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Abstract The filamentous ‘Pf’ bacteriophages of Pseudomonas aeruginosa play roles in biofilm formation and virulence, but mechanisms governing Pf prophage activation in biofilms are unclear. Here, we identify a prophage regulatory module, KKP (kinase-kinase-phosphatase), that controls virion production of co-resident Pf prophages and mediates host defense against diverse lytic phages. KKP consists of Ser/Thr kinases PfkA and PfkB, and phosphatase PfpC. The kinases have multiple host targets, one of which is MvaU, a host nucleoid-binding protein and known prophage-silencing factor. Characterization of KKP deletion and overexpression strains with transcriptional, protein-level and prophage-based approaches indicates that shifts in the balance between kinase and phosphatase activities regulate phage production by controlling MvaU phosphorylation. In addition, KKP acts as a tripartite toxin-antitoxin system that provides defense against some lytic phages. A conserved lytic phage replication protein inhibits the KKP phosphatase PfpC, stimulating toxic kinase activity and blocking lytic phage production. Thus, KKP represents a phosphorylation-based mechanism for prophage regulation and antiphage defense. The conservation of KKP gene clusters in >1000 diverse temperate prophages suggests that integrated control of temperate and lytic phage infection by KKP-like regulatory modules may play a widespread role in shaping host cell physiology.

The monitoring of neutron ambient dose equivalent rate in a radiation field is of significant importance as it can reflect the operational status of nuclear facilities and provide radiation protection information. Currently, the commonly used monitoring instrument is the A-B type dose equivalent rate meter based on a single detector and a single moderator. However, its response curve differs from the “neutron fluence-ambient dose equivalent conversion coefficient,” leading to measurement errors. In this study, in order to improve the accuracy of neutron dosimeter measurement, a feasibility study was carried out on the joint monitoring of neutron dose rate based on neutrons and instant γ-rays. Lead, borated polyethylene, polymethyl methacrylate, and sodium chloride were used to establish a conversion object. Monte Carlo simulations were performed to calculate the neutron responses of elements B, H, Cl, Pb, C and O. Then, these response curves were combined with the response curves of the LB6411 dosimeter to obtain a new response curve closer to the “neutron fluence-ambient dose equivalent conversion coefficient”. The linear fitting coefficients were calculated by using the differential evolution algorithm. The results demonstrate that the modified response curve is closely to the \begin{document}$h_{\phi} $\end{document} response curve. The relative discrepancies are within 50% for the energy range of 1×10−8-16 MeV. The study indicates the feasibility of joint measurement of neutron and prompt gamma-ray for monitoring neutron ambient dose equivalent rate, providing new directions and support for neutron dosimeter calibration and development.

Bacterial cellulose (BC) is an exopolysaccharide with unique properties that has been applied in various fields. However, the dense and intertwined nature of BC fibers limits its use in certain applications, including 3D printing scaffolds for bone regeneration. In this work, a controllable BC-based bio-ink for 3D printing was successfully prepared by modifying the neat BC through maleic acid (MA) treatment, aiming to promote bone tissue regeneration. To achieve homogeneous BC dispersions while preserving its crystalline and chemical properties, BC was modified by MA solution (60 %, w/V) with solid-liquid ratio from 1꞉5 to 1꞉50 (w/V) to obtain MA-BC dispersions. The analysis results from microstructure, chemical group, crystallinity, and wettability indicated that the BC/MA solution with ratio of 1꞉30 demonstrated the best pre-treatment performance to obtain MA-BC. Subsequently, by combining MA-BC with gelatin, we successfully formulated MA-BC-GEL gels with favorable rheological properties and compression modulus, which can be used as promising bio-inks for 3D bioprinting applications. In vitro tests demonstrated 1꞉30 MA-BC possessed excellent biocompatibility, a significant ability to express the alkaline phosphatase gene and osteogenic-related genes, and facilitated the formation of mineralized nodules. The utilization of this novel bio-ink in scaffold preparation for bone regeneration highlights the promising application of modified BC in bone tissue engineering field.

Lesion mimic often exhibits leaf disease-like symptoms even in the absence of pathogen infection, and is characterized by a hypersensitive-response (HR) that closely linked to plant disease resistance. Despite this, only a few lesion mimic genes have been identified in wheat. In this investigation, a lesion mimic wheat mutant named je0297 was discovered, showing no alteration in yield components when compared to the wild type (WT). Segregation ratio analysis of the F2 individuals resulting from the cross between the WT and the mutant revealed that the lesion mimic was governed by a single recessive gene in je0297. Using Bulked segregant analysis (BSA) and exome capture sequencing, we mapped the lesion mimic gene designated as lm6 to chromosome 6BL. Further gene fine mapping using 3315 F2 individuals delimited the lm6 within a 1.18 Mb region. Within this region, we identified 16 high-confidence genes, with only two displaying mutations in je0297. Notably, one of the two genes, responsible for encoding flavonol synthase, exhibited altered expression levels. Subsequent phenotype analysis of TILLING mutants confirmed that the gene encoding flavonol synthase was indeed the causal gene for lm6. Transcriptome sequencing analysis revealed that the DEGs between the WT and mutant were significantly enriched in KEGG pathways related to flavonoid biosynthesis, including flavone and flavonol biosynthesis, isoflavonoid biosynthesis, and flavonoid biosynthesis pathways. Furthermore, more than 30 pathogen infection-related (PR) genes exhibited upregulation in the mutant. Corresponding to this expression pattern, the flavonoid content in je0297 showed a significant decrease in the 4th leaf, accompanied by a notable accumulation of reactive oxygen, which likely contributed to the development of lesion mimic in the mutant. This investigation enhances our comprehension of cell death signaling pathways and provides a valuable gene resource for the breeding of disease-resistant wheat.

Abstract Background Headache is a common occurrence after endoscopic endonasal surgery (EES) for pituitary adenomas and significantly impacts the quality of life of patients. This study aims to investigate the effectiveness of nasal irrigation in relieving postoperative headache after EES. Methods A retrospective analysis was conducted on a cohort of 101 patients (Cohort I) who underwent EES for pituitary adenomas to explore the risk factors associated with postoperative headache. Another cohort of 72 patients (Cohort II) who received adjuvant nasal irrigation following surgery was enrolled for further analysis. The Headache Impact Test (HIT-6) was used to score the severity of headache, and patients with a HIT score > 55 were classified as having headache. Results In Cohort I, 21.78% of patients experienced headache one month after EES, which decreased to 5.94% at the three-month follow-up. Multivariate analysis revealed that postoperative nasal sinusitis (OR = 3.88, 95%CI 1.16–13.03, p = 0.028) and Hardy’s grade C-D (OR = 10.53, 95%CI 1.02-109.19, p = 0.049) independently predicted the presence of postoperative headache at one month. At the three-month follow-up, patients with sinusitis had higher HIT-6 scores compared to those without sinusitis (44.43 ± 9.78 vs. 39.72 ± 5.25, p = 0.017). In Cohort II, the incidence of sinusitis at three months was significantly lower than that in Cohort I (p = 0.028). Importantly, both the incidence of headache and HIT-6 scores in Cohort II were significantly lower than those in Cohort I at the one- and three-month follow-ups. Conclusions Postoperative sinusitis is an independent risk factor for the development of headache following EES for pituitary adenomas. Prophylactic nasal irrigation helps relieve postoperative headache, possibly by preventing the occurrence of sinusitis.

ABSTRACTIn order to achieve the goal of preparing functional textiles using tea saponin, in this work, carboxymethylated tea saponin (CTS) was used to modify cotton fabrics by an industrial rolling and baking process, and then functional textiles could be obtained after coordination with Fe3+, which could remove Cr species from water by photocatalytic reduction and adsorption processes. High CTS concentrations and higher treatment temperatures led to an increase in the carboxyl group content (QCOOH) and Fe content (QFe) of the obtained Fe-CTS-Cotton. The increase in the QFe value of the functional textiles favored the photocatalytic reduction of Cr(VI). Fe-CTS-Cotton with high QCOOH values showed excellent adsorption performance for the generated Cr(III) ions during the adsorption process. Therefore, the high photocatalytic reduction efficiency and strong Cr(III) ion trapping ability were the reasons for the recycling of Fe-CTS-cotton as a hybrid photocatalyst for enhanced removal of Cr(VI).

ABSTRACTFlavonoids in ginkgo biloba L. leaf (abbreviated as GBL) extracts exhibited superior biological activity, but their light color limited their development in the field of textiles. Therefore, this work innovatively used GBL extracts as textile functional finishing agent, through exhaustion dyeing process endowed protein fabrics the multifunction. Flavonoids of GBL in protein fabrics showed outstanding rubbing and washing fastness, becuase of their formed strong affinity by electrostatic attraction, hydrogen bond and van der Waals force. Moreover, the flavonoid content on protein fibers was enhanced by the GBL extract concentration increase, treating time stretch, temperature improve. Fourier-transform infrared spectroscopy and X-ray photoelectron spectroscopy result that flavonoids in GBL extracts adsorbent the fibers. In addition, the treated protein fabrics possessed good antioxidant, antibacterial and heavy metal protective performance. Finally,GBL dyed silk fabrics exhibited stronger functionalities than GBL dyed wool fabrics. This work provides the methods that reuse GBL waste and functionalization of protein fabric.

Abstract Background Induction of mutation through chemical mutagenesis is a novel approach for preparing diverse germplasm. Introduction of functional alleles in the starch biosynthetic genes help in the improvement of the quality and yield of cereals. Results In the present study, a set of 350 stable mutant lines were used to evaluate dynamic variation of the total starch contents. A megazyme kits were used for measuring the total starch content, resistant starch, amylose, and amylopectin content. Analysis of variance showed significant variation (p

The erect leaf plays a crucial role in determining plant architecture, with its growth and development regulated by genetic factors. However, there has been a lack of comprehensive studies on the regulatory mechanisms governing wheat lamina joint development, thus failing to meet current breeding demands. In this study, a wheat erect leaf mutant, mths29, induced via fast neutron mutagenesis, was utilized for QTL fine mapping and investigation of lamina joint development. Genetic analysis of segregating populations derived from mths29 and Jimai22 revealed that the erect leaf trait was controlled by a dominant single gene. Using BSR sequencing and map-based cloning techniques, the QTL responsible for the erect leaf trait was mapped to a 1.03 Mb physical region on chromosome 5A. Transcriptome analysis highlighted differential expression of genes associated with cell division and proliferation, as well as several crucial transcription factors and kinases implicated in lamina joint development, particularly in the boundary cells of the preligule zone in mths29. These findings establish a solid foundation for understanding lamina joint development and hold promise for potential improvements in wheat plant architecture.

Abstract Background Plant height (PH) and spike compactness (SC) are important agronomic traits that affect yield improvement in wheat crops. The identification of the loci or genes responsible for these traits is thus of great importance for marker-assisted selection in wheat breeding. Results In this study, we used a recombinant inbred line (RIL) population with 139 lines derived from a cross between the mutant Rht8-2 and the local wheat variety NongDa5181 (ND5181) to construct a high-density genetic linkage map by applying the Wheat 40 K Panel. We identified seven stable QTLs for PH (three) and SC (four) in two environments using the RIL population, and found that Rht8-B1 is the causal gene of qPH2B.1 by further genetic mapping, gene cloning and gene editing analyses. Our results also showed that two natural variants from GC to TT in the coding region of Rht8-B1 resulted in an amino acid change from G (ND5181) to V (Rht8-2) at the 175th position, reducing PH by 3.6%~6.2% in the RIL population. Moreover, gene editing analysis suggested that the height of T2 generation in Rht8-B1 edited plants was reduced by 5.6%, and that the impact of Rht8-B1 on PH was significantly lower than Rht8-D1. Additionally, analysis of the distribution of Rht8-B1 in various wheat resources suggested that the Rht8-B1b allele has not been widely utilized in modern wheat breeding. Conclusions The combination of Rht8-B1b with other favorable Rht genes might be an alternative approach for developing lodging-resistant crops. Our study provides important information for marker-assisted selection in wheat breeding.

Cannabis fructus (Cannabis sativa L.) belongs to the mulberry family, which is one of the earliest cultivated crops by humans and has industrial, agricultural, and medicinal values. In this study, the effect of carbon ion beam irradiation on the physiological and biochemical pathways of cannabis fructus was analyzed by multi-omics. Compared to the unirradiated cannabis fructus stem, 2,891 differentially-expressed genes, 1,145 differentially-expressed proteins, and 954 altered ubiquitination modification sites were identified in cannabis fructus irradiated by carbon ion beam irradiation (60 Gy dosage). Correlation analyses between proteomic, transcriptomic, and ubiquitin modification groups were carried out, and we found that the carbon fixation pathway, fatty acid synthesis pathway, JA synthesis, and glutathione metabolism pathway were enriched in relevant protein levels, and activates the MAPK signaling pathway regulated by gene expression. Further analysis found that the content of some proteins (LOX, AOC, and MDR) was correlated with their respective transcriptional levels, and the content of some proteins (APX, G-6-PD, GST, GAPHD, FBA, AOS, PR1, and ChiB) was correlated with their ubiquitination levels. In addition, M2 generation cannabis fructus seeds exhibited a larger volume, higher thousand-grain weight, and increased linolenic acid content compared to the control group, which was consistent with the trends of our multi-omics analyses. In summary, we demonstrated that 60 Gy carbon ion beam irradiation can enhance the carbon fixation pathway in cannabis fructus and enhance linolenic acid synthesis. Taken together, our multi-omics analysis of the response of cannabis fructus to carbon ion beam irradiation provides a theoretical foundation for readily producing cannabis fructus varieties with advantageous traits in the future.

Abstract Differentiation therapy using small molecules is a promising strategy for improving the prognosis of glioblastoma (GBM). Histone acetylation plays an important role in cell fate determination. Nevertheless, whether histone acetylation in specific sites determines GBM cells fate remains to be explored. Through screening from a 349 small molecule-library, we identified that histone deacetylase inhibitor (HDACi) MS-275 synergized with 8-CPT-cAMP was able to transdifferentiate U87MG GBM cells into neuron-like cells, which were characterized by cell cycle arrest, rich neuron biomarkers, and typical neuron electrophysiology. Intriguingly, acetylation tags of histone 3 at lysine 9 (H3K9ac) were decreased in the promoter of multiple oncogenes and cell cycle genes, while ones of H3K9ac and histone 3 at lysine 14 (H3K14ac) were increased in the promoter of neuron-specific genes. We then compiled a list of genes controlled by H3K9ac and H3K14ac, and proved that it is a good predictive power for pathologic grading and survival prediction. Moreover, cAMP agonist combined with HDACi also induced glioma stem cells (GSCs) to differentiate into neuron-like cells through the regulation of H3K9ac/K14ac, indicating that combined induction has the potential for recurrence-preventive application. Furthermore, the combination of cAMP activator plus HDACi significantly repressed the tumor growth in a subcutaneous GSC-derived tumor model, and temozolomide cooperated with the differentiation-inducing combination to prolong the survival in an orthotopic GSC-derived tumor model. These findings highlight epigenetic reprogramming through H3K9ac and H3K14ac as a novel approach for driving neuron-fate-induction of GBM cells.

Plant height is one of the most important agronomic traits that affects yield in wheat, owing to that the utilization of dwarf or semi-dwarf genes is closely associated with lodging resistance. In this study, we identified a semi-dwarf mutant, jg0030, induced by γ-ray mutagenesis of the wheat variety ‘Jing411’ (wild type). Compared with the ‘Jing411’, plant height of the jg0030 mutant was reduced by 7%-18% in two years’ field experiments, and the plants showed no changes in yield-related traits. Treatment with gibberellic acid (GA) suggested that jg0030 is a GA-sensitive mutant. Analysis of the frequency distribution of plant height in 297 F3 families derived from crossing jg0030 with the ‘Jing411’ indicated that the semi-dwarf phenotype is controlled by a major gene. Using the wheat 660K SNP array-based Bulked Segregant Analysis (BSA) and the exome capture sequencing-BSA assay, the dwarf gene was mapped on the long arm of chromosome 2B. We developed a set of KASP markers and mapped the dwarf gene to a region between marker PH1 and PH7. This region encompassed a genetic distance of 55.21 cM, corresponding to a physical distance of 98.3 Mb. The results of our study provide a new genetic resource and linked markers for wheat improvement in molecular breeding programs.

Abstract Particle surface morphology is an important factor influencing sand structure and mechanical properties. In this study, the effect of sand particle sphericity on sand direct shear performance is investigated by using the discrete element method (DEM). Two ways are adapted to simulate different approaching methods from round particles to irregular sand. The macroresponse shows that irregular sand has a higher shear strength at lower normal stress than round particles. The shape of the particle has less influence on shear strength at higher normal stress. The irregular shape of sand leads to an increase in the shear band proportion. However, the shear band proportion is not related to the sphericity. Under all conditions, particles within the shear band have a larger average rotation angle than those outside the shear band. When the particle shape approaches round (regardless of the round particle proportion and particle shape), the average rotation angle of particles within and without shear bands increase, while the coordinate number and contact anisotropy decrease.

Fructooligosaccharides (FOS) promote the proliferation of Bifidobacterium, especially Bifidobacterium pseudolongum in C57BL/6J mice. However, the response of intestinal microbes to FOS is influenced by host genotypes. Therefore, we compared the intestinal microbiota of four commonly used mice before and after FOS intervention, including C57BL/6J, BALB/c, Institute Cancer Research (ICR), and Kunming (KM) mice. The intestinal microbiota of the four genotypes exhibited similarities in composition but differences in relative abundance. Bifidobacterium was significantly increased to different degrees in the four genotypes of mice after FOS intervention, and Akkermansia and Bacteroides were also significantly increased in BALB/c and KM mice. Lactobacillus and Alistipes levels were unchanged or decreased. Within the genus Bifidobacterium, B. pseudolongum was the dominant species in the four genotypes of mice and proliferated significantly after FOS intervention, with dramatic proliferation in C57BL/6J mice (9.49%). Furthermore, eight strains of B. pseudolongum were screened from the feces of mice with four genotypes, and there was a great difference in the ability and manner of utilizing FOS among the strains. The strains from C57BL/6J mice exhibited the strongest utilization of 1-kestose (GF2), whereas other strains could utilize both GF2 and nistose (GF3) weakly. The gut microbial analysis of mice with different genotypes complemented our previous studies. The results provided the background strains of the different mouse genotypes and suggested a correlation between the utilization ability and the response of the strains to FOS. Further studies on the utilization ability of strains and competition in the intestine will contribute to the understanding of the mechanisms of the intestinal microbial response to diet.

Abstract Background Prolactinoma is the major cause of hyperprolactinemia, and dopamine agonists (DAs) are generally the first-line treatment for them. Several studies have reviewed the recurrent rate of hyperprolactinemia after DAs withdrawal. However, few of them have concerned the recurrence risk of prolactinoma following the withdrawal of DAs. Methods Three medical databases, PubMed, EMBASE and Cochrane library, were retrieved up to February, 14, 2021 to identify studies related to recurrence of prolactinoma and withdrawal of DAs. Statistical analyses including meta-analysis, sensitivity analysis, meta-regression, funnel plot and Egger test were performed through software R. Results A total of 3225 studies were retrieved from the three data bases, and 13 studies consisted of 616 patients and 19 arms were finally included in this systematic analysis. There was no significant heterogeneity among the included studies, and fixed effect model was thus used. The pooled recurrence proportion of prolactinoma after withdrawal of DA was 2% with a 95% confidence interval (CI) of 1–3%. Conclusion Our study showed a very low recurrent rate of prolactinomas after DAs withdrawal. Much more prospective studies with larger cases and longer follow-up period are encouraged to confirm our finding. Trial registration Registration number CRD42021245888 (PROSPERO).

In a short amount of time, the COVID-19 pandemic has played havoc on social security, and people infected with coronavirus may have suffered from both physical and mental health issues requiring treatment. The purpose of our study was to examine the effect of perceived discrimination on anxiety in patients with coronavirus and to observe the role of psychological resilience as a mediator in this process. 376 patients with coronavirus were given a questionnaire, and 26 of them participated in in-depth interviews. Our results demonstrated that perceived discrimination in patients with coronavirus was predictive of anxiety and that strong perceptions of discrimination reduced patients’ psychological resilience levels, thereby triggering severe anxiety. Furthermore, psychological resilience was demonstrated to be a significant predictor of anxiety severity. Psychological resilience has been shown to act as a mediator between perceived discrimination and anxiety. As a response to COVID-19, the government, the media, and the general public should treat patients with coronavirus scientifically and rationally, minimize the secondary psychological damage caused by the perception of discrimination to the special groups of society represented by patients with coronavirus during the pandemic, correct the erroneous stigma generated by the traditional communication process, and prevent the spread of the psychosocial virus.

Novel genetic variations can be obtained by inducing mutations in the plant which help to achieve novel traits. The useful mutant can be obtained through radiation mutation in a short period which can be used as a new material to produce new varieties with high yield and good quality wheat. In this paper, the proteomic analysis of wheat treated with different doses of 12C and 7Li ion beam radiation at the seedling stage was carried out through a Tandem Mass Tag (TMT) tagging quantitative proteomic analysis platform based on high-resolution liquid chromatography-mass spectrometry, and the traditional 60Co-γ-ray radiation treatment for reference. A total of 4,764 up-regulated and 5,542 down-regulated differentially expressed proteins were identified. These proteins were mainly enriched in the KEGG pathway associated with amino acid metabolism, fatty acid metabolism, carbon metabolism, photosynthesis, signal transduction, protein synthesis, and DNA replication. Functional analysis of the differentially expressed proteins showed that the oxidative defense system in the plant defense system was fully involved in the defense response after 12C ion beam and 7Li ion beam radiation treatments. Photosynthesis and photorespiration were inhibited after 12C ion beam and 60Co-γ-ray irradiation treatments, while there was no effect on the plant with 7Li ion beam treatment. In addition, the synthesis of biomolecules such as proteins, as well as multiple signal transduction pathways also respond to radiations. Some selected differentially expressed proteins were verified by Parallel Reaction Monitoring (PRM) and qPCR, and the experimental results were consistent with the quantitative results of TMT. The present study shows that the physiological effect of 12C ion beam radiation treatment is different as compared to the 7Li ion beam, but its similar to the 60Co-γ ray depicting a significant effect on the plant by using the same dose. The results of this study will provide a theoretical basis for the application of 12C and 7Li ion beam radiation in the mutation breeding of wheat and other major crops and promote the development of heavy ion beam radiation mutation breeding technology.

Pseudomonas aeruginosa is an important opportunistic pathogen in cystic fibrosis patients and immunocompromised individuals, and the toxin–antitoxin (TA) system is involved in bacterial virulence and phage resistance. However, the roles of TA systems in P. aeruginosa are relatively less studied and no phage Cro-like regulators were identified as TA components. Here, we identified and characterized a chromosome-encoded prophage Cro-like antitoxin (CrlA) in the clinical isolate P. aeruginosa WK172. CrlA neutralized the toxicity of the toxin CrlA (CrlT) which cleaves mRNA, and they formed a type II TA system. Specifically, crlA and crlT are co-transcribed and their protein products interact with each other directly. The autorepression of CrlA is abolished by CrlT through the formation of the CrlTA complex. Furthermore, crlTA is induced in the stationary phase, and crlA is expressed at higher levels than crlT. The excess CrlA inhibits the infection of lytic Pseudomonas phages. CrlA is widely distributed among Pseudomonas and in other bacterial strains and may provide antiphage activities.

ObjectivesAlthough several studies have reviewed the suicidal risk of antidepressants, the conclusions remain inconsistent. We, therefore, performed a meta-analysis of observational studies to address the association between exposure to antidepressants, especially selective serotonin reuptake inhibitors (SSRIs) and the risk of suicide and suicide attempt in children and adolescents.MethodsMEDLINE and Embase were searched from January 1990 to April 2021. Seventeen cohort and case-control studies were identified that reported suicide or suicide attempt in children and young adults (aged 5–25 years) who were exposed to any antidepressants. We extracted the estimates and corresponding 95% confidence intervals (CIs) from each publication.ResultsThe results showed that antidepressant exposure significantly increased the risk of suicide and suicide attempt when compared with no antidepressant usage among children and adolescents. The pooled relative risk (RR) was 1.38 (95% CI: 1.16–1.64; I2 = 83.1%). Among the antidepressants, SSRI use was associated with an increased risk of suicide and suicide attempt, and the pooled RR was 1.28 (95% CI: 1.09–1.51; I2 = 68.8%). In subgroup analysis, the attempted suicidal risk of antidepressant and SSRI was significantly increased (RR = 1.35, 95% CI: 1.13–1.61; I2 = 86.2% for all antidepressants; and RR = 1.26, 95% CI: 1.06–1.48; I2 = 73.8% for SSRIs), while the completed suicidal risk of antidepressant and SSRI was not statistically significant (RR = 2.32, 95% CI: 0.82–6.53; I2 = 6.28% for all antidepressants; and RR = 1.88, 95% CI: 0.74–4.79; I2 = 52.0% for SSRIs). In addition, the risk of suicide and suicide attempt between SSRIs and other antidepressants was similar (RR 1.13, 95% CI: 0.87–1.46, I2 = 32.4%).ConclusionThe main findings of this meta-analysis provide some evidence that antidepressant exposure seems to have an increased suicidal risk among children and young adults. Since untreated depression remains one of the largest risk factors for suicide and the efficacy of antidepressants is proven, clinicians should evaluate carefully their patients and be cautious with patients at risk to have treatment emergence or worsening of suicidal ideation (TESI/TWOSI) when prescribing antidepressants to children and young patients.

Heading date (HD) is an important trait for wide adaptability and yield stability in wheat. The Vernalization 1 (VRN1) gene is a key regulatory factor controlling HD in wheat. The identification of allelic variations in VRN1 is crucial for wheat improvement as climate change becomes more of a threat to agriculture. In this study, we identified an EMS-induced late-heading wheat mutant je0155 and crossed it with wide-type (WT) Jing411 to construct an F2 population of 344 individuals. Through Bulk Segregant Analysis (BSA) of early and late-heading plants, we identified a Quantitative Trait Locus (QTL) for HD on chromosome 5A. Further genetic linkage analysis limited the QTL to a physical region of 0.8 Mb. Cloning and sequencing revealed three copies of VRN-A1 in the WT and mutant lines; one copy contained a missense mutation of C changed to T in exon 4 and another copy contained a mutation in intron 5. Genotype and phenotype analysis of the segregation population validated that the mutations in VRN-A1 contributed to the late HD phenotype in the mutant. Expression analysis of C- or T-type alleles in exon 4 of the WT and mutant lines indicated that this mutation led to lower expression of VRN-A1, which resulted in the late-heading of je0155. This study provides valuable information for the genetic regulation of HD and many important resources for HD refinement in wheat breeding programs.

Multi-ovary wheat (three pistil) is a unique germplasm for the seed production of hybrid wheat. The purpose of the present study was to transfer the multi-ovary trait to semi-dwarf plants to increase the production of grains in wheat crops. Therefore, tall, semi-dwarf, and dwarf plants were crossed with plants with the three-pistil trait. A three-pistil tall plant was used as the female parent, while tall (Synthetic hexaploid), semi-dwarf, and dwarf plants were used as male parents. F1 and F2 progenies with parents were planted in 2015-16 using RCBD. The outcome of the crosses showed that multi-ovary tall plants gave significant difference for all five traits (days to maturity, plant height, number of seeds per spike, grain weight per spike, and grain yield per unit area) in both generations. The greatest number of grains per spike and grain yield per unit area were obtained from the cross of three-pistil tall and dwarf parent (P1/P6) in the F1 and F2 generations. The cross also resulted in a significant reduction in height (96 cm). Further heterosis studies conducted with crosses between three-pistil tall and dwarf parent (P1/P6) showed the greatest heterosis and heterobeltiosis for the number of grains per spike (60.0 and 26.19%, respectively) and grain yield per m2 (27.68 and 2.85%, respectively). In the case of grain weight per spike, the heterosis value was also positive and significant (17.7). Meanwhile, for other traits, their values were negative for heterosis and heterobeltiosis. High numbers of grains and grain weight were found to be associated with positive heterobeltiosis and in turn the grain yield per m2, but plant height and maturity had negative affirmation with heterobeltiosis. Heterosis studies also indicated the dominant gene action for the three-pistil trait. Thus, the study clearly signified that grain yield can be increased by using the multi-ovary genotype with the semi-dwarf height. This new germplasm will be helpful for breeders to increase the production of wheat crops in the southern climate of Pakistan.

The wheat AP2 family gene Q controls domestication traits, including spike morphology and threshability, which are critical for the widespread cultivation and yield improvement of wheat. Although many studies have investigated the molecular mechanisms of the Q gene, its direct target genes, especially those controlling spike morphology, are not clear, and its regulatory pathways are not well established. In this study, we conducted gene mapping of a wheat speltoid spike mutant and found that a new allele of the Q gene with protein truncation played a role in spike morphology variation in the mutant. Dynamic expression levels of the Q gene throughout the spike development process suggested that the transcript abundances of the mutant were decreased at the W6 and W7 scales compared to those of the WT. We identified several mutation sites on the Q gene and showed that mutations in different domains resulted in distinct phenotypes. In addition, we found that the Q gene produced three transcripts via alternative splicing and that they exhibited differential expression patterns in nodes, internodes, flag leaves, and spikes. Finally, we identified several target genes directly downstream of Q, including TaGRF1-2D and TaMGD-6B, and proposed a possible regulatory network. This study uncovered the target genes of Q, and the results can help to clarify the mechanism of wheat spike morphology and thereby improve wheat grain yield.

Induced mutagenesis is a powerful approach for the creation of novel germplasm and the improvement of agronomic traits. The evaluation of mutagenic effects and functional variations in crops is needed for breeding mutant strains. To investigate the mutagenic effects of gamma-ray irradiation in wheat, this study characterized genomic variations of wheat early heading mutant (eh1) as compared to wild-type (WT) Zhongyuan 9 (ZY9). Whole-genome resequencing of eh1 and ZY9 produced 737.7 Gb sequencing data and identified a total of 23,537,117 homozygous single nucleotide polymorphism (SNP) and 1,608,468 Indel. Analysis of SNP distribution across the chromosome suggests that mutation hotspots existed in certain chromosomal regions. Among the three subgenomes, the variation frequency in subgenome D was significantly lower than in subgenomes A and B. A total of 27.8 Gb data were obtained by exome-capturing sequencing, while 217,948 SNP and 13,554 Indel were identified. Variation annotation in the gene-coding sequences demonstrated that 5.0% of the SNP and 5.3% of the Indel were functionally important. Characterization of exomic variations in 12 additional gamma-ray-induced mutant lines further provided additional insights into the mutagenic effects of this approach. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) analysis suggested that genes with functional variations were enriched in several metabolic pathways, including plant–pathogen interactions and ADP binding. Kompetitive allele-specific PCR (KASP) genotyping with selected SNP within functional genes indicated that 85.7% of the SNPs were polymorphic between the eh1 and wild type. This study provides a basic understanding of the mechanism behind gamma-ray irradiation in hexaploid wheat.

Abstract Background Heading time is one of the most important agronomic traits in wheat, as it largely affects both adaptation to different agro-ecological conditions and yield potential. Identification of genes underlying the regulation of wheat heading and the development of diagnostic markers could facilitate our understanding of genetic control of this process. Results In this study, we developed 400 recombinant inbred lines (RILs) by crossing a γ-ray-induced early heading mutant (eh1) with the late heading cultivar, Lunxuan987. Bulked Segregant Analysis (BSA) of both RNA and DNA pools consisting of various RILs detected a quantitative trait loci (QTL) for heading date located on chromosomes 5B, and further genetic linkage analysis limited the QTL to a 3.31 cM region. We then identified a large deletion in the first intron of the vernalization gene VRN-B1 in eh1, and showed it was associated with the heading phenotype in the RIL population. However, it is not the mutation loci that resulted in early heading phonotype in the mutant compared to that of wildtype. RNA-seq analysis suggested that Vrn-B3 and several newly discovered genes, including beta-amylase 1 (BMY1) and anther-specific protein (RTS), were highly expressed in both the mutant and early heading pool with the dominant Vrn-B1 genotype compared to that of Lunxuan987 and late heading pool. Enrichment analysis of differentially expressed genes (DEGs) identified several key pathways previously reported to be associated with flowering, including fatty acid elongation, starch and sucrose metabolism, and flavonoid biosynthesis. Conclusion The development of new markers for Vrn-B1 in this study supplies an alternative solution for marker-assisted breeding to optimize heading time in wheat and the DEGs analysis provides basic information for VRN-B1 regulation study.

Abstract Background Wheat mutant resources with phenotypic variation have been developed in recent years. These mutants might carry favorable mutation alleles, which have the potential to be utilized in the breeding process. Plant architecture and yield-related features are important agronomic traits for wheat breeders and mining favorable alleles of these traits will improve wheat characteristics. Results Here we used 190 wheat phenotypic mutants as material and by analyzing their SNP variation and phenotypic data, mutation alleles for plant architecture and yield-related traits were identified, and the genetic effects of these alleles were evaluated. In total, 32 mutation alleles, including three pleiotropic alleles, significantly associated with agronomic traits were identified from the 190 wheat mutant lines. The SNPs were distributed on 12 chromosomes and were associated with plant height (PH), tiller number, flag leaf angle (FLA), thousand grain weight (TGW), and other yield-related traits. Further phenotypic analysis of multiple lines carrying the same mutant allele was performed to determine the effect of the allele on the traits of interest. PH-associated SNPs on chromosomes 2BL, 3BS, 3DL, and 5DL might show additive effects, reducing PH by 10.0 cm to 31.3 cm compared with wild type, which means that these alleles may be favorable for wheat improvement. Only unfavorable mutation alleles that reduced TGW and tiller number were identified. A region on chromosome 5DL with mutation alleles for PH and TGW contained several long ncRNAs, and their sequences shared more than 90% identity with cytokinin oxidase/dehydrogenase genes. Some of the mutation alleles we mined were colocalized with previously reported QTLs or genes while others were novel; these novel alleles could also result in phenotypic variation. Conclusion Our results demonstrate that favorable mutation alleles are present in mutant resources, and the region between 409.5 to 419.8 Mb on chromosome 5DL affects wheat plant height and thousand grain weight.

Stem elongation is a critical phase for yield determination and, as a major trait, is targeted for manipulation for improvement in bread wheat (Triticum aestivum L.). In a previous study, we characterized a mutant showing rapid stem elongation but with no effect on plant height at maturity. The present study aimed to finely map the underlying mutated gene, qd1, in this mutant. By analyzing an F2 segregating population consisting of 606 individuals, we found that the qd1 gene behaved in a dominant manner. Moreover, by using the bulked segregant RNA sequencing (BSR-seq)-based linkage analysis method, we initially mapped the qd1 gene to a 13.55 Mb region on chromosome 4B (from 15.41 to 28.96 Mb). This result was further confirmed in F2 and BC3F2 segregating populations. Furthermore, by using transcriptome sequencing data, we developed 14 Kompetitive Allele-Specific PCR (KASP) markers and then mapped the qd1 gene to a smaller and more precise 5.08 Mb interval from 26.80 to 31.88 Mb. To develop additional markers to finely map the qd1 gene, a total of 4,481 single-nucleotide polymorphisms (SNPs) within the 5.08 Mb interval were screened, and 25 KASP markers were developed based on 10x-depth genome resequencing data from both wild-type (WT) and mutant plants. The qd1 gene was finally mapped to a 1.33 Mb interval from 28.86 to 30.19 Mb on chromosome 4B. Four candidate genes were identified in this region. Among them, the expression pattern of only TraesCS4B02G042300 in the stems was concurrent with the stem development of the mutant and WT. The qd1 gene could be used in conjunction with molecular markers to manipulate stem development in the future.

Plant height is a key agronomic trait that is closely to the plant morphology and lodging resistance in wheat. However, at present, the few dwarf genes widely used in wheat breeding have narrowed wheat genetic diversity. In this study, we selected a semi-dwarf wheat mutant dwarf33 that exhibits decreased plant height with little serious negative impact on other agronomic traits. Genetic analysis and mutant gene mapping indicated that dwarf33 contains a new recessive semi-dwarf gene Rht-SN33d, which was mapped into ~1.3 Mb interval on the 3DL chromosome. The gibberellin metabolism-related gene TraesCS3D02G542800, which encodes gibberellin 2-beta-dioxygenase, is considered a potential candidate gene of Rht-SN33d. Rht-SN33d reduced plant height by approximately 22.4% in mutant dwarf33. Further study revealed that shorter stem cell length may be the main factor causing plant height decrease. In addition, the coleoptile length of dwarf33 was just 9.3% shorter than that of wild-type Shaannong33. These results will help to expand our understanding of new mechanisms of wheat height regulation, and obtain new germplasm for wheat improvement.

Manipulation of genes involved in starch synthesis could significantly affect wheat grain weight and yield. The starch-branching enzyme (SBE) catalyzes the formation of branch points by cleaving the α-1,4 linkage in polyglucans and reattaching the chain via an α-1,6 linkage. Three types of SBE isoforms (SBEI, SBEII, and SBEIII) exist in higher plants, with the number of SBE isoforms being species-specific. In this study, the coding sequence of the wheat TaSBEIII gene was amplified. After the multiple sequence alignment of TaSBEIII genome from 20 accessions in a wheat diversity panel, one SNP was observed in TaSBEIII-A, which formed the allelic marker allele-T. Based on this SNP at 294 bp (C/T), a KASP molecular marker was developed to distinguish allelic variation among the wheat genotypes for thousand grain weight (TGW). The results were validated using 262 accessions of mini core collection (MCC) from China, 153 from Pakistan, 53 from CIMMYT, and 17 diploid and 18 tetraploid genotypes. Association analysis between TaSBEIII-A allelic variation and agronomic traits found that TaSBEIII-A was associated with TGW in mini core collection of China (MCC). The accessions possessing Allele-T had higher TGW than those possessing Allele-C; thus, Allele-T was a favorable allelic variation. By analyzing the frequency of the favorable allelic variation Allele-T in MCC, it increased from pre-1950 (25%) to the 1960s (45%) and increased continuously from 1960 to 1990 (80%). The results suggested that the KASP markers can be utilized in grain weight improvement, which ultimately improves wheat yield by marker-assisted selection in wheat breeding. The favorable allelic variation allele-T should be valuable in enhancing grain yield by improving the source and sink simultaneously. Furthermore, the newly developed KASP marker validated in different genetic backgrounds could be integrated into a breeding kit for screening high TGW wheat.

Several health benefits are obtained from resistant starch, also known as healthy starch. Enhancing resistant starch with genetic modification has huge commercial importance. The variation of resistant starch content is narrow in wheat, in relation to which limited improvement has been attained. Hence, there is a need to produce a wheat population that has a wide range of variations in resistant starch content. In the present study, stable mutants were screened that showed significant variation in the resistant starch content. A megazyme kit was used for measuring the resistant starch content, digestible starch, and total starch. The analysis of variance showed a significant difference in the mutant population for resistant starch. Furthermore, four diverse mutant lines for resistant starch content were used to study the quantitative expression patterns of 21 starch metabolic pathway genes; and to evaluate the candidate genes for resistant starch biosynthesis. The expression pattern of 21 starch metabolic pathway genes in two diverse mutant lines showed a higher expression of key genes regulating resistant starch biosynthesis (GBSSI and their isoforms) in the high resistant starch mutant lines, in comparison to the parent variety (J411). The expression of SBEs genes was higher in the low resistant starch mutants. The other three candidate genes showed overexpression (BMY, Pho1, Pho2) and four had reduced (SSIII, SBEI, SBEIII, ISA3) expression in high resistant starch mutants. The overexpression of AMY and ISA1 in the high resistant starch mutant line JE0146 may be due to missense mutations in these genes. Similarly, there was a stop_gained mutation for PHO2; it also showed overexpression. In addition, the gene expression analysis of 21 starch metabolizing genes in four different mutants (low and high resistant starch mutants) shows that in addition to the important genes, several other genes (phosphorylase, isoamylases) may be involved and contribute to the biosynthesis of resistant starch. There is a need to do further study about these new genes, which are responsible for the fluctuation of resistant starch in the mutants.

Blast is caused by the host-specific lineages of the fungus Magnaporthe oryzae and is the most important destructive disease in major crop plants, including rice and wheat. The first wheat blast outbreak that occurred in Bangladesh in 2016 and the recent epidemic in Zambia were caused by the M. oryzae Triticum (MoT) pathotype, a fungal lineage belonging to M. oryzae. Although a few reported wheat cultivars show modest resistance to MoT, the patterns of genetic variation and diversity of this pathotype make it crucial to identify additional lines of resistant wheat germplasm. Nearly 40 rice blast resistant and susceptible genes have so far been cloned. Here, we used BLAST analysis to locate two rice blast susceptible genes in the wheat reference genome, bsr-d1 and bsr-k1, and identified six identical homologous genes located on subgenomes A, B, and D. We uncovered a total of 171 single nucleotide polymorphisms (SNPs) in an ethyl methanesulfonate (EMS)-induced population, with mutation densities ranging from 1/1107.1 to 1/230.7 kb through Targeting Induced Local Lesions IN Genomes (TILLING) by sequencing. These included 81 SNPs located in exonic and promoter regions, and 13 coding alleles that are predicted to have severe effects on protein function, including two pre-mature mutants that might affect wheat blast resistance. The loss-of-function alleles identified in this study provide insights into new wheat blast resistant lines, which represent a valuable breeding resource.

Activation of the cyclic adenosine monophosphate/protein kinase A (cAMP/PKA) pathway induces glial differentiation of glioblastoma (GBM) cells, but the mechanism by which microRNA (miRNA) regulate this process remains poorly understood. In this study, by performing miRNA genomics and loss‐ and gain‐of‐function assays in dibutyryl‐cAMP‐treated GBM cells, we identified a critical negative regulator, hsa‐miR‐1275, that modulates a set of genes involved in cancer progression, stem cell maintenance, and cell maturation and differentiation. Additionally, we confirmed that miR‐1275 directly and negatively regulates the protein expression of glial fibrillary acidic protein (GFAP), a marker of mature astrocytes. Of note, tri‐methyl‐histone H3 (Lys27) (H3K27me3), downstream of the PKA/polycomb repressive complex 2 (PRC2) pathway, accounts for the downregulation of miR‐1275. Furthermore, decreased miR‐1275 expression and induction of GFAP expression were also observed in dibutyryl‐cAMP‐treated primary cultured GBM cells. In a patient‐derived glioma stem cell tumor model, a cAMP elevator and an inhibitor of H3K27me3 methyltransferase inhibited tumor growth, induced differentiation, and reduced expression of miR‐1275. In summary, our study shows that epigenetic inhibition of miR‐1275 by the cAMP/PKA/PRC2/H3K27me3 pathway mediates glial induction of GBM cells, providing a new mechanism and novel targets for differentiation‐inducing therapy.

The stems of cereal crops provide both mechanical support for lodging resistance and a nutrient supply for reproductive organs. Elongation, which is considered a critical phase for yield determination in winter wheat (Triticum aestivum L.), begins from the first node detectable to anthesis. Previously, we characterized a heavy ion beam triggered wheat mutant qd, which exhibited an altered stem elongation pattern without affecting mature plant height. In this study, we further analyzed mutant stem developmental characteristics by using transcriptome data. More than 40.87 Mb of clean reads including at least 36.61 Mb of unique mapped reads were obtained for each biological sample in this project. We utilized our transcriptome data to identify 124,971 genes. Among these genes, 4,340 differentially expressed genes (DEG) were identified between the qd and wild-type (WT) plants. Compared to their WT counterparts, qd plants expressed 2,462 DEGs with downregulated expression levels and 1878 DEGs with upregulated expression levels. Using DEXSeq, we identified 2,391 counting bins corresponding to 1,148 genes, and 289 of them were also found in the DEG analysis, demonstrating differences between qd and WT. The 5,199 differentially expressed genes between qd and WT were employed for GO and KEGG analyses. Biological processes, including protein-DNA complex subunit organization, protein-DNA complex assembly, nucleosome organization, nucleosome assembly, and chromatin assembly, were significantly enriched by GO analysis. However, only benzoxazinoid biosynthesis pathway-associated genes were enriched by KEGG analysis. Genes encoding the benzoxazinoid biosynthesis enzymes Bx1, Bx3, Bx4, Bx5, and Bx8_9 were confirmed to be differentially expressed between qd and WT. Our results suggest that benzoxazinoids could play critical roles in regulating the stem elongation phenotype of qd.

Agronomic traits such as heading date (HD), plant height (PH), thousand grain weight (TGW), and spike length (SL) are important factors affecting wheat yield. In this study, we constructed a high-density genetic linkage map using the Wheat55K SNP Array to map quantitative trait loci (QTLs) for these traits in 207 recombinant inbred lines (RILs). A total of 37 QTLs were identified, including 9 QTLs for HD, 7 QTLs for PH, 12 QTLs for TGW, and 9 QTLs for SL, which explained 3.0–48.8% of the phenotypic variation. Kompetitive Allele Specific PCR (KASP) markers were developed based on sequencing data and used for validation of the stably detected QTLs on chromosomes 3A, 4B and 6A using 400 RILs. A QTL cluster on chromosome 4B for PH and TGW was delimited to a 0.8 Mb physical interval explaining 12.2–22.8% of the phenotypic variation. Gene annotations and analyses of SNP effects suggested that a gene encoding protein Photosynthesis Affected Mutant 68, which is essential for photosystem II assembly, is a candidate gene affecting PH and TGW. In addition, the QTL for HD on chromosome 3A was narrowed down to a 2.5 Mb interval, and a gene encoding an R3H domain-containing protein was speculated to be the causal gene influencing HD. The linked KASP markers developed in this study will be useful for marker-assisted selection in wheat breeding, and the candidate genes provide new insight into genetic study for those traits in wheat.

Blautia is a genus of anaerobic bacteria with probiotic characteristics that occur widely in the feces and intestines of mammals. Based on phenotypic and phylogenetic analyses, some species in the genera Clostridium and Ruminococcus have been reclassified as Blautia, so to date, there are 20 new species with valid published names in this genus. An extensive body of research has recently focused on the probiotic effects of this genus, such as biological transformation and its ability to regulate host health and alleviate metabolic syndrome. This article reviews the origin and biological characteristics of Blautia and the factors that affect its abundance and discusses its role in host health, thus laying a theoretical foundation for the development of new functional microorganisms with probiotic properties.

The utilizing of traditional chemical stabilizers could improve soil engineering properties but also results in brittle behavior and causes environmental problems. This study investigates the feasibility of the combined utilization of an ecofriendly biopolymer and fiber inclusions as an alternative to traditional cement for reinforcing soft soil. A series of unconfined compression tests were conducted to examine the combined effect of the biopolymer and fibers on the stress–strain characteristics, strength improvement, failure pattern, and reinforcement mechanism of soft soil. The results show that the biopolymer associated with fibers has an unconfined compressive strength similar to that of fiber-reinforced soil. However, it then increases with different curing times and conditions, which can be up to 1.5 MPa–2.5 MPa. The combined effect of fibers and the biopolymer is not simply equivalent to the sum of the effects of each individual material. The fiber shows its role instantly after being mixed into soil, whereas the effect of biopolymer gradually appears with sample curing time. The biopolymer plays a dominant role in increasing the peak unconfined compressive strength and brittleness of soil, while the amount of fiber is crucial for reducing soil brittleness and increasing ductility. It is shown that the biopolymer not only contributes to the particle bonding force but also facilitates the reinforcement efficiency of fibers in the soil. The fibers in return assist in reducing the soil brittleness arising from biopolymer cementation and provide residual resistance after post-peak failure.

To scientifically and accurately evaluate the status of the development of green airports in China, evaluation methods of green, ecological airports are established in this paper. To address the shortcomings in subjective and objective weighting methods, we propose a combination weighting method based on Spearman’s rank correlation coefficient and evaluation grades based on interval approximation. At the same time, by taking into account resource conservation, environmental friendliness, operation efficiency, and people-oriented service, we propose an evaluation index system and an interval number for each index. Lastly, the theory is applied to five large airports in different regions of China. Analysis of the evaluation results shows that Shanghai Pudong International Airport (PVG) and Guangzhou Baiyun International Airport (CAN) have the highest scores for the resource conservation and environmental friendliness indexes, thus indicating that the development of a green ecological airport is closely related to its passenger transportation scale and economic strength. All considered airports showed the need for upgrading public service facilities and constructing intelligent equipment. The method proposed in this paper is reasonable and reliable; therefore, it can provide guidance for the evaluation and construction of green, ecological airports.

Drug resistance is a major cause for the failure of cancer chemotherapy or targeted therapy. However, the molecular regulatory mechanisms controlling the dynamic evolvement of drug resistance remain poorly understood. Thus, it is important to develop methods for identifying key gene regulatory mechanisms of the resistance to specific drugs. In this study, we developed a data-driven computational framework, DryNetMC, using a differential regulatory network-based modeling and characterization strategy to quantify and prioritize key genes underlying cancer drug resistance. The DryNetMC does not only infer gene regulatory networks (GRNs) via an integrated approach, but also characterizes and quantifies dynamical network properties for measuring node importance. We used time-course RNA-seq data from glioma cells treated with dbcAMP (a cAMP activator) as a realistic case to reconstruct the GRNs for sensitive and resistant cells. Based on a novel node importance index that comprehensively quantifies network topology, network entropy and expression dynamics, the top ranked genes were verified to be predictive of the drug sensitivities of different glioma cell lines, in comparison with other existing methods. The proposed method provides a quantitative approach to gain insights into the dynamic adaptation and regulatory mechanisms of cancer drug resistance and sheds light on the design of novel biomarkers or targets for predicting or overcoming drug resistance.

Solid-state fermentation (SSF) has regained interest owing to its advantages in solid waste treatment and fermentation industries. However, heterogeneous heat and mass transfer are often caused by the absence of free water and noticeable water loss from microbial utilization and moisture evaporation in SSF. It is necessary to explore more effective ways to solve issues of water loss and water supplement in SSF based on online capillary water monitoring, because capillary water is the dominant form of water that is present and lost in substrate. Two novel capillary-water supply strategies were proposed, established and evaluated using three selected reference strains, including water-retention materials and negative-pressure auto-controlled irrigation (NPACI). This study employed superabsorbent polymer, a kind of water-retention material to enhance enzyme productivity with the most significant increase of 2.47 times. Moreover, the combination of NPACI and 0.1% superabsorbent polymers increased productivity by 2.80-fold, together with lowered gradients of temperature, moisture and products. Furthermore, a modified liquid-supply SSF was constructed through successful capillary water control by proposed humidity control strategies. This modified SSF system could address the shortcomings of inhomogeneous culture of traditional SSF.

Stress granules are conserved cytosolic ribonucleoprotein (RNP) compartments that undergo dynamic assembly and disassembly by phase separation in response to stressful conditions. Gene mutations may lead to aberrant phase separation of stress granules eliciting irreversible protein aggregations. A selective autophagy pathway called aggrephagy may partially alleviate the cytotoxicity mediated by these protein aggregates. Cells must perceive when and where the stress granules are transformed into toxic protein aggregates to initiate autophagosomal engulfment for subsequent autolysosomal degradation, therefore, maintaining cellular homeostasis. Indeed, defective aggrephagy has been causally linked to various neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). In this review, we discuss stress granules at the intersection of autophagy and ALS pathogenesis.

Abstract Salinity stress has become an increasing threat to food security worldwide and elucidation of the mechanism for salinity tolerance is of great significance. Induced mutation, especially spaceflight mutagenesis, is one important method for crop breeding. In this study, we show that a spaceflight-induced wheat mutant, named salinity tolerance 1 (st1), is a salinity-tolerant line. We report the characteristics of transcriptomic sequence variation induced by spaceflight, and show that mutations in genes associated with sodium ion transport may directly contribute to salinity tolerance in st1. Furthermore, GO and KEGG enrichment analysis of differentially expressed genes (DEGs) between salinity-treated st1 and wild type suggested that the homeostasis of oxidation-reduction process is important for salt tolerance in st1. Through KEGG pathway analysis, “Butanoate metabolism” was identified as a new pathway for salinity responses. Additionally, key genes for salinity tolerance, such as genes encoding arginine decarboxylase, polyamine oxidase, hormones-related, were not only salt-induced in st1 but also showed higher expression in salt-treated st1 compared with salt-treated WT, indicating that these genes may play important roles in salinity tolerance in st1. This study presents valuable genetic resources for studies on transcriptome variation caused by induced mutation and the identification of salt tolerance genes in crops.

Abstract Background Transient starch provides carbon and energy for plant growth, and its synthesis is regulated by the joint action of a series of enzymes. Starch synthesis IV (SSIV) is one of the important starch synthase isoforms, but its impact on wheat starch synthesis has not yet been reported due to the lack of mutant lines. Results Using the TILLING approach, we identified 54 mutations in the wheat gene TaSSIVb-D, with a mutation density of 1/165 Kb. Among these, three missense mutations and one nonsense mutation were predicted to have severe impacts on protein function. In the mutants, TaSSIVb-D was significantly down-regulated without compensatory increases in the homoeologous genes TaSSIVb-A and TaSSIVb-B. Altered expression of TaSSIVb-D affected granule number per chloroplast; compared with wild type, the number of chloroplasts containing 0–2 granules was significantly increased, while the number containing 3–4 granules was decreased. Photosynthesis was affected accordingly; the maximum quantum yield and yield of PSII were significantly reduced in the nonsense mutant at the heading stage. Conclusions These results indicate that TaSSIVb-D plays an important role in the formation of transient starch granules in wheat, which in turn impact the efficiency of photosynthesis. The mutagenized population created in this study allows the efficient identification of novel alleles of target genes and could be used as a resource for wheat functional genomics.

Summary: Glioblastoma multiforme (GBM) is among the most aggressive of human cancers. Although differentiation therapy has been proposed as a potential approach to treat GBM, the mechanisms of induced differentiation remain poorly defined. Here, we established an induced differentiation model of GBM using cAMP activators that specifically directed GBM differentiation into astroglia. Transcriptomic and proteomic analyses revealed that oxidative phosphorylation and mitochondrial biogenesis are involved in induced differentiation of GBM. Dibutyryl cyclic AMP (dbcAMP) reverses the Warburg effect, as evidenced by increased oxygen consumption and reduced lactate production. Mitochondrial biogenesis induced by activation of the CREB-PGC1α pathway triggers metabolic shift and differentiation. Blocking mitochondrial biogenesis using mdivi1 or by silencing PGC1α abrogates differentiation; conversely, overexpression of PGC1α elicits differentiation. In GBM xenograft models and patient-derived GBM samples, cAMP activators also induce tumor growth inhibition and differentiation. Our data show that mitochondrial biogenesis and metabolic switch to oxidative phosphorylation drive the differentiation of tumor cells. : Xing et al. show that the metabolic shift from glycolysis to oxidative phosphorylation drives differentiation of GBM cells into astrocytes by cAMP activation. Mechanistically, the cAMP-CREB-PGC1α signal mediates mitochondrial biogenesis, which leads to metabolic reprogramming, induced differentiation, and tumor growth inhibition. Keywords: glioblastoma, induced differentiation, Warburg effect, metabolic reprogramming, oxidative phosphorylation, glycolysis, mitochondrial biogenesis, cyclic adenosine monophosphate, cAMP, PPARγ coactivator-1α, PGC1α

Crop productivity is highly dependent on the application of N fertilizers, but ever-increasing N application is causing serious environmental impacts. To facilitate the development of new wheat cultivars that can thrive in low N growth conditions, key loci and genes associated with wheat responses to low N must be identified. In this GWAS and t-test study of 190 M6 mutant wheat lines (Jing 411-derived) based on genotype data from the wheat 660k SNP array, we identified a total of 221 significant SNPs associated four seedling phenotypic traits that have been implicated in resistance to low N: relative root length, relative shoot length, relative root weight, and relative shoot weight. Notably, we detected large numbers of significantly associated SNP in what appear to be genomic 'hotspots' for resistance to low N on chromosomes 2A and 6B, strongly suggesting that these regions are functionally related to the resistance phenotypes that we observed in some of the mutant lines. Moreover, the candidate genes, including genes encoding high-affinity nitrate transporter 2.1, gibberellin responsive protein, were identified for resistance to low N. This study raises plausible mechanistic hypotheses that can be evaluated in future applied or basic efforts by breeders or plant biologists seeking to develop new high-NUE wheat cultivars.

Starch is synthesized from a series of reactions catalyzed by enzymes. ADP-glucose pyrophosphorylase (AGPase) initiates the synthesis pathway and synthesizes ADP-glucose, the substrate of starch synthase (SS), of which SSIV is an isoform. Mutations of the AGPase subunit and SSIV-coding genes affect starch content and cause variation in the number of granules. Here, we pyramided the functional mutation alleles of the AGPase subunit gene TaAGP.L-B1 and the SSIV-coding gene TaSSIVb-D to elucidate their synergistic effects on other key starch biosynthesis genes and their impact on starch content. Both the TaAGP.L-B1 and TaSSIVb-D genes were expressed in wheat grain development, and the expression level of TaAGP.L-B1 was higher than that of TaSSIVb-D. The TaAGP.L-B1 gene was downregulated in the agp.L-B1 single and agp.L-B1/ssIV-D double mutants at 12 to 18 days after flowering (DAF). TaSSIVb-D expression was significantly reduced at 6 DAF in both ssIV-D single and double mutants. In the agp.L-B1/ssIV-D double mutant, TaGBSSII was upregulated, while TaAGPSS, TaSSI, and TaSBEII were downregulated. Under the interaction of these genes, the total starch and amylopectin contents were significantly decreased in agp.L-B1 and agp.L-B1/ssIV-D mutants. The results suggested that the mutations of TaAGP.L-B1 and TaSSIVb-D genes resulted in variation in the expression patterns of the other four starch synthetic genes and led to a reduction in starch and amylopectin contents. These mutants could be used further as germplasm for resistant starch analysis.

Fructooligosaccharides (FOS) are considered prebiotics and have been proven to selectively promote the growth of Bifidobacterium in the gut. This study aimed to clarify the effects of FOS intake on the composition of luminal and mucosal microbiota in mice. Briefly, mice were fed a 0% or 25% FOS (w/w)-supplemented diet for four weeks, and the composition of luminal and mucosal microbiota, especially the Bifidobacterium, was analyzed by sequencing the V3−V4 region of 16S rRNA and groEL gene, respectively. After FOS intervention, there were significant increases in the total and wall weights of the cecum and the amount of total short-chain fatty acids (SCFAs) in the cecal contents of the mice. At the phylum level, the results showed a significant increase in the relative abundance of Actinobacteria in the contents and mucosa from the cecum to the distal colon in the FOS group. Besides Bifidobacterium, a significant increase was observed in the relative abundance of Coprococcus in all samples at the genus level, which may be partially related to the increase in butyric acid levels in the luminal contents. Furthermore, groEL sequencing revealed that Bifidobacterium pseudolongum was almost the sole bifidobacterial species in the luminal contents (>98%) and mucosa (>89%). These results indicated that FOS can selectively promote B. pseudolongum proliferation in the intestine, either in the lumen or the mucosa from the cecum to the distal colon. Further studies are required to reveal the competitive advantage of B. pseudolongum over other FOS-metabolizing bacteria and the response mechanisms of B. pseudolongum to FOS.

Mutated genetic resources play an important role in gene/allele characterization. Currently, there are few hexaploid winter wheat mutated resources available. Here, we developed a hexaploid winter wheat resource by inducing mutations via EMS treatment by the single seed descent method. A broad mutation spectrum with high mutation frequency (∼19%) on phenotypic variations was identified. These mutations included spike, leaf and seed morphology, plant architecture, and heading date variations. To evaluate the efficiency of the resource for reverse genetic analysis, allelic variations in the TaAGP.L-B1 gene, encoding the AGPase large subunit, were screened by the TILLING approach. Four missense mutations were identified and one allele in line E3-1-3, resulted in an amino acid change predicated to have severe effects on gene function. The other three mutations were predicted to have no effect. Results of gene expression patterns and grain starch content demonstrated that the novel allele in E3-1-3 altered the function of TaAGP.L-B1. Our results indicated that this mutated genetic wheat resource contained broad spectrum phenotypic and genotypic variations, that may be useful for wheat improvement, gene discovery, and functional genomics.

Chloroplast development is an integral part of plant survival and growth, and occurs in parallel with chlorophyll biosynthesis. However, little is known about the mechanisms underlying chloroplast development in hexaploid wheat. Here, we obtained a spaceflight-induced wheat albino mutant mta. Chloroplast ultra-structural observation showed that chloroplasts of mta exhibit abnormal morphology and distribution compared to wild type. Photosynthetic pigments content was also significantly decreased in mta. Transcriptome and chloroplast proteome profiling of mta and wild type were done to identify differentially expressed genes (DEGs) and proteins (DEPs), respectively. In total 4,588 DEGs including 1,980 up- and 2,608 down-regulated, and 48 chloroplast DEPs including 15 up- and 33 down-regulated were identified in mta. Classification of DEGs revealed that most were involved in chloroplast development, chlorophyll biosynthesis, or photosynthesis. Besides, transcription factors such as PIF3, GLK and MYB which might participate in those pathways were also identified. The correlation analysis between DEGs and DEPs revealed that the transcript-to-protein in abundance was functioned into photosynthesis and chloroplast relevant groups. Real time qPCR analysis validated that the expression level of genes encoding photosynthetic proteins was significantly decreased in mta. Together, our results suggest that the molecular mechanism for albino leaf color formation in mta is a thoroughly regulated and complicated process. The combined analysis of transcriptome and proteome afford comprehensive information for further research on chloroplast development mechanism in wheat. And spaceflight provides a potential means for mutagenesis in crop breeding.

Wheat is a staple food commodity grown worldwide, and wheat starch is a valuable source of energy and carbon that constitutes 80% of the grain weight. Manipulation of genes involved in starch synthesis significantly affects wheat grain weight and yield. TaSSIV plays an important role in starch synthesis and its main function is granule formation. To mine and stack more favorable alleles, single nucleotide polymorphisms (SNPs) of TaSSIV-A, B, and D were investigated across 362 wheat accessions by Ecotype-Targeting Induced Local Lesions IN Genome (EcoTILLING). As a result, a total of 38 SNPs in the amplified regions of three TaSSIV genes were identified, of which 10, 15, and 13 were in TaSSIV-A, B, and D, respectively. These 38 SNPs were evaluated by using KASP and six SNPs showed an allele frequency >5% whereas the rest were TaSSIV–A and three for TaSSIV–B. The results of an association study in the Chinese mini core collection with thousand grain weight (TGW) and spike length (SPL) showed that Hap-2-1A was significantly associated with TGW and Hap-3-1B with SPL. Allelic frequency and geographic distribution indicated that the favored haplotype (Hap-2-1A) has been positively selected in Chinese wheat breeding. These results suggested that the Kompetitive Allele Specific PCR (KASP) markers can be applied in starch improvement to ultimately improve wheat yield by marker assisted selection in wheat breeding.