Post-hybridization introgression and natural selection promoted genomic divergence of Aegilops speltoides and the four S*-genome diploid species.

Understanding how different driving forces have promoted biological divergence and speciation is one of the central issues in evolutionary biology. The Triticum/Aegilops species complex contains 13 diploid species belonging to the A-, B- and D-lineages and offers an ideal system to address the evolutionary dynamics of lineage fusion and splitting. Here, we sequenced the whole genomes of one S-genome species (Aegilops speltoides) of the B-lineage and four S*-genome diploid species (Aegilops bicornis, Aegilops longissima, Aegilops sharonensis and Aegilops searsii) of the D-lineage at the population level. We performed detailed comparisons of the five species and with the other four representative A-, B- and D-lineage species. Our estimates identified frequent genetic introgressions from A- and B-lineages to the D-lineage species. A remarkable observation is the contrasting distributions of putative introgressed loci by the A- and B-lineages along all the seven chromosomes to the extant D-lineage species. These genetic introgressions resulted in high levels of genetic divergence at centromeric regions between Ae. speltoides (B-lineage) and the other four S*-genome diploid species (D-lineage), while natural selection is a potential contributor to divergence among the four S*-genome species at telomeric regions. Our study provides a genome-wide view on how genetic introgression and natural selection acted together yet chromosome-regionally divided to promote genomic divergence among the five S- and S*-genome diploid species, which provides new and nuanced insights into the evolutionary history of the Triticum/Aegilops species complex.

Decreased RNA-binding protein heterogeneous nuclear ribonucleoprotein U improves multiple myeloma sensitivity to lenalidomide.

Multiple myeloma (MM) is an incurable plasma cell cancer in the bone marrow. Immunomodulatory drugs, such as lenalidomide (LEN) and pomalidomide, are backbone agents in MM treatment, and LEN resistance is commonly seen in the MM clinic. In this study, we presented that heterogeneous nuclear ribonucleoprotein U (hnRNPU) affected MM resistance to LEN via the regulation of target mRNA translation. hnRNPULow MM cells exhibited upregulated CRBN and IKZF1 proteins, stringent IKZF1/3 protein degradation upon LEN addition and increased sensitivity to LEN. RNA pulldown assays and RNA electrophoretic mobility shift assays revealed that hnRNPU bound to the 3'-untranslated region of CRBN and IKZF1 mRNA. A sucrose gradient assay suggested that hnRNPU specifically regulated CRBN and IKZF1 mRNA translation. The competition of hnRNPU binding to its target mRNAs by small RNAs with hnRNPU-binding sites restored MM sensitivity to LEN. hnRNPU function in vivo was confirmed in an immunocompetent MM mouse model constructed by the inoculation of Crbn-humanized murine 5TGM1 cells into CrbnI391V/+ mice. Overall, this study suggests a novel mechanism of LEN sensitivity in which hnRNPU represses CRBN and IKZF1 mRNA translation.

Single-cell sequencing reveals the correlation of aggrephagy signaling and multiple myeloma immune microenvironment composition.

Aggrephagy, a type of autophagy, degrades the aggregation of misfolded protein in cells. However, the role of aggrephagy in multiple myeloma (MM) has not been fully demonstrated. In this study, we first investigated the correlation between aggrephagy signaling, MM immune microenvironment composition and disease prognosis. Single-cell RNA-seq data, including the expression profiles of 12,187 single cells from seven MM bone marrow (BM) and seven healthy BM samples, were analyzed by non-negative matrix factorization for 44 aggrephagy-related genes. Bulk RNA-seq cohorts from the Gene Expression Omnibus database were used to evaluate the prognostic value of aggrephagy-related immune cell subtypes and predict immune checkpoint blockade immunotherapeutic response in MM. Compared with healthy BM, MM BM exhibited different patterns of aggrephagy-related gene expression. In MM BM, macrophages, CD8+ T cells, B cells and natural killer cells could be grouped into four to nine aggrephagy-related subclusters. The signature of aggrephagy signaling molecule expression in the immune cells correlates with the patient's prognosis. Our investigation provides a novel view of aggrephagy signaling in MM tumor microenvironment cells, which might be a prognostic indicator and potential target for MM treatment.

Histone methyltransferase KMT5C drives liver cancer progression and directs therapeutic response to PARP inhibitors.

BACKGROUND AND AIMS: Epigenetic plasticity is a major challenge in cancer-targeted therapy. However, the molecular basis governing this process has not yet been clearly defined. Despite the considerable success of poly(ADP-ribose) polymerase inhibitors (PARPi) in cancer therapy, the limited response to PARPi, especially in HCC, has been a bottleneck in its clinical implications. Herein, we investigated the molecular basis of the histone methyltransferase KMT5C (lysine methyltransferase 5C) that governs PARPi sensitivity and explored a potential therapeutic strategy for enhancing PARPi efficacy. APPROACH AND RESULTS: We identified KMT5C, a trimethyltransferase of H4K20, as a targetable epigenetic factor that promoted liver tumor growth in mouse de novo MYC/Trp53-/- and xenograft liver tumor models. Notably, induction of KMT5C by environmental stress was crucial for DNA repair and HCC cell survival. Mechanistically, KMT5C interacted with the pivotal component of homologous recombination repair, RAD51, and promoted RAD51/RAD54 complex formation, which was essential for the activation of dsDNA breaks repair. This effect depended on the methyltransferase activity of KMT5C. We further demonstrated that the function of KMT5C in promoting HCC progression was dependent on RAD51. Importantly, either a pharmacological inhibitor (A196) or genetic inhibition of KMT5C sensitized liver cancer cells to PARPi. CONCLUSIONS: KMT5C played a vital role in promoting liver cancer progression by activating the DNA repair response. Our results revealed a novel therapeutic approach using the KMT5C inhibitor A196, concurrent with olaparib, as a potential HCC therapy.

Structural damage in the C. elegans epidermis causes release of STA-2 and induction of an innate immune response.

The epidermis constantly encounters invasions that disrupt its architecture, yet whether the epidermal immune system utilizes damaged structures as danger signals to activate self-defense is unclear. Here, we used a C. elegans epidermis model in which skin-penetrating infection or injury activates immune defense and antimicrobial peptide (AMP) production. By systemically disrupting each architectural component, we found that only disturbance of the apical hemidesmosomes triggered an immune response and robust AMP expression. The epidermis recognized structural damage through hemidesmosomes associated with a STAT-like protein, whose disruption led to detachment of STA-2 molecules from hemidesmosomes and transcription of AMPs. This machinery enabled the epidermis to bypass certain signaling amplification and directly trigger AMP production when subjected to extensive architectural damage. Together, our findings uncover an evolutionarily conserved mechanism for the epithelial barriers to detect danger and activate immune defense.

Reliable Determination of Contact Angle from the Liquid Fence.

Traditional methods of measuring contact angles often face difficulties in precisely defining the three-phase contact points. A novel method for accurately defining three-phase contact points based on liquid fences is proposed in this article. The tested liquid is placed in a cubic liquid fence composed of a pair of narrow strips of the tested solid and a pair of transparent wide strips. The transparent wide strip serves as the measurement window, and the surface tension of the liquid on it can be almost ignored. In experimental measurements, the horizontal coordinates of the end points of the liquid profile are fixed by the liquid fence, thus determining the horizontal coordinates of the three-phase contact points, which helps to accurately survey the contact angle. Additionally, since the parameters of the liquid fence are known, the size of the contact angle can also be calculated by measuring the height of the liquid level dome inside the liquid fence. Using the electric wetting effect as an example, we experimentally extracted a series of liquid contour maps with circular tops and square columns under varying voltages. The relationship curve between contact angle and voltage variation was obtained using the above methods, and a contact angle variation tendency seemed to agree well with the theoretical value.

Feasibility Analysis of Individualized Low Flow Rate Abdominal Contrast-Enhanced Computed Tomography in Chemotherapy Patients: Dual-Source Computed Tomography With Low Tube Voltage.

PURPOSE: The aim of the study is to investigate the feasibility of using dual-source computed tomography (CT) combined with low flow rate and low tube voltage for postchemotherapy image assessment in cancer patients. METHODS: Ninety patients undergoing contrast-enhanced CT scans of the upper abdomen were prospectively enrolled and randomly assigned to groups A, B, and C (n = 30 each). In group A, patients underwent scans at 120 kVp with 448 mgI/kg. Patients in group B underwent scans at 100 kVp with 336 mgI/kg. Patient in group C underwent scans at 70 kVp with of 224 mgI/kg. Quantitative measurements including the CT number, standard deviation of CT number, signal-to-noise ratio, contrast-to-noise ratio, subjective reader scores, and the volume and flow rate of contrast agent were evaluated for each group. RESULTS: There was no statistically significant difference in the subjective image scores within the three groups except for the kidney (all P > 0.05). Group C showed significantly higher CT values, lower noise levels, and higher signal-to-noise ratio and contrast-to-noise ratio values in the majority of the regions of interest compared to the other groups (P < 0.05). In group C, the contrast agent dose was decreased by 46% compared to group A (79.48 ± 12.24 vs 42.7 ± 8.6, P < 0.01), and the contrast agent injection rate was reduced by 22% (2.7 ± 0.41 vs 2.1 ± 0.4, P < 0.01). CONCLUSIONS: The use of 70 kVp tube voltage combined with low iodine flow rates prove to be a more effective approach in solving the challenge of compromised blood vessels in postchemotherapy tumor patients, without reducing image quality and diagnostic confidence.

The role of monocyte/macrophage chemokines in pathogenesis of osteoarthritis: A review.

Osteoarthritis (OA) is one of the most common degenerative diseases characterised by joint pain, swelling and decreased mobility, with its main pathological features being articular synovitis, cartilage degeneration and osteophyte formation. Inflammatory cytokines and chemokines secreted by activated immunocytes can trigger various inflammatory and immune responses in articular cartilage and synovium, contributing to the genesis and development of OA. A series of monocyte/macrophage chemokines, including monocyte chemotaxis protein (MCP)-1/CCL2, MCP2/CCL8, macrophage inflammatory protein (MIP)-1α/CCL3, MIP-1ß/CCL4, MIP-3α/CCL20, regulated upon activation, normal T-cell expressed and secreted /CCL5, CCL17 and macrophage-derived chemokine/CCL22, was proven to transmit cell signals by binding to G protein-coupled receptors on recipient cell surface, mediating and promoting inflammation in OA joints. However, the underlying mechanism of these chemokines in the pathogenesis of OA remains still elusive. Here, published literature was reviewed, and the function and mechanisms of monocyte/macrophage chemokines in OA pathogenesis were summarised. The symptoms and disease progression of OA were found to be effectively alleviated when the expression of these chemokines is inhibited. Elucidating these mechanisms could contribute to further understand how OA develops and provide potential targets for the early diagnosis of arthritis and drug treatment to delay or even halt OA progression.

Efficacy and safety of topical minocycline foam (FMX101 4%) in treatment of Chinese subjects with moderate-to-severe facial acne vulgaris: A phase 3, multi-centre, randomized, double-blind, vehicle-controlled study.

BACKGROUND: FMX101 4%, as a topical foam formulation of minocycline, has been approved by US Food and Drug Administration for the treatment of moderate-to-severe acne vulgaris (AV). OBJECTIVE: To evaluate the efficacy and safety of FMX101 4% in treating Chinese subjects with moderate-to-severe facial AV. METHODS: This was a multi-centre, randomized, double-blind, vehicle-controlled phase 3 study in Chinese subjects with moderate-to-severe AV. Eligible subjects were randomized 2:1 to receive either FMX101 4% or vehicle foam treatment for 12 weeks. The primary efficacy endpoint was the change in inflammation lesion count (ILC) from baseline at week 12. The key secondary endpoint was the treatment success rate according to Investigator's Global Assessment (IGA) at week 12. RESULTS: In total, 372 subjects were randomized into two groups (FMX101 4% group, n = 248; vehicle group, n = 124). After 12 weeks treatment, the reduction in ILC from baseline was statistically significant in favour of FMX101 4%, compared with vehicle foam (-21.0 [0.08] vs. -12.3 [1.14]; LSM [SE] difference, -8.7 [1.34]; 95% CI [-11.3, -6.0]; p < 0.001). FMX101 4% treatment yielded significantly higher IGA treatment success rate at week 12 as compared to the control treatment (8.06% vs. 0%). Applying FMX101 4% also resulted in significant reduction in noninflammatory lesion count (nILC) versus vehicle foam at week 12 (-19.4 [1.03] vs. -14.9 [1.47]; LSM [SE] difference, -4.5 [1.74]; 95% CI [-8.0, -1.1]; p = 0.009). Most treatment-emergent adverse events (TEAEs) were mild-to-moderate in severity, and no treatment-related treatment-emergent serious adverse event (TESAE) occurred. Thus, FMX101 4% was considered to be a safe and well-tolerated product during the 12-week treatment period. CONCLUSION: FMX101 4% treatment for 12 weeks could lead to significantly reduced ILC and nILC, and improved IGA treatment success rate in Chinese subjects with moderate-to-severe facial AV. It also showed a well acceptable safe and tolerability profile.

Safety and feasibility of single-port nephroscopy combined with a needle electrode technique to treat dorsal SRCs.

Objective The aim of this study was to explore the safety and feasibility of single-port nephroscopy combined with a needle electrode technique to unroof single dorsal simple renal cysts (SRCs). Methods This was a retrospective analysis of the clinical data for 18 patients with single dorsal SRCs treated with single-port nephroscopy and a needle electrode technique at Zhongshan City People's Hospital from August 2021 to August 2022. The basic information included the cyst condition, surgical methods and recurrence rate, and follow-up was conducted with CT imaging. Results The surgery was successful in all 18 patients. The duration of surgery ranged from 24-46 minutes, with an average of 35.83±1.62 minutes; the intraoperative bleeding volume ranged from 2-20 ml, with an average of 9.0±1.3 ml; and the visual analog scale (VAS) score within 24 hours after surgery ranged from 1-6 points, with an average of 2.72±0.36 points. There were no significant postoperative complications, such as bleeding, urinary fistula, or infection. All drainage tubes were removed on the first day after surgery. After 1 year of postoperative follow-up, one patient experienced recurrence, for a recurrence rate of 5.6%. Conclusion Single-port nephroscopy combined with a needle electrode technique is a safe, feasible, and effective minimally invasive surgical approach for treating single dorsal SRCs.

Dendrobium Nobile Alcohol Extract Extends the Lifespan of Caenorhabditis elegans via hsf-1 and daf-16.

Dendrobium nobile is a traditional Chinese herb with anti-inflammatory, antioxidant, and neuroprotective properties. However, its antiaging effects are unclear. Herein, we studied the aging-related functions and the mechanism of action of the alcohol extract of Dendrobium nobile (DnAE) in the model organism Caenorhabditis elegans. The results indicated that 1 mg/mL DnAE slowed lipofuscin accumulation, decreased the levels of reactive oxygen species, elevated superoxide dismutase activity, enhanced oxidative and heat stress resistance, extended the lifespan of nematodes, protected their dopamine neurons from 6-hydroxydopamine-induced neurodegeneration, and reduced Aß-induced neurotoxicity. DnAE upregulated the mRNA expression of the transcription factors DAF-16 and HSF-1, promoted the nuclear localization of DAF-16, and enhanced the fluorescence intensity of HSP-16.2. However, it had no effect on the lifespan of DAF-16 mutants. Thus, DnAE can significantly extend lifespan, enhance heat stress tolerance, and delay age-related diseases through a DAF-16-dependent pathway.

A retrospective analysis of comorbidities in patients with psoriasis at a single centre.

Introduction: Psoriasis is a chronic inflammatory disease occurring worldwide. It is currently considered a multi-system disease, which is associated with several comorbidities. Aim: To deeply understand the clinical characteristics of psoriasis comorbidities and explore the relationship between psoriasis comorbidities, different subtypes and related influencing factors. Material and methods: This retrospective study analysed data from the electronic inpatient medical record system of dermatology and non-dermatology departments at a tertiary hospital in China. We collected relevant demographic data and clinical features of all patients diagnosed with psoriasis from January 2013 to September 2023. Results: This study ultimately included a total of 1097 patients with psoriasis. Psoriasis vulgaris was the most common among the subtypes of psoriasis, with 957 (87.2%) cases. The sample consisted of 65.6% of males and 34.4% of females, with an average age of 53.5 ±15.2 years. Common comorbidities of psoriasis included hypertension (38.2%), hyperlipidaemia (29.4%), type 2 diabetes mellitus (24.6%), fatty liver disease (21.4%), coronary heart disease (21.0%), tumours (15.5%), gastroduodenal disease (14.4%), osteoarthropathy (11.8%), and cerebrovascular disease (10.8%). The incidence of hypertension (p = 0.015), hyperuricemia (p < 0.001), osteoarthropathy (p < 0.001), and autoimmune disease (p = 0.003) among different subtypes of psoriasis showed statistically significant differences. In addition, gender, smoking and alcohol consumption all have significant impacts on the distribution of comorbidities. Conclusions: The distribution of psoriasis comorbidities and complications varies among different subtypes of psoriasis. Lifestyles such as smoking and alcohol abuse, as well as gender, are also associated with the occurrence of psoriasis comorbidities.

LINC00963 promotes the malignancy and metastasis of lung adenocarcinoma by stabilizing Zeb1 and exosomes-induced M2 macrophage polarization.

BACKGROUND: Long intergenic non-coding RNA 00963 (LINC00963) is an oncogenic lncRNA in human cancers. However, little is known on how it impacts the pathogenesis of lung adenocarcinoma (LUAD). METHODS: Biological effects on proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) were examined by CCK-8, colony formation, EdU incorporation, transwell, and immunofluorescence assays, respectively. Macrophage polarization was evaluated by flow cytometry. Ubiquitination of Zeb1 was examined by co-immunoprecipitation. The location of LINC00963 in LUAD tissues and cell lines was tested by FISH assay. The LINC00963/HNRNPA2B1/Siah1 mRNA complex interaction was verified using RNA pull-down and immunoprecipitation assays. The exact roles of LINC00963 were further validated in metastasis and xenograft models. RESULTS: Higher LINC00963 expression in LUAD patients positively correlated with shorter overall survival, higher stages, and metastasis. LINC00963 mainly localized in the cytoplasm and aggravated malignant phenotypes of LUAD cells in vitro and metastasis in vivo. Mechanistically, LINC00963 directly interacted HNRNPA2B1 protein to trigger the degradation of Siah1 mRNA, which inhibited the ubiquitination and degradation of Zeb1. Moreover, exosomal LINC00963 derived from LUAD cells induced M2 macrophage polarization and promoted LUAD growth and metastasis. CONCLUSION: By stabilizing Zeb1 in cancer cells and delivering exosomes to induce M2 macrophage polarization, LINC00963 promoted the malignancy and metastasis of LUAD. Targeting LINC00963 may become a valuable therapeutic target for LUAD.

Interface Engineering Induced Electron Redistribution at PtNs /NiTe-Ns Interfaces for Promoting pH-Universal and Chloride-Tolerant Hydrogen Evolution Reaction.

Exploring highly efficient hydrogen evolution reaction (HER) electrocatalysts for large-scale water electrolysis in the full potential of hydrogen (pH) range is highly desirable, but it remains a significant challenge. Herein, a simple pathway is proposed to synthesize a hybrid electrocatalyst by decorating small metallic platinum (Pt) nanosheets on a large nickel telluride nanosheet (termed as PtNs /NiTe-Ns). The as-prepared PtNs /NiTe-Ns catalyst only requires overpotentials of 72, 162, and 65 mV to reach a high current density of 200 mA cm-2 in alkaline, neutral and acidic conditions, respectively. Theoretical calculations reveal that the combination of metallic Pt and NiTe-Ns subtly modulates the electronic redistribution at their interface, improves the charge-transfer kinetics, and enhances the performance of Ni active sites. The synergy between the Pt site and activated Ni site near the interface in PtNs /NiTe-Ns promotes the sluggish water-dissociation kinetics and optimizes the subsequent oxyhydrogen/hydrogen intermediates (OH*/H*) adsorption, accelerating the HER process. Additionally, the superhydrophilicity and superaerophobicity of PtNs /NiTe-Ns facilitate the mass transfer process and ensure the rapid desorption of generated bubbles, significantly enhancing overall alkaline water/saline water/seawater electrolysis catalytic activity and stability.

Introducing Nanozymes: New Horizons in Periodontal and Dental Implant Care.

The prevalence of periodontal and peri-implant diseases has been increasing worldwide and has gained a lot of attention. As multifunctional nanomaterials with enzyme-like activity, nanozymes have earned a place in the biomedical field. In periodontics and implantology, nanozymes have contributed greatly to research on maintaining periodontal health and improving implant success rates. To highlight this progress, we review nanozymes for antimicrobial therapy, anti-inflammatory therapy, tissue regeneration promotion, and synergistic effects in periodontal and peri-implant diseases. The future prospects of nanozymes in periodontology and implantology are also discussed along with challenges.

Metabolic phenotype analysis of Trichophyton rubrum after laser irradiation.

BACKGROUND: Biological phenotypes are important characteristics of microorganisms, and often reflect their genotype and genotype changes. Traditionally, Trichophyton rubrum (T. rubrum) phenotypes were detected using carbon source assimilation tests, during which the types of tested substances are limited. In addition, the operation is complicated, and only one substance can be tested at once. To observe the changes of the metabolic phenotype of T. rubrum after laser irradiation, a high-throughput phenotype microarray system was used to analyze the metabolism of different carbon, nitrogen, phosphorus and sulfur source substrates in a Biolog metabolic phenotyping system. RESULTS: The strain of T. rubrum used in this study can effectively utilize 33 carbon, 20 nitrogen, 16 phosphorus, and 13 sulfur source substrates prior to laser irradiation. After laser irradiation, the strain was able to utilize 10 carbon, 12 nitrogen, 12 phosphorus, and 8 sulfur source substrates. The degree of utilization was significantly decreased compared with the control. Both groups efficiently utilized saccharides and organic acids as carbon sources as well as some amino acids as nitrogen sources for growth. The number of substrates utilized by T. rubrum after laser irradiation were significantly reduced, especially carbon substrates. Some substrates utilization degree in the laser treated group was higher than control, such as D-glucosamine, L-glutamine, D-2-Phospho-Glyceric Acid, D-glucosamine-6-phosphate, and D-methionine. CONCLUSION: Laser irradiation of T. rubrum may lead to changes in the metabolic substrate and metabolic pathway, thus weakening the activity of the strain.

Evolutionary roles of polyploidization-derived structural variations in the phenotypic diversification of Panax species.

Genomic structural variations (SVs) are widespread in plant and animal genomes and play important roles in phenotypic novelty and species adaptation. Frequent whole genome duplications followed by (re)diploidizations have resulted in high diversity of genome architecture among extant species. In this study, we identified abundant genomic SVs in the Panax genus that are hypothesized to have occurred through during the repeated polyploidizations/(re)diploidizations. Our genome-wide comparisons demonstrated that although these polyploidization-derived SVs have evolved at distinct evolutionary stages, a large number of SV-intersecting genes showed enrichment in functionally important pathways related to secondary metabolites, photosynthesis and basic cellular activities. In line with these observations, our metabolic analyses of these Panax species revealed high diversity of primary and secondary metabolites both at the tissue and interspecific levels. In particular, genomic SVs identified at ginsenoside biosynthesis genes, including copy number variation and large fragment deletion, appear to have played important roles in the evolution and diversification of ginsenosides. A further herbivore deterrence experiment demonstrated that, as major triterpenoidal saponins found exclusively in Panax, ginsenosides provide protection against insect herbivores. Our study provides new insights on how polyploidization-derived SVs have contributed to phenotypic novelty and plant adaptation.

Phylogenomic and population genomic analyses reveal the spatial-temporal dynamics of diversification of the Nigella arvensis complex (Ranunculaceae) in the Aegean archipelago.

The continental-shelf islands of the Aegean Sea provide an ideal geographical setting for evolutionary-biogeographical studies but disentangling the relationships between palaeogeographical history and the times, orders of modes of taxon divergence is not straightforward. Here, we used phylogenomic and population genomic approaches, based on orthologous gene sequences and transcriptome-derived SNP data, to reconstruct the spatial-temporal evolution of the Aegean Nigella arvensis complex (Ranunculaceae; 11 out of 12 taxa). The group's early diversification in the Early/Mid-Pliocene (c. 3.77 Mya) resulted in three main lineages (Greek mainland vs. central Aegean + Turkish mainland/eastern Aegean islands), while all extant taxa are of Late Plio-/Early Pleistocene origin (c. 3.30-1.59 Mya). Demographic modelling of the outcrossing taxa uncovered disparate modes of (sub)speciation, including divergence with gene flow on the Greek mainland, para- or peripatric diversification across eastern Aegean islands, and a 'mixing-isolation-mixing (MIM)' mode of subspeciation in the Cyclades. The two selfing species (N. stricta, N. doerfleri) evolved independently from the outcrossers. Present-day island configurations are clearly insufficient to explain the spatial-temporal history of lineage diversification and modes of (sub)speciation in Aegean Nigella. Moreover, our identification of positively selected genes in almost all taxa calls into question that this plant group represents a case of 'non-adaptive' radiation. Our study revealed an episodic diversification history of the N. arvensis complex, giving new insight into the modes and drivers of island speciation and adaption across multiple spatiotemporal scales.

Host shift promotes divergent evolution between closely related holoparasitic species.

Distinct hosts have been hypothesized to possess the potential for affecting species differentiation and genome evolution of parasitic organisms. However, what host shift history is experienced by the closely related parasites and whether disparate evolution of their genomes occur remain largely unknown. Here, we screened horizontal gene transfer (HGT) events in a pair of sister species of holoparasitic Boschniakia (Orobanchaceae) having obligate hosts from distinct families to recall the former host-parasite associations and performed a comparative analysis to investigate the difference of their organelle genomes. Except those from the current hosts (Ericaceae and Betulaceae), we identified a number of HGTs from Rosaceae supporting the occurrence of unexpected ancient host shifts. Different hosts transfer functional genes which changed nuclear genomes of this sister species. Likewise, different donors transferred sequences to their mitogenomes, which vary in size due to foreign and repetitive elements rather than other factors found in other parasites. The plastomes are both severely reduced, and the degree of difference in reduction syndrome reaches the intergeneric level. Our findings provide new insights into the genome evolution of parasites adapting to different hosts and extend the mechanism of host shift promoting species differentiation to parasitic plant lineages.

Characterization and application of a lactate and branched chain amino acid metabolism related gene signature in a prognosis risk model for multiple myeloma.

BACKGROUND: About 10% of hematologic malignancies are multiple myeloma (MM), an untreatable cancer. Although lactate and branched-chain amino acids (BCAA) are involved in supporting various tumor growth, it is unknown whether they have any bearing on MM prognosis. METHODS: MM-related datasets (GSE4581, GSE136337, and TCGA-MM) were acquired from the Gene Expression Omnibus (GEO) database and the Cancer Genome Atlas (TCGA) database. Lactate and BCAA metabolism-related subtypes were acquired separately via the R package "ConsensusClusterPlus" in the GSE4281 dataset. The R package "limma" and Venn diagram were both employed to identify lactate-BCAA metabolism-related genes. Subsequently, a lactate-BCAA metabolism-related prognostic risk model for MM patients was constructed by univariate Cox, Least Absolute Shrinkage and Selection Operator (LASSO), and multivariate Cox regression analyses. The gene set enrichment analysis (GSEA) and R package "clusterProfiler"were applied to explore the biological variations between two groups. Moreover, single-sample gene set enrichment analysis (ssGSEA), Microenvironment Cell Populations-counter (MCPcounte), and xCell techniques were applied to assess tumor microenvironment (TME) scores in MM. Finally, the drug's IC50 for treating MM was calculated using the "oncoPredict" package, and further drug identification was performed by molecular docking. RESULTS: Cluster 1 demonstrated a worse prognosis than cluster 2 in both lactate metabolism-related subtypes and BCAA metabolism-related subtypes. 244 genes were determined to be involved in lactate-BCAA metabolism in MM. The prognostic risk model was constructed by CKS2 and LYZ selected from this group of genes for MM, then the prognostic risk model was also stable in external datasets. For the high-risk group, a total of 13 entries were enriched. 16 entries were enriched to the low-risk group. Immune scores, stromal scores, immune infiltrating cells (except Type 17 T helper cells in ssGSEA algorithm), and 168 drugs'IC50 were statistically different between two groups. Alkylating potentially serves as a new agent for MM treatment. CONCLUSIONS: CKS2 and LYZ were identified as lactate-BCAA metabolism-related genes in MM, then a novel prognostic risk model was built by using them. In summary, this research may uncover novel characteristic genes signature for the treatment and prognostic of MM.