Loureirin hydrogel promotes healing of radionuclide-contaminated wounds by regulating angiogenesis and immune cells.

Radionuclide-contaminated wounds face clinical dilemmas such as repeated erosion and ulceration and are difficult to heal. In this work, we aimed to develop a biodegradable hydrogel with a beneficial effect on radionuclide-contaminated wounds and initially investigated the mechanism of action of the hydrogel. The hydrogel was produced through the ring-opening polymerization of polycaprolactone (PCL) triggered by polyethylene glycol (PEG), and its physicochemical properties were characterized by gel permeation chromatography, nuclear magnetic resonance, rheological properties testing, and other techniques. The low critical solution temperatures were 30 °C and 46 °C, which are suitable for the human body to realize the degradable properties of the hydrogel. A radionuclide-contaminated wound model was established, which proved that the biodegradable hydrogel had good healing properties and did not form secondary lesions. The effect was better than clinically used EGF or VB12. Pathological results showed that mature granulation tissue formed on the 7th day after the injury, and by the 10th day after the injury, the scab had completely fallen off, the epithelial coverage had reached over 70% and the wound was essentially completely healed. Additionally, the hydrogel affects immune metabolism, regulates immune cell function, promotes the formation of new blood vessels and granular tissue, and effectively accelerates the healing process of radionuclide-contaminated wounds.

The complete plastome of Saxifraga giraldiana Engler and its phylogenetic analysis.

Saxifraga giraldiana Engler is a common subalpine and alpine plant belonging to Saxifragaceae. However, the genetic diversity of this species has remained to be explored. In this study, we have assembled and characterized the complete chloroplast genome of S. giraldiana, filling this knowledge gap and uncovering its genetic composition. The chloroplast genome is 147,267 bp long and contains 131 genes, including 85 protein-coding genes, 38 tRNA genes, and eight rRNA genes. Furthermore, we have performed a phylogenetic analysis of 19 representative species within Saxifraga. As a result, we have found that S. giraldiana, together with S. implicans and S. stellariifolia, forms a monophyletic group. These findings have implications for the conservation and utilization of S. giraldiana.

Anlotinib inhibits cervical cancer cell proliferation and invasion by suppressing cytokine secretion in activated cancer-associated fibroblasts.

Objective: The aim of this study was to investigate whether anlotinib could exert an inhibitory effect on the proliferation and invasion of cervical cancer cells by inhibiting cytokines secreted by activated cancer-associated fibroblasts (CAFs). Methods: CAFs were isolated from cervical cancer tissues and experimentally studied in vivo and in vitro. Molecular biology experimental methods were used to verify whether anlotinib could inhibit the pro-carcinogenic effects of CAFs derived from cervical cancer tissues. Results: CAFs promote the proliferation and invasion of cervical cancer cells. Anlotinib inhibited the activation of CAFs and suppressed the promotion of cervical cancer cells by CAFs. Anlotinib inhibited the expression of multiple cytokines within CAFs and suppressed the release of interleukin (IL)-6 (IL-6) and IL-8. In vivo studies have shown that anlotinib diminished the growth of xenografted cervical cancer cells, and treatment in combination with docetaxel had an even more significant tumor growth inhibitory effect. Conclusion: Anlotinib inhibits the pro-cancer effects of CAFs by suppressing the activation of CAFs and the secretion of pro-cancer cytokines. Our findings suggest that the combination of anlotinib and docetaxel may be a potential strategy for the treatment of refractory cervical cancer.

Integrative analysis regarding the correlation between collagen-related genes and prostate cancer.

PURPOSE: Prostate cancer (PCa) is a common malignancy in men, with an escalating mortality rate attributed to Recurrence and metastasis. Recent studies have illuminated collagen's critical regulatory role within the tumor microenvironment, significantly influencing tumor progression. Accordingly, this investigation is dedicated to examining the relationship between genes linked to collagen and the prognosis of PCa, with the objective of uncovering any possible associations between them. METHODS: Gene expression data for individuals with prostate cancer were obtained from the TCGA repository. Collagen-related genes were identified, leading to the development of a risk score model associated with biochemical recurrence-free survival (BRFS). A prognostic nomogram integrating the risk score with essential clinical factors was crafted and evaluated for efficacy. The influence of key collagen-related genes on cellular behavior was confirmed through various assays, including CCK8, invasion, migration, cell cloning, and wound healing. Immunohistochemical detection was used to evaluate PLOD3 expression in prostate cancer tissue samples. RESULTS: Our study identified four key collagen-associated genes (PLOD3, COL1A1, MMP11, FMOD) as significant. Survival analysis revealed that low-risk groups, based on the risk scoring model, had significantly improved prognoses. The risk score was strongly associated with prostate cancer prognosis. Researchers then created a nomogram, which demonstrated robust predictive efficacy and substantial clinical applicability.Remarkably, the suppression of PLOD3 expression notably impeded the proliferation, invasion, migration, and colony formation capabilities of PCa cells. CONCLUSION: The risk score, derived from four collagen-associated genes, could potentially act as a precise prognostic indicator for BRFS of patients. Simultaneously, our research has identified potential therapeutic targets related to collagen. Notably, PLOD3 was differentially expressed in cancer and para-cancer tissues in clinical specimens and it also was validated through in vitro studies and shown to suppress PCa tumorigenesis following its silencing.

The complete plastome of Thalictrum elegans Wall. ex Royle and its phylogenetic analysis.

Thalictrum elegans Wall. ex Royle, a species within the family Ranunculaceae, is mainly distributed along forest margins and grassy slopes at altitudes 2700-4000 m on the Qinghai-Tibetan Plateau. Despite its wide distribution in alpine ecosystems, its genetic diversity remains poorly understood. In this study, we assembled and characterized the complete chloroplast genome of T. elegans, addressing a significant gap in our understanding of its genetic composition. The chloroplast genome is 155,864 base pairs long and contains 131 genes, including 86 protein-coding genes, 37 tRNA genes, and 8 rRNA genes. Phylogenetic analysis of 15 representative Thalictrum species revealed that the genus can be classified into three clades. T. elegans along with another nine other species formed the largest monophyletic clade and is most closely related to T. petaloideum and T. foliosum. These findings enhance our understanding of the genetic diversity of T. elegans and contribute to its conservation and utilization.

Evaluating a worldwide wheat collection for resistance to Hessian fly biotype 'Great Plains'.

Hessian fly (HF), Mayetiola destructor, is a major insect pest that causes severe losses in grain yield and quality of wheat (Triticum aestivum). Growing resistant cultivars is the most cost-effective approach to minimize wheat yield losses caused by HF. In this study, 2,496 wheat accessions were screened for resistance to the HF biotype 'Great Plains' (GP) in the greenhouse experiments. To purify seeds from heterogeneous resistant accessions, we recovered single resistant plants from 331 accessions that had at least one resistant plant after HF infestation of a global collection of 1,595 accessions and confirmed 27 accessions with high resistance (HR), and 91 accessions with moderate resistance (MR) to the GP biotype using purified seeds. Screening of 203 U.S. winter wheat accessions in three experiments identified 63 HR and 28 MR accessions; and screening of three additional Asian panels identified 4 HR and 25 MR accessions. Together, this study identified 96 HR accessions and 144 MR accessions. Analysis of the geographic distribution of these HR and MR accessions revealed that these countries with HF as a major wheat pest usually showed higher frequencies of resistant accessions, with the highest frequency of HR (81.3%) and MR (30.6%) accessions identified from the U.S. In addition, phenotyping of 39 wheat accessions that carry known HF resistance genes showed that all the accessions except H1H2 remain effective against GP biotype. Some of these newly identified resistant accessions may contain new HF resistance genes and can be valuable sources for developing HF resistant wheat cultivars.

Superlong cycle-life sodium-ion batteries supported by electrode/active material interaction and heteroatom doping: Mechanism and application.

To achieve both the capacity and stability of metal sulfides simultaneously remains a significant challenge. In this study, we have synthesized the manganese-doped copper sulfide three-dimensional (3D) hollow flower-like sphere (M/CuS-NSC), encapsulated in a nitrogen and sulfur co-doped carbon. The hollow lamellae structure allows the rational self-aggregation process of numerous active surface area enlarged nanosheets, thereby enhancing electrochemical activity. The subsurface framework characterized by CSC bonds enhances the pseudo-capacitive properties. Furthermore, the transformation of sulfur and the isomerization of carbon contribute to the enhancement of sodium ion storage. The incorporation of Mn into CuS lattice increases the interplanar distance, providing additional space for the accommodation of sodium ions. Mn doping facilitates the localization of electrons near the Fermi level, thereby improving conductivity. Additionally, Cu foils coated with M/CuS-NSC-2 engage with the electrolyte and sulfur, initiating the reaction sequence through the formation of Cu9S8. Consequently, M/CuS-NSC-2 exhibits highly reversible capacities of 676.24 mAh g-1 after 100 cycles at 0.1 A g-1 and 511.52 mAh g-1 after 10000 cycles at 10 A g-1, with an average attenuation ratio of only 0.009 %. In this study, we propose an effective strategy that combines structural design with heteroatom doping, providing a novel approach to enhance the electrochemical performance of monometallic sulfide.

Global richness patterns of alpine genus Gentiana depend on multiple factors.

Environmental factors impact species richness differently across taxonomic groups, and understanding the geographic patterns and drivers influencing alpine plant richness remains limited. This study compiled global distribution data of 404 species of Gentiana, an alpine genus, and analyzed the relative effects of different environmental factors and several previously proposed models on the variation of Gentiana richness. By evaluating the effects of range size and regions on the relationships between Gentiana richness and environmental factors, we found that all tested environmental factors had weak effects on richness variation for all species and wide-ranging species, while habitat heterogeneity was the best predictor for narrow-ranging species. Habitat heterogeneity was the main driver of richness variation in Europe and Asia, but not in North America. The multiple regression model that included variables for energy, water, seasonality, habitat heterogeneity and past climate change had the highest explanatory power, but it still explained less than 50% of the variation in species richness for all Gentiana species at both global and regional scale, except for Europe. The limited explanatory power of environmental factors in explaining species richness patterns for all species, along with the variations observed among regions, suggest that other factors, such as evolutionary processes and biogeographic history may have also influenced the geographic patterns of Gentiana species richness. In conclusion, our results indicate a limited influence of climate factors on alpine species richness, while habitat heterogeneity, along with its impacts on speciation and dispersal, likely play significant roles in shaping the richness of alpine Gentiana species.

[Resources and utilization of medicinal plants in countries and regions involved in "the Belt and Road" Initiative].

The protection, development, and utilization of medicinal plant resources are important cornerstones of maintaining human health. However, due to factors such as the reduction of high-quality land resources, deterioration of ecological environments, and excessive and disorderly resource development, medicinal plant resources are becoming scarce, and some of them are insufficiently supplied. With the proposal of "the Belt and Road" Initiative, the cooperation between China and "the Belt and Road" partners(the countries and regions involved in "the Belt and Road" Initiative)is increasingly close, which provides a new opportunity for carrying out trade of medicinal plant resources and alleviating the problem of imbalance and relative inadequacy of medicinal plant resources in countries. This study first determined the distribution and species information of plant resources in countries and regions involved in "the Belt and Road" Initiative by investigating the database of plant distribution and that of medicinal plant resources. Then, according to the published data from the International Union for Conservation of Nature(IUCN) and the Convention on International Trade in Endangered Species of Wild Fauna and Flora(CITES), this study identified the rare and endangered medicinal plants and the medicinal plants under trade control in countries and regions involved in "the Belt and Road" Initiative and finally sorted out the list of potential medicinal plant resources in countries and regions involved in "the Belt and Road" Initiative that can be used by China. This data resource can not only be used for the overall protection of important endangered species but also scientifically guide the development and utilization of medicinal resources, providing guidance and a theoretical basis for the sustainable development of medicinal plant resources in countries and regions involved in "the Belt and Road" Initiative.

The predictive significance of chromobox family members in prostate cancer in humans.

PURPOSE: The Chromobox (CBX) family proteins are crucial elements of the epigenetic regulatory machinery and play a significant role in the development and advancement of cancer. Nevertheless, there is limited understanding regarding the role of CBXs in development or progression of prostate cancer (PCa). Our objective is to develop a unique prognostic model associated with CBXs to improve the accuracy of predicting outcomes of patients with PCa. METHODS: Data from TCGA and GEO databases were analyzed to assess differential expression, prognostic value, gene pathway enrichment, and immune cell infiltration. COX regression analysis was utilized to identify the independent prognostic factors that impact disease-free survival (DFS). The expression of CBX2 and FOXP3+ cells infiltration was verified by immunohistochemical staining of clinical tissue sections. In vitro proliferation, migration and invasion assay were conducted to examine the function of CBX2. RNA-seq was employed to examine the CBX2 related pathway enrichment. RESULTS: CBX2, CBX3, CBX4, and CBX8 were upregulated, while CBX6 and CBX7 were downregulated in PCa tissues. CBXs expression varied by stage and grade. Elevated expression of CBX1, CBX2, CBX3, CBX4 and CBX8 is correlated with poor outcome. CBX2 expression, T stage, and Gleason score were independent prognostic factors. The expression level of CBX2 in PCa tissues was significantly higher than that in adjacent normal tissues. More Treg infiltration was observed in the group with high CBX2 expression. CBX2 expression affected PCa cell growth, migration, and invasion. CONCLUSIONS: CBX2 is involved in the development and advancement of PCa, suggesting its potential as a reliable prognostic indicator for PCa patients.

Amber rainbow ribbon effect in broadband optical metamaterials.

Using the trapped rainbow effect to slow down or even stop light has been widely studied. However, high loss and energy leakage severely limited the development of rainbow devices. Here, we observed the negative Goos-Hänchen effect in film samples across the entire visible spectrum. We also discovered an amber rainbow ribbon and an optical black hole due to perfect back reflection in optical waveguides, where little light leaks out. Not only does the amber rainbow ribbon effect show an automatic frequency selection response, as predicted by single frequency theoretical models and confirmed by experiments, it also shows spatial periodic regulation, resulting from broadband omnidirectional visible metamaterials prepared by disordered assembly systems. This broadband light trapping system could play a crucial role in the fields of optical storage and information processing when being used to construct ultra-compact modulators and other tunable devices.

Naringenin Inhibits Acid Sphingomyelinase-Mediated Membrane Raft Clustering to Reduce NADPH Oxidase Activation and Vascular Inflammation.

Macrophage inflammation and oxidative stress promote atherosclerosis progression. Naringenin is a naturally occurring flavonoid with antiatherosclerotic properties. Here, we elucidated the effects of naringenin on monocyte/macrophage endothelial infiltration and vascular inflammation. We found naringenin inhibited oxidized low-density lipoprotein (oxLDL)-induced pro-inflammatory cytokines such as IL-1ß, IL-6, and TNF-α toward an M2 macrophage phenotype and inhibited oxLDL-induced TLR4 (Toll-like receptor 4) membrane translocation and downstream NF-κB transcriptional activity. Results from flow cytometric analysis showed that naringenin reduced monocyte/macrophage infiltration in the aorta of high-fat-diet-treated ApoE-deficient mice. The aortic cytokine levels were also inhibited in naringenin-treated mice. Further, we found that naringenin reduced lipid raft clustering and acid sphingomyelinase (ASMase) membrane gathering and inhibited the TLR4 and NADPH oxidase subunit p47phox membrane recruitment, which reduced the inflammatory response. Recombinant ASMase treatment or overexpression of ASMase abolished the naringenin function and activated macrophage and vascular inflammation. We conclude that naringenin inhibits ASMase-mediated lipid raft redox signaling to attenuate macrophage activation and vascular inflammation.

Indirubin mediates adverse intestinal reactions in guinea pigs by downregulating the expression of AchE through AhR.

Indirubin is the main component of the traditional Chinese medicine Indigo naturalis (IN), a potent agonist of aryl hydrocarbon receptors (AhRs). In China, IN is used to treat psoriasis and ulcerative colitis, and indirubin is used for the treatment of chronic myelogenous leukaemia. However, IN and indirubin have adverse reactions, such as abdominal pain, diarrhoea, and intussusception, and their specific mechanism is unclear.The purpose of our research was to determine the specific mechanism underlying the adverse effects of IN and indirubin. By tracking the modifications in guinea pigs after the intragastric administration of indirubin for 28 days.The results demonstrate that indirubin could accelerate bowel movements and decrease intestinal acetylcholinesterase (AchE) expression. Experiments with NCM460 cells revealed that indirubin significantly reduced the expression of AchE, and the AchE levels were increased after the silencing of AhR and re-exposure to indirubin.This study showed that the inhibition of AchE expression by indirubin plays a key role in the occurrence of adverse reactions to indirubin and that the underlying mechanism is related to AhR-mediated AchE downregulation.

Establishment of a prognostic risk prediction model incorporating disulfidptosis-related lncRNA for patients with prostate cancer.

PURPOSE: Prostate cancer (PCa) is one of the major tumor diseases that threaten men's health globally, and biochemical recurrence significantly impacts its prognosis. Disulfidptosis, a recently discovered cell death mechanism triggered by intracellular disulfide accumulation leading to membrane rupture, is a new area of research in the context of PCa. Currently, its impact on PCa remains largely unexplored. This study aims to investigate the correlation between long non-coding RNAs (lncRNAs) associated with disulfidptosis and the prognosis of PCa, seeking potential connections between the two. METHODS: Transcriptomic data for a PCa cohort were obtained from the Cancer Genome Atlas database. Disulfidptosis-related lncRNAs (DDRLs) were identified through differential expression and Pearson correlation analysis. DDRLs associated with biochemical recurrence-free survival (BRFS) were precisely identified using univariate Cox and LASSO regression, resulting in the development of a risk score model. Clinical factors linked to BRFS were determined through both univariate and multivariate Cox analyses. A prognostic nomogram combined the risk score with key clinical variables. Model performance was assessed using Receiver Operating Characteristic (ROC) curves, Decision Curve Analysis (DCA), and calibration curves. The functional impact of a critical DDRL was substantiated through assays involving CCK8, invasion, migration, and cell cloning. Additionally, immunohistochemical (IHC) staining for the disulfidptosis-related protein SLC7A11 was conducted. RESULTS: The prognostic signature included AC026401.3, SNHG4, SNHG25, and U73166.1 as key components. The derived risk score from these signatures stood as one of the independent prognostic factor for PCa patients, correlating with poorer BRFS in the high-risk group. By combining the risk score with clinical variables, a practical nomogram was created, accurately predicting BRFS of PCa patients. Notably, silencing AC026401.3 significantly hindered PCa cell proliferation, invasion, migration, and colony formation. IHC staining revealed elevated expression of the dithiosulfatide-related protein SLC7A11 in tumor tissue. CONCLUSIONS: A novel prognostic signature for PCa DDRLs, possessing commendable predictive power, has been constructed, simultaneously providing potential therapeutic targets associated with disulfidptosis, among which AC026401.3 has been validated in vitro and demonstrated inhibition of PCa tumorigenesis after its silencing.

EBV abortive lytic cycle promotes nasopharyngeal carcinoma progression through recruiting monocytes and regulating their directed differentiation.

Epstein-Barr virus (EBV) is associated with several types of human cancer including nasopharyngeal carcinoma (NPC). The activation of EBV to the lytic cycle has been observed in advanced NPC and is believed to contribute to late-stage NPC development. However, how EBV lytic cycle promotes NPC progression remains elusive. Analysis of clinical NPC samples indicated that EBV reactivation and immunosuppression were found in advanced NPC samples, as well as abnormal angiogenesis and invasiveness. To investigate the role of the EBV lytic cycle in tumor development, we established a system that consists of two NPC cell lines, respectively, in EBV abortive lytic cycle and latency. In a comparative analysis using this system, we found that the NPC cell line in EBV abortive lytic cycle exhibited the superior chemotactic capacity to recruit monocytes and polarized their differentiation toward tumor-associated macrophage (TAM)-like phenotype and away from DCs, compared to EBV-negative or EBV-latency NPC cells. EBV-encoded transcription activator ZTA is responsible for regulating monocyte chemotaxis and TAM phenotype by up-regulating the expression of GM-CSF, IL-8, and GRO-α. As a result, TAM induced by EBV abortive lytic cycle promotes NPC angiogenesis, invasion, and migration. Overall, this study elucidated the role of the EBV lytic life cycle in the late development of NPC and revealed a mechanism underlying the ZTA-mediated establishment of the tumor microenvironment (TME) that promotes NPC late-stage progression.

α-mangostin derivatives ameliorated mouse DSS-induced chronic colitis via regulating Th17/Treg balance.

Th17 cell, an important subpopulation of helper T cell, plays an important role in the development of inflammatory bowel disease (IBD) and is thought to be a potential target for the treatment of IBD. In our previous study, we demonstrated that α-mangostin could relieve lupus nephritis via inhibiting Th17 cell function. In our preliminary study, we obtained four derivatives by adding chemical modification of α-mangostin which could also inhibit Th17 cell differentiation in vitro. In this study, we constructed a chronic IBD mouse model and demonstrated the therapeutic effects of α-mangostin and its derivatives as therapeutic agents for IBD. In compounds treating groups, intestinal inflammation showed significant improvement in symptoms which included weight loss, high disease activity index, colon length shorten and the change of intestinal flora. We also found that compounds could effectively either suppress the number of Th17 cell or increase the number of Treg cell detected by flow cytometry, thus reducing the Th17/Treg ratio and suppressing the level of intestinal inflammation. Notably, IL17-F levels, rather than IL17-A, were reduced in the colon of mice of compounds treating groups. Thus, α-mangostin and its derivatives ameliorate DSS-induced chronic colitis in mice by regulating Th17/Treg balance to alleviate intestinal inflammation and can modulate the intestinal microbial community. These results suggest that α-mangostin and its derivatives may be the new therapeutic option for chronic colitis.

Global multifaceted biodiversity patterns, centers, and conservation needs in angiosperms.

The Convention on Biological Diversity seeks to conserve at least 30% of global land and water areas by 2030, which is a challenge but also an opportunity to better preserve biodiversity, including flowering plants (angiosperms). Herein, we compiled a large database on distributions of over 300,000 angiosperm species and the key functional traits of 67,024 species. Using this database, we constructed biodiversity-environment models to predict global patterns of taxonomic, phylogenetic, and functional diversity in terrestrial angiosperms and provide a comprehensive mapping of the three diversity facets. We further evaluated the current protection status of the biodiversity centers of these diversity facets. Our results showed that geographical patterns of the three facets of plant diversity exhibited substantial spatial mismatches and nonoverlapping conservation priorities. Idiosyncratic centers of functional diversity, particularly of herbaceous species, were primarily distributed in temperate regions and under weaker protection compared with other biodiversity centers of taxonomic and phylogenetic facets. Our global assessment of multifaceted biodiversity patterns and centers highlights the insufficiency and unbalanced conservation among the three diversity facets and the two growth forms (woody vs. herbaceous), thus providing directions for guiding the future conservation of global plant diversity.

Predicting extubation in patients with traumatic cervical spinal cord injury using the diaphragm electrical activity during a single maximal maneuver.

BACKGROUND: The unsuccessful extubation in patients with traumatic cervical spinal cord injuries (CSCI) may result from impairment diaphragm function and monitoring of diaphragm electrical activity (EAdi) can be informative in guiding extubation. We aimed to evaluate whether the change of EAdi during a single maximal maneuver can predict extubation outcomes in CSCI patients. METHODS: This is a retrospective study of CSCI patients requiring mechanical ventilation in the ICU of a tertiary hospital. A single maximal maneuver was performed by asking each patient to inhale with maximum strength during the first spontaneous breathing trial (SBT). The baseline (during SBT before maximal maneuver), maximum (during the single maximal maneuver), and the increase of EAdi (ΔEAdi, equal to the difference between baseline and maximal) were measured. The primary outcome was extubation success, defined as no reintubation after the first extubation and no tracheostomy before any extubation during the ICU stay. RESULTS: Among 107 patients enrolled, 50 (46.7%) were extubated successfully at the first SBT. Baseline EAdi, maximum EAdi, and ΔEAdi were significantly higher, and the rapid shallow breathing index was lower in patients who were extubated successfully than in those who failed. By multivariable logistic analysis, ΔEAdi was independently associated with successful extubation (OR 2.03, 95% CI 1.52-3.17). ΔEAdi demonstrated high diagnostic accuracy in predicting extubation success with an AUROC 0.978 (95% CI 0.941-0.995), and the cut-off value was 7.0 µV. CONCLUSIONS: The increase of EAdi from baseline SBT during a single maximal maneuver is associated with successful extubation and can help guide extubation in CSCI patients.

Diversification of flowering plants in space and time.

The rapid diversification and high species richness of flowering plants is regarded as 'Darwin's second abominable mystery'. Today the global spatiotemporal pattern of plant diversification remains elusive. Using a newly generated genus-level phylogeny and global distribution data for 14,244 flowering plant genera, we describe the diversification dynamics of angiosperms through space and time. Our analyses show that diversification rates increased throughout the early Cretaceous and then slightly decreased or remained mostly stable until the end of the Cretaceous-Paleogene mass extinction event 66 million years ago. After that, diversification rates increased again towards the present. Younger genera with high diversification rates dominate temperate and dryland regions, whereas old genera with low diversification dominate the tropics. This leads to a negative correlation between spatial patterns of diversification and genus diversity. Our findings suggest that global changes since the Cenozoic shaped the patterns of flowering plant diversity and support an emerging consensus that diversification rates are higher outside the tropics.