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Background Castor bean ( Ricinus communis L.) is an important oil crop, which belongs to the Euphorbiaceae family. The seed oil of castor bean is currently the only commercial source of ricinoleic acid that can be used for producing about 2000 industrial products. However, it remains largely unknown regarding the origin, domestication, and the genetic basis of key traits of castor bean. Results Here we perform a de novo chromosome-level genome assembly of the wild progenitor of castor bean. By resequencing and analyzing 505 worldwide accessions, we reveal that the accessions from East Africa are the extant wild progenitors of castor bean, and the domestication occurs ~ 3200 years ago. We demonstrate that significant genetic differentiation between wild populations in Kenya and Ethiopia is associated with past climate fluctuation in the Turkana depression ~ 7000 years ago. This dramatic change in climate may have caused the genetic bottleneck in wild castor bean populations. By a genome-wide association study, combined with quantitative trait locus analysis, we identify important candidate genes associated with plant architecture and seed size. Conclusions This study provides novel insights of domestication and genome evolution of castor bean, which facilitates genomics-based breeding of this important oilseed crop and potentially other tree-like crops in future.

Background Malania oleifera Chun et Lee (Olacaceae), an evergreen broad-leaved woody tree native to southwest China, is an important oilseed tree. Its seed oil has a high level of nervonic acid (cis-tetracos-15-enoic acid, over 60%), which is essential for human health. M. oleifera seed oil is a promising source of nervonic acid, but little is known about the physiological and molecular mechanisms underlying its biosynthesis. Results In this study, we recorded oil accumulation at four stages of seed development. Using a high-throughput RNA-sequencing technique, we obtained 55,843 unigenes, of which 29,176 unigenes were functionally annotated. By comparison, 22,833 unigenes had a two-fold or greater expression at the fast oil accumulation stage than at the initial stage. Of these, 198 unigenes were identified as being functionally involved in diverse lipid metabolism processes (including de novo fatty acid synthesis, carbon chain elongation and modification, and triacylglycerol assembly). Key genes (encoding KCS, KCR, HCD and ECR), putatively responsible for nervonic acid biosynthesis, were isolated and their expression profiles during seed development were confirmed by quantitative real-time PCR analysis. Also, we isolated regulatory factors (such as WRI1, ABI3 and FUS3) that are putatively involved in the regulation of oil biosynthesis and seed development. Conclusion Our results provide novel data on the physiological and molecular mechanisms of nervonic acid biosynthesis and oil accumulation in M. oleifera seeds, and will also serve as a starting point for biotechnological genetic engineering for the production of nervonic acid resources.

Infants and toddlers with mild traumatic brain injury (mTBI) and minor subdural hematoma (SDH) were found to have a higher risk of requiring neurosurgical intervention (NI). However, the ability to identify patients with mTBI and minor SDH who require NI remains limited. This study aims to develop a nomogram to predict NI in these patients. A nomogram predicting NI was established using demographic, clinical, radiographic, and laboratory data from patients with mTBI and minor SDH. The least absolute shrinkage and selection operator (LASSO) regression and best subsets regression (BSR) methods were employed to identify variables and select predictive factors. A nomogram was constructed using multivariable logistic regression. The model’s performance was evaluated using the area under the receiver operating characteristic curve, calibration curves, the Hosmer–Lemeshow test, and decision curve analysis. Immediate seizures, anemia, and subarachnoid space depth were identified as significant predictive factors by the BSR, leading to the development of a nomogram. The AUC for this nomogram, obtained through bootstrap validation (resampling = 500), was 0.893 (95% CI, 0.844–0.942). The model demonstrated good calibration, and decision curve analysis showed that when the threshold probability ranged from 7 to 83%, using the nomogram to predict NI provided a net benefit. A novel nomogram has been developed to accurately assess the risk of NI in children under 3 years of age with mTBI and minor SDH, potentially aiding in clinical decision-making.

The LATERAL ORGAN BOUNDARIES DOMAIN (LBD) gene family has been well-studied in Arabidopsis and play crucial roles in the diverse growth and development processes including establishment and maintenance of boundary of developmental lateral organs. In this study we identified and characterized 38 LBD genes in Lotus japonicus (LjLBD) and 57 LBD genes in Medicago truncatula (MtLBD), both of which are model legume plants that have some specific development features absent in Arabidopsis. The phylogenetic relationships, their locations in the genome, genes structure and conserved motifs were examined. The results revealed that all LjLBD and MtLBD genes could be distinctly divided into two classes: Class I and II. The evolutionary analysis showed that Type I functional divergence with some significantly site-specific shifts may be the main force for the divergence between Class I and Class II. In addition, the expression patterns of LjLBD genes uncovered the diverse functions in plant development. Interestingly, we found that two LjLBD proteins that were highly expressed during compound leaf and pulvinus development, can interact via yeast two-hybrid assays. Taken together, our findings provide an evolutionary and genetic foundation in further understanding the molecular basis of LBD gene family in general, specifically in L. japonicus and M. truncatula.

Background Glioblastoma (GBM) is a relatively prevalent primary tumor of the central nervous system in children, characterized by its high malignancy and mortality rates, along with the intricate challenges of achieving complete surgical resection. Recently, an increasing number of studies have focused on the crucial role of super-enhancers (SEs) in the occurrence and development of GBM. This study embarks on the task of evaluating the effectiveness of MZ1, an inhibitor of BRD4 meticulously designed to specifically target SEs, within the intricate framework of GBM. Methods The clinical data of GBM patients was sourced from the Chinese Glioma Genome Atlas (CGGA) and the Gene Expression Profiling Interactive Analysis 2 (GEPIA2), and the gene expression data of tumor cell lines was derived from the Cancer Cell Line Encyclopedia (CCLE). The impact of MZ1 on GBM was assessed through CCK-8, colony formation assays, EdU incorporation analysis, flow cytometry, and xenograft mouse models. The underlying mechanism was investigated through RNA-seq and ChIP-seq analyses. Results In this investigation, we made a noteworthy observation that MZ1 exhibited a substantial reduction in the proliferation of GBM cells by effectively degrading BRD4. Additionally, MZ1 displayed a notable capability in inducing significant cell cycle arrest and apoptosis in GBM cells. These findings were in line with our in vitro outcomes. Notably, MZ1 administration resulted in a remarkable decrease in tumor size within the xenograft model with diminished toxicity. Furthermore, on a mechanistic level, the administration of MZ1 resulted in a significant suppression of pivotal genes closely associated with cell cycle regulation and epithelial-mesenchymal transition (EMT). Interestingly, our analysis of RNA-seq and ChIP-seq data unveiled the discovery of a novel prospective oncogene, SDC1, which assumed a pivotal role in the tumorigenesis and progression of GBM. Conclusion In summary, our findings revealed that MZ1 effectively disrupted the aberrant transcriptional regulation of oncogenes in GBM by degradation of BRD4. This positions MZ1 as a promising candidate in the realm of therapeutic options for GBM treatment.

• In most legumes, two typical features found in leaves are diverse compound forms and the pulvinus-driven nyctinastic movement. Many genes have been identified for leaf-shape determination, but the underlying nature of leaf movement as well as its association with the compound form remains largely unknown. • Using forward-genetic screening and whole-genome resequencing, we found that two allelic mutants of Medicago truncatula with unclosed leaflets at night were impaired in MtDWARF4A (MtDWF4A), a gene encoding a cytochrome P450 protein orthologous to Arabidopsis DWARF4. • The mtdwf4a mutant also had a mild brassinosteroid (BR)-deficient phenotype bearing pulvini without significant deficiency in organ identity. Both mtdwf4a and dwf4 could be fully rescued by MtDWF4A, and mtdwf4a could close their leaflets at night after the application of exogenous 24-epi-BL. Surgical experiments and genetic analysis of double mutants revealed that the failure to exhibit leaf movement in mtdwf4a is a consequence of the physical obstruction of the overlapping leaflet laminae, suggesting a proper geometry of leaflets is important for their movement in M. truncatula. • These observations provide a novel insight into the nyctinastic movement of compound leaves, shedding light on the importance of open space for organ movements in plants.

Glioblastoma multiforme (GBM) is one of the most malignant primary tumors in humans. Despite standard therapeutic strategy with tumor resection combined with radiochemotherapy, the prognosis remains disappointed. Recently, deubiquitinating enzymes (DUBs) has been reported as potential cancer therapy targets due to their multifunctions involved in the regulation of tumorigenesis, cell cycle, apoptosis, and autophagy. In this study, we found that knockdown of ubiquitin specific protease (USP5), a family member of DUB, could significantly suppress GBM cell line U251 and DBTRG-05MG proliferation and colony formation by inducing cell cycle G1/S arrest, which was correlated with downregulation of CyclinD1 protein level. CyclinD1 had been reported to play a critical role in the tumorigenesis and development of GBM via regulating cell cycle transition. Overexpression of USP5 could significantly extend the half-life of CyclinD1, while knockdown of USP5 decreased the protein level of CyclinD1, which could be restored by proteasome inhibitor MG-132. Indeed, USP5 was found to directly interact with CyclinD1, and decrease its K48-linked polyubiquitination level. Furthermore, knockdown of USP5 in U251 cells remarkably inhibited tumor growth in vivo . Taken together, these findings demonstrate that USP5 plays a critical role in tumorigenesis and progression of GBM by stabilizing CyclinD1 protein. Targeting USP5 could be a potential therapeutic strategy for GBM.

Background The relationship between lipid profiles and intracranial hemorrhage (ICH) has garnered increasing attention. The ratio of low-density lipoprotein to high-density lipoprotein (LHR) is one of the key lipid profile indices. However, studies investigating the association between LHR and the prognosis of critically ill ICH patients remain limited. Methods Data for this study were obtained from the MIMIC-IV 3.1 database. Initially, the association between LHR and short-term outcomes in ICH patients, including ICU mortality, in-hospital mortality, and 28-day mortality, was analyzed using Cox regression in both continuous and categorical models. Additionally, restricted cubic spline (RCS), subgroup, and sensitivity analyses were conducted to further validate our findings. Results The study included 873 critically ill ICH patients, among whom 20.3% (177/873) succumbed within 28 days. Higher LHR was independently associated with lower short-term mortality in ICH patients (28-day mortality: HR = 0.82, 95% CI: 0.68 ~ 0.99, P  = 0.039; In-hospital mortality: HR = 0.7, 95% CI: 0.55 ~ 0.89, P  = 0.004; ICU mortality: HR = 0.66, 95% CI: 0.48 ~ 0.92, P  = 0.015). The RCS revealed a linear relationship between LHR and short-term all-cause mortality. Subgroup analyses demonstrated consistent results. The optimal cutoff value for LHR was determined to be 1.21. Comparing the mortality risk between the low-LHR and high-LHR groups, the high-LHR group exhibited higher survival rates (28-day mortality, P  = 0.0052; In-hospital mortality, P  = 0.019; ICU mortality, P  = 0.044). Furthermore, higher LHR was also correlated with lower disease severity scores (SAPS-II: r = -0.158, P  < 0.001, OASIS: r = -0.117, P  = 0.006). Conclusion LHR was negatively associated with short-term mortality in critically ill ICH patients. It may aid clinicians in identifying high-risk individuals and providing timely interventions.

Background An increased incidence of brain abscesses was observed post-COVID-19 pandemic. However, it remains unclear how the COVID-19 pandemic influenced the epidemiology of brain abscesses. This study aimed to investigate changes in the epidemiology of brain abscesses pre- and post-COVID-19 pandemic. Methods A retrospective study of demographic, clinical, radiological, and laboratory characteristics of patients with brain abscesses in Children's Hospital of Soochow University from 2015–2023 was performed. Results A total of 34 patients were admitted to the hospital during the study. The post-COVID-19 cohort had an average of 5.5 cases/year, which is a 129.2% increase compared to the pre-COVID-19 cohort's average of 2.4 cases/year. Additionally, the rates of fever upon admission (86.36% vs 50%, p  = 0.04) and experiencing high-grade fever within 6 weeks before admission (40.91% vs 8.33%, p  = 0.044) were significantly increased. A potential rise in the rate of intensive care unit admission was observed (36.36% vs 8.33%, p  = 0.113). The average value of globulin in the post-COVID cohort was significantly higher compared to the pre-COVID cohort (31.60 ± 5.97 vs 25.50 ± 5.08, p  = 0.009). Streptococcal infections were the predominant cause of brain abscesses in both cohorts (40% vs 43.75%, p  = 0.57). Conclusions There was a significant increase in the number of brain abscess patients after the COVID-19 pandemic. This underscores the importance of children receiving the streptococcal vaccine.

The development of ω -3 fatty acid-rich vegetable oils is essential to enrich the production of functional foods. Sacha Inchi ( Plukenetia volubilis L.) is a unique oilseed crop with much potential. Its seeds contain rich polyunsaturated fatty acids (PUFAs), especially linoleic acid (LA, C18:2) and α -linolenic acid (ALA, C18:3). Endoplasmic reticulum -located ω -6 and ω -3 fatty acid desaturases (FAD) are responsible for the biosynthesis of LA and ALA, respectively, in plant seeds. Here, we isolated two full-length FAD genes from Sacha Inchi, named PvFAD2 and PvFAD3 , which encoded predicted amino acid residues of 384 and 379 in protein, respectively. Protein sequence and subcellular localization analysis revealed that they were located in the endoplasmic reticulum (ER). Heterologous expression in Saccharomyces cerevisiae confirmed that PvFAD2 and PvFAD3 could catalyze LA and ALA synthesis, respectively. The stability and catalytic efficiency of the PvFAD3 protein may be closely related to temperature. In transgenic tobacco, using seed-specific expression promoters, PvFAD2 and PvFAD3 significantly promotes the production of LA (from 68% to 70.5%) and ALA (from 0.7% to 3.1%) in seed oil. These results show that PvFAD2 and PvFAD3 do, indeed, function as crucial enzymes for PUFAs biosynthesis, and provide a key gene source for the sustainable production of lipids with tailored fatty acid compositions via genetic engineering in other oil crops.