Hybrid transmission of PS-GS4QAM and QPSK data in the form of a PS-16QAM mm-wave signal enabled by optical asymmetrical dual-SSB modulation.

The independent optical dual-single-sideband (dual-SSB) signal generation and detection can be achieved by an optical in-phase/quadrature (I/Q) modulator and one single photodiode (PD). The dual-SSB signal is able to carry two different information. After PD detection, the optical dual-SSB signal can be converted into an electrical millimeter-wave (mm-wave) signal. Therefore, the optical dual-SSB signal generation and detection technique can be employed in the radio-over-fiber (RoF) system to achieve higher system spectral efficiency and reduce system architecture complexity. However, the I/Q modulator's nonideal property results in the amplitude imbalance of the optical dual-SSB signal, and then the crosstalk can occur. Moreover, after PD detection, the generated mm-wave signal based on the optical dual-SSB modulation has a relatively low signal-to-noise ratio (SNR), which restricts the system performance. In this paper, we propose an optical asymmetrical dual-SSB signal generation and detection scheme based on the probabilistic shaping (PS) technology, to decrease the influence of the optical dual-SSB signal's amplitude imbalance and to enhance the system performance in the scenario of the limited SNR. The dual-SSB in our scheme is composed of the left sideband (LSB) in probabilistic-shaping geometric-shaping 4-ary quadrature amplitude modulation (PS-GS4QAM) format and the right sideband (RSB) in quadrature phase-shift keying (QPSK) format. The transmitter digital signal processing (DSP) generates a dual-SSB signal to drive the optical I/Q modulator. The I/Q modulator implements an electrical-to-optical conversion and generates an optical dual-SSB signal. After PD detection, the optical dual-SSB signal is converted into a PS-16QAM mm-wave signal. In our simulation, compared with the normal 16QAM scenario, the PS-16QAM scenario exhibits a ∼1.2 dB receiver sensitivity improvement at the hard-decision forward error correction (HD-FEC) threshold of 3.8×10-3. Therefore, in our experiment, based on the PS technology, we design a dual-SSB signal including a 5 Gbaud LSB-PS-GS4QAM at -15 GHz and a 5 Gbaud RSB-QPSK at 20 GHz. After 5 km standard single-mode fiber (SSMF) transmission and PD detection, the dual-SSB signal is converted into a 5 Gbaud PS-16QAM mm-wave signal at 35 GHz. Then, the generated PS-16QAM signal is sent into a 1.2 m single-input-single-output (SISO) wireless link. In the DSP at the receiver end, the dual-SSB signal can be recovered from the mm-wave signal, and the PS-GS4QAM and QPSK data carried by the dual-SSB signal can be separated. The bit error rates (BERs) of the LSB-PS-GS4QAM and the RSB-QPSK in our experiment can be below the HD-FEC threshold of 3.8×10-3. The results demonstrate that our scheme can tolerate the I/Q modulator's nonideal property and performs well in the scenario of a relatively low SNR.

Linoleic acid-derived diol 12,13-DiHOME enhances NLRP3 inflammasome activation in macrophages.

12,13-dihydroxy-9z-octadecenoic acid (12,13-DiHOME) is a linoleic acid diol derived from cytochrome P-450 (CYP) epoxygenase and epoxide hydrolase (EH) metabolism. 12,13-DiHOME is associated with inflammation and mitochondrial damage in the innate immune response, but how 12,13-DiHOME contributes to these effects is unclear. We hypothesized that 12,13-DiHOME enhances macrophage inflammation through effects on NOD-like receptor protein 3 (NLRP3) inflammasome activation. To test this hypothesis, we utilized human monocytic THP1 cells differentiated into macrophage-like cells with phorbol myristate acetate (PMA). 12,13-DiHOME present during lipopolysaccharide (LPS)-priming of THP1 macrophages exacerbated nigericin-induced NLRP3 inflammasome activation. Using high-resolution respirometry, we observed that priming with LPS+12,13-DiHOME altered mitochondrial respiratory function. Mitophagy, measured using mito-Keima, was also modulated by 12,13-DiHOME present during priming. These mitochondrial effects were associated with increased sensitivity to nigericin-induced mitochondrial depolarization and reactive oxygen species production in LPS+12,13-DiHOME-primed macrophages. Nigericin-induced mitochondrial damage and NLRP3 inflammasome activation in LPS+12,13-DiHOME-primed macrophages were ablated by the mitochondrial calcium uniporter (MCU) inhibitor, Ru265. 12,13-DiHOME present during LPS-priming also enhanced nigericin-induced NLRP3 inflammasome activation in primary murine bone marrow-derived macrophages. In summary, these data demonstrate a pro-inflammatory role for 12,13-DiHOME by enhancing NLRP3 inflammasome activation in macrophages.

Cardioprotective response and senescence in aged sEH null female mice exposed to LPS.

Deterioration of physiological systems, like the cardiovascular system, occurs progressively with age impacting an individual's health and increasing susceptibility to injury and disease. Cellular senescence has an underlying role in age-related alterations and can be triggered by natural aging or prematurely by stressors such as the bacterial toxin lipopolysaccharide (LPS). The metabolism of polyunsaturated fatty acids by CYP450 enzymes produces numerous bioactive lipid mediators that can be further metabolized by soluble epoxide hydrolase (sEH) into diol metabolites, often with reduced biological effects. In our study, we observed age-related cardiac differences in female mice, where young mice demonstrated resistance to LPS injury, and genetic deletion or pharmacological inhibition of sEH using trans-4-[4-(3-adamantan-1-yl-ureido)-cyclohexyloxy]-benzoic acid attenuated LPS-induced cardiac dysfunction in aged female mice. Bulk RNA-sequencing analyses revealed transcriptomics differences in aged female hearts. The confirmatory analysis demonstrated changes to inflammatory and senescence gene markers such as Il-6, Mcp1, Il-1ß, Nlrp3, p21, p16, SA-ß-gal, and Gdf15 were attenuated in the hearts of aged female mice where sEH was deleted or inhibited. Collectively, these findings highlight the role of sEH in modulating the aging process of the heart, whereby targeting sEH is cardioprotective.NEW & NOTEWORTHY Soluble epoxide hydrolase (sEH) is an essential enzyme for converting epoxy fatty acids to their less bioactive diols. Our study suggests deletion or inhibition of sEH impacts the aging process in the hearts of female mice resulting in cardioprotection. Data indicate targeting sEH limits inflammation, preserves mitochondria, and alters cellular senescence in the aged female heart.

Dual high-order QAM-modulated mm-wave signal transmission in the Q-band enabled by simple IM/DD architecture and bandpass delta-sigma modulation.

The intensity-modulation (IM)/direct-detection (DD) systems have been proven effective and low-cost due to their simple system architecture. However, the Mach-Zehnder modulator (MZM) of the IM/DD systems only reserves its driving signal intensity. Therefore, the IM/DD systems are generally unable to transmit vector signals and have a restricted spectrum efficiency and channel capacity. Similarly, the radio-over-fiber (RoF) transmission systems based on IM/DD are limited by their simple architecture and generally cannot transmit high-order quadrature amplitude modulation (QAM) signals, which hinders the improvement of their spectrum efficiency. To address the challenges, we propose a novel, to the best of our knowledge, scheme to simultaneously transmit the dual independent high-order QAM-modulated millimeter-wave (mm-wave) signals in the RoF system with a simple IM/DD architecture, enabled by precoding-based optical carrier suppression (OCS) modulation and bandpass delta-sigma modulation (BP-DSM). The dual independent signals can carry different information, which increases channel capacity and improves spectrum efficiency and system flexibility. Based on our proposed scheme, we experimentally demonstrate the dual 512-QAM mm-wave signal transmission in the Q-band (33-50 GHz) under three different scenarios: 1) dual single-carrier (SC) signal transmission, 2) dual orthogonal-frequency-division-multiplexing (OFDM) signal transmission, and 3) hybrid SC and OFDM signal transmission. We achieve high-fidelity transmission of dual 512-QAM vector signals over a 5 km single-mode fiber (SMF) and a 1-m single-input single-output (SISO) wireless link operating in the Q-band, with the bit error rates (BERs) of all three scenarios below the hard decision forward error correction (HD-FEC) threshold of 3.8 × 10-3. To the best of our knowledge, this is the first time dual high-order QAM-modulated mm-wave signal transmission has been achieved in a RoF system with a simple IM/DD architecture.

SC and OFDM hybrid coherent optical transmission scheme based on 1-bit bandpass delta-sigma modulation.

High-order quadrature amplitude modulation (QAM) can effectively improve the capacity and spectral efficiency of coherent optical transmission systems. However, as the modulation order increases, the signal becomes less tolerant to noise and nonlinear effects during transmission, and the implementation cost also increases. We propose a single carrier (SC) and orthogonal frequency division multiplexing (OFDM) hybrid coherent optical transmission scheme based on a 1-bit bandpass (BP) delta-sigma modulation (DSM). The driving I-channel and Q-channel signals for the optical in-phase/quadrature (I/Q) modulator carry SC-modulated and OFDM-modulated transmitter data, respectively. Optical quadrature-phase-shift-keying (QPSK) modulation is realized by the 1-bit DSM quantizer and I/Q modulator, which can effectively suppress quantization noise and reduce the complexity of digital signal processing (DSP) and the performance requirements of optoelectronic devices. In addition, the hybrid transmission of SC and OFDM can balance the advantages of both to meet the variable channel conditions and complex application scenarios. High-fidelity transmission of SC 512QAM and OFDM 512QAM hybrid signals, in the form of a 60 Gbaud optical QPSK signal, over 60 km single-mode fiber-28 (SMF-28) is verified by offline experiments, and the bit error rates (BERs) of both SC 512QAM and OFDM 512QAM are below the hard-decision forward-error correction (HD-FEC) threshold of 3.8e-3.

Cardioprotective Action of a Novel Synthetic 19,20-EDP Analog Is Sirt Dependent.

ABSTRACT: Mounting evidence suggests that cytochrome P450 epoxygenase-derived metabolites of docosahexaenoic acid, called epoxydocosapentaenoic acids (EDPs), limit mitochondrial damage after cardiac injury. In particular, the 19,20-EDP regioisomer has demonstrated potent cardioprotective action. Thus, we investigated our novel synthetic 19,20-EDP analog SA-22 for protection against cardiac ischemia-reperfusion (IR) injury. Isolated C57BL/6J mouse hearts were perfused through Langendorff apparatus for 20 minutes to obtain baseline function, followed by 30 minutes of global ischemia. Hearts were then treated with vehicle, 19,20-EDP, SA-22, or SA-22 with the pan-sirtuin inhibitor nicotinamide or the SIRT3-selective inhibitor 3-(1H-1,2,3-triazol-4-yl) pyridine (3-TYP) at the start of 40 minutes reperfusion (N = 5-8). We assessed IR injury-induced changes in recovery of myocardial function, using left ventricular developed pressure and systolic and diastolic pressure change. Tissues were assessed for electron transport chain function, SIRT1 and SIRT3, optic atrophy type 1, and caspase-1. We also used H9c2 cells in an in vitro model of hypoxia/reoxygenation injury (N = 3-6). Hearts perfused with SA-22 had significantly improved postischemic left ventricular developed pressure, systolic and diastolic recovery (64% of baseline), compared with vehicle control (15% of baseline). In addition, treatment with SA-22 led to better catalytic function observed in electron transport chain and SIRT enzymes. The protective action of SA-22 resulted in reduced activation of pyroptosis in both hearts and cells after injury. Interestingly, although nicotinamide cotreatment worsened functional outcomes, cell survival, and attenuated sirtuin activity, it failed to completely attenuate SA-22-induced protection against pyroptosis, possibly indicating EDPs exert cytoprotection through pleiotropic mechanisms. In short, these data demonstrate the potential of our novel synthetic 19,20-EDP analog, SA-22, against IR/hypoxia-reoxygenation injury and justify further development of therapeutic agents based on 19,20-EDP.

PINK1-dependent and Parkin-independent mitophagy is involved in reprogramming of glycometabolism in pancreatic cancer cells.

Cancer cells rely on glycolysis to generate ATP for survival. However, inhibiting glycolysis is insufficient for the eradication of cancer cells because glycolysis-suppressed cells undergo metabolic reprogramming toward mitochondrial oxidative phosphorylation. We previously described that upon glycolytic suppression in pancreatic cancer cells, intracellular glycometabolism is shifted toward mitochondrial oxidative phosphorylation in an autophagy-dependent manner for cellular survival. Here, we hypothesized that mitophagy, which selectively degrades mitochondria via autophagy, is involved in mitochondrial activation under metabolic reprogramming. We revealed that glycolytic suppression notably increased mitochondrial membrane potential and mitophagy in a pancreatic cancer cell model (PANC-1). PTEN-induced kinase 1 (PINK1), a ubiquitin kinase that regulates mitophagy in healthy cells, regulated mitochondrial activation through mitophagy by glycolytic suppression. However, Parkin, a ubiquitin ligase regulated by PINK1 in healthy cells to induce mitophagy, was not involved in the PINK1-dependent mitophagy of the cancer glycometabolism. These results imply that cancer cells and healthy cells have different regulatory pieces of machinery for mitophagy, and inhibition of cancer-specific mechanisms may be a potential strategy for cancer therapy targeting metabolic reprogramming.