Chromosome-level genome assembly of a cliff plant Taihangia rupestris var. ciliata provides insights into its adaptation and demographic history.

BACKGROUND: Cliffs are recognized as one of the most challenging environments for plants, characterized by harsh conditions such as drought, infertile soil, and steep terrain. However, they surprisingly host ancient and diverse plant communities and play a crucial role in protecting biodiversity. The Taihang Mountains, which act as a natural boundary in eastern China, support a rich variety of plant species, including many unique to cliff habitats. However, it is little known how cliff plants adapt to harsh habitats and the demographic history in this region. RESULTS: To better understand the demographic history and adaptation of cliff plants in this area, we analyzed the chromosome-level genome of a representative cliff plant, T. rupestris var. ciliata, which has a genome size of 769.5 Mb, with a scaffold N50 of 104.92 Mb. The rapid expansion of transposable elements may have contributed to the increasing genome and its ability to adapt to unique and challenging cliff habitats. Comparative analysis of the genome evolution between Taihangia and non-cliff plants in Rosaceae revealed a significant expansion of gene families associated with oxidative phosphorylation, which is likely a response to the abiotic stresses faced by cliff plants. This expansion may explain the long-term adaptation of Taihangia to harsh cliff environments. The effective population size of the two varieties has continuously decreased due to climatic fluctuations during the Quaternary period. Furthermore, significant differences in gene expression between the two varieties may explain the varied leaf phenotypes and adaptations to harsh conditions in different natural distributions. CONCLUSION: Our study highlights the extraordinary adaptation of T. rupestris var. ciliata, shedding light on the evolution of cliff plants worldwide.

Hippo kinases Mst1 and Mst2 maintain NK cell homeostasis by orchestrating metabolic state and transcriptional activity.

Natural killer (NK) cells play a crucial role in immune response against viral infections and tumors. However, further investigation is needed to better understand the key molecules responsible for determining the fate and function of NK cells. In this study, we made an important discovery regarding the involvement of the Hippo kinases Mst1 and Mst2 as novel regulators in maintaining mouse NK cell homeostasis. The presence of high Mst1 and Mst2 (Mst1/2) activity in NK cells is essential for their proper development, survival and function in a canonical Hippo signaling independent mode. Mechanistically, Mst1/2 induce cellular quiescence by regulating the processes of proliferation and mitochondrial metabolism, thereby ensuring the development and survival of NK cells. Furthermore, Mst1/2 effectively sense IL-15 signaling and facilitate the activation of pSTAT3-TCF1, which contributes to NK cell homeostasis. Overall, our investigation highlights the crucial role of Mst1/2 as key regulators in metabolic reprogramming and transcriptional regulation for mouse NK cell survival and function, emphasizing the significance of cellular quiescence during NK cell development and functional maturation.

Efgartigimod as rescue treatment in acute phase of neuromyelitis optica spectrum disorder: A Case Report.

Introduction: Neuromyelitis optica spectrum disorder (NMOSD) is a central nervous system demyelinating disease. Current therapy methods, however, have limited effect on acute attacks except for intravenous methylprednisolone (IVMP). Efgartigimod is a first-in-class novel human immunoglobulin G1 (IgG1) Fc fragment approved for the treatment of generalized myasthenia gravis. Its capacity to rapidly decrease serum IgG levels, including pathogenic autoantibodies, positions it as a potentially effective option for managing the acute phase of NMOSD. Case presentation: We report the case of a 59-year-old female patient with acute NMOSD, presenting with vision loss and numbness in all four limbs. Despite an initial inadequate response to intravenous methylprednisolone (IVMP), the addition of Efgartigimod to her treatment regimen led to rapid improvement, notably including a significant reduction in serum aquaporin-4 antibody titers, total IgG levels, and inflammation cytokine levels. Furthermore, no adverse events were reported during a four-month follow-up period. Conclusion: As an adjunct to glucocorticoid therapy, Efgartigimod has proven effective and safe for this patient. However, to ascertain its potential as a novel therapeutic option for acute NMOSD, larger-scale prospective clinical trials are required.

Automation function and malfunction: effects on human performance in accident handling tasks.

By conducting a mixed-design experiment using simplified accident handling tasks performed by two-person teams, this study examined the effects of automation function and condition (before, during, and after malfunction) on human performance. Five different and non-overlapping functions related to human information processing model were considered and their malfunctions were set in a first-failure way. The results showed that while the automation malfunction impaired task performance, the performance degradation for information analysis was more severe than response planning. Contrary to other functions, the situation awareness for response planning and response implementation tended to increase during malfunctioning and decrease after. In addition, decreased task performance reduced trust in automation, and malfunctions in earlier stages of information processing resulted in lower trust. Suggestions provided for the design and training related to automation emphasise the importance of high-level cognitive support and the benefit of involving automation error handling in training.

The effects of automation function and malfunction on human performance are important for design and training. The experimental results in this study revealed the significance of high-level cognitive support. Also, introducing automation error handling in training can be helpful in improving situation awareness of the teams.

Climatic niche evolution and niche conservatism of Nymphaea species in Africa, South America, and Australia.

BACKGROUND: Interest in the evolution of climatic niches, particularly in understanding the potential adaptive responses of species under climate change, has increased both theoretically and within macroecological studies. These studies have provided valuable insights into how climatic traits of species influence their niche evolution. In this study, we aim to investigate whether niche conservatism plays a role in the species diversification of Nymphaea, a group of aquatic plants with a cosmopolitan distribution that is facing severe habitat loss. We will use climatic models and phylogenetic data for 23 species to reconstruct Nymphaea's niche evolution, measure niche overlap, and assess disparity through time while testing for evolutionary models. RESULTS: There was a lot of overlap in niches both within and between groups, especially for species that can be found in many places. The breadth and peaks of the niche profile varied depending on the bioclimatic variables, which suggested that the species evolved differently to cope with changes in climate. The analysis also showed that evolutionary changes happened across the phylogeny, with weak to moderate signals. The morphological disparity index (MDI) values indicated that there were disparities within subclades over time but not between or among them. Niche reconstruction and evolution analysis revealed both convergent and divergent evolution among various variables. For example, N. immutabilis, N. atrans, N. violancea, and N. nouchali evolved towards intermediate temperatures for bio2 and bio3 (isothermity) while moving towards extreme temperatures for bio8 and bio9 (wettest and driest average quarterly temperatures). CONCLUSION: Our study will improve our understanding of how changes in climatic niches are potentially driving the evolution of Nymphaea. It has significant scientific implications for the limits, assemblages, evolution, and diversification of species. This information is crucial for the ongoing efforts of conservation and management, particularly considering the inevitable effects of climate change.

Molecular analyses display the increasing diversity of Podostemaceae in China.

•Four newly recorded species of Podostemaceae from southern China were identified by molecular and morphological evidence.•17 plastomes of Podostemaceae were newly sequenced and two novel polymorphic barcodes (ccsA and ndhA) detected.•Our findings reveal greater species richness (15 species from five genera) of Podostemaceae in China and supply molecular resources for research on taxonomy and phylogenomics of this enigmatic aquatic family.

Assembly and comparative analysis of the first complete mitochondrial genome of the invasive water hyacinth, Eichhornia crassipes.

Eichhornia crassipes is an aquatic plant in tropical and subtropical regions, renowned for its notorious invasive tendencies. In this study, we assembled the complete mitogenome of E. crassipes into a single circle molecule of 397,361 bp. The mitogenome has 58 unique genes, including 37 protein-coding genes (PCGs), 18 tRNA genes, three rRNA genes, and 47 % GC content. Sixteen (6.93 %) homologous fragments, ranging from 31 bp to 8548 bp, were identified, indicating the transfer of genetic material from chloroplasts to mitochondria. In addition, we detected positive selection in six PCGs (ccmB, ccmC, ccmFC, nad3, nad4 and sdh4), along with the identification of 782 RNA editing sites across 37 mt-PCGs. These findings suggest a potential contribution to the robust adaptation of this invasive plant to the stressful environment. Lastly, we inferred that phylogenetic conflicts of E. crassipes between the plastome and mitogenome may be attributed to the difference in nucleotide substitution rates between the two organelle genomes. In conclusion, our study provided vital genomic resources for further understanding the invasive mechanism of this species and exploring the dynamic evolution of mitogenomes within the monocot clade.

Identification of Y‒linked biomarkers and exploration of immune infiltration of normal-appearing gray matter in multiple sclerosis by bioinformatic analysis.

Background: The knowledge of normal‒appearing cortical gray matter (NAGM) in multiple sclerosis (MS) remains unclear. In this study, we aimed to identify diagnostic biomarkers and explore the immune infiltration characteristics of NAGM in MS through bioinformatic analysis and validation in vivo. Methods: Differentially expressed genes (DEGs) were analyzed. Subsequently, the functional pathways of the DEGs were determined. After screening the overlapping DEGs of MS with two machine learning methods, the biomarkers' efficacy and the expression levels of overlapping DEGs were calculated. Quantitative reverse transcription polymerase chain reaction (qRT‒PCR) identified the robust diagnostic biomarkers. Additionally, infiltrating immune cell populations were estimated and correlated with the biomarkers. Finally, the characteristics of immune infiltration of NAGM from MS were evaluated. Results: A total of 98 DEGs were identified. They participated in sensory transduction of the olfactory system, synaptic signaling, and immune responses. Nine overlapping genes were screened by machine learning methods. After verified by ROC curve, four genes, namely HLA‒DRB1, RPS4Y1, EIF1AY and USP9Y, were screened as candidate biomarkers. The mRNA expression of RPS4Y1 and USP9Y was significantly lower in MS patients than that in the controls. They were selected as the robust diagnostic biomarkers for male MS patients. RPS4Y1 and USP9Y were both positively correlated with memory B cells. Moreover, naive CD4+ T cells and monocytes were increased in the NAGM of MS patients compared with those in controls. Conclusions: Low expressed Y‒linked genes, RPS4Y1 and USP9Y, were identified as diagnostic biomarkers for MS in male patients. The inhomogeneity of immune cells in NAGM might exacerbate intricate interplay between the CNS and the immune system in the MS.

The chromosome-level genome of the submerged plant Cryptocoryne crispatula provides insights into the terrestrial-freshwater transition in Araceae.

Plant terrestrialization (i.e. the transition to a terrestrial environment) is a significant evolutionary event that has been intensively studied. While certain plant lineages, particularly in angiosperms, have re-adapted to freshwater habitats after colonizing terrene, however, the molecular mechanism of the terrestrial-freshwater (T-F) transition remains limited. Here, the basal monocot Araceae was selected as the study object to explore the T-F transition adaptation mechanism by comparative genomic analysis. Our findings revealed that the substitution rates significantly increased in the lineage of freshwater Araceae, which may promote their adaptation to the freshwater habitat. Additionally, 20 gene sets across all four freshwater species displayed signs of positive selection contributing to tissue development and defense responses in freshwater plants. Comparative synteny analysis showed that genes specific to submerged plants were enriched in cellular respiration and photosynthesis. In contrast, floating plants were involved in regulating gene expression, suggesting that gene and genome duplications may provide the original material for plants to adapt to the freshwater environment. Our study provides valuable insights into the genomic aspects of the transition from terrestrial to aquatic environments in Araceae, laying the groundwork for future research in the angiosperm.

Exploring the genetic diversity and population structure of Ailanthus altissima using chloroplast and nuclear microsatellite DNA markers across its native range.

Understanding how anthropogenic disturbances affect the genetics of tree species is crucial; however, how tree populations in the wild can tolerate these activities remains unexplored. Given the ongoing and intensifying anthropogenic disturbances, we conducted a study using Ailanthus altissima to gain new insights into the effects of these pressures on genetic variability in undisturbed and disturbed forests. We analyzed the genetic diversity and population structure of A. altissima using nuclear (EST-SSR) and chloroplast (cpSSR) microsatellite markers. The genetic diversity across the 34 studied populations based on EST-SSRs was found to be moderate to high (nH E = 0.547-0.772) with a mean nH E of 0.680. Bayesian clustering, principal coordinate analysis (PCoA), and discriminant analysis of principal component (DAPC) consistently divided the populations into three distinct groups based on EST-SSRs. Allelic combinations of 92 different chloroplast size variants from 10 cpSSR loci resulted in a total of 292 chloroplast haplotypes. The mean haplotype diversity was relatively high (cpH E = 0.941), and the mean haplotype richness was 2.690, averaged across the 34 populations of A. altissima. Values of F ST in A. altissima from chloroplast and nuclear markers were 0.509 and 0.126, respectively. Modeling results showed evidence for population range contraction during the Last Glacial Maximum with subsequent population expansion in the Holocene and the future. Although genetic variation did not differ substantially across disturbed and undisturbed sites, there were small trends indicating higher genetic diversity and population bottlenecks in disturbed forests. As a result, disrupted ecosystems might display surprising genetic patterns that are difficult to predict and should not be overlooked.

Haplotype-resolved genome assembly provides insights into the evolution of S-locus supergene in distylous Nymphoides indica.

Distyly has evolved independently in numerous animal-pollinated angiosperm lineages. Understanding of its molecular basis has been restricted to a few species, primarily Primula. Here, we investigate the genetic architecture of the single diallelic locus (S-locus) supergene, a linkage group of functionally associated genes, and explore how it may have evolved in distylous Nymphoides indica, a lineage of flowering plants not previously investigated. We assembled haplotype-resolved genomes, used read-coverage-based genome-wide association study (rb-GWAS) to locate the S-locus supergene, co-expression network analysis to explore gene networks underpinning the development of distyly, and comparative genomic analyses to investigate the origins of the S-locus supergene. We identified three linked candidate S-locus genes - NinBAS1, NinKHZ2, and NinS1 - that were only evident in the short-styled morph and were hemizygous. Co-expression network analysis suggested that brassinosteroids contribute to dimorphic sex organs in the short-styled morph. Comparative genomic analyses indicated that the S-locus supergene likely evolved via stepwise duplications and has been affected by transposable element activities. Our study provides novel insight into the structure, regulation, and evolution of the supergene governing distyly in N. indica. It also provides high-quality genomic resources for future research on the molecular mechanisms underlying the striking evolutionary convergence in form and function across heterostylous taxa.

Prevalence and Characteristics of Hospital Nurse Leaders' Turnover Intention.

OBJECTIVE: This project aims to identify the prevalence of acute care nurse leader turnover intention and the contributing factors. BACKGROUND: Previous research has identified that nurse leaders often quit around 1 year after stepping into a leadership position. More in-depth investigations of the phenomenon are needed. METHODS: The 2018 National Sample Survey of Registered Nurses data were used in this quantitative, cross-sectional study. The sample of nurse leaders was drawn from survey participants. Characteristics of interest in this study were listed in the survey questionnaire and divided into 5 categories: education, primary nursing employment, race, marital status, and age. RESULTS: A total of 50 273 participants completed the survey. The final sample size of nurse leaders was 1310 based on the eligibility criteria. The characteristics of the nurse leaders with turnover intention were reported in the 5 previously identified categories. Age, federally assisted student loans, and hours worked in a typical week predicted turnover intention. Low dissatisfaction and ability to practice to the full extent of knowledge, education, and training were strongly associated with nurse leader turnover intention. CONCLUSIONS: The study findings contribute to a more in-depth discovery of the causes of nurse leader turnover and future interventional research.

Extraction of Silicon-Containing Nanoparticles from an Agricultural Soil for Analysis by Single Particle Sector Field and Time-of-Flight Inductively Coupled Plasma Mass Spectrometry.

The increased use of silica and silicon-containing nanoparticles (Si-NP) in agricultural applications has stimulated interest in determining their potential migration in the environment and their uptake by living organisms. Understanding the fate and behavior of Si-NPs will require their accurate analysis and characterization in very complex environmental matrices. In this study, we investigated Si-NP analysis in soil using single-particle ICP-MS. A magnetic sector instrument was operated at medium resolution to overcome the impact of polyatomic interferences (e.g., 14N14N and 12C16O) on 28Si determinations. Consequently, a size detection limit of 29 ± 3 nm (diameter of spherical SiO2 NP) was achieved in Milli-Q water. Si-NP were extracted from agricultural soil using several extractants, including Ca(NO3)2, Mg(NO3)2, BaCl2, NaNO3, Na4P2O7, fulvic acid (FA) and Na2H2EDTA. The best extraction efficiency was found for Na4P2O7, for which the size distribution of Si-NP in the leachates was well preserved for at least one month. On the other hand, Ca(NO3)2, Mg(NO3)2 and BaCl2 were relatively less effective and generally led to particle agglomeration. A time-of-flight ICP-MS was also used to examine the nature of the extracted Si-NP on a single-particle basis. Aluminosilicates accounted for the greatest number of extracted NP (~46%), followed by NP where Si was the only detected metal (presumably SiO2, ~30%).

Supramolecular assemblies with spatio-temporal sequential drug delivery capability treat spinal cord injury via neuroprotection and immunoregulation.

Spinal cord injury (SCI) can result in irreversible motor and sensory deficits. However, up to data, clinical first-line drugs have ambiguous benefits and debilitating side effects, mainly due to the insufficient accumulation, poor physiological barrier penetration, and lack of spatio-temporal controlled release at lesion tissue. Herein, we proposed a supramolecular assemblies composed of hyperbranched polymer-formed core/shell structure through host-guest interactions. Such HPAA-BM@CD-HPG-C assemblies co-loaded with p38 inhibitor (SB203580) and insulin-like growth factor 1(IGF-1) are able to achieve time- and space-programmed sequential delivery benefiting from their cascaded responsiveness. The core-shell disassembly of HPAA-BM@CD-HPG-C occurs in acidic micro-environment around lesion, achieving preferentially the burst release of IGF-1 to protect survival neurons. Subsequently, the HPAA-BM cores containing SB203580 are endocytosed by the recruited macrophages and degraded by intracellular GSH, accelerating the release of SB203580 to promote the conversion from M1 to M2 macrophage. Hence, the successive synergy of neuroprotection and immunoregulation effects contribute to subsequent nerve repair and locomotor recovery as demonstrated in vitro and in vivo studies. Thus, our fabrication provides a strategy that multiple drugs co-delivery in a spatio-temporal selective manner adapting to the disease progression through self-cascaded disintegration, are expected to realize multidimensional precise treatment of SCI.

Reference genome of California walnut, Juglans californica, and resemblance with other genomes in the order Fagales.

Juglans californica, California walnut, is a vulnerable small tree that is locally abundant but restricted to woodland and chaparral habitats of Southern California threatened by urbanization and land use change. This species is the dominant species in a unique woodland ecosystem in California. It is one of 2 endemic California walnut species (family Juglandaceae). The other species, Northern California black walnut (J. hindsii), has been suggested controversially to be a variety of J. californica. Here, we report a new, chromosome-level assembly of J. californica as part of the California Conservation Genomics Project (CCGP). Consistent with the CCGP common methodology across ~150 genomes, we used Pacific Biosciences HiFi long reads and Omni-C chromatin-proximity sequencing technology to produce a de novo assembled genome. The assembly comprises 137 scaffolds spanning 551,065,703 bp, has a contig N50 of 30 Mb, a scaffold N50 of 37 Mb, and BUSCO complete score of 98.9%. Additionally, the mitochondrial genome has 701,569 bp. In addition, we compare this genome with other existing high-quality Juglans and Quercus genomes, which are in the same order (Fagales) and show relatively high synteny within the Juglans genomes. Future work will utilize the J. californica genome to determine its relationship with the Northern California walnut and assess the extent to which these 2 endemic trees might be at risk from fragmentation and/or climate warming.

Mesoporous polydopamine delivering 8-gingerol for the target and synergistic treatment to the spinal cord injury.

In the treatment of spinal cord injury (SCI), the complex process of secondary injury is mainly responsible for preventing SCI repair or even exacerbating the injury. In this experiment, we constructed the 8-gingerol (8G)-loaded mesoporous polydopamine (M-PDA), M@8G, as the in vivo targeting nano-delivery platform, and investigated the therapeutic effects of M@8G in secondary SCI and its related mechanisms. The results indicated that M@8G could penetrate the blood-spinal cord barrier to enrich the spinal cord injury site. Mechanism research has shown that all of the M-PDA,8G and M@8G displayed the anti-lipid peroxidation effect, and then M@8G can inhibit the secondary SCI by suppressing the ferroptosis and inflammation. In vivo assays showed that M@8G significantly diminished the local injury area, reduced axonal and myelin loss, thus improving the neurological and motor recovery in rats. Based on the analysis of cerebrospinal fluid samples from patients, ferroptosis occurred locally in SCI and continued to progress in patients during the acute phase of SCI as well as the stage after their clinical surgery. This study showcases effective treatment of SCI through the aggregation and synergistic effect of M@8G in focal areas, providing a safe and promising strategy for the clinical treatment of SCI.

Transcription factor TOX maintains the expression of Mst1 in controlling the early mouse NK cell development.

Rationale: TOX is a DNA-binding factor required for the development of multiple immune cells and the formation of lymph nodes. However, the temporal regulation mode of TOX on NK cell development and function needs to be further explored. Methods: To investigate the role of TOX in NK cells at distinct developmental phases, we deleted TOX at the hematopoietic stem cell stage (Vav-Cre), NK cell precursor (CD122-Cre) stage and late NK cell developmental stage (Ncr1-Cre), respectively. Flow cytometry was used to detect the development and functional changes of NK cell when deletion of TOX. RNA-seq was used to assess the differences in transcriptional expression profile of WT and TOX-deficient NK cells. Published Chip-seq data was exploited to search for the proteins directly interact with TOX in NK cells. Results: The deficiency of TOX at the hematopoietic stem cell stage severely retarded NK cell development. To a less extent, TOX also played an essential role in the physiological process of NKp cells differentiation into mature NK cells. Furthermore, the deletion of TOX at NKp stage severely impaired the immune surveillance function of NK cells, accompanied by down-regulation of IFN-γ and CD107a expression. However, TOX is dispensable for mature NK cell development and function. Mechanistically, by combining RNA-seq data with published TOX ChIP-seq data, we found that the inactivation of TOX at NKp stage directly repressed the expression of Mst1, an important intermediate kinase in Hippo signaling pathway. Mst1 deficient at NKp stage gained the similar phenotype with Toxfl/flCD122Cre mice. Conclusion: In our study, we conclude that TOX coordinates the early mouse NK cell development at NKp stage by maintaining the expression of Mst1. Moreover, we clarify the different dependence of the transcription factor TOX in NK cells biology.

Prevalence, correlates, and network analysis of depression and its association with quality of life in survivors with myocardial infarction during the COVID-19 pandemic.

BACKGROUND: Depression is common among myocardial infarction (MI) survivors and is strongly associated with poor quality of life (QOL). The aim of this study was to examine the prevalence, correlates and the network structure of depression, and its association with QOL in MI survivors during the COVID-19 pandemic. METHODS: This cross-sectional study evaluated depression and QOL in MI survivors with the Chinese version of the nine-item Patient Health Questionnaire (PHQ-9) and the World Health Organization Quality of Life-BREF (WHOQOL-BREF), respectively. Univariable analyses, multivariable analyses, and network analyses were performed. RESULTS: The prevalence of depression (PHQ-9 total score ≥ 5) among 565 MI survivors during the COVID-19 pandemic was 38.1 % (95 % CI: 34.1-42.1 %), which was significantly associated with poor QOL. Patients with depression were less likely to consult a doctor regularly after discharge, and more likely to experience more severe anxiety symptoms and fatigue. Item PHQ4 "Fatigue" was the most central symptom in the network, followed by PHQ6 "Guilt" and PHQ2 "Sad mood". The flow network showed that PHQ4 "Fatigue" had the highest negative association with QOL. CONCLUSION: Depression was prevalent among MI survivors during the COVID-19 pandemic and was significantly associated with poor QOL. Those who failed to consult a doctor regularly after discharge or reported severe anxiety symptoms and fatigue should be screened for depression. Effective interventions for MI survivors targeting central symptoms, especially fatigue, are needed to reduce the negative impact of depression and improve QOL.