Adaptive evolution of the enigmatic Takakia now facing climate change in Tibet.

The most extreme environments are the most vulnerable to transformation under a rapidly changing climate. These ecosystems harbor some of the most specialized species, which will likely suffer the highest extinction rates. We document the steepest temperature increase (2010-2021) on record at altitudes of above 4,000 m, triggering a decline of the relictual and highly adapted moss Takakia lepidozioides. Its de-novo-sequenced genome with 27,467 protein-coding genes includes distinct adaptations to abiotic stresses and comprises the largest number of fast-evolving genes under positive selection. The uplift of the study site in the last 65 million years has resulted in life-threatening UV-B radiation and drastically reduced temperatures, and we detected several of the molecular adaptations of Takakia to these environmental changes. Surprisingly, specific morphological features likely occurred earlier than 165 mya in much warmer environments. Following nearly 400 million years of evolution and resilience, this species is now facing extinction.

Sapap4 deficiency leads to postsynaptic defects and abnormal behaviors relevant to hyperkinetic neuropsychiatric disorder in mice.

Postsynaptic proteins play critical roles in synaptic development, function, and plasticity. Dysfunction of postsynaptic proteins is strongly linked to neurodevelopmental and psychiatric disorders. SAP90/PSD95-associated protein 4 (SAPAP4; also known as DLGAP4) is a key component of the PSD95-SAPAP-SHANK excitatory postsynaptic scaffolding complex, which plays important roles at synapses. However, the exact function of the SAPAP4 protein in the brain is poorly understood. Here, we report that Sapap4 knockout (KO) mice have reduced spine density in the prefrontal cortex and abnormal compositions of key postsynaptic proteins in the postsynaptic density (PSD) including reduced PSD95, GluR1, and GluR2 as well as increased SHANK3. These synaptic defects are accompanied by a cluster of abnormal behaviors including hyperactivity, impulsivity, reduced despair/depression-like behavior, hypersensitivity to low dose of amphetamine, memory deficits, and decreased prepulse inhibition, which are reminiscent of mania. Furthermore, the hyperactivity of Sapap4 KO mice could be partially rescued by valproate, a mood stabilizer used for mania treatment in humans. Together, our findings provide evidence that SAPAP4 plays an important role at synapses and reinforce the view that dysfunction of the postsynaptic scaffolding protein SAPAP4 may contribute to the pathogenesis of hyperkinetic neuropsychiatric disorder.

Fluacrypyrim Protects Hematopoietic Stem and Progenitor Cells against Irradiation via Apoptosis Prevention.

Ionizing radiation (IR)-induced hematopoietic injury has become a global concern in the past decade. The underlying cause of this condition is a compromised hematopoietic reserve, and this kind of hematopoietic injury could result in infection or bleeding, in addition to lethal mishaps. Therefore, developing an effective treatment for this condition is imperative. Fluacrypyrim (FAPM) is a recognized effective inhibitor of STAT3, which exhibits anti-inflammation and anti-tumor effects in hematopoietic disorders. In this context, the present study aimed to determine whether FAPM could serve as a curative agent in hematopoietic-acute radiation syndrome (H-ARS) after total body irradiation (TBI). The results revealed that the peritoneally injection of FAPM could effectively promote mice survival after lethal dose irradiation. In addition, promising recovery of peripheral blood, bone marrow (BM) cell counts, hematopoietic stem cell (HSC) cellularity, BM colony-forming ability, and HSC reconstituting ability upon FAPM treatment after sublethal dose irradiation was noted. Furthermore, FAPM could reduce IR-induced apoptosis in hematopoietic stem and progenitor cells (HSPCs) both in vitro and in vivo. Specifically, FAPM could downregulate the expressions of p53-PUMA pathway target genes, such as Puma, Bax, and Noxa. These results suggested that FAPM played a protective role in IR-induced hematopoietic damage and that the possible underlying mechanism was the modulation of apoptotic activities in HSCs.

Ecological patterns and processes in the vertical dimension of terrestrial ecosystems.

Climatic gradients such as latitude and elevation are considered primary drivers of global biogeography. Yet, alongside these macro-gradients, the vertical space and structure generated by terrestrial plants form comparable climatic gradients but at a fraction of the distance. These vertical gradients provide a spectrum of ecological space for species to occur and coexist, increasing biodiversity. Furthermore, vertical gradients can serve as pathways for evolutionary adaptation of species traits, leading to a range of ecological specialisations. In this review, we explore the ecological evidence supporting the proposition that the vertical gradient serves as an engine driving the ecology and evolution of species and shaping larger biogeographical patterns in space and time akin to elevation and latitude. Focusing on vertebrate and invertebrate taxa, we synthesised how ecological patterns within the vertical dimension shape species composition, distribution and biotic interactions. We identify three key ecological mechanisms associated with species traits that facilitate persistence within the vertical environment and draw on empirical examples from the literature to explore these processes. Looking forward, we propose that the vertical dimension provides an excellent study template to explore timely ecological and evolutionary questions. We encourage future research to also consider how the vertical dimension will influence the resilience and response of animal taxa to global change.

rhTPO Ameliorates Radiation-Induced Long-Term Hematopoietic Stem Cell Injury in Mice.

Exposure to medium and high doses of ionizing radiation (IR) can induce long-term bone marrow (BM) suppression. We previously showed that recombinant human thrombopoietin (rhTPO) significantly promotes recovery from hematopoietic-acute radiation syndrome, but its effect on long-term BM suppression remains unknown. C57BL/6 mice were exposed to 6.5 Gy γ-rays of total body irradiation (TBI) at a dose-rate of 63.01 cGy per minute, and the mice were treated with rhTPO (100 µg; intramuscular injection) or vehicle at 2 h after TBI. All mice were killed one or two months after TBI for analysis of peripheral blood cell counts, long-term hematopoietic stem cell (HSC) frequency, and BM-derived clonogenic activity. The HSC self-renewal capacity was analyzed by BM transplantation. The levels of reactive oxygen species (ROS) production and ratios of γH2AX+ and p16, p53, and p21 mRNA in HSCs were measured by flow cytometry and real-time polymerase chain reaction, respectively. Treatment with rhTPO reduced long-term myelosuppression by improving long-term hematopoietic reconstitution (p < 0.05) after transplantation and resting state maintenance of HSCs (p < 0.05). Moreover, rhTPO treatment was associated with a sustained reduction in long-term ROS production, reduction of long-term DNA damage, diminished p53/p21 mRNA expression, and prevention of senescence after TBI. This study suggests rhTPO is an effective agent for treating IR-induced long-term BM injury because it regulates hematopoietic remodeling and HSC cycle disorder through the ROS/p53/p21/p16 pathway long term after IR.

Morphological and behavioural differences facilitate tropical butterfly persistence in variable environments.

The thermal biology of ectotherms largely determines their abundance and distributions. In general, tropical species inhabiting warm and stable thermal environments tend to have low tolerance to cold and variable environments, which may restrict their expansion into temperate climates. However, the distribution of some tropical species does extend into cooler areas such as tropical borders and high elevation tropical mountains. Behavioural and morphological differences may therefore play important roles in facilitating tropical species to cope with cold and variable climates at tropical edges. We used field-validated biophysical models to estimate body temperatures of butterflies across elevational gradients at three sites in southern China and assessed the contribution of behavioural and morphological differences in facilitating their persistence in tropical and temperate climates. We investigated the effects of temperature on the activity of 4,844 individuals of 144 butterfly species along thermal gradients and tested whether species of different climatic affinities-tropical and widespread (distributed in both temperate and tropical regions)-differed in their thermoregulatory strategies (i.e. basking). In addition, we tested whether thermally related morphology or the strength of solar radiation (when butterflies were recorded) was related to such differences. We found that activities of tropical species were restricted (low abundance) at low air temperatures compared to widespread species. Active tropical species were also more likely to bask at cooler body temperatures than widespread species. Heat gain from behavioural thermoregulation was higher for tropical species (when accounting for species abundance), and heat gain correlated with larger thorax widths but not with measured solar radiation. Our results indicate that physiological intolerance to cold temperatures in tropical species may be compensated through behavioural and morphological responses in thermoregulation in variable subtropical environments. Increasing climatic variability with climate change may render tropical species more vulnerable to cold weather extremes compared to widespread species that are more physiologically suited to variable environments.

Identification by comparative transcriptomics of core regulatory genes for higher alcohol production in a top-fermenting yeast at different temperatures in beer fermentation.

Undesirable flavor caused by excessive higher alcohols restrains the development of the wheat beer industry. To clarify the regulation mechanism of the metabolism of higher alcohols in wheat beer brewing by the top-fermenting yeast Saccharomyces cerevisiae S17, the effect of temperature on the fermentation performance and transcriptional levels of relevant genes was investigated. The strain S17 produced 297.85 mg/L of higher alcohols at 20 °C, and the production did not increase at 25 °C, reaching about 297.43 mg/L. Metabolite analysis and transcriptome sequencing showed that the metabolic pathways of branched-chain amino acids, pyruvate, phenylalanine, and proline were the decisive factors that affected the formation of higher alcohols. Fourteen most promising genes were selected to evaluate the effects of single-gene deletions on the synthesis of higher alcohols. The total production of higher alcohols by the mutants Δtir1 and Δgap1 was reduced by 23.5 and 19.66% compared with the parent strain S17, respectively. The results confirmed that TIR1 and GAP1 are crucial regulatory genes in the metabolism of higher alcohols in the top-fermenting yeast. This study provides valuable knowledge on the metabolic pathways of higher alcohols and new strategies for reducing the amounts of higher alcohols in wheat beer.

Vibsanin A sensitizes human acute myeloid leukemia cells to tyrosine kinase inhibitor-induced myeloid differentiation via activation of PKC and upregulation of Lyn.

Differentiation therapies have been proposed to overcome the impaired cell differentiation in acute myeloid leukemia (AML). However, thus far the all-trans retinoic acid-based differentiation therapy has been the only successful modality in treating acute promyelocytic leukemia. Here, we showed that vibsanin A, a novel protein kinase C (PKC) activator, sensitized AML cells to tyrosine kinase inhibitor (TKI)-induced differentiation. Vibsanin A augmented the ability of TKIs to induce growth inhibition and G1 cell cycle arrest of AML cells. Mechanistically, PKC activation was involved in the differentiation-inducing effects of combining vibsanin A with TKIs. Moreover, we found that vibsanin A enhanced TKI-induced Lyn expression and suppression of Lyn interfered with AML cell differentiation, indicating an essential role for Lyn expression in the combination-induced differentiation. Finally, combining vibsanin A and TKIs enhanced the activation of the Raf/MEK/ERK cascade. Together, this is the first study to evaluate the synergy of vibsanin A and TKIs in AML cell differentiation. Our study lays the foundation in assessing new opportunities for the combination of vibsanin A and TKIs as a promising approach for future differentiation therapy.

SERS-based lateral flow assay for quantitative detection of C-reactive protein as an early bio-indicator of a radiation-induced inflammatory response in nonhuman primates.

In accidental irradiation situations, rapid in-field evaluation of acute radiation syndrome is critical for effective triage and timely medical treatment of irradiated individuals. A surface-enhanced Raman scattering (SERS)-based lateral flow assay was developed for the quantitative detection of C-reactive protein (CRP) as an early bio-indicator of a radiation-induced inflammatory response in nonhuman primates. Raman reporter-embedded gold-core silver-shell nanoparticles with built-in hot spots were synthesized and conjugated with a CRP detection antibody to serve as SERS tags in the lateral flow assay. The proposed SERS-based lateral flow assay can rapidly detect CRP with a limit of detection of 0.01 ng mL-1 and quantitative analysis ability. Furthermore, the assay was applied to evaluate the CRP levels in plasma samples of irradiated nonhuman primates at 0 to 80 h after exposure to sublethal (4 Gy) and lethal (8 Gy) doses of total body irradiation (n = 3 animals per group). The plasma CRP levels increase rapidly within few hours after irradiation. The CRP level peaks are observed at 12 or 24 h after irradiation, with a concentration of 201.30, 386.06 and 475.18 µg mL-1 for the 4 Gy irradiated animals and 197.14, 69.52 and 358.03 µg mL-1 for the 8 Gy irradiated animals. The results indicate the potential application of the proposed SERS-based lateral flow assay to serve as a rapid and accurate point-of-care biodosimetry assay for the quantitative detection of bio-indicators to triage irradiated individuals in the field of a radiation accident.

Colors of night: climate-morphology relationships of geometrid moths along spatial gradients in southwestern China.

Color lightness of insects is an important ecological trait affecting their performance through multiple functions such as thermoregulation, UV protection and disease resistance. The geographical pattern of color lightness in diurnal insects are relatively well understood and largely driven by thermal melanism through the enhancement of insect activity. In nocturnal insects, however, the ecological function of color lightness in response to climatic factors is poorly understood, particularly at small spatial scales. In this study, we investigated color lightness of nocturnal moth assemblages along environmental gradients. Using geometrid moths collected with comparable methodologies (light trapping), we examined assemblage-level changes in color lightness across elevational gradients and vertical strata (canopy vs understory) across three climatically different locations in Yunnan, China. The results showed that moths are darker in color at higher elevations. Such patterns are most apparent in canopy assemblages. In addition, the strength of the elevational pattern on color lightness varied across location, being most pronounced in the canopy of the subalpine site. These patterns are likely driven by UV protection and/or thermoregulation. Our study highlights the importance of abiotic factors such as temperature and solar radiation in structuring morphological patterns of nocturnal ectothermic assemblages along elevational gradients of climatically harsh environments.

Three new cytotoxic oleanane triterpenoid saponins from Cylindrokelupha dalatensis.

Three new minor oleanane triterpenoid saponins, cylindrosides B (1), C (2), and D (3), were isolated from the seed of Cylindrokelupha dalatensis using chromatographic method. Their structures were established on the basis of the chemical and spectroscopic evidences. They displayed significant antitumor activity in vitro against HL60 cancer cell lines and IC50 values were 7.15 ± 0.63, 10.07 ± 0.97, and 4.74 ± 0.57 µM, respectively, by MTT method.

Chondrogenic differentiation of ChM-I gene transfected rat bone marrow-derived mesenchymal stem cells on 3-dimensional poly (L-lactic acid) scaffold for cartilage engineering.

We have explored the role of Chondromodulin-I (ChM-I) in chondrogenesis of bone marrow-derived mesenchymal stem cells (BMSCs) in 3-dimensional (3D) scaffold for cartilage tissue engineering. BMSCs of Sprague Dawley (SD) rats were cultured on poly-(L-lactic acid) [PLLA] scaffolds with different pore sizes (80-200 µm, 200-450 µm) with or without surface modification by chitosan. Cell viability, proliferation, and morphology were measured using confocal microscope and the CCK-8 method. Untransfected BMSCs, BMSCs expressing pcDNA3.1(+), BMSCs expressing plasmid pcDNA3.1 (+)/ChM-I were cultured on 3D scaffolds in standard growth medium or transforming growth factor-ß1 (TGF-ß1) supplemented chondrogenic induction medium in vitro for 3 weeks and the expression of collagen type II was determined. Cell-scaffolds constructs were implanted subcutaneously for 3 months in vivo. BMSCs had a higher viability and proliferation in PLLA scaffolds of pore size 200-450 µm than that of 80-200 µm, and surface modification with chitosan did not enhance cell attachment. The ChM-I gene enhanced chondrogenesis and increased collagen type II synthesis. Immunohistochemistry from in vivo study showed enhanced cartilage regeneration in BMSCs expressing pcDNA3.1 (+)/ChM-I on 3D PLLA scaffolds. It also demonstrated that TGF-ß1 might promote chondrogenesis of rat BMSCs by synergizing with the ChM-I gene. ChM-I could be beneficial to future applications in cartilage repair.

Cropland Microclimate and Leaf-nesting Behavior Shape the Growth of Caterpillar under Future Warming.

Predicting performance responses of insects to climate change is crucial for biodiversity conservation and pest management. While most projections on insects' performance under climate change have used macro-scale weather station data, few incorporated the microclimates within vegetation that insects inhabit and their feeding behaviors (e.g., leaf-nesting: building leaf nests or feeding inside). Here, taking advantage of relatively homogenous vegetation structures in agricultural fields, we built microclimate models to examine fine-scale air temperatures within two important crop systems (maize and rice) and compared microclimate air temperatures to temperatures from weather stations. We deployed physical models of caterpillars and quantified effects of leaf-nesting behavior on operative temperatures of two Lepidoptera pests: Ostrinia furnacalis (Pyralidae) and Cnaphalocrocis medinalis (Crambidae). We built temperature-growth rate curves and predicted the growth rate of caterpillars with and without leaf-nesting behavior based on downscaled microclimate changes under different climate change scenarios. We identified widespread differences between microclimates in our crop systems and air temperatures reported by local weather stations. Leaf-nesting individuals in general had much lower body temperatures compared to non-leaf-nesting individuals. When considering microclimates, we predicted leaf-nesting individuals grow slower compared to non-leaf-nesting individuals with rising temperature. Our findings highlight the importance of considering microclimate and habitat-modifying behavior in predicting performance responses to climate change. Understanding the thermal biology of pests and other insects would allow us to make more accurate projections on crop yields and biodiversity responses to environmental changes.

Heterogenetic mechanism in high-temperature Daqu fermentation by traditional craft and mechanical craft: From microbial assembly patterns to metabolism phenotypes.

The mechanical process has a widely usage in large-scale high-temperature Daqu (HTD) enterprises, however, the quality of the mechanical HTD is gapped with the HTD by traditional process. Currently, the understanding of the mechanism behind this phenomenon is still over-constrained. To this end, the discrepancies in fermentation parameters, enzymatic characteristics, microbial assembly and succession patterns, metabolic phenotypes were compared between traditional HTD and mechanical HTD in this paper. The results showed that mechanical process altered the temperature ramping procedure, resulting in a delayed appearance of the peak temperature. This alteration shifted the assembly pattern of the initial bacterial community from determinism to stochasticity, while having no impact on the stochastic assembly pattern of the fungal community. Concurrently, mechanical pressing impeded the accumulation of arginase, tetramethylpyrazine, trimethylpyrazine, 2-methoxy-4-vinylphenol, and butyric acid, as the target dissimilarities in metabolism between traditional HTD and mechanical HTD. Pearson correlation analysis combined with the functional prediction further demonstrated that Bacillus, Virgibacillus, Oceanobacillus, Kroppenstedtia, Lactobacillus, and Monascus were mainly contributors to metabolic variances. The Redundancy analysis (RDA) of fermented environmental factors on functional ASVs indicated that high temperature, high acid and low moisture were key positive drivers on the microbial metabolism for the characteristic flavor in HTD. Based on these results, heterogeneous mechanisms between traditional HTD and mechanical HTD were explored, and controllable metabolism targets were as possible strategies to improve the quality of mechanical HTD.

Single-dose Administration of Recombinant Human Thrombopoietin Enhances Survival and Hematopoietic Reconstruction in Canines Irradiated with 3 Gy Gamma Radiation.

We conducted this study to investigate the radioprotective effects of recombinant human thrombopoietin (rhTPO) on beagle dogs irradiated with 3.0 Gy 60Co gamma rays. Fifteen healthy adult beagles were randomly assigned to a control group with alleviating care, and 5 and 10 µg/kg rhTPO treatment group. All animals received total-body irradiation using 60Co γ-ray source at a dose of 3.0 Gy (dose rate was 69.1 cGy/min). The treatment group received intramuscular injection of rhTPO 5 and 10 µg/kg at 2 h postirradiation, and the control group was administrated the same volume of normal saline. The survival rate, clinical signs, peripheral hemogram, serum biochemistry, and histopathological examination of animals in each group were assessed. Single administration of 10 µg/kg rhTPO at 2 h postirradiation promoted the recovery of multilineage hematopoiesis and improved the survival rate of beagles irradiated with 3 Gy 60Co γ rays. The administration of 10 µg/kg rhTPO alleviated fever and bleeding, reduced the requirement for supportive care, and may have mitigated multiple organ damage.

Cylindroside A, a new triterpenoid saponin from Cylindrokelupha dalatensis and its cytotoxic activity.

A new triterpenoid saponin, named cylindroside A (1), was isolated from the seeds of Cylindrokelupha dalatensis (Kosterm.) T.L. Wu by using chromatographic method. The structure of 1 was established by comprehensive spectroscopic analysis and chemical degradation. Compound 1 displayed significant antitumor activity in vitro against BCG and MCF-7 cancer cell lines and IC50 values were 4.17 ± 0.23 and 3.07 ± 0.66 µM by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method, respectively.

Chaperonin co-expression and chemical modification enables production of active microbial transglutaminase from E. coli cytoplasm.

Microbial transglutaminase (MTG) is a usable enzyme for biomacromolecule modification. In the present study, a "molecular chaperonin" strategy was developed to produce MTG in E. coli cytoplasm with high expression level and a "small molecule-mediated chemical modification" strategy was adopted to strip propeptide chaperonin efficiently during purification. Propeptide (Pro) was expressed separately as a chaperonin to facilitate MTG expression in E. coli cytoplasm with a yield up to 300 mg or about 9 kU from 1 L fed-batch culture. Furthermore, small molecular chemicals were applied to interfere the interaction between MTG and Pro. Chemical acetylation was identified as a suitable method to strip Pro resulting in pure MTG with high specific activity up to 49.6 U/mg. The purified acetylated MTG was characterized by MS analysis. The deconvoluted mass and Peptide Sequence Tags analysis confirmed acetylation on amino groups of MTG protein. Finally, the applications of obtained MTG were demonstrated via protein polymerization of bovine serum albumin and PEGylation of human interferon-α2b. Our method provides MTG with high purity and specific activity as well as unique merit with masked amino groups thus avoiding self-polymerization and cross-linking between MTG and substrates.

[Effect of Recombinant Human Thrombopoietin (rhTPO) on Long-term Hematopoietic Recovery in Mice with Acute Radiation Sickness and Relative Mechanism].

OBJECTIVE: To investigate the effect and relative mechanism of Recombinant Human Thrombopoietin (rhTPO) on long-term hematopoietic recovery in mice with acute radiation sickness. METHODS: Mice were intramuscularly injected with rhTPO (100 µg/kg) 2 hours after total body irradiation with 60Co γ-rays (6.5 Gy). Moreover, six months after irradiation, peripheral blood, hematopoietic stem cells (HSC) ratio, competitive transplantation survival rate and chimerization rate, senescence rate of c-kit+ HSC, and p16 and p38 mRNA expression of c-kit+ HSC were detected. RESULTS: Six months after 6.5 Gy γ-ray irradiation, there were no differences in peripheral blood white blood cells, red blood cells, platelets, neutrophils and bone marrow nucleated cells in normal group, irradiated group and rhTPO group (P>0.05). The proportion of hematopoietic stem cells and multipotent progenitor cells in mice of irradiated group was significantly decreased after irradiation (P<0.05), but there was no significant changes in rhTPO group (P>0.05). The counts of CFU-MK and BFU-E in irradiated group were significantly lower than that in normal group, and rhTPO group was higher than that of the irradiated group(P<0.05). The 70 day survival rate of recipient mice in normal group and rhTPO group was 100%, and all mice died in irradiation group. The senescence positive rates of c-kit+ HSC in normal group, irradiation group and rhTPO group were 6.11%, 9.54% and 6.01%, respectively (P<0.01). Compared with the normal group, the p16 and p38 mRNA expression of c-kit+ HSC in the irradiated mice were significantly increased (P<0.01), and it was markedly decreased after rhTPO administration (P<0.01). CONCLUSION: The hematopoietic function of mice is still decreased 6 months after 6.5 Gy γ-ray irradiation, suggesting that there may be long-term damage. High-dose administration of rhTPO in the treatment of acute radiation sickness can reduce the senescence of HSC through p38-p16 pathway and improve the long-term damage of hematopoietic function in mice with acute radiation sickness.

A classification scheme for mixed-species bird flocks.

The literature on mixed-species flocks references a wide variety of bird associations. These studies, however, have used an array of unstructured characteristics to describe flocks, ranging from the temporal occurrence of flocking to the identity and behavioural features of constituent members, with little consensus on which key traits define and characterize a mixed-species flock. Moreover, although most studies report species-specific roles, there is no clear consensus about what these roles signify nor how to define them. This lack of consistency limits our ability to compare flocks from different habitats, regions and species pools. To unify this sizable body of literature, we reviewed and synthesized 538 studies on mixed-species flocks. We propose 13 categories to classify mixed-species flocks using behavioural and physical traits at the flock and participant level, as well as the habitat where the flock occurs. Lastly, we discuss the historical terminology for different species roles and propose definitions to clarify and distinguish among nuclear, leader, sentinel, and flock-following species. We envision that these guidelines will provide a universal language for mixed-species flock research, paving the way for future comparisons and new insight between different regions and systems. This article is part of the theme issue 'Mixed-species groups and aggregations: shaping ecological and behavioural patterns and processes'.

RNA N6-methyladenosine modification-based biomarkers for absorbed ionizing radiation dose estimation.

Radiation triage and biological dosimetry are critical for the medical management of massive potentially exposed individuals following radiological accidents. Here, we performed a genome-wide screening of radiation-responding mRNAs, whose N6-methyladenosine (m6A) levels showed significant alteration after acute irradiation. The m6A levels of three genes, Ncoa4, Ate1 and Fgf22, in peripheral blood mononuclear cells (PBMCs) of mice showed excellent dose-response relationships and could serve as biomarkers of radiation exposure. Especially, the RNA m6A of Ncoa4 maintained a high level as long as 28 days after irradiation. We demonstrated its responsive specificity to radiation, conservation across the mice, monkeys and humans, and the dose-response relationship in PBMCs from cancer patients receiving radiation therapy. Finally, NOCA4 m6A-based biodosimetric models were constructed for estimating absorbed radiation doses in mice or humans. Collectively, this study demonstrated the potential feasibility of RNA m6A in radiation accidents management and clinical applications.