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The development of vaccines, which induce effective immune responses while ensuring safety and affordability, remains a substantial challenge. In this study, we proposed a vaccine model of a restructured "head-to-tail" dimer to efficiently stimulate B cell response. We also demonstrate the feasibility of using this model to develop a paramyxovirus vaccine through a low-cost rice endosperm expression system. Crystal structure and small-angle X-ray scattering data showed that the restructured hemagglutinin-neuraminidase (HN) formed tetramers with fully exposed quadruple receptor binding domains and neutralizing epitopes. In comparison with the original HN antigen and three traditional commercial whole virus vaccines, the restructured HN facilitated critical epitope exposure and initiated a faster and more potent immune response. Two-dose immunization with 0.5 µg of the restructured antigen (equivalent to one-127th of a rice grain) and one-dose with 5 µg completely protected chickens against a lethal challenge of the virus. These results demonstrate that the restructured HN from transgenic rice seeds is safe, effective, low-dose useful, and inexpensive. We provide a plant platform and a simple restructured model for highly effective vaccine development.
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Oryza , Paramyxovirinae , Vacunas Virales , Animales , Pollos , Virus de la Enfermedad de Newcastle , Oryza/genética , Diseño Universal , Epítopos , Anticuerpos AntiviralesRESUMEN
BACKGROUND & AIMS: Because pancreatic cancer responds poorly to chemotherapy and immunotherapy, it is necessary to identify novel targets and compounds to overcome resistance to treatment. METHODS: This study analyzed genomic single nucleotide polymorphism sequencing, single-cell RNA sequencing, and spatial transcriptomics. Ehf-knockout mice, KPC (LSL-KrasG12D/+, LSL-Trp53R172H/+ and Pdx1-Cre) mice, CD45.1+ BALB/C nude mice, and CD34+ humanized mice were also used as subjects. Multiplexed immunohistochemistry and flow cytometry were performed to investigate the proportion of tumor-infiltrated C-X-C motif chemokine receptor 2 (CXCR2)+ neutrophils. In addition, multiplexed cytokines assays and chromatin immunoprecipitation assays were used to examine the mechanism. RESULTS: The TP53 mutation-mediated loss of tumoral EHF increased the recruitment of CXCR2+ neutrophils, modulated their spatial distribution, and further induced chemo- and immunotherapy resistance in clinical cohorts and preclinical syngeneic mice models. Mechanistically, EHF deficiency induced C-X-C motif chemokine ligand 1 (CXCL1) transcription to enhance in vitro and in vivo CXCR2+ neutrophils migration. Moreover, CXCL1 or CXCR2 blockade completely abolished the effect, indicating that EHF regulated CXCR2+ neutrophils migration in a CXCL1-CXCR2-dependent manner. The depletion of CXCR2+ neutrophils also blocked the in vivo effects of EHF deficiency on chemotherapy and immunotherapy resistance. The single-cell RNA-sequencing results of PDAC treated with Nifurtimox highlighted the therapeutic significance of Nifurtimox by elevating the expression of tumoral EHF and decreasing the weightage of CXCL1-CXCR2 pathway within the microenvironment. Importantly, by simultaneously inhibiting the JAK1/STAT1 pathway, it could significantly suppress the recruitment and function of CXCR2+ neutrophils, further sensitizing PDAC to chemotherapy and immunotherapies. CONCLUSIONS: The study demonstrated the role of EHF in the recruitment of CXCR2+ neutrophils and the promising role of Nifurtimox in sensitizing pancreatic cancer to chemotherapy and immunotherapy.
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Quimiocina CXCL1 , Resistencia a Antineoplásicos , Infiltración Neutrófila , Neutrófilos , Neoplasias Pancreáticas , Receptores de Interleucina-8B , Animales , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/inmunología , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/metabolismo , Receptores de Interleucina-8B/genética , Receptores de Interleucina-8B/metabolismo , Receptores de Interleucina-8B/antagonistas & inhibidores , Humanos , Infiltración Neutrófila/efectos de los fármacos , Resistencia a Antineoplásicos/genética , Neutrófilos/inmunología , Neutrófilos/metabolismo , Neutrófilos/efectos de los fármacos , Ratones , Quimiocina CXCL1/metabolismo , Quimiocina CXCL1/genética , Línea Celular Tumoral , Ratones Noqueados , Microambiente Tumoral , Inmunoterapia/métodos , Ratones Desnudos , Proteína p53 Supresora de Tumor/metabolismo , Proteína p53 Supresora de Tumor/genética , Ratones Endogámicos BALB C , Antineoplásicos/farmacología , Transducción de Señal , Mutación , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/inmunología , Carcinoma Ductal Pancreático/tratamiento farmacológico , Carcinoma Ductal Pancreático/patologíaRESUMEN
OBJECTIVE: The objective of this study is to improve the efficacy of CLDN18.2/CD3 bispecific T-cell engagers (BiTEs) as a promising immunotherapy against pancreatic ductal adenocarcinoma (PDAC). DESIGN: Humanised hCD34+/hCD3e+, Trp53R172HKrasG12DPdx1-Cre (KPC), pancreas-specific Cldn18.2 knockout (KO), fibroblast-specific Fcgr1 KO and patient-derived xenograft/organoid mouse models were constructed. Flow cytometry, Masson staining, Cell Titer Glo assay, virtual drug screening, molecular docking and chromatin immunoprecipitation were conducted. RESULTS: CLDN18.2 BiTEs effectively inhibited early tumour growth, but late-stage efficacy was significantly diminished. Mechanically, the Fc fragment of BiTEs interacted with CD64+ cancer-associated fibroblasts (CAFs) via activation of the SYK-VAV2-RhoA-ROCK-MLC2-MRTF-A-α-SMA/collagen-I pathway, which enhanced desmoplasia and limited late-stage infiltration of T cells. Molecular docking analysis found that vilanterol suppressed BiTEs-induced phosphorylation of VAV2 (Y172) in CD64+ CAFs and weakened desmoplasia. Additionally, decreased cyclic guanosine-adenosine monophosphate synthase/stimulator of interferon genes (STING) activity reduced proliferation of TCF-1+PD-1+ stem-like CD8+ T cells, which limited late-stage effects of BiTEs. Finally, vilanterol and the STING agonist synergistically boosted the efficacy of BiTEs by inhibiting the activation of CD64+ CAFs and enriching proliferation of stem-like CD8+ T cells, resulting in sustained anti-tumour activity. CONCLUSION: Vilanterol plus the STING agonist sensitised PDAC to CLDN18.2 BiTEs and augmented efficacy as a potential novel strategy.
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BACKGROUND: Triple-negative breast cancer (TNBC) is a highly heterogeneous and clinically aggressive disease. Accumulating evidence indicates that tertiary lymphoid structures (TLSs) and tumor budding (TB) are significantly correlated with the outcomes of patients who have TNBC, but no integrated TLS-TB profile has been established to predict their survival. The objective of this study was to investigate the relationship between the TLS/TB ratio and clinical outcomes of patients with TNBC using artificial intelligence (AI)-based analysis. METHODS: The infiltration levels of TLSs and TB were evaluated using hematoxylin and eosin staining, immunohistochemistry staining, and AI-based analysis. Various cellular subtypes within TLS were determined by multiplex immunofluorescence. Subsequently, the authors established a nomogram model, conducted calibration curve analyses, and performed decision curve analyses using R software. RESULTS: In both the training and validation cohorts, the antitumor/protumor model established by the authors demonstrated a positive correlation between the TLS/TB index and the overall survival (OS) and relapse-free survival (RFS) of patients with TNBC. Notably, patients who had a high percentage of CD8-positive T cells, CD45RO-positive T cells, or CD20-positive B cells within the TLSs experienced improved OS and RFS. Furthermore, the authors developed a comprehensive TLS-TB profile nomogram based on the TLS/TB index. This novel model outperformed the classical tumor-lymph node-metastasis staging system in predicting the OS and RFS of patients with TNBC. CONCLUSIONS: A novel strategy for predicting the prognosis of patients with TNBC was established through integrated AI-based analysis and a machine-learning workflow. The TLS/TB index was identified as an independent prognostic factor for TNBC. This nomogram-based TLS-TB profile would help improve the accuracy of predicting the prognosis of patients who have TNBC.
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Estructuras Linfoides Terciarias , Neoplasias de la Mama Triple Negativas , Humanos , Neoplasias de la Mama Triple Negativas/patología , Estructuras Linfoides Terciarias/patología , Inteligencia Artificial , Recurrencia Local de Neoplasia , PronósticoRESUMEN
OBJECTIVE: Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal tumour with limited treatment options. Here, we identified syndecan binding protein (SDCBP), also known as syntenin1, as a novel targetable factor in promoting PDAC tumour progression. We also explored a therapeutic strategy for suppressing SDCBP expression. DESIGN: We used samples from patients with PDAC, human organoid models, LSL-KrasG12D/+mice, LSL-Trp53R172H/+ and Pdx1-Cre (KPC) mouse models, and PDX mouse models. Immunostaining, colony formation assay, ethynyl-2-deoxyuridine incorporation assay, real-time cell analysis, cell apoptosis assay, automated cell tracking, invadopodia detection and gelatin degradation assays, coimmunoprecipitation, and pull-down assays were performed in this study. RESULTS: The median overall survival and recurrence-free survival rates in the high-SDCBP group were significantly shorter than those in the low-SDCBP group. In vitro and in vivo studies have demonstrated that SDCBP promotes PDAC proliferation and metastasis. Mechanically, SDCBP inhibits CK1δ/ε-mediated YAP-S384/S387 phosphorylation, which further suppresses ß-TrCP-mediated YAP1 ubiquitination and proteasome degradation by directly interacting with YAP1. SDCBP interacts with the TAD domain of YAP1, mainly through its PDZ1 domain. Preclinical KPC mouse cohorts demonstrated that zinc pyrithione (ZnPT) suppresses PDAC tumour progression by suppressing SDCBP. CONCLUSIONS: SDCBP promotes the proliferation and metastasis of PDAC by preventing YAP1 from ß-TrCP-mediated proteasomal degradation. Therefore, ZnPT could be a promising therapeutic strategy to inhibit PDAC progression by suppressing SDCBP.
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Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Ratones , Animales , Proteínas con Repetición de beta-Transducina/metabolismo , Neoplasias Pancreáticas/patología , Páncreas/patología , Carcinoma Ductal Pancreático/patología , Proliferación Celular , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Sinteninas/metabolismo , Neoplasias PancreáticasRESUMEN
Pestiviruses, including classical swine fever virus, remain a concern for global animal health and are responsible for major economic losses of livestock worldwide. Despite high levels of vaccination, currently available commercial vaccines are limited by safety concerns, moderate efficacy, and required high doses. The development of new vaccines is therefore essential. Vaccine efforts should focus on optimizing antigen presentation to enhance immune responses. Here, we describe a simple herringbone-dimer strategy for efficient vaccine design, using the classical swine fever virus E2 expressed in a rice endosperm as an example. The expression of rE2 protein was identified, with the rE2 antigen accumulating to 480 mg/kg. Immunological assays in mice, rabbits, and pigs showed high antigenicity of rE2. Two immunizations with 284 ng of the rE2 vaccine or one shot with 5.12 µg provided effective protection in pigs without interference from pre-existing antibodies. Crystal structure and small-angle X-ray scattering results confirmed the stable herringbone dimeric conformation, which had two fully exposed duplex receptor binding domains. Our results demonstrated that rice endosperm is a promising platform for precise vaccine design, and this strategy can be universally applied to other Flaviviridae virus vaccines.
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Virus de la Fiebre Porcina Clásica , Peste Porcina Clásica , Oryza , Vacunas Virales , Animales , Porcinos , Conejos , Ratones , Peste Porcina Clásica/prevención & control , Anticuerpos Antivirales , Proteínas del Envoltorio Viral , InmunidadRESUMEN
A realistic first-principle-based spin Hamiltonian is constructed for the type-II multiferroic NiI_{2}, using a symmetry-adapted cluster expansion method. Besides single ion anisotropy and isotropic Heisenberg terms, this model further includes the Kitaev interaction and a biquadratic term, and can well reproduce striking features of the experimental helical ground state, that are, e.g., a proper screw state, canting of rotation plane, propagation direction, and period. Using this model to build a phase diagram, it is demonstrated that, (i) the in-plane propagation direction of ⟨11[over ¯]0⟩ is determined by the Kitaev interaction, instead of the long-believed exchange frustrations and (ii) the canting of rotation plane is also dominantly determined by Kitaev interaction, rather than interlayer couplings. Furthermore, additional Monte Carlo simulations reveal three equivalent domains and different topological defects. Since the ferroelectricity is induced by spins in type-II multiferroics, our work also implies that Kitaev interaction is closely related to the multiferroicity of NiI_{2}.
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In this paper, we focus on developing a high efficient algorithm for solving d-dimension time-fractional diffusion equation (TFDE). For TFDE, the initial function or source term is usually not smooth, which can lead to the low regularity of exact solution. And such low regularity has a marked impact on the convergence rate of numerical method. In order to improve the convergence rate of the algorithm, we introduce the space-time sparse grid (STSG) method to solve TFDE. In our study, we employ the sine basis and the linear element basis for spatial discretization and temporal discretization, respectively. The sine basis can be divided into several levels, and the linear element basis can lead to the hierarchical basis. Then, the STSG can be constructed through a special tensor product of the spatial multilevel basis and the temporal hierarchical basis. Under certain conditions, the function approximation on standard STSG can achieve the accuracy order O(2-JJ) with O(2JJ) degrees of freedom (DOF) for d=1 and O(2Jd) DOF for d>1, where J denotes the maximal level of sine coefficients. However, if the solution changes very rapidly at the initial moment, the standard STSG method may reduce accuracy or even fail to converge. To overcome this, we integrate the full grid into the STSG, and obtain the modified STSG. Finally, we obtain the fully discrete scheme of STSG method for solving TFDE. The great advantage of the modified STSG method can be shown in the comparative numerical experiment.
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BACKGROUND: Sjogren's syndrome (SS) is an autoimmune disorder characterized by the destruction of exocrine glands, resulting in dry mouth and eyes. Currently, there is no effective treatment for SS, and the mechanisms associated with inadequate salivary secretion are poorly understood. METHODS: In this study, we used NOD mice model to monitor changes in mice's salivary secretion and water consumption. Tissue morphology of the submandibular glands was examined by H&E staining, and Immunohistochemical detected the expression of AQP5 (an essential protein in salivary secretion). Global gene expression profiling was performed on submandibular gland tissue of extracted NOD mice model using RNA-seq. Subsequently, a series of bioinformatics analyses of transcriptome sequencing was performed, including differentially expressed genes (DEGs) identification, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, PPI network construction, hub gene identification, and the validity of diagnostic indicators using the dataset GSE40611. Finally, IFN-γ was used to treat the cells, the submandibular gland tissue of NOD mice model was extracted, and RT-qPCR was applied to verify the expression of hub genes. RESULTS: We found that NOD mice model had reduced salivary secretion and increased water consumption. H&E staining suggests acinar destruction and basement membrane changes in glandular tissue. Immunohistochemistry detects a decrease in AQP5 immunostaining within acinar. In transcriptome sequencing, 42 overlapping DEGs were identified, and hub genes (REN, A2M, SNCA, KLK3, TTR, and AZGP1) were identified as initiating targets for insulin signaling. In addition, insulin signaling and cAMP signaling are potential pathways for regulating salivary secretion and constructing a regulatory relationship between target-cAMP signaling-salivary secretion. CONCLUSION: The new potential targets and signal axes for regulating salivary secretion provide a strategy for SS therapy in a clinical setting.
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Low-cost underwater wireless optical communication (UOWC) systems are attractive for high-speed connections among unmanned vehicles or devices in various underwater applications. Here we demonstrate a high-speed and low-cost UOWC system using a low-resolution digital to analog converter (DAC), a single-pixel mini-sized light-emitting diode (mini-LED), and digital pre-compensation (DPC). The enabled DPC scheme comprises digital pre-distortion (DPD), digital pre-emphasis (DPE), and digital resolution enhancer (DRE), which pre-compensate for mini-LED nonlinearity, the bandwidth limitation of the mini-LED and avalanche photodiode detector, and DAC resolution limitation, respectively. The simulation results show that the in-band signal-to-quantization noise ratio can be increased by 6.8 dB using DRE based on a 4-bit DAC. To further improve the system capacity, we tune the level of DPE in order to optimize the trade-off between the residual inter-symbol interference and signal-to-noise ratio. With the combination of optimized DPE and DRE, we obtain a 21.1% higher data rate compared with full DPE only and demonstrate the transmission of 6.9 Gb/s PAM-8 signal over a 2-m distance underwater based on a single-pixel mini-LED and 4-bit DAC. This paper reports a cost-effective UOWC system first using a low-resolution DAC and DPC, which offers a promising path toward low-cost underwater optical wireless networks.
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High-bandwidth GaN-based mini-LEDs on the c-sapphire substrate are promising candidates for underwater optical wireless communication (UOWC) systems due to their compatibility with the mature LED fabrication process. Here we fabricate and characterize mini-LEDs based on a single-layer InGaN active region with a peak emission wavelength around 484â nm for high-speed UOWC links. Since the LED diameter affects the trade-off between the modulation bandwidth and the optical modulation amplitude, mini-LEDs with varying mesa diameters from 100 µm to 175 µm are fabricated for the measurement. The 150 µm mini-LED with a 3-dB optical bandwidth of 906â MHz performs the best and enables the transmission of a net 4 Gb/s PAM-4 signal over 2 m of underwater distance using only linear equalization. This UOWC system has achieved, to the best of our knowledge, the highest net data rate and the highest data-rate-distance product based on a single-pixel mini-LED.
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BACKGROUND: Intestinal dysfunction is a common complication of acute pancreatitis. MiR155 may be involved in the occurrence and development of intestinal dysfunction mediated by acute pancreatitis, but the specific mechanism is not clear. AIMS: To investigate the effect of miR155 on severe acute pancreatitis (SAP)-associated intestinal dysfunction and its possible mechanism in a mice model. METHODS: In this study, SAP mice model was induced by intraperitoneal injection of caerulein and LPS in combination. Adeno-associated virus (AAV) was given by tail vein injection before the SAP model. The pancreatic and intestinal histopathology changes were analyzed. Cecal tissue was collected for 16S rRNA Gene Sequencing. Intestinal barrier proteins ZO-1 and E-cad were measured by Immunohistochemistry Staining and Western Blot, respectively. Intestinal tissue miR155 and inflammatory factors TNF-α, IL-1ß, and IL-6 were detected by Q-PCR. The expression levels of protein associated with TNF-α and TLR4/MYD88 pathway in the intestinal were detected. RESULTS: In miR155 overexpression SAP group, the levels of tissue inflammatory factor were significantly increased, intestinal barrier proteins were significantly decreased, and the injury of intestinal was aggravated. Bacterial 16S rRNA sequencing was performed, showing miR155 promotes gut microbiota dysbiosis. The levels of TNF-α, TLR4, and MYD88 in the intestinal were detected, suggesting that miR155 may regulate gut microbiota and activate the TLR4/MYD88 pathway, thereby affecting the release of inflammatory mediators and regulating SAP-related intestinal injury. After application of miR155-sponge, imbalance of intestinal flora and destruction of intestinal barrier-related proteins have been alleviated. The release of inflammatory mediators decreased, and the histopathology injury of intestinal was improved obviously. CONCLUSION: MiR155 may play an important role in SAP-associated intestinal dysfunction. MiR155 can significantly alter the intestinal microecology, aggravated intestinal inflammation through TLR4/MYD88 pathway, and disrupts the intestinal barrier in SAP mice.
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MicroARNs , Pancreatitis , Enfermedad Aguda , Animales , Modelos Animales de Enfermedad , Humanos , Inflamación/metabolismo , Mediadores de Inflamación/metabolismo , Mucosa Intestinal/metabolismo , Ratones , MicroARNs/genética , MicroARNs/metabolismo , Factor 88 de Diferenciación Mieloide/genética , Factor 88 de Diferenciación Mieloide/metabolismo , Pancreatitis/inducido químicamente , Pancreatitis/complicaciones , Pancreatitis/metabolismo , ARN Ribosómico 16S/genética , Receptor Toll-Like 4/genética , Receptor Toll-Like 4/metabolismo , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
BACKGROUND: A prediction model for 30-day readmission in patients with acute pancreatitis (AP) was needed. AIMS: To develop a nomogram to predict 30-day readmission in patients with AP and validate the usefulness of serum indicators after discharge for the prediction of 30-day readmission. METHODS: This was a retrospective cohort study enrolling patients with the first attack of AP. Baseline characteristics, clinical profiles, and serum indicators after discharge were compared. Multivariate logistic regression analysis and a nomogram were employed to determine the independent risk factors for 30-day readmission. RESULTS: A total of 7.32% (121/1653) of the patients were readmitted within 30 days after discharge. Different etiologies (biliary pancreatitis (adjusted odds ratio (AdjOR), 9.63; 95% confidence interval (CI), 1.28-72.52; P = 0.028), other causes (AdjOR, 9.37; 95% CI, 1.15-76.12, P = 0.026), mixed causes (AdjOR, 10.76; 95% CI, 1.27-91.35; P = 0.03) compared with alcoholic pancreatitis)), infected pancreatitis necrosis (IPN) (AdjOR, 2.3; 95% CI, 1.2-4.42; P = 0.013), total bilirubin level ≥ 20.5 µmol/L (AdjOR, 2.42; 95% CI, 1.23-4.77; P = 0.01), glucose level ≥ 6.1 mmol/L (AdjOR, 1.93; 95% CI, 1.16-3.19; P = 0.011), and albumin level < 40 g/L (AdjOR, 4.25; 95% CI, 2.44-7.41; P < 0.001) were independently associated with 30-day readmission. A nomogram incorporating these factors demonstrated good discrimination, calibration, and clinical utility. Serum indicators after discharge added predictive value compared with clinical variables alone (AUC, 0.78 vs. 0.685; P = 0.0001). CONCLUSIONS: The nomogram combining etiology, IPN, and serum indicators after discharge has favorable predictive performance for 30-Day readmission. The close monitoring and reexamination of serum indicators are essential for AP patients at high risk.
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Pancreatitis , Readmisión del Paciente , Enfermedad Aguda , Humanos , Nomogramas , Pancreatitis/complicaciones , Estudios Retrospectivos , Factores de RiesgoRESUMEN
The bandwidth upgrade required in short-reach optical communications has prompted the need for detection schemes that combine field reconstruction with a cost-effective subsystem architecture. Here we propose an asymmetric self-coherent detection (ASCD) scheme for the field reconstruction of self-coherent (SC) complex double-sideband (DSB) signals based on a direct-detection (DD) receiver with two reception paths. Each reception path consists of a photodiode (PD) and an analog-to-digital converter for the detection of a part of the received optical signal that experiences a different optical transfer function via the configuration of an optical filter. We derive an analytical solution to reconstructing the signal field and show the optimal filter response in optimizing the signal SNR. Further, we numerically characterize the theoretical performance of a specific ASCD scheme based on a chromatic dispersion filter and validate the principle of the ASCD scheme in a proof-of-concept experiment. The ASCD scheme approaches the electrical spectral efficiency of coherent detection with a cost-effective DD receiver, which shows the potential for high-speed short-reach links required by edge cloud communications and mobile X-haul systems.
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The effective spin Hamiltonian method has drawn considerable attention for its power to explain and predict magnetic properties in various intriguing materials. In this review, we summarize different types of interactions between spins (hereafter, spin interactions, for short) that may be used in effective spin Hamiltonians as well as the various methods of computing the interaction parameters. A detailed discussion about the merits and possible pitfalls of each technique of computing interaction parameters is provided.
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Fenómenos Magnéticos , Imanes , Modelos TeóricosRESUMEN
We propose and demonstrate the asymmetric direct detection (ADD) of polarization division multiplexed single-sideband (PDM-SSB) signals with orthogonal offset carriers. ADD exploits the photocurrent difference to eliminate the Y-Pol interference in the X-Pol, and the X-Pol signal intensity to eliminate the X-Pol interference in the Y-Pol without resorting to iterative algorithms. This enables not only low-complexity signal linearization but also a simplified receiver front-end composed of a single optical filter, two single-ended photodiodes and two analog-to-digital converters (ADC). In the experiment, we first perform a parametric study of the proposed scheme at 40 Gbaud in the back-to-back configuration (B2B) to evaluate the performance impact of different system parameters including the carrier to signal power ratio (CSPR), the matched filter roll-off, and the filter guard band. Next, we demonstrate the transmission of 416 Gbit/s PDM 16-QAM signal over 80 km single-mode fiber (SMF) below the soft-decision forward error correction (SD-FEC) threshold of 2×10-2. We also numerically study the effectiveness of a 2×2 multiple-input-multiple-output MIMO equalizer in alleviating the inter-polarization linear crosstalk resulting from the non-orthogonal PDM-SSB signals due to polarization-dependent loss (PDL), which is not negligible for potential on-chip implementation of ADD.
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We propose the asymmetric direct detection (ADD) of twin-single sideband (SSB) signals based on a simple receiver front-end composed of one optical filter and two photodiodes. ADD exploits the photocurrent difference between a filtered and unfiltered signal pair to reconstruct and linearize the received twin-SSB signal with a high electrical spectral efficiency (ESE). We evaluate the performance impact of the critical system parameters on ADD and demonstrate 231 Gb/s net rate 16-QAM twin-SSB transmission with 6.03 b/s/Hz ESE over an 80 km standard single-mode fiber below the ${1} \times {{10}^{ - 2}}$1×10-2 hard-decision forward error correction threshold. We also found that the bit error rate performance of ADD is robust against the relative center wavelength drifting of the optical filter.
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Probabilistic shaping (PS) allows tunable spectral efficiency that is suitable for realizing high throughput intra-data center transceivers. In this Letter, we integrate the cost-minimizing distribution matching (CMDM) in the probability amplitude shaping scheme to generate PS-PAM signals with ultra-short symbol block lengths for reduced serial processing delay. We detail the principle of CMDM and present two different methods of implementation. We demonstrate that CMDM enables the transmission of single wavelength net 200 Gbit/s PS-PAM-8 over 2 km of single-mode fiber (SMF). We show that similar performance is achievable using a constant composition distribution matcher, yet requiring 10 times longer symbol block lengths. We also report, to the best of our knowledge, the first demonstration of net 800 Gbit/s transmission over 2 km of SMF using a packaged 4-λ electro-absorption modulated laser transmitter optical sub-assembly (TOSA).
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Neuroligin1 is an important synaptic cell adhesion molecule that modulates the function of synapses through protein-protein interactions. Yet, it remains unclear whether the regulation of synaptic transmission in the spinal cord by neruoligin1 contributes to the development of postoperative pain. In a rat model of postoperative pain induced by plantar incision, we conducted Western blot study to examine changes in the expression of postsynaptic membrane of neuroligin1, postsynaptic density 95 (PSD-95), and α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptor GluA1 and GluA2 subunits in the spinal cord dorsal horn after injury. The interaction between neuroligin1 and PSD-95 was further determined by using coimmunoprecipitation. Protein levels of neuroligin1 and GluA1, but not GluA2 and PSD-95, were significantly increased in the postsynaptic membrane of the ipsilateral dorsal horn at 3 h and 1 day after incision, as compared to that in control group (naïve). A greater amount of PSD-95 was coimmunoprecipitated with neuroligin1 at 3 h after incision than that in the control group. Intrathecal administration of small interfering RNAs (siRNAs) targeting neuroligin1 suppressed the expression of neuroligin1 in the spinal cord. Importantly, pretreatment with intrathecal neuroligin1 siRNA2497, but not scrambled siRNA or vehicle, prevented the upregulation of GluA1 expression at 3 h after incision, inhibited the enhanced neuroligin1/PSD-95 interaction, and attenuated postoperative pain. Together, current findings suggest that downregulation of spinal neuroligin1 expression may ameliorate postoperative pain through inhibiting neuroligin1/PSD-95 interaction and synaptic targeting of GluA1 subunit. Accordingly, spinal neuroligin1 may be a potential new target for postoperative pain treatment.
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Moléculas de Adhesión Celular Neuronal/metabolismo , Homólogo 4 de la Proteína Discs Large/metabolismo , Regulación hacia Abajo , Dolor Postoperatorio/metabolismo , Subunidades de Proteína/metabolismo , Receptores AMPA/metabolismo , Asta Dorsal de la Médula Espinal/metabolismo , Sinapsis/metabolismo , Animales , Extremidades/cirugía , Inyecciones Espinales , Masculino , Dolor Postoperatorio/etiología , Unión Proteica , ARN Interferente Pequeño/metabolismo , Ratas Sprague-Dawley , Reproducibilidad de los Resultados , Asta Dorsal de la Médula Espinal/patología , Regulación hacia ArribaRESUMEN
We propose to combine 4D trellis-coded modulation (TCM) with transmitter-side Tomlinson-Harashima precoding (THP) in IM/DD transmissions, and experimentally investigate the achieved performance improvement. Theoretically, THP can approximately produce an end-to-end additive white Gaussian noise (AWGN) channel even with severe bandwidth limitation, allowing TCM to maintain its coding gain in the presence of inter-symbol interference. In our experiments with off-the-shelf commercial components, which limit the 3 dB bandwidth of the system to be ~3.5 GHz, the combination of TCM and THP shows a better receiver sensitivity for various system bit rates from 56 Gbit/s to 112 Gbit/s, considering the KP4 threshold of BER = 2 × 10-4. In the 112 Gbit/s back-to-back (B2B) transmission, with the help of THP the receiver sensitivity is improved by 3.3 dB using 4D-PAM4 TCM at the KP4 FEC threshold compared with using conventional PAM4. In addition, combining TCM and THP also helps to lower the BER floor.