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In this paper, we discuss building blocks that enable the exploitation of optical capacities beyond 100 Gb?s. Optical networks will benefit from more flexibility and agility in their network elements, especially from coherent transceivers. To achieve capacities of 400 Gb?s and more, coherent transceivers will operate at higher symbol rates. This will be made possible with higher bandwidth components using new electro-optic technologies implemented with indium phosphide and silicon photonics. Digital signal processing will benefit from new algorithms. Multi-dimensional modulation, of which some formats are already in existence in current flexible coherent transceivers, will provide improved tolerance to noise and fiber nonlinearities. Constellation shaping will further improve these tolerances while allowing a finer granularity in the selection of capacity. Frequency-division multiplexing will also provide improved tolerance to the nonlinear characteristics of fibers. Algorithms with reduced computation complexity will allow the implementation, at speeds, of direct pre-compensation of nonlinear propagation effects. Advancement in forward error correction will shrink the performance gap with Shannon's limit. At the network control and management level, new tools are being developed to achieve a more efficient utilization of networks. This will also allow for network virtualization, orchestration, and management. Finally, FlexEthernet and FlexOTN will be put in place to allow network operators to optimize capacity in their optical transport networks without manual changes to the client hardware.

Stroke is an acute cerebrovascular disorder caused by sudden decrease or interruption of blood flow in brain arteries. Deficiency of timely and effective reperfusion of ischemic brain tissue can lead to irreversible brain injury and neurological dysfunction. Currently, recombinant tissue plasminogen activator (rt-PA) is the only appropriate thrombolytic agent which is approved by FDA for patients with acute ischemic stoke. However, due to the limitation of very narrow therapeutic time window and severe intracranial hemorrhagic complication, the outcome of stroke treatment mediated by rt-PA still remains unsatisfactory. Therefore, it is urgent to find new alternative drugs or develop novel drug delivery system to achieve better outcomes. In recent years, with the rapid development of nanotechonology, nanomaterials as a drug delivery system can provide new strategies and methods to carry t-PA specifically to the occlusion site and provide advanced treatment for stroke. In this review, we briefly introduced the physiopathologic mechanisms of thrombolysis and focused on the comparison of the t-PA mediated thrombolysis and t-PA conjugated nanomaterial mediated thrombolysis.

Increasing areas of artificial afforestation and poplar monoculture in China have led to serious problems with insect pests. The development of genetic engineering technology, such as transgenic modification with Bacillus thuringiensis (Bt) genes, provides novel solutions to the pest problem. We generated a Bt-Cry1Ah1 gene incorporating codon optimization and transferred it into Populus deltoides × P. euramericana cv “Nanlin895” using an Agrobacterium-mediated method. The resulting Bt-Cry1Ah1 transgenic poplars were planted in the field with permission from the State Forestry Administration in 2017. Field and laboratory studies were conducted in Jiangsu, China, to investigate the effects of these transgenic poplars expressing the Cry1Ah1 protein on target and non-target pests and their parasitic natural enemy. Target pests included Hyphantria cunea (Lepidoptera, Arctiidae), Micromelalopha troglodyta (Lepidoptera, Notodontidae), and Clostera anachoreta (Lepidoptera, Notodontidae). Plagiodera versicolora (Coleoptera, Chrysomelidae) served as the non-target pest. Laboratory trials showed that the six transgenic poplar lines exhibited resistance against the target insects. The corrected mortality rates of the target pest larvae fed leaves from the six lines were as high as 87.0%, significantly higher than that of the control. However, the corrected mortality rate of the non-target pest larvae was markedly lower and did not differ significantly from that of the control. Field experiments showed that transgenic poplar exhibited resistance against H. cunea and M. troglodyta. Field mortality rates were slightly higher than laboratory mortality rates. In addition, we investigated Chouioia cunea (Hymenoptera, Eulophidae) as a parasitoid of H. cunea pupae that had been fed transgenic poplar leaves. The emergence time, parasitism rate, and abundance of C. cunea did not differ significantly from those of the control. Therefore, Bt-Cry1Ah1 transgenic poplar can be used to effectively control damage by target insect pests without negatively affecting non-target insects and parasitoids.

Analog radio-over-fiber (A-RoF) solutions for mobile fronthaul are regaining wide attention due to their high spectral efficiency and low complexity. However, the performance of A-RoF is usually limited by the fiber link fidelity. In this Letter, we propose and experimentally demonstrate an optical continuous pulse position modulation-based analog radio-over-fiber (OCPPM-RoF) scheme, in which the amplitudes of wireless waveforms are mapped to the time-domain positions of optical pulses to decouple the additive noise. The de-modulation of OCPPM-RoF signals is performed by a frequency-domain continuous position estimation (FD-CPE) algorithm including cross-power spectrum calculation and weighted least square for accurate delay estimation. In the experiment, by adopting appropriate pulse width factors, the recovered signal-to-noise ratio (SNR) can be flexibly adjusted within a wide range from 31.8 to 54.0 dB, supporting the transmission of various formats from 256-QAM to 65536-QAM. The results indicate that OCPPM-RoF can be a promising candidate for future fronthaul.

Ethnopharmacological Relevance: Increasing evidence suggests that ferroptosis, an iron-dependent form of cell death characterized by lipid peroxidation, may play a substantial role in the traumatic brain injury (TBI) pathophysiology. 3-n-butylphthalide (NBP), a compound extracted from the seeds of Apium graveolens Linn (Chinese celery) and used in China to treat ischemic stroke, has demonstrated encouraging anti-reactive oxygen species (ROS) effects. Ascertaining whether NBP can inhibit ferroptosis and its mechanism could potentially expand its use in models of neurological injury and neurodegenerative diseases., Methods and Results: In this study, we used erastin-induced in vitro ferroptosis models (HT22 cells, hippocampal slices, and primary neurons) and an in vivo controlled cortical impact mouse model. Our study revealed that NBP administration mitigated erastin-induced death in HT-22 cells and decreased ROS levels, lipid peroxidation, and mitochondrial superoxide indicators, resulting in mitochondrial protection. Moreover, the ability of NBP to inhibit ferroptosis was confirmed in organotypic hippocampal slice cultures and a TBI mouse model. NBP rescued neurons, inhibited microglial activation, and reduced iron levels in the brain tissue. The protective effect of NBP can be partly attributed to the inhibition of the AHR-CYP1B1 axis, as evidenced by RNA-seq and CYP1B1 overexpression/inhibition experiments in HT22 cells and primary neurons., Conclusions: Our study underscores that NBP inhibition of the AHR-CYP1B1 axis reduces ferroptosis in neuronal damage and ameliorates brain injury., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

With the exponential growth in data density and user ends of wireless networks, fronthaul is tasked with supporting aggregate bandwidths exceeding thousands of gigahertz while accommodating high-order modulation formats. However, it must address the bandwidth and noise limitations imposed by optical links and devices in a cost-efficient manner. Here we demonstrate a high-fidelity fronthaul system enabled by self-homodyne digital-analog radio-over-fiber superchannels, using a broadband electro-optic comb and uncoupled multicore fiber. This self-homodyne superchannel architecture not only offers capacity boosting but also supports carrier-recovery-free reception. Our approach achieves a record-breaking 15,000 GHz aggregated wireless bandwidth, corresponding to a 0.879 Pb/s common public radio interface (CPRI) equivalent data rate. Higher-order formats up to 1,048,576 quadrature-amplitude-modulated (QAM) are showcased at a 100 Tb/s class data rate. Furthermore, we employ a packaged on-chip electro-optic comb as the sole optical source to reduce the cost, supporting a data rate of 100.5 Tb/s with the 1024-QAM format. These demonstrations propel fronthaul into the era of Pb/s-level capacity and exhibit the promising potential of integrated-photonics implementation, pushing the boundaries to new heights in terms of capacity, fidelity, and cost., (© 2024. The Author(s).)

The transplantation of bone marrow mesenchymal stem cells (MSCs) in stroke is hindered by the restricted rates of survival and differentiation. Ginsenoside compound K (CK), is reported to have a neuroprotective effect and regulate energy metabolism. We applied CK to investigate if CK could promote the survival of MSCs and differentiation into brain microvascular endothelial-like cells (BMECs), thereby alleviating stroke symptoms. Therefore, transwell and middle cerebral artery occlusion (MCAO) models were used to mimic oxygen and glucose deprivation (OGD) in vitro and in vivo, respectively. Our results demonstrated that CK had a good affinity for GLUT1, which increased the expression of GLUT1 and the production of ATP, facilitated the proliferation and migration of MSCs, and activated the HIF-1α/VEGF signaling pathway to promote MSC differentiation. Moreover, CK cooperated with MSCs to protect BMECs, promote angiogenesis and vascular density, enhance neuronal and astrocytic proliferation, thereby reducing infarct volume and consequently improving neurobehavioral outcomes. These results suggest that the synergistic effects of CK and MSCs could potentially be a promising strategy for stroke., (© 2024 John Wiley & Sons Ltd.)

Objective: Chronic subdural hematoma (CSDH) is a neurological condition with high recurrence rates, primarily observed in the elderly population. Although several risk factors have been identified, predicting CSDH recurrence remains a challenge. Given the potential of machine learning (ML) to extract meaningful insights from complex data sets, our study aims to develop and validate ML models capable of accurately predicting postoperative CSDH recurrence., Methods: Data from 447 CSDH patients treated with consecutive burr-hole irrigations at Wenzhou Medical University's First Affiliated Hospital (December 2014-April 2019) were studied. 312 patients formed the development cohort, while 135 comprised the test cohort. The Least Absolute Shrinkage and Selection Operator (LASSO) method was employed to select crucial features associated with recurrence. Eight machine learning algorithms were used to construct prediction models for hematoma recurrence, using demographic, laboratory, and radiological features. The Border-line Synthetic Minority Over-sampling Technique (SMOTE) was applied to address data imbalance, and Shapley Additive Explanation (SHAP) analysis was utilized to improve model visualization and interpretability. Model performance was assessed using metrics such as AUROC, sensitivity, specificity, F1 score, calibration plots, and decision curve analysis (DCA)., Results: Our optimized ML models exhibited prediction accuracies ranging from 61.0% to 86.2% for hematoma recurrence in the validation set. Notably, the Random Forest (RF) model surpassed other algorithms, achieving an accuracy of 86.2%. SHAP analysis confirmed these results, highlighting key clinical predictors for CSDH recurrence risk, including age, alanine aminotransferase level, fibrinogen level, thrombin time, and maximum hematoma diameter. The RF model yielded an accuracy of 92.6% with an AUC value of 0.834 in the test dataset., Conclusion: Our findings underscore the efficacy of machine learning algorithms, notably the integration of the RF model with SMOTE, in forecasting the recurrence of postoperative chronic subdural hematoma. Leveraging the RF model, we devised an online calculator that may serve as a pivotal instrument in tailoring therapeutic strategies and implementing timely preventive interventions for high-risk patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Ni, Zhu, Qian, Li, Xing, Zhou, Chen, Huang, Yang and Zhuge.)

Background: Postoperative pneumonia (POP) is one of the primary complications after aneurysmal subarachnoid hemorrhage (aSAH) and is associated with postoperative mortality, extended hospital stay, and increased medical fee. Early identification of pneumonia and more aggressive treatment can improve patient outcomes. We aimed to develop a model to predict POP in aSAH patients using machine learning (ML) methods., Methods: This internal cohort study included 706 patients with aSAH undergoing intracranial aneurysm embolization or aneurysm clipping. The cohort was randomly split into a train set (80%) and a testing set (20%). Perioperative information was collected from participants to establish 6 machine learning models for predicting POP after surgical treatment. The area under the receiver operating characteristic curve (AUC), precision-recall curve were used to assess the accuracy, discriminative power, and clinical validity of the predictions. The final model was validated using an external validation set of 97 samples from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database., Results: In this study, 15.01% of patients in the training set and 12.06% in the testing set with POP after underwent surgery. Multivariate logistic regression analysis showed that mechanical ventilation time (MVT), Glasgow Coma Scale (GCS), Smoking history, albumin level, neutrophil-to-albumin Ratio (NAR), c-reactive protein (CRP)-to-albumin ratio (CAR) were independent predictors of POP. The logistic regression (LR) model presented significantly better predictive performance (AUC: 0.91) than other models and also performed well in the external validation set (AUC: 0.89)., Conclusion: A machine learning model for predicting POP in aSAH patients was successfully developed using a machine learning algorithm based on six perioperative variables, which could guide high-risk POP patients to take appropriate preventive measures., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Li, Zhang, Wang, Ye, Zhu and Zhuge.)

Driven by the scarcity of effective treatment options in clinical settings, the present study aimed to identify a new potential target for Alzheimer's disease (AD) treatment. We focused on Lars2, an enzyme synthesizing mitochondrial leucyl-tRNA, and its role in maintaining mitochondrial function. Bioinformatics analysis of human brain transcriptome data revealed downregulation of Lars2 in AD patients compared to healthy controls. During in vitro experiments, the knockdown of Lars2 in mouse neuroblastoma cells (neuro-2a cells) and primary cortical neurons led to morphological changes and decreased density in mouse hippocampal neurons. To explore the underlying mechanisms, we investigated how downregulated Lars2 expression could impede the phosphatidylinositol 3-kinase/protein kinase B (PI3K-AKT) pathway, thereby mitigating AKT's inhibitory effect on glycogen synthase kinase 3 beta (GSK3β). This led to the activation of GSK3β, causing excessive phosphorylation of Tau protein and subsequent neuronal degeneration. During in vivo experiments, knockout of lars2 in hippocampal neurons confirmed cognitive impairment through the Barnes maze test, the novel object recognition test, and nest-building experiments. Additionally, immunofluorescence assays indicated an increase in p-tau, atrophy in the hippocampal region, and a decrease in neurons following Lars2 knockout. Taken together, our findings indicate that Lars2 represents a promising therapeutic target for AD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Automatic test paper design is critical in education to reduce workloads for educators and facilitate an efficient teaching process. However, current designs fail to satisfy the realistic teaching requirements of educators, including the consideration of both test quality and efficiency. This is the main reason why teachers still manually construct tests in most teaching environments. In this paper, the quality of tests is quantitatively defined while considering multiple objectives, including a flexible coverage of knowledge points, cognitive levels, and question difficulty. Then, a model based on the technique of linear programming is delicately designed to explore the optimal results for this newly defined problem. However, this technique is not efficient enough, which cannot obtain results in polynomial time. With the consideration of both test quality and generation efficiency, this paper proposes a genetic algorithm (GA) based method, named dynamic programming guided genetic algorithm with adaptive selection (DPGA-AS). In this method, a dynamic programming method is proposed in the population initialization part to improve the efficiency of the genetic algorithm. An adaptive selection method for the GA is designed to avoid prematurely falling into the local optimal for better test quality. The question bank used in our experiments is assembled based on college-level calculus questions from well-known textbooks. The experimental results show that the proposed techniques can construct test papers with both high effectiveness and efficiency. The computation time of the test assembly problem is reduced from 3 hours to 2 seconds for a 5000-size question bank as compared to a linear programming model with similar test quality. The test quality of the proposed method is better than the other baselines.

The digital radio-over-fiber (D-RoF) transmission with two-level coding (TLC) is proposed and demonstrated in this Letter. A joint design considering the importance of quantization bits, the protection ability of forward error correction (FEC), and the bit error ratio of quadrature amplitude modulation (QAM) symbols is realized. In TLC-based D-RoF systems, the more significant bits among quantization bits are protected by a FEC and are assigned to the least reliable bits of modulated QAM symbols. Conversely, the less significant bits, without FEC protection, are allocated to the more reliable bits of QAM symbols. Experiments on an 11-km standard single-mode fiber transmission are conducted to evaluate the performance. The results indicate that, with a maximum iteration number of 2, compared to the conventional bit-interleaved coded modulation (BICM) with all bits encoded, the D-RoF based on TLC attains nearly identical performance under the 0.34% error vector magnitude threshold of 65536QAM wireless signals, specifically achieving complexity reductions of 54.55% and 67.66% for 16QAM and 64QAM optical transmissions, respectively.

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

The digital-analog radio-over-fiber (DA-RoF) scheme offers a high-fidelity and spectrally efficient solution for future mobile fronthaul. However, to be implemented in the low-cost directly modulated laser with direct detection (DML-DD) link, both the digital and analog parts in DA-RoF modulation would suffer from the composite second-order (CSO) and composite triple beat (CTB) caused by the chirp-dispersion interaction. In this Letter, we propose and experimentally demonstrate a computationally efficient composite triple beat cancellation (CTB-C) algorithm for DA-RoF fronthaul in the dispersion-uncompensated C-band DML-DD link. The CSO and CTB are suppressed at the receiver-side DSP based on the theoretical model of these nonlinear distortions. In the proof-of-concept experiment, a 1.2-dB improvement in the recovered signal-to-noise ratio (SNR) is obtained with 5.5-GHz 1024-QAM orthogonal frequency division multiplexing (OFDM) signal after 10-km standard single-mode fiber (SSMF) transmission. The proposed CTB-C technique does not require the training process and performs close to the Volterra-based feed-forward equalizer (VFE) under the complexity constraint.

Multi-model data can enhance brain tumor segmentation for the rich information it provides. However, it also introduces some redundant information that interferes with the segmentation estimation, as some modalities may catch features irrelevant to the tissue of interest. Besides, the ambiguous boundaries and irregulate shapes of different grade tumors lead to a non-confidence estimate of segmentation quality. Given these concerns, we exploit an uncertainty-guided U-shaped transformer with multiple heads to construct drop-out format masks for robust training. Specifically, our drop-out masks are composed of boundary mask, prior probability mask, and conditional probability mask, which can help our approach focus more on uncertainty regions. Extensive experimental results show that our method achieves comparable or higher results than previous state-of-the-art brain tumor segmentation methods, achieving average dice coefficients of [Formula: see text] and Hausdorff distance of 4.91 on the BraTS2021 dataset. Our code is freely available at https://github.com/chaineypung/BTS-UGT., (© 2023. International Federation for Medical and Biological Engineering.)

The CRISPR genome editing technology is a crucial tool for enabling revolutionary advancements in plant genetic improvement. This review shows the latest developments in CRISPR/Cas9 genome editing system variants, discussing their benefits and limitations for plant improvement. While this technology presents immense opportunities for plant breeding, it also raises serious biosafety concerns that require careful consideration, including potential off-target effects and the unintended transfer of modified genes to other organisms. This paper highlights strategies to mitigate biosafety risks and explores innovative plant gene editing detection methods. Our review investigates the international biosafety guidelines for gene-edited crops, analyzing their broad implications for agricultural and biotechnology research and advancement. We hope to provide illuminating and refined perspectives for industry practitioners and policymakers by evaluating CRISPR genome enhancement in plants.