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Abstract Stroke is a neurological complication that can occur in patients admitted to the intensive care unit (ICU) for non-neurological conditions, leading to increased mortality and prolonged hospital stays. The incidence of stroke in ICU settings is notably higher compared to the general population, and delays in diagnosis can lead to irreversible neurological damage. Early diagnosis of stroke is critical to protect brain tissue and treat neurological defects. Therefore, we developed a machine learning model to diagnose stroke in patients with acute neurological manifestations in the ICU. We retrospectively collected data on patients’ underlying diseases, blood coagulation tests, procedures, and medications before neurological symptom onset from 206 patients at the Chungbuk National University Hospital ICU (July 2020–July 2022) and 45 patients at Chungnam National University Hospital between (July 2020–March 2023). Using the Categorical Boosting (CatBoost) algorithm with Bayesian optimization for hyperparameter selection and k-fold cross-validation to mitigate overfitting, we analyzed model-feature relationships with SHapley Additive exPlanations (SHAP) values. Internal model validation yielded an average accuracy of 0.7560, sensitivity of 0.8959, specificity of 0.7000, and area under the receiver operating characteristic curve (AUROC) of 0.8201. External validation yielded an accuracy of 0.7778, sensitivity of 0.7500, specificity of 0.7931, and an AUROC of 0.7328. These results demonstrated the model’s effectiveness in diagnosing stroke in non-neurological ICU patients with acute neurological manifestations using their electronic health records, making it valuable for the early detection of stroke in ICU patients.

Abstract Respiratory distress is a common chief complaint in neonates admitted to the neonatal intensive care unit. Despite the increasing use of non-invasive ventilation in neonates with respiratory difficulty, some of them require advanced airway support. Delayed intubation is associated with increased morbidity, particularly in urgent unplanned cases. Early and accurate prediction of the need for intubation may provide more time for preparation and increase safety margins by avoiding the late intubation at high-risk infants. This study aimed to predict the need for intubation within 3 h in neonates initially managed with non-invasive ventilation for respiratory distress during the first 48 h of life using a multimodal deep neural network. We developed a multimodal deep neural network model to simultaneously analyze four time-series data collected at 1-h intervals and 19 variables including demographic, physiological and laboratory parameters. Evaluating the dataset of 128 neonates with respiratory distress who underwent non-invasive ventilation, our model achieved an area under the curve of 0.917, sensitivity of 85.2%, and specificity of 89.2%. These findings demonstrate promising results for the multimodal model in predicting neonatal intubation within 3 h.

Abstract Cereblon (CRBN) is a substrate recruiter for CRL4CRBN E3 ubiquitin ligase system playing a plethora of pivotal roles for biological systems. Here, we identified DNAJB1 (DJ1) as endogenous substrate of CRBN and report how CRBN influences the aggregation and toxicity of alpha-synuclein (α-SYN) via modulation of DJ1. CRBN interferes with molecular activities of DJ1 in vitro, in cells, and in vivo resulting in a reduced disaggregation of α-SYN fibrils, increased formation of preformed fibrils (PFFs) of α-SYN, and high susceptibility of mice to MPTP and PFF-induced neurotoxicity. Depletion of Crbn improves the behavioral and biochemical responses of mice towards neurotoxic insult. Finally, we designed a peptide inhibitor to inhibit the recruitment of DJ1 to CRBN for ubiquitination, resulting in an enhanced supply of DJ1 to counteract the toxicity of aggregated α-SYN. Our data has important implications for development of CRBN-targeting therapies that could prevent or delay progression of neurodegenerative synucleinopathy.

Abstract Energy homeostasis and sleep have a bidirectional relationship. Cereblon (CRBN) regulates energy levels by ubiquitinating the AMP-activated protein kinase(AMPK), an energy sensor. However, whether CRBN participates in sleep is unclear. Here, we examine sleep–wake patterns in Crbn +/+ and Crbn −/− mice during 24-h baseline, 6-h sleep deprivation (SD), and following 6-h recovery sleep (RS). At baseline, overall sleep patterns are similar between genotypes. However, SD decreases CRBN expression in Crbn +/+ mice and increases phospho-Tau, phospho-α-synuclein, DNAJA1 (DJ2), and DNAJB1 (DJ1) in both genotypes, with Crbn −/− mice showing a lesser extent of increase in p-Tau and p-α-synuclein and a higher level of heat shock protein 70 (HSP70), DJ2, and DJ1. During RS, Crbn −/ − mice show increased slow-wave activity in the low-delta range (0.5–2.5 Hz), suggesting higher homeostatic sleep propensity associated with AMPK hyperactivation. By illuminating the role of CRBN in regulating sleep–wake behaviors through AMPK, we suggest CRBN as a potential therapeutic target for managing sleep disorders and preventing neurodegeneration.

Abstract The Araliaceae contain many valuable species in medicinal and industrial aspects. We performed intensive phylogenomics using the plastid genome (plastome) and 45S nuclear ribosomal DNA sequences. A total of 66 plastome sequences were used, 13 of which were newly assembled in this study, 12 from new sequences, and one from existing data. While Araliaceae plastomes showed conserved genome structure, phylogenetic reconstructions based on four different plastome datasets revealed phylogenetic discordance within the Asian Palmate group. The divergence time estimation revealed that splits in two Araliaceae subfamilies and the clades exhibiting phylogenetic discordances in the Asian Palmate group occurred at two climatic optima, suggesting that global warming events triggered species divergence, particularly the rapid diversification of the Asian Palmate group during the Middle Miocene. Nucleotide substitution analyses indicated that the Hydrocotyloideae plastomes have undergone accelerated AT-biased mutations (C-to-T transitions) compared with the Aralioideae plastomes, and the acceleration may occur in their mitochondrial and nuclear genomes as well. This implies that members of the genus Hydrocotyle, the only aquatic plants in the Araliaceae, have experienced a distinct evolutionary history from the other species. We also discussed the intercontinental disjunction in the genus Panax and proposed a hypothesis to complement the previously proposed hypothesis. Our results provide the evolutionary trajectory of Araliaceae and advance our current understanding of the evolution of Araliaceae species.

Abstract Agastache rugosa, also known as Korean mint, is a perennial plant from the Lamiaceae family that is traditionally used for various ailments and contains antioxidant and antibacterial phenolic compounds. Molecular breeding of A. rugosa can enhance secondary metabolite production and improve agricultural traits, but progress in this field has been delayed due to the lack of chromosome-scale genome information. Herein, we constructed a chromosome-level reference genome using Nanopore sequencing and Hi-C technology, resulting in a final genome assembly with a scaffold N50 of 52.15 Mbp and a total size of 410.67 Mbp. Nine pseudochromosomes accounted for 89.1% of the predicted genome. The BUSCO analysis indicated a high level of completeness in the assembly. Repeat annotation revealed 561,061 repeat elements, accounting for 61.65% of the genome, with Copia and Gypsy long terminal repeats being the most abundant. A total of 26,430 protein-coding genes were predicted, with an average length of 1,184 bp. The availability of this chromosome-scale genome will advance our understanding of A. rugosa’s genetic makeup and its potential applications in various industries.

Abstract Ilex is a monogeneric plant group (containing approximately 600 species) in the Aquifoliaceae family and one of the most commonly used medicinal herbs. However, its taxonomy and phylogenetic relationships at the species level are debatable. Herein, we obtained the complete chloroplast genomes of all 19 Ilex types that are native to Hong Kong. The genomes are conserved in structure, gene content and arrangement. The chloroplast genomes range in size from 157,119 bp in Ilex graciliflora to 158,020 bp in Ilex kwangtungensis. All these genomes contain 125 genes, of which 88 are protein-coding and 37 are tRNA genes. Four highly varied sequences (rps16-trnQ, rpl32-trnL, ndhD-psaC and ycf1) were found. The number of repeats in the Ilex genomes is mostly conserved, but the number of repeating motifs varies. The phylogenetic relationship among the 19 Ilex genomes, together with eight other available genomes in other studies, was investigated. Most of the species could be correctly assigned to the section or even series level, consistent with previous taxonomy, except Ilex rotunda var. microcarpa, Ilex asprella var. tapuensis and Ilex chapaensis. These species were reclassified; I. rotunda was placed in the section Micrococca, while the other two were grouped with the section Pseudoaquifolium. These studies provide a better understanding of Ilex phylogeny and refine its classification.

Abstract A novel nano-plasmonic sensing platform based on vertical conductive bridge was suggested as an alternative geometry for taking full advantages of unique properties of conductive junction while substantially alleviating burdens in lithographic process. The effects of various geometrical parameters on the plasmonic properties were systematically investigated. Theoretical simulation on this structure demonstrates that the presence of vertical conductive bridge with smaller diameter sandwiched between two adjacent thin nanodiscs excites a bridged mode very similar to the charge transfer plasmon and exhibits a remarkable enhancement in the extinction efficiency and the sensitivity when the electric field of incident light is parallel to the conductive bridge. Furthermore, for the electric field perpendicular to the bridge, another interesting feature is observed that two magnetic resonance modes are excited symmetrically through open-gaps on both sides of the bridge together with strongly enhanced electric field intensity, which provides a very favorable environment as a surface enhanced Raman scattering substrate for fluid analysis. These results verify a great potential and versatility of our approach for use as a nanoplasmonic sensing platform. In addition, we demonstrated the feasibility of fabrication process of vertical conductive bridge and high tunability in controlling the bridge width.

Abstract Both genomes in chloroplasts and mitochondria of plant cell are usually inherited from maternal parent, with rare exceptions. To characterize the inheritance patterns of the organelle genomes in cucumber (Cucumis sativus var. sativus), two inbred lines and their reciprocal F1 hybrids were analyzed using an next generation whole genome sequencing data. Their complete chloroplast genome sequences were de novo assembled, and a single SNP was identified between the parental lines. Two reciprocal F1 hybrids have the same chloroplast genomes with their maternal parents. Meanwhile, 292 polymorphic sites were identified between mitochondrial genomes of the two parental lines, which showed the same genotypes with their paternal parents in the two reciprocal F1 hybrids, without any recombination. The inheritance patterns of the chloroplast and mitochondria genomes were also confirmed in four additional cucumber accessions and their six reciprocal F1 hybrids using molecular markers derived from the identified polymorphic sites. Taken together, our results indicate that the cucumber chloroplast genome is maternally inherited, as is typically observed in other plant species, whereas the large cucumber mitochondrial genome is paternally inherited. The combination of DNA markers derived from the chloroplast and mitochondrial genomes will provide a convenient system for purity test of F1 hybrid seeds in cucumber breeding.

Calcium flux must be carefully controlled during the phagocytosis of apoptotic cells (efferocytosis), although how this occurs is not fully understood. Here, the authors show that the Cereblon E3 ligase regulates Orai1 degradation and subsequently SOCE-mediated calcium influx.

Microvilli can participate in adhesion or migration of T cells, but whether they are involved in function regulation is unclear. Here the authors show that T cell microvilli form budding vesicles containing T cell signalling components for deposition onto antigen presenting cells (APC) and modulation of APC functions.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.