Low ACADM expression predicts poor prognosis and suppressive tumor microenvironment in clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) represents a highly frequent renal cancer subtype. However, medium-chain acyl-CoA dehydrogenase (ACADM) encodes an important enzyme responsible for fatty acid ß-oxidation (FAO) and its association with prognosis and immunity in cancers has rarely been reported. Therefore, the present work focused on exploring ACADM's expression and role among ccRCC cases. We used multiple public databases and showed the hypo levels of ACADM protein and mRNA within ccRCC. Additionally, we found that ACADM down-regulation showed a remarkable relation to the advanced stage, high histological grade, as well as dismal prognostic outcome. As suggested by Kaplan-Meier curve analysis, cases showing low ACADM levels displayed shorter overall survival (OS) as well as disease-free survival (DFS). Moreover, according to univariate/multivariate Cox regression, ACADM-mRNA independently predicted the prognosis of ccRCC. In addition, this work conducted immunohistochemistry for validating ACADM protein expression and its prognostic role in ccRCC samples. KEGG and GO analyses revealed significantly enriched genes related to ACADM expression during fatty acid metabolism. The low-ACADM group with more regulatory T-cell infiltration showed higher expression of immune negative regulation genes and higher TIDE scores, which might contribute to poor response to immunotherapies. In conclusion, our results confirmed that downregulated ACADM predicted a poor prognosis for ccRCC and a poor response to immunotherapy. Our results provide important data for developing immunotherapy for ccRCC.

Feasibility of implant placement in healed mandibular molar sites: A retrospective cone beam computed tomography study.

STATEMENT OF PROBLEM: Implant placement in the mandibular molar sites plays a crucial role in the restoration of edentulous mandibles. However, the evaluation of bone quantity before implant surgery using cone beam computed tomography (CBCT) is lacking. PURPOSE: The purpose of this clinical study was to evaluate CBCT images of edentulous patients to analyze the feasibility of implant placement in healed mandibular molar sites. MATERIAL AND METHODS: The CBCT data of 138 patients were analyzed in the sagittal plane for measurements of mandibular bone height (MBH), superior bone height (SBH), inferior bone height (IBH), buccal bone width (BBW), lingual bone width (LBW), and alveolar bone widths (ABWs). The edentulous sites were categorized according to the bone quantity and complexity of the implant surgery. Multivariate analysis of variance (MANOVA) was used to analyze the site, sex, and age-related variations. An independent t test was used to compare the difference of bone dimension in different sites and between sexes. One-way ANOVA followed by post hoc tests were used to analyze the difference between different age groups. Categorical variables were presented as number of events and percentages. The chi-squared test was used to compare categorical variables (α=.05). RESULTS: A total of 534 sites of interest were recorded, including 274 hemimandibles. A significant difference in BBW was found between the first and second molar sites. Men had higher MBH, SBH, IBH, and BBW than women. The distribution of implant surgical complexity in the conventional group was 63.5%, while the buccolingual tilted implant group accounted for 17.0%, and the complicated group accounted for 19.5%. Of the 274 hemimandibles, an implant could be placed directly at molar sites in 88% of situations. CONCLUSIONS: The BBW at the mandibular second molar site was greater than that at the first molar site. The amount of available bone in the SBH and BBW was greater in men than in women at the healed molar sites. Age did not significantly affect the complexity of the implant surgery. Implants can be placed directly in healed mandibular molar sites in most patients who require a complete arch mandibular implant-supported restoration.

Preliminary study of low-pressure ionization chamber for online dose monitoring in FLASH carbon ion radiotherapy.

The FLASH effect of carbon ion therapy has recently attracted significant attention from the scientific community. However, the radiobiological mechanism of the effect and the exact therapeutic conditions are still under investigation. Therefore, the dosimetry accuracy is critical for testing hypotheses about the effect and quantifying FLASH Radiotherapy. In this paper, the FLASH ionization chamber at low-pressure was designed, and its dose rate dependence was verified with the Faraday cup. In addition, the dose response was tested under the air pressure of the ionization chamber of 10 mbar, 80 mbar and 845 mbar, respectively. The results showed that when the pressure was 10 mbar, the dose linearity was verified and calibrated at the dose rate of ∼50 Gy s-1, and the residuals were less than 2%. In conclusion, the FLASH ionization chamber is a promising instrument for online dose monitoring.

Autotransplantation for Restoration of Dentition Defects After Excision of Jaw Cysts.

Bone defect caused by jaw cystectomy has always been the main factor affecting postoperative wound healing and is also the common cause of maxillofacial bone defect, which brings challenges to the subsequent restoration of missing teeth. In this paper, the authors report a 22-year-old young woman who had a mandibular cyst in the left lower posterior tooth area. She underwent mandibular bone cyst excision and simultaneous extraction of teeth 36 and 37. One and two months after the removal of the mandibular bone cyst, autologous tooth transplantation was performed in stages from tooth 28 to tooth 36 and from tooth 18 to tooth 37. The case shows that tooth autotransplantation is a viable option for the restoration of dentition defects after the excision of jaw cysts, which can promote the healing of the bone defect after the operation.

Branched-chain amino acid catabolic defect promotes α-cell proliferation via activating mTOR signaling.

Elevated circulating level of branched-chain amino acids (BCAAs) is closely related to the development of type 2 diabetes. However, the role of BCAA catabolism in various tissues in maintaining glucose homeostasis remains largely unknown. Pancreatic α-cells have been regarded as amino acid sensors in recent years. Therefore, we generated α-cell specific branched-chain alpha-ketoacid dehydrogenase E1α subunit (BCKDHA) knockout (BCKDHA-αKO) mice to decipher the effects of BCAA catabolism in α-cells on whole-body energy metabolism. BCKDHA-αKO mice showed normal body weight, body fat, and energy expenditure. Plasma glucagon level and glucose metabolism also remained unchanged in BCKDHA-αKO mice. Whereas, the deletion of BCKDHA led to increased α-cell number due to elevated cell proliferation in neonatal mice. In vitro, only leucine among BCAAs promoted aTC1-6 cell proliferation, which was blocked by the agonist of BCAA catabolism BT2 and the inhibitor of mTOR Rapamycin. Like Rapamycin, BT2 attenuated leucine-stimulated phosphorylation of S6 in αTC1-6 cells. Elevated phosphorylation level of S6 protein in pancreatic α-cells was also observed in BCKDHA-αKO mice. These results suggest that local accumulated leucine due to defective BCAA catabolism promotes α-cell proliferation through mTOR signaling, which is insufficient to affect glucagon secretion and whole-body glucose homeostasis.

Diadenosine tetraphosphate modulated quorum sensing in bacteria treated with kanamycin.

BACKGROUND: The dinucleotide alarmone diadenosine tetraphosphate (Ap4A), which is found in cells, has been shown to affect the survival of bacteria under stress. RESULTS: Here, we labeled Ap4A with biotin and incubated the labeled Ap4A with the total proteins extracted from kanamycin-treated Escherichia coli to identify the Ap4A binding protein in bacteria treated with kanamycin. Liquid chromatography‒mass spectrometry (LCMS) and bioinformatics were used to identify novel proteins that Ap4A interacts with that are involved in biofilm formation, quorum sensing, and lipopolysaccharide biosynthesis pathways. Then, we used the apaH knockout strain of E. coli K12-MG1655, which had increased intracellular Ap4A, to demonstrate that Ap4A affected the expression of genes in these three pathways. We also found that the swarming motility of the apaH mutant strain was reduced compared with that of the wild-type strain, and under kanamycin treatment, the biofilm formation of the mutant strain decreased. CONCLUSIONS: These results showed that Ap4A can reduce the survival rate of bacteria treated with kanamycin by regulating quorum sensing (QS). These effects can expand the application of kanamycin combinations in the treatment of multidrug-resistant bacteria.

Post-Subfunctionalization Functions of HIF-1αA and HIF-1αB in Cyprinid Fish: Fine-Tuning Mitophagy and Apoptosis Regulation Under Hypoxic Stress.

Hypoxia-inducible factor 1 (HIF-1) is a crucial transcriptional factor that can restore oxygen balance in the body by regulating multiple vital activities. Two HIF-1α copies were retained in cyprinid fish after experiencing a teleost-specific genome duplication. How the "divergent collaboration" of HIF-1αA and HIF-1αB proceeds in regulating mitophagy and apoptosis under hypoxic stress in cells of cyprinid fish remains unclear. In this study, zebrafish HIF-1αA/B expression plasmids were constructed and transfected into the epithelioma papulosum cyprini cells and were subjected to hypoxic stress. HIF-1αA induced apoptosis through promoting ROS generation and mitochondrial depolarization when cells were subjected to oxygen deficiency. Conversely, HIF-1αB was primarily responsible for mitophagy induction, prompting ATP production to mitigate apoptosis. HIF-1αA did not induce mitophagy in the mitochondria and lysosomes co-localization assay but it was involved in the regulation of different mitophagy pathways. Over-expression of HIF-1αA increased the expression of bnip3, fundc1, Beclin1, and foxo3, suggesting it has a dual role in mitochondrial autophagy and cell death. Each duplicated copy also experienced functional divergence and target shifting in the regulation of complexes in the mitochondrial electron transport chain (ETC). Our findings shed light on the post-subfunctionalization function of HIF-1αA and HIF-1αB in zebrafish to fine-tune regulation of mitophagy and apoptosis following hypoxia exposure.

Acetyltransferases CBP/p300 Control Transcriptional Switch of ß-Catenin and Stat1 Promoting Osteoblast Differentiation.

CREB-binding protein (CBP) (CREBBP) and p300 (EP300) are multifunctional histone acetyltransferases (HATs) with extensive homology. Germline mutations of CBP or p300 cause skeletal abnormalities in humans and mice. However, the precise roles of CBP/p300 in bone homeostasis remain elusive. Here, we report that conditional knockout of CBP or p300 in osteoblasts results in reduced bone mass and strength due to suppressed bone formation. The HAT activity is further confirmed to be responsible for CBP/p300-mediated osteogenesis using A-485, a selective inhibitor of CBP/p300 HAT. Mechanistically, CBP/p300 HAT governs osteogenic gene expression in part through transcriptional activation of ß-catenin and inhibition of Stat1. Furthermore, acetylation of histone H3K27 and the transcription factor Foxo1 are demonstrated to be involved in CBP/p300 HAT-regulated ß-catenin and Stat1 transcription, respectively. Taken together, these data identify acetyltransferases CBP/p300 as critical regulators that promote osteoblast differentiation and reveal an epigenetic mechanism responsible for maintaining bone homeostasis. © 2023 American Society for Bone and Mineral Research (ASBMR).

Jaw Osteomyelitis of Impacted Tooth After Radiotherapy: A Report of a Case.

Maxillofacial radiotherapy has a significant negative impact on oral health and impacted teeth often lead to diseases such as jaw cysts and periapical periodontitis. This article reports a case of jaw osteomyelitis (with both impacted teeth and periodontitis) occurring 10 years after radiotherapy for nasopharyngeal carcinoma. There is no systematic treatment plan for patients with both pathogenic factors in clinical practice, so it is important to develop a systematic and complete treatment plan before radiotherapy and chemotherapy. The periodontal treatment of patients receiving radiotherapy and the timing of extraction of impacted teeth are mainly discussed.

Identification of genes related to glucose metabolism and analysis of the immune characteristics in Alzheimer's disease.

OBJECTIVE: Glucose metabolism plays a crucial role in the progression of Alzheimer's disease (AD). The purpose of this study is to identify genes related to glucose metabolism in AD by bioinformatics, construct an early AD prediction model from the perspective of glucose metabolism, and analyze the characteristics of immune cell infiltration. METHODS: AD-related modules and genes were screened by weighted gene co-expression network analysis (WGCNA). The GO and KEEG enrichment analysis were used to explore the potential biological functions of glucose metabolism related genes (GMRGs) in AD. The Least Absolute Shrinkage Selection Operator (LASSO) method was used to construct an early AD prediction model based on GMRGs. Then, the receiver operating characteristic curve (ROC) and nomogram were introduced to evaluate the effectiveness of this model. Finally, CIBERSORT and single-cell analysis were applied for illustrating the immune characteristics in AD patients. RESULTS: A total of 462 differential expressed genes (DEGs) were obtained between Non-Alzheimer's disease (ND,) and AD groups. The genes in the blue module had the highest correlation with AD by WGCNA analysis. We found 18 intersected genes among DEGs, blue model genes and GMRGs according to the Venn diagram. The GO and KEEG enrichment analysis showed that these 18 genes were mainly involved in the production of metabolites and energy, glycolysis, amino acid biosynthesis and so on. The early AD prediction model including ENO2, TPI1, AEBP1, HERC1, PCSK1, PREPL, SLC25A4, UQCRC2, CHST6, DDIT4, ACSS1 and SUCLA2 was constructed by LASSO analysis. The area under the curve (AUC) of this model in brain tissues was 0.942. Then, we draw the nomogram of this model and the C-index was 0.942. The model was further validated in blood samples and the AUC was 0.644. Immune cell infiltration analysis showed that the proportion of plasma cells, T cells follicular helper and activated NK cells in AD group were significantly lower than ND group, while the proportion of M1 macrophages, neutrophils, T cells CD4 naive and γ-δ T cells was significantly increased when compared with the ND group. Additionally, the specific GMRGs such as ENO2, DDIT4, and SUCLA2 are significantly correlated with certain immune cells such as plasma cells, follicular helper T cells, and M1 macrophages. Single-cell analysis results suggested that the increased macrophages in AD was associated with the up-regulation of AEBP1, DDIT4 and ACSS1. CONCLUSIONS: The diagnosis model based on the twelve GMRGs has strong predictive ability and can be used as early diagnosis biomarkers for AD. In addition, these GMRGs closely associate with AD development by influencing the glucose metabolism of immune cells.

Discovery of a Novel Class of Benzimidazole-Based Nicotinic Acetylcholine Receptor Modulators: Positive and Negative Modulation Arising from Overlapping Allosteric Sites.

Here, we present the discovery of a novel class of benzimidazole-based allosteric modulators of nicotinic acetylcholine receptors (nAChRs). The modulators were developed based on a compound (1) exhibiting positive modulatory activity at α4ß2 nAChR in a compound library screening by functional characterization of 100 analogues of 1 at nAChRs. Two distinct series of positive and negative allosteric modulators (PAMs and NAMs, respectively) comprising benzimidazole as a shared structural moiety emerged from this SAR study. The PAMs mediated weak modulation of α4ß2 and α6ß2ß3, whereas the NAMs exhibited essentially equipotent inhibition of α4ß2, α6ß2ß3, α6ß4ß3, and α3ß4 nAChRs, with analogue 9j [2-(2,4-dichlorophenoxy)-1,3-dimethyl-1-H-benzo[d]imidazole-3-ium] displaying high-nanomolar and low-micromolar IC50 values at the ß2- and ß4-containing receptor subtypes, respectively. We propose that the PAMs and NAMs act through overlapping sites in the nAChR, and these findings thus underline the heterogenous modes of modulation that can arise from a shared allosteric site in the receptor.

Identification of 5-HT2 Serotonin Receptor Modulators through the Synthesis of a Diverse, Tropane- and Quinuclidine-alkaloid-Inspired Compound Library.

The recombination of natural product (NP) fragments in unprecedented ways has emerged as an important strategy for bioactive compound discovery. In this context, we propose that privileged primary fragments predicted to be enriched in activity against a specific target class can be coupled to diverse secondary fragments to engineer selectivity among closely related targets. Here, we report the synthesis of an alkaloid-inspired compound library enriched in spirocyclic ring fusions, comprising 58 compounds from 12 tropane- or quinuclidine-containing scaffolds, all of which can be considered pseudo-NPs. The library displays excellent predicted drug-like properties including high Fsp3 content and Lipinski's rule-of-five compliance. Targeted screening against selected members of the serotonin and dopamine G protein-coupled receptor family led to the identification of several hits that displayed significant agonist or antagonist activity against 5-HT2A and/or 5-HT2C, and subsequent optimization of one of these delivered a lead dual 5-HT2B/C antagonist with a highly promising selectivity profile.

A large-scale whole-exome sequencing mutant resource for functional genomics in wheat.

Hexaploid wheat (Triticum aestivum), a major staple crop, has a remarkably large genome of ~14.4 Gb (containing 106 913 high-confidence [HC] and 159 840 low-confidence [LC] genes in the Chinese Spring v2.1 reference genome), which poses a major challenge for functional genomics studies. To overcome this hurdle, we performed whole-exome sequencing to generate a nearly saturated wheat mutant database containing 18 025 209 mutations induced by ethyl methanesulfonate (EMS), carbon (C)-ion beams, or γ-ray mutagenesis. This database contains an average of 47.1 mutations per kb in each gene-coding sequence: the potential functional mutations were predicted to cover 96.7% of HC genes and 70.5% of LC genes. Comparative analysis of mutations induced by EMS, γ-rays, or C-ion beam irradiation revealed that γ-ray and C-ion beam mutagenesis induced a more diverse array of variations than EMS, including large-fragment deletions, small insertions/deletions, and various non-synonymous single nucleotide polymorphisms. As a test case, we combined mutation analysis with phenotypic screening and rapidly mapped the candidate gene responsible for the phenotype of a yellow-green leaf mutant to a 2.8-Mb chromosomal region. Furthermore, a proof-of-concept reverse genetics study revealed that mutations in gibberellic acid biosynthesis and signalling genes could be associated with negative impacts on plant height. Finally, we built a publically available database of these mutations with the corresponding germplasm (seed stock) repository to facilitate advanced functional genomics studies in wheat for the broad plant research community.

Comparative analysis of the molecular response characteristics in Platycodon grandiflorus irradiated with heavy ion beams and X-rays.

The response of plants to radiation is an essential topic in both space plant cultivation and mutation breeding by radiation. In this study, heavy ion beams (HIB) generated by the ground accelerator and X-rays (XR) were used as models of high linear energy transfer (LET) and low LET radiation to study the molecular response mechanism of Platycodon grandiflorus (P. grandiflorus) seedlings after irradiation. The gene and protein expression profiles of P. grandiflorus after 15 Gy HIB and 20 Gy XR radiation were analyzed by transcriptome and proteome. The results showed that the number of differentially expressed genes (DEGs) induced by HIB radiation was less than that of XR group, but HIB radiation induced more differentially expressed proteins (DEPs). Both HIB and XR radiation activated genes of RNA silencing, double-strand break repair and cell catabolic process. DNA replication and cell cycle related genes were down-regulated. The genes of cell wall and external encapsulating structure were up-regulated after HIB radiation. The gene expression of protein folding and glucan biosynthesis increased after XR radiation. Protein enrichment analysis indicated that HIB radiation resulted in differential protein enriched in photosynthesis and secondary metabolite biosynthesis pathways, while XR radiation induced differential protein of glyoxylate and dicarboxylate metabolism and carbon metabolism. After HIB and XR radiation, the genes of antioxidant system and terpenoid and polyketide metabolic pathways presented different expression patterns. HIB radiation led to the enrichment of non-homologous end-joining pathway. The results will contribute to understanding the biological effects of plants under space radiation.

Multi-generation study of heavy ion beam-induced mutations and agronomic trait variations to accelerate rice breeding.

Heavy ion beam (HIB) is an effective physical mutagen that has been widely used in plant mutational breeding. Systemic knowledge of the effects caused by different HIB doses at developmental and genomic levels will facilitate efficient breeding for crops. Here we examined the effects of HIB systematically. Kitaake rice seeds were irradiated by ten doses of carbon ion beams (CIB, 25 - 300 Gy), which is the most widely used HIB. We initially examined the growth, development and photosynthetic parameters of the M1 population and found that doses exceeding 125 Gy caused significant physiological damages to rice. Subsequently, we analyzed the genomic variations in 179 M2 individuals from six treatments (25 - 150 Gy) via whole-genome sequencing (WGS). The mutation rate peaks at 100 Gy (2.66×10-7/bp). Importantly, we found that mutations shared among different panicles of the same M1 individual are at low ratios, validating the hypothesis that different panicles may be derived from different progenitor cells. Furthermore, we isolated 129 mutants with distinct phenotypic variations, including changes in agronomic traits, from 11,720 M2 plants, accounting for a 1.1% mutation rate. Among them, about 50% possess stable inheritance in M3. WGS data of 11 stable M4 mutants, including three lines with higher yields, reveal their genomic mutational profiles and candidate genes. Our results demonstrate that HIB is an effective tool that facilitates breeding, that the optimal dose range for rice is 67 - 90% median lethal dose (LD50), and that the mutants isolated here can be further used for functional genomic research, genetic analysis, and breeding.

Physiological and Transcriptomic Analyses Reveal the Effects of Carbon-Ion Beam on Taraxacum kok-saghyz Rodin Adventitious Buds.

Taraxacum kok-saghyz Rodin (TKS) has great potential as an alternative natural-rubber (NR)-producing crop. The germplasm innovation of TKS still faces great challenges due to its self-incompatibility. Carbon-ion beam (CIB) irradiation is a powerful and non-species-specific physical method for mutation creation. Thus far, the CIB has not been utilized in TKS. To better inform future mutation breeding for TKS by the CIB and provide a basis for dose-selection, adventitious buds, which not only can avoid high levels of heterozygosity, but also further improve breeding efficiency, were irradiated here, and the dynamic changes of the growth and physiologic parameters, as well as gene expression pattern were profiled, comprehensively. The results showed that the CIB (5-40 Gy) caused significant biological effects on TKS, exhibiting inhibitory effects on the fresh weight and the number of regenerated buds and roots. Then,15 Gy was chosen for further study after comprehensive consideration. CIB-15 Gy resulted in significant oxidative damages (hydroxyl radical (OH•) generation activity, 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging activity and malondialdehyde (MDA) content) and activated the antioxidant system (superoxide dismutase (SOD), catalase (CAT), peroxidase (POD), and ascorbate peroxidase (APX)) of TKS. Based on RNA-seq analysis, the number of differentially expressed genes (DEGs) peaked at 2 h after CIB irradiation. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that DNA-replication-/repair- (mainly up-regulated), cell-death- (mainly up-regulated), plant-hormone- (auxin and cytokinin, which are related to plant morphogenesis, were mainly down-regulated), and photosynthesis- (mainly down-regulated) related pathways were involved in the response to the CIB. Furthermore, CIB irradiation can also up-regulate the genes involved in NR metabolism, which provides an alternative strategy to elevate the NR production in TKS in the future. These findings are helpful to understand the radiation response mechanism and further guide the future mutation breeding for TKS by the CIB.

Role of serum- and glucocorticoid-inducible kinase 1 in the regulation of hepatic gluconeogenesis.

Excessive hepatic gluconeogenesis partially accounts for the occurrence of type 2 diabetes mellitus. Serum- and glucocorticoid inducible-kinase 1 (SGK1) is linked to the development of metabolic syndrome, such as obesity, hypertension, and hyperglycemia. However, the regulatory role of SGK1 in glucose metabolism of liver remains uncertain. Our microarray analysis showed that SGK1 expression was strongly induced by 8-Br-cAMP and suppressed by metformin in primary mouse hepatocytes. Hepatic SGK1 expression was markedly increased in obese and diabetic mice. Metformin treatment decreased hepatic SGK1 expression levels in db/db mice. Inhibition or knockdown of SGK1 suppressed gluconeogenesis in primary mouse hepatocytes, with decreased expressions of key gluconeogenic genes. Furthermore, SGK1 silencing in liver decreased hepatic glucose production in C57BL/6 mice. Knockdown of SGK1 had no impact on CREB phosphorylation level but increased AKT and FoxO1 phosphorylation levels with decreased expressions of transcription factors including FoxO1 and hepatocyte nuclear factors. Adenovirus-mediated expression of dominant-negative AMPK antagonized metformin-suppressed SGK1 expression induced by 8-Br-cAMP. These findings demonstrate that hepatic specific silence of SGK1 might be a potential therapeutic strategy for type 2 diabetes.

Integrative transcriptome and metabolome revealed the molecular mechanism of Bacillus megaterium BT22-mediated growth promotion in Arabidopsis thaliana.

Plant growth-promoting rhizobacteria (PGPR) can promote plant growth and protect plants from pathogens, which contributes to sustainable agricultural development. Several studies have reported their beneficial characteristics in facilitating plant growth and development and enhancing plant stress resistance through different mechanisms. However, there is still a challenge to study the molecular mechanism of plant response to PGPR. We integrated the transcriptome and metabolome of Arabidopsis thaliana (Arabidopsis) to understand its responses to the inoculation with an isolated PGPR strain (BT22) of Bacillus megaterium. Fresh shoot weight, dry shoot weight and leaf number of Arabidopsis were increased by BT22 treatment, showing a positive growth-promoting effect. According multi-omics analysis, 878 differentially expressed genes (296 up-regulated, 582 down-regulated) and 139 differentially expressed metabolites (66 up-regulated, 73 down-regulated) response to BT22 inoculation. GO enrichment results indicate that the up-regulated genes mainly enriched in the regulation of growth and auxin response pathways. In contrast, the down-regulated genes mainly enriched in wounding response, jasmonic acid and ethylene pathways. BT22 inoculation regulated plant hormone signal transduction of Arabidopsis, including auxin and cytokinin response genes AUX/IAA, SAUR, and A-ARR related to cell enlargement and cell division. The contents of nine flavonoids and seven phenylpropanoid metabolites were increased, which help to induce systemic resistance in plants. These results suggest that BT22 promoted Arabidopsis growth by regulating plant hormone homeostasis and inducing metabolome reprogramming.

Comparison and Characterization of Phenotypic and Genomic Mutations Induced by a Carbon-Ion Beam and Gamma-ray Irradiation in Soybean (Glycine max (L.) Merr.).

Soybean (Glycine max (L.) Merr.) is a nutritious crop that can provide both oil and protein. A variety of mutagenesis methods have been proposed to obtain better soybean germplasm resources. Among the different types of physical mutagens, carbon-ion beams are considered to be highly efficient with high linear energy transfer (LET), and gamma rays have also been widely used for mutation breeding. However, systematic knowledge of the mutagenic effects of these two mutagens during development and on phenotypic and genomic mutations has not yet been elucidated in soybean. To this end, dry seeds of Williams 82 soybean were irradiated with a carbon-ion beam and gamma rays. The biological effects of the M1 generation included changes in survival rate, yield and fertility. Compared with gamma rays, the relative biological effectiveness (RBE) of the carbon-ion beams was between 2.5 and 3.0. Furthermore, the optimal dose for soybean was determined to be 101 Gy to 115 Gy when using the carbon-ion beam, and it was 263 Gy to 343 Gy when using gamma rays. A total of 325 screened mutant families were detected from out of 2000 M2 families using the carbon-ion beam, and 336 screened mutant families were found using gamma rays. Regarding the screened phenotypic M2 mutations, the proportion of low-frequency phenotypic mutations was 23.4% when using a carbon ion beam, and the proportion was 9.8% when using gamma rays. Low-frequency phenotypic mutations were easily obtained with the carbon-ion beam. After screening the mutations from the M2 generation, their stability was verified, and the genome mutation spectrum of M3 was systemically profiled. A variety of mutations, including single-base substitutions (SBSs), insertion-deletion mutations (INDELs), multinucleotide variants (MNVs) and structural variants (SVs) were detected with both carbon-ion beam irradiation and gamma-ray irradiation. Overall, 1988 homozygous mutations and 9695 homozygous + heterozygous genotype mutations were detected when using the carbon-ion beam. Additionally, 5279 homozygous mutations and 14,243 homozygous + heterozygous genotype mutations were detected when using gamma rays. The carbon-ion beam, which resulted in low levels of background mutations, has the potential to alleviate the problems caused by linkage drag in soybean mutation breeding. Regarding the genomic mutations, when using the carbon-ion beam, the proportion of homozygous-genotype SVs was 0.45%, and that of homozygous + heterozygous-genotype SVs was 6.27%; meanwhile, the proportions were 0.04% and 4.04% when using gamma rays. A higher proportion of SVs were detected when using the carbon ion beam. The gene effects of missense mutations were greater under carbon-ion beam irradiation, and the gene effects of nonsense mutations were greater under gamma-ray irradiation, which meant that the changes in the amino acid sequences were different between the carbon-ion beam and gamma rays. Taken together, our results demonstrate that both carbon-ion beam and gamma rays are effective techniques for rapid mutation breeding in soybean. If one would like to obtain mutations with a low-frequency phenotype, low levels of background genomic mutations and mutations with a higher proportion of SVs, carbon-ion beams are the best choice.

The bright side of ecological stressors.

Ecological stressors are considered to negatively affect biological systems; however, corresponding responses to stressors can be complex, depending on the ecological functions and the number and duration of the stressors. Mounting evidence indicates potential benefits of stressors. Here, we develop an integrative framework to understand stressor-induced benefits by clarifying three categories of mechanisms: seesaw effects, cross-tolerance, and memory effects. These mechanisms operate across various organizational levels (e.g., individual, population, community) and can be extended to an evolutionary context. One remaining challenge is to develop scaling approaches for linking stressor-induced benefits across organizational levels. Our framework provides a novel platform for predicting the consequences of global environmental changes and informing management strategies in conservation and restoration practices.