest that H3.3-enriched enhancer chromatin serves as a platform for H3K27Ac-mediated BRD4 recruitment, which interacts with and retains AR at enhancers, resulting in transcription reprogramming. In addition, HIRA KO deregulates glucocorticoid- (GR) driven transcription of genes co-regulated by AR and GR, suggesting a common H3.3/HIRA-dependent mechanism of nuclear receptors function. Expression of HIRA complex proteins is increased in PC compared with normal prostate tissue, especially in high-risk PC groups, and is associated with a negative prognosis. Collectively, our results demonstrate function of HIRA-dependent H3.3 pathway in regulation of nuclear receptors activity.

Inhibition of RAS-driven signaling and tumorigenesis with a pan-RAS monobody targeting the Switch I/II pocket.

RAS mutants are major therapeutic targets in oncology with few efficacious direct inhibitors available. The identification of a shallow pocket near the Switch II region on RAS has led to the development of small-molecule drugs that target this site and inhibit KRAS(G12C) and KRAS(G12D). To discover other regions on RAS that may be targeted for inhibition, we have employed small synthetic binding proteins termed monobodies that have a strong propensity to bind to functional sites on a target protein. Here, we report a pan-RAS monobody, termed JAM20, that bound to all RAS isoforms with nanomolar affinity and demonstrated limited nucleotide-state specificity. Upon intracellular expression, JAM20 potently inhibited signaling mediated by all RAS isoforms and reduced oncogenic RAS-mediated tumorigenesis in vivo. NMR and mutation analysis determined that JAM20 bound to a pocket between Switch I and II, which is similarly targeted by low-affinity, small-molecule inhibitors, such as BI-2852, whose in vivo efficacy has not been demonstrated. Furthermore, JAM20 directly competed with both the RAF(RBD) and BI-2852. These results provide direct validation of targeting the Switch I/II pocket for inhibiting RAS-driven tumorigenesis. More generally, these results demonstrate the utility of tool biologics as probes for discovering and validating druggable sites on challenging targets.

An Electrochemiluminescent Sensor Based on Glycosyl Imprinting and Aptamer for the Detection of Cancer-Related Extracellular Vesicles.

Cancer-related extracellular vesicles (EVs) are considered important biomarkers for cancer diagnosis because they can convey a large amount of information about tumor cells. In order to detect cancer-related EVs efficiently, an electrochemiluminescence (ECL) sensor for the specific identification and highly sensitive detection of EVs in the plasma of cancer patients was constructed based on dual recognitions by glycosyl-imprinted polymer (GIP) and aptamer. The characteristic glycosyl Neu5Ac-α-(2,6)-Gal-ß-(1-4)-GlcNAc trisaccharide on the surface of EVs was used as a template molecule and 3-aminophenylboronic acid as a functional monomer to form a glycosyl-imprinted polymer by electropolymerization. After glycosyl elution, the imprinted film specifically recognized and adsorbed the EVs in the sample, and then the CD63 aptamer-bipyridine ruthenium (Aptamer-Ru(bpy)) was added to combine with the CD63 glycoprotein on the extracellular vesicle's surface, thus providing secondary recognition of the EVs. Finally, the EVs were quantitatively detected according to the ECL signal produced by the labeled bipyridine ruthenium. When more EVs were captured by the imprinted film, more probes were obtained after incubation, and the ECL signal was stronger. Under the optimized conditions, the ECL signal showed a good linear relationship with the concentration of EVs in the range of 9.5 × 102 to 9.5 × 107 particles/mL, and the limit of detection was 641 particles/mL. The GIP sensor can discriminate between the EV contents of cancer patients and healthy controls with high accuracy. Because of its affordability, high sensitivity, and ease of use, it is anticipated to be employed for cancer early detection and diagnosis.

Joint signal-to-signal beat interference mitigation for the field recovery of symmetric carrier-assisted differential detection with low carrier-to-signal power ratio.

As a combination of direct detection and coherent detection technologies, self-coherent detection has the advantages of low cost and optical field recovery ability. However, most of the self-coherent detection techniques are limited to single sideband (SSB) signals. Recently, carrier-assisted differential detection (CADD) has been proposed to realize complex-valued double sideband (DSB) signals, but it requires a high carrier-to-signal power ratio (CSPR) to mitigate the signal-to-signal beat interference (SSBI). Later, a more cost-effective symmetric CADD (S-CADD) has been proposed while the required CSPR is still high. In order to alleviate the high requirements of CSPR, we propose a scheme based on the joint of digital pre-distortion (DPD) at transmitter and clipping at receiver to further improve the S-CADD system performance. This joint processing can not only solve the problem of non-uniform distribution of subcarrier signal-to-noise ratio (SNR) caused by non-ideal transfer function, but also the error propagation problem caused by enhanced SSBI under low CSPR. After the validation of the 64 Gbaud 16-ary quadrature amplitude modulation (16-QAM) orthogonal frequency division multiplexing (OFDM) signal transmitted over 80 km standard single mode fiber (SSMF), the CSPR required by the proposed scheme to reach the 20% soft decision-forward error correction (SD-FEC) and 7% hard decision-forward error correction (HD-FEC) can be reduced by 1.3 dB and 2.8 dB, respectively, with a comparison of the conventional S-CADD. The results show the potential of the proposed scheme in the short-reach optical transmissions.

Non-sweep DC component estimation method for a virtual-carrier assisted Kramers-Kronig receiver.

The Kramers-Kronig (KK) receiver has attracted much attention in short-range optical interconnection because of its ability to recover the phase of the signal from the intensity information through KK algorithm. In high-speed KK systems, such as virtual-carrier (VC) assisted ones, an alternating current (AC) coupled photo-detector (PD) is preferred due to relaxing the requirements of analog-to-digital converter (ADC) and electronic amplifier by filtering direct current (DC) component. However, the loss of the DC component will cause the KK algorithm to break down, so it is necessary to accurately recover DC value in the digital domain with multiple-sweep. In this paper, we propose what we believe is a novel non-sweep DC component estimation scheme based on optimized digital carrier-to-signal power ratio (OD-CSPR) method, which can accurately estimate the DC component with only 3-4 iterations in the scenario of VC-assisted KK receiver optical transmission. The scheme utilizes the one-dimensional search optimization algorithm based on golden section search and parabolic interpolation without sweeping. The simulation and experimental results of the proposed non-sweep OD-CSPR method show that the DC component can be estimated accurately in a large CSPR range, and the system performance is close to that of the conventional DC-sweep method. Compared with the typical defined digital CSPR (DD-CSPR) based optimization method, the proposed one can realize optical signal-to-noise ratio (OSNR) gains of 0.9 dB in the back-to-back (B2B) and 0.7 dB under 80 km fiber transmission scenarios respectively with a total bit rate of 160Gb/s.

Pairwise Tomlinson-Harashima precoding for multiple-lane IM-DD transmissions.

As for the photonic interconnection based on the multiple-lane intensity modulation direct detection (IM-DD) transmission, both intra-channel inter-symbol-interference (ISI) originating from bandwidth constraint, and inter-channel performance discrepancy emerging from inter-channel component differences are the major bottleneck for the throughput enhancement. Here, we propose a pairwise Tomlinson-Harshima precoding (P-THP) scheme, in order to simultaneously deal with both intra-channel ISI and inter-channel performance discrepancy. The effective function of the proposed P-THP scheme is experimentally evaluated by transmitting 4-channel 81-GBaud PAM4 signals over 2 km standard single-mode fiber (SSMF). Compared with the conventional scheme with only applying THP on individual wavelength channel, the required optical received power (ROP) under the back-to-back (B2B) transmission can be reduced by 0.75∼1 dB with the help of proposed P-THP in different experimental component configurations, at the 7% hard decision forward error correction (HD-FEC) threshold of BER = 3.8 × 10-3. After the 2 km SSMF transmission, only the use of proposed P-THP can guarantee to reach the designated HD-FEC threshold, leading to a net rate of >600 Gbit/s.

Simultaneous realization of high gain and low DMG of four-mode EDFA under bidirectional hybrid-mode pump.

We theoretically and experimentally verify that, the bidirectional hybrid-mode pumping scheme can address the optimization problem of trade-off between high gain and low differential modal gain (DMG) of four-mode erbium-doped fiber amplifier (4M-EDFA), in comparison with traditional both forward and backward hybrid-mode pumping scheme. It is noticed that, when the total pump power is fixed, the bidirectional hybrid-mode pumping scheme can not only achieve higher gain, but also suppress DMG due to different overlap integrals for the forward and backward pumping schemes. The bidirectional hybrid-mode pumped 4M-EDFA is developed with the forward pumping at LP02 mode and the backward pumping at LP21 mode, under a pump power ratio of 30%:70%. Thus, we can achieve an average gain of up to 21.16 dB and a low DMG of 0.43 dB at 1550 nm, and an average gain of up to 20.64 dB with a DMG of less than 1.6 dB over the C-band. In particular, the bidirectional hybrid-mode pumping scheme allows us to tailor the gain characteristics of the few-mode erbium-doped fiber amplifiers (FM-EDFAs), by adjusting the power ratio between forward and backward pumps.

The predictive value of cumulative atherogenic index of plasma (AIP) for cardiovascular outcomes: a prospective community-based cohort study.

BACKGROUND: Atherogenic index of plasma (AIP) has been reported as a critical predictor on the risks and clinical outcomes of cardiovascular diseases (CVDs), and we aimed to explore the potential predictive value of cumulative AIP on major adverse cardiac events (MACE), stroke, myocardial infarction (MI) and cardiovascular mortality. METHODS: A large-scale community-based prospective cohort was established from December 2011 to April 2012 and followed up in May to July 2014. The endpoint outcomes were obtained before December 31, 2021. AIP was calculated as the logarithmically transformed ratio of triglyceride (TG) to high-density lipoprotein cholesterol (HDL-c) and cumulative AIP was the average value of AIP in 2012 and 2014. RESULTS: An overall of 3820 participants (36.1% male) with mean (SD) age of 59.1 (8.7) years, were enrolled. Within a median follow-up of 7.5 years, a total of 371 (9.7%) participants were documented with MACE, 293 (7.7%) participants developed stroke, 68 (1.8%) suffered from MI and 65 (1.7%) experienced cardiovascular mortality. Multivariable Cox regression analysis revealed significant associations between cumulative AIP and the risk of MACE, stroke and MI. Regarding MACE, individuals with one higher unit of cumulative AIP were associated with 75% increment on the incidence of going through MACE in fully adjusted model, while categorizing participants into four groups, individuals in the highest cumulative AIP quartile were significantly associated with increased incidence of MACE (HR = 1.76, 95%CI: 1.27-2.44, p < 0.001 in fully adjusted model), stroke (HR = 1.69, 95%CI: 1.17-2.45, p = 0.005) and MI (HR = 2.82, 95%CI: 1.18-6.72, p = 0.019). But not a significant association was observed between cumulative AIP and cardiovascular mortality. In subgroup analysis, the association of cumulative AIP and the incidence of stroke was more pronounced in the elderly (HR: 0.89 vs. 2.41 for the age groups < 65 years and ≥ 65 years, p for interaction = 0.018). CONCLUSIONS: A higher cumulative AIP was significantly associated with an increased risk of MACE, stroke and MI independent of traditional cardiovascular risk factors in a community-based population, and the association of cumulative AIP and stroke was particularly pronounced in the elderly population.

SfREPAT38, a pathogen response gene (REPAT), is involved in immune response of Spodoptera frugiperda larvae through mediating Toll signalling pathway.

REPAT (response to pathogen) is an immune-associated gene family that plays important roles in insect immune response to pathogens. Although nine REPAT genes have been identified in Spodoptera frugiperda (Lepidoptera: Noctuidae) currently, their functions and mechanisms in the immune response to pathogens still remain unclear. Therefore, SfREPAT38, a pathogen response gene (REPAT) of S. frugiperda, was characterised and its function was analysed. The results showed that SfREPAT38 contains a signal peptide and a transcription activator MBF2 (multi-protein bridging factor 2) domain. Quantitative real-time polymerase chain reaction analysis showed that SfREPAT38 was highly expressed in the sixth-instar larvae (L6) and was the highest in expression in the midgut of L6. We found that the expression of SfREPAT38 could be activated by challenge with four microbial pathogens (Bacillus thuringiensis, Metarhizium anisopliae, Spodoptera exigua nuclearpolyhedrosis and Escherichia coli), except 12 h after E. coli infection. Furthermore, the SfREPAT38 expression levels significantly decreased at 24, 48 and 72 h after SfREPAT38 dsRNA injection or feeding. Feeding with SfREPAT38 dsRNA significantly decreased the weight gain of S. frugiperda, and continuous feeding led to the death of S. frugiperda larvae from the fourth day. Moreover, SfREPAT38 dsRNA injection resulted in a significant decrease of weight gain on the fifth day. Silencing SfREPAT38 gene down-regulated the expression levels of immune genes belonging to the Toll pathway, including SPZ, Myd88, DIF, Cactus, Pell and Toll18W. After treatment with SfREPAT38 dsRNA, S. frugiperda became extremely sensitive to the B. thuringiensis infection, and the survival rate dramatically increased, with 100% mortality by the eighth day. The weight of S. frugiperda larvae was also significantly lower than that of the control groups from the second day onwards. In addition, the genes involved in the Toll signalling pathway and a few antibacterial peptide related genes were down-regulated after treatment. These results showed that SfREPAT38 is involved in the immune response of S. frugiperda larvae through mediating Toll signalling pathway.

Blind frequency offset estimation method based on a minimum phase correction error for a full spectrum modulated NFDM system.

To improve the spectral efficiency of a full spectrum modulated nonlinear frequency division multiplexing (FS-NFDM) system, a blind frequency offset estimation (FOE) method has been proposed. The approach based on the minimum phase correction error can achieve high estimation accuracy of sub-MHz without need of any training symbols. Furthermore, in order to reduce the computational complexity, an eigenvalue-shift method is used to get a coarse search interval of FO, and then the one-dimensional optimization algorithm based on golden section search and parabolic interpolation is used to get the optimal FOE for the coarse search interval. The feasibility and reliability of the proposed blind FOE approach have been demonstrated in both BTB and fiber transmission scenarios. Compared with the grid search method, the proposed solving scheme can save hundreds of times of the searches. The experimental results reveal that the proposed method is robust to the amplified spontaneous emission noise and phase noise and has the capabilities of a wide FOE range and a high FOE accuracy.

Multiple-signal-joint-processing-based guard interval shortening method for a CS-NFDM system.

Aiming to further improve the spectral efficiency (SE) of a continuous spectrum modulated nonlinear frequency division multiplexing (CS-NFDM) system, we propose a novel ,to the best of our knowledge, multiple-signal-joint-processing (MSJP)-based guard interval (GI) shortening method. In this method, multiple NFDM time-domain signals are jointly processed as a whole to carry out nonlinear Fourier transform and inverse nonlinear Fourier transform (NFT-INFT) operations. These operations can fuse the multiple NFDM time-domain signals together, which is equivalent to the corresponding inverse process of a fiber transmission. Experimental results show that the normalized SE of the proposed method can reach 0.99 when approaching the limit value of 1 and obtain a 2.33 dB Q2-factor improvement compared with the pre-dispersion compensation (PDC) method under the same GI of 0.03 ns in an 80 km SSMF transmission of a 46 GHz signal bandwidth. Furthermore, in comparison with the PDC method, the proposed method can achieve 32.86% normalized SE improvement in the 1120 km SSMF transmission of 32 GHz signal bandwidth under the SD-FEC of 2.4E-2.

Experimental demonstration of optical waveform transmission with multiple-eigenvalue 16-APSK modulation.

The multi-eigenvalue multiplexing-based discrete spectrum-modulated nonlinear frequency-division multiplexing (DS-NFDM) system with higher-order modulation format has been demonstrated experimentally. After designing the coefficients of the eigenvalue set and the constellation point distribution of 16-amplitude phase shift keying (16-APSK), the realizations of 14-, 30-, and 46-eigenvalue multiplexed DS-NFDM signals have been implemented. The results show that 46-eigenvalue and 30-eigenvalue multiplexed DS-NFDM signals can transmit 50 km and 400 km over a nonzero dispersion-shifted fiber (NZDSF) under soft-decision forward error correction (SD-FEC) threshold of 2.4E-2, respectively. This demonstration shows for the first time, to the best of our knowledge, the record for multiplexed eigenvalue number and data rate of the multiple-eigenvalue-based DS-NFDM system.

On the multipath interference mitigation for high-speed IM-DD transmissions with Nyquist subcarrier modulation.

The performance of high-speed intensity modulation direct detection (IM-DD) transmissions is severely degraded due to the occurrence of multipath interference (MPI), especially when a higher-order modulation format is utilized. Here, we propose and demonstrate, for the first time to the best of our knowledge, that a Nyquist subcarrier modulation (Nyquist-SCM) format inherently exhibits resistance to the MPI. We experimentally evaluate the MPI tolerance by transmitting 56 Gbit/s PAM-4 signals and Nyquist-SCM 16QAM signals over the 2 km standard single-mode fiber (SSMF) when the C-band semiconductor laser with a linewidth of 1.7 MHz is utilized. In comparison with the PAM-4 format, the Nyquist-SCM 16QAM format can lead to an enhanced MPI tolerance of 4 dB at the KP4-FEC threshold of BER = 2 × 10-4. In addition, even with the help of MPI mitigation for the PAM-4 signals based on two newly reported methods, the utilization of Nyquist-SCM 16QAM signal can still guarantee an improved MPI tolerance of 1 dB.

Single wavelength MDM-PDM 800-Gb/s net data rate transmission over a standard multimode fiber employing a Kramers-Kronig receiver.

We propose a high-speed multimode fiber short-reach optical interconnect system based on a Kramers-Kronig (KK) field reconstruction with the mode division multiplexing (MDM) and polarization division multiplexing (PDM) technology. In this work, the LP01, LP21a, LP21b, and LP02 modes are selected as independent channels to carry information. The demonstration achieved the 800 Gb/s net data rate per wavelength with a bit-rate-distance-product (BDP) of 8 Tb/s·km. To the best of our knowledge, this is the highest experimental record of a single wavelength BDP over the SMMF with KK detection. In addition, we discuss the system performance after all multiple-input multiple-output (MIMO) and partial MIMO processing and give guidance on the trade-off between system performance and computational resource.