Harnessing the power of microbes: Enhancing soybean growth in an acidic soil through AMF inoculation rather than P-fertilization.

The low phosphorus (P) availability of acidic soils severely limits leguminous plant growth and productivity. Improving the soil P nutritional status can be achieved by increasing the P-content through P-fertilization or stimulating the mineralization of organic P via arbuscular mycorrhizal fungi (AMF) application; however, their corresponding impacts on plant and soil microbiome still remain to be explored. Here, we examined the effects of AMF-inoculation and P-fertilization on the growth of soybean with different P-efficiencies, as well as the composition of rhizo-microbiome in an acidic soil. The growth of recipient soybean NY-1001, which has a lower P-efficiency, was not significantly enhanced by AMF-inoculation or P-fertilization. However, the plant biomass of higher P-efficiency transgenic soybean PT6 was significantly increased by 46.74%-65.22% through AMF-inoculation. Although there was no discernible difference in plant biomass between PT6 and NY-1001 in the absence of AMF-inoculation and P-fertilization, PT6 had approximately 1.9-2.5 times the plant biomass of NY-1001 after AMF-inoculation. Therefore, the growth advantage of higher P-efficiency soybean was achieved through the assistance of AMF rather than P-fertilization in available P-deficient acidic soil. Most nitrogen (N)-fixing bacteria and some functional genes related to N-fixation were abundant in endospheric layer, as were the P-solubilizing Pseudomonas plecoglossicida, and annotated P-metabolism genes. These N-fixing and P-solubilizing bacteria were positive correlated with each other. Lastly, the two most abundant phytopathogenic fungi species accumulated in endospheric layer, they exhibited positive correlations with N-fixing bacteria, but displayed negative interactions with the majority of the other dominant non-pathogenic genera with potential antagonistic activity.

SbMYC2 mediates jasmonic acid signaling to improve drought tolerance via directly activating SbGR1 in sorghum.

KEY MESSAGE: SbMYC2 functions as a key regulator under JA signaling in enhancing drought tolerance of sorghum through direct activating SbGR1. Drought stress is one of the major threats to crop yield. In response to drought stress, functions of basic helix-loop-helix (bHLH) transcription factors (TFs) have been reported in Arabidopsis and rice, but little is known for sorghum. Here, we characterized the function of SbMYC2, a bHLH TF in sorghum, and found that SbMYC2 responded most significantly to PEG-simulated drought stress and JA treatments. Overexpression of SbMYC2 significantly enhanced drought tolerance in Arabidopsis, rice and sorghum. In addition, it reduced reactive oxygen species (ROS) accumulation and increased chlorophyll content in sorghum leaves. While silencing SbMYC2 by virus-induced gene silencing (VIGS) resulted in compromised drought tolerance of sorghum seedlings. Moreover, SbMYC2 can directly activate the expression of GLUTATHIONE-DISULFIDE REDUCTASE gene SbGR1. SbGR1 silencing led to significantly weakened drought tolerance of sorghum, and higher ROS accumulation and lower chlorophyll content in sorghum leaves were detected. In addition, SbMYC2 can interact with SbJAZs, suppressors of JA signaling, and thus can mediate JA signaling to activate SbGR1, thereby regulating sorghum's tolerance to drought stress. Overall, our findings demonstrate that bHLH TF SbMYC2 plays an important role in sorghum's response to drought stress, thus providing one theoretical basis for genetic enhancement of sorghum and even rice.

miR-497-5p promoted neuronal injury in ischemic stroke by inhibiting the BDNF/TrkB/PI3K/Akt pathway.

The aim of this study was to investigate the molecular mechanism by which miR-497-5p regulates neuronal injury after ischemic stroke through the BDNF/TrkB/Akt signaling pathway. PC12 cells were used to construct a stroke injury model by oxygen-glucose deprivation/reoxygenation (OGD/R). The expression level of miR-497-5p was measured by RT-qPCR. CCK-8 kit was used to detect cell viability. Cell apoptosis and reactive oxygen species (ROS) were detected by flow cytometry. MDA and SOD detection kits were used to detect MDA content and SOD activity. A double luciferase reporter system was used to verify the targeting relationship between miR-497-5p and BDNF. The expression of BDNF, TrkB, p-TrkB, Akt and p-Akt was detected by Western blot. We have found that miR-497-5p expression was inhibited after treatment with OGD/R. Simultaneously, cell apoptosis, MDA content and ROS were upregulated, while cell viability and SOD were significantly decreased in PC12 cells. The effects of OGD/R on PC12 cells were reversed with the downregulation of miR-497-5p. A double luciferase reporter assay demonstrated that miR-497-5p negatively targets BDNF. BDNF inhibited cell apoptosis and oxidative stress injury in PC12 cells. These findings suggest that miR-497-5p aggravates neuronal injury in experimental model of ischemic stroke by inhibiting the BDNF/TrkB/PI3K/Akt signaling pathway.

A modified natural small molecule inhibits triple-negative breast cancer growth by interacting with Tubb3.

BACKGROUND: Triple-negative breast cancer (TNBC) is a malignant tumor without specific therapeutic targets and a poor prognosis. Chemotherapy is currently the first-line therapeutic option for TNBC. However, due to the heterogeneity of TNBC, not all of TNBC patients are responsive to chemotherapeutic agents. Therefore, the demand for new targeted agents is critical. ß-tubulin isotype III (Tubb3) is a prognostic factor associated with cancer progression, including breast cancer, and targeting Tubb3 may lead to improve TNBC disease control. Shikonin, the active compound in the roots of Lithospermun erythrorhizon suppresses the growth of various types of tumors, and its efficacy can be improved by altering its chemical structure. PURPOSE: In this work, the anti-TNBC effect of a shikonin derivative (PMMB276) was investigated, and its mechanism was also investigated. STUDY DESIGN/METHODS: This study combines flow cytometry, immunofluorescence staining, immunoblotting, immunoprecipitation, siRNA silencing, and the iTRAQ proteomics assay to analyze the inhibition potential of PMMB276 on TNBC. In vivo study was performed, Balb/c female murine models with or without the small molecule treatments. RESULTS: Herein, we screened 300 in-house synthesized analogs of shikonin against TNBC and identified a novel small molecule, PMMB276; it suppressed cell proliferation, induced apoptosis, and arrested the cell cycle at the G2/M phase, suggesting that it could have a tumor suppressive role in TNBC. Tubb3 was identified as the target of PMMB276 using proteomic and biological activity analyses. Meanwhile, PMMB276 regulated microtubule dynamics in vitro by inducing microtubule depolymerization and it could act as a tubulin stabilizer by a different process than that of paclitaxel. Moreover, suppressing or inhibiting Tubb3 with PMMB276 reduced the growth of breast cancer in an experimental mouse model, indicating that Tubb3 plays a significant role in TNBC progression. CONCLUSION: The findings support the therapeutic potential of PMMB276, a Tubb3 inhibitor, as a treatment for TNBC. Our findings might serve as a foundation for the utilization of shikonin and its derivatives in the development of anti-TNBC.

Triple-transgenic soybean in conjunction with glyphosate drive patterns in the rhizosphere microbial community assembly.

Plant roots continuously influence the rhizosphere, which also serves as a recruitment site for microorganisms with desirable functions. The development of genetically engineered (GE) crop varieties has offered unparalleled yield advantages. However, in-depth research on the effects of GE crops on the rhizosphere microbiome is currently insufficient. We used a triple-transgenic soybean cultivar (JD606) that is resistant to insects, glyphosate, and drought, along with its control, ZP661, and JD606 treated with glyphosate (JD606G). Using 16S and ITS rDNA sequencing, their effects on the taxonomy and function of the bacterial and fungal communities in the rhizosphere, surrounding, and bulk soil compartment niches were determined. Alpha diversity demonstrated a strong influence of JD606 and JD606G on bacterial Shannon diversity. Both treatments significantly altered the soil's pH and nitrogen content. Beta diversity identified the soil compartment niche as a key factor with a significant probability of influencing the bacterial and fungal communities associated with soybeans. Further analysis showed that the rhizosphere effect had a considerable impact on bacterial communities in JD606 and JD606G soils but not on fungal communities. Microbacterium, Bradyrhizobium, and Chryseobacterium were found as key rhizobacterial nodes. In addition, the LEfSe analysis identified biomarker taxa with plant-beneficial attributes, demonstrating rhizosphere-driven microbial recruitment. FUNGuild, Bugbase, and FAPROTAX functional predictions showed that ZP661 soils had more plant pathogen-associated microbes, while JD606 and JD606G soils had more stress-tolerance, nitrogen, and carbon cycle-related microbes. Bacterial rhizosphere networks had more intricate topologies than fungal networks. Furthermore, correlation analysis revealed that the bacteria and fungi with higher abundances exhibited varying degrees of positive and negative correlations. Our findings shed new light on the niche partitioning of bacterial and fungal communities in soil. It also indicates that following triple-transgenic soybean cultivation and glyphosate application, plant roots recruit microbes with beneficial taxonomic and functional traits in the rhizosphere.

Genome-Wide Comparison and Functional Characterization of HMGR Gene Family Associated with Shikonin Biosynthesis in Lithospermum erythrorhizon.

3-hydroxy-3-methylglutaryl-CoA reductase (HMGR), as the rate-limiting enzyme in the mevalonate pathway, is essential for the biosynthesis of shikonin in Lithospermum erythrorhizon. However, in the absence of sufficient data, the principles of a genome-wide in-depth evolutionary exploration of HMGR family members in plants, as well as key members related to shikonin biosynthesis, remain unidentified. In this study, 124 HMGRs were identified and characterized from 36 representative plants, including L. erythrorhizon. Vascular plants were found to have more HMGR family genes than nonvascular plants. The phylogenetic tree revealed that during lineage and species diversification, the HMGRs evolved independently and intronless LerHMGRs emerged from multi-intron HMGR in land plants. Among them, Pinus tabuliformis and L. erythrorhizon had the most HMGR gene duplications, with 11 LerHMGRs most likely expanded through WGD/segmental and tandem duplications. In seedling roots and M9 cultured cells/hairy roots, where shikonin biosynthesis occurs, LerHMGR1 and LerHMGR2 were expressed significantly more than other genes. The enzymatic activities of LerHMGR1 and LerHMGR2 further supported their roles in catalyzing the conversion of HMG-CoA to mevalonate. Our findings provide insight into the molecular evolutionary properties and function of the HMGR family in plants and a basis for the genetic improvement of efficiently produced secondary metabolites in L. erythrorhizon.

Safety and efficacy of anlotinib hydrochloride capsules in advanced non-small-cell lung cancer: a multicenter, real-world study.

Objective: To investigate the safety and efficacy of anlotinib hydrochloride capsules in stage III-IV non-small-cell lung cancer (NSCLC). Methods: NSCLC patients received anlotinib monotherapy or combination therapy. The primary end point was adverse reactions during anlotinib treatment and the secondary end point was progression-free survival. Results: During anlotinib treatement, 41.85% (167/399) of patients experienced adverse reactions, and the monotherapy group had a lower incidence than the combination group (36.89 vs 49.68%; p = 0.012). The median progression-free survival of patients in the monotherapy group was significantly lower than that in the combination group (5 vs 6 months; p = 0.0119). Conclusion: Compared with anlotinib monotherapy, combination therapy resulted in longer PFS and a higher incidence of adverse reactions in patients with NSCLC.

Design, synthesis and biological evaluation of novel modified dual-target shikonin derivatives for colorectal cancer treatment.

Warburg effect provides energy and material essential for tumor proliferation, the reverse of Warburg effect provides insights into the development of a novel anti-cancer strategy. Pyruvate kinase 2 (PKM2) and pyruvate dehydrogenase kinase 1 (PDK1) are two key enzymes in tumor glucose metabolism pathway that not only contribute to the Warburg effect through accelerating aerobic glycolysis, but also serve as druggable target for colorectal cancer (CRC). Considering that targeting PKM2 or PDK1 alone does not seem to be sufficient to remodel abnormal glucose metabolism and achieve significant antitumor activity, a series of novel benzenesulfonyl shikonin derivatives were designed to regulate PKM2 and PDK1 simultaneously. By means of molecular docking and antiproliferative screen, we found that compound Z10 could act as the combination of PKM2 activator and PDK1 inhibitor, thereby significantly inhibited glycolysis that reshaping tumor metabolism. Moreover, Z10 could inhibit proliferation, migration and induce apoptosis in CRC cell HCT-8. Finally, the in vivo anti-tumor activity of Z10 was evaluated in a colorectal cancer cell xenograft model in nude mice and the results demonstrated that Z10 induced tumor cell apoptosis and inhibited tumor cell proliferation with lower toxicity than shikonin. Our findings indicated that it is feasible to alter tumor energy metabolism through multi-target synergies, and the dual-target benzenesulfonyl shikonin derivative Z10 could be a potential anti-CRC agent.

The sex determination gene of Populus deltoides, PdFERR, interacts with ERF96 to promote the development of female flower organs.

The female-specifically expressed response regulator (PdFERR) gene in Populus deltoides, a sex determination gene (an orthologous gene of ARR17 in Populus tremula), was found to promote femaleness in heterologous expression lines of Arabidopsis. None of the genes in the Arabidopsis genome seem to be orthologous to PdFERR. Although originating from two evolutionarily distant plants, the dioecious poplar FERR might promote femaleness in the hermaphroditic Arabidopsis through an evolutionary consistent regulatory pathway. However, there is no molecular evidence to support this viewpoint. In this study, to identify the shared downstream orthologous gene of PdFERR, we used yeast two-hybrid assay to screen potential interactors of PdFERR in Arabidopsis. We identified the ethylene response factor 96 (AtERF96) and confirmed the interaction via in vivo and in vitro assays. The ERF96 orthologous gene in P. deltoides was also experimentally confirmed to interact with PdFERR. PdFERR could then promote femaleness in poplar or Arabidopsis through interactions with ERF96, which provide a new perspective for understanding the PdFERR gene regulating sex differentiation.

TERT Mutations in Non-Small Cell Lung Cancer: Clinicopathologic Features and Prognostic Implications.

Introduction: The associations between the clinical characteristics of non-small cell lung cancer (NSCLC) and mutations in telomerase reverse transcriptase (TERT) gene remain unclear. In this study, we used next-generation sequencing (NGS) to investigate the incidence rate and clinical correlates of TERT mutations in patients with NSCLC. Methods: In total, 283 tumor samples from patients with NSCLC were tested using an NGS panel from September 2017 to May 2020. The genetic testing results and clinical data of all patients were collected. Results: TERT mutations were found in 30 patients, which were significantly associated with age, smoking history, sex, and metastasis (P < 0.05). Survival analyses showed that patients who carried TERT mutations had a poorer prognosis. Of the 30 TERT-mutation carriers, 17 harbored epidermal growth factor receptor (EGFR) mutations, which were significantly associated with sex, histopathology type, and metastasis (P < 0.05; overall survival [OS], 21 months; 95% confidence interval [CI], 8.153-33.847 months). Three TERT mutation patients harbored Kirsten rat sarcoma virus (KRAS) mutations, which were significantly associated with metastasis risk (P < 0.05), KRAS mutations carriers had a worse prognosis, with an OS of 10 months (95% CI, 8.153-33.847 months). Multivariate Cox regression analyses showed that age, cancer stage, and TERT mutation carrier status were independent risk factors for NSCLC, and the TERT mutation was 2.731 times higher than that without TERT mutation (95% CI, 1.689-4.418, P < 0.001). Conclusions: TERT mutations were present in 11% of patients with NSCLC. TERT mutations were associated with age, smoking history, sex, and distant metastasis. Co-mutations in TERT and EGFR/KRAS indicated a poor prognosis. The co-mutations of TERT and EGFR differed according to sex, histopathology type, and metastasis, whereas TERT and KRAS co-mutations were only associated with patient metastasis. Age, cancer stage, and TERT mutation carrier status were independent risk factors for poor prognosis in patients with NSCLC.

The proposed role of MSL-lncRNAs in causing sex lability of female poplars.

Labile sex expression is frequently observed in dioecious plants, but the underlying genetic mechanism remains largely unknown. Sex plasticity is also observed in many Populus species. Here we carried out a systematic study on a maleness-promoting gene, MSL, detected in the Populus deltoides genome. Our results showed that both strands of MSL contained multiple cis-activating elements, which generated long non-coding RNAs (lncRNAs) promoting maleness. Although female P. deltoides did not have the male-specific MSL gene, a large number of partial sequences with high sequence similarity to this gene were detected in the female poplar genome. Based on sequence alignment, the MSL sequence could be divided into three partial sequences, and heterologous expression of these partial sequences in Arabidopsis confirmed that they could promote maleness. Since activation of the MSL sequences can only result in female sex lability, we propose that MSL-lncRNAs might play a role in causing sex lability of female poplars.

Mycorrhizae Enhance Soybean Plant Growth and Aluminum Stress Tolerance by Shaping the Microbiome Assembly in an Acidic Soil.

Strongly acidic soils are characterized by high aluminum (Al) toxicity and low phosphorus (P) availability, which suppress legume plant growth and nodule development. Arbuscular mycorrhizal fungi (AMF) stimulate rhizobia and enhance plant P uptake. However, it is unclear how this symbiotic soybean-AMF-rhizobial trio promotes soybean growth in acidic soils. We examined the effects of AMF and rhizobium addition on the growth of two soybean genotypes, namely, Al-tolerant and Al-sensitive soybeans as well as their associated bacterial and fungal communities in an acidic soil. With and without rhizobial addition, AMF significantly increased the fresh shoot and root biomass of Al-tolerant soybean by 47%/87% and 37%/24%, respectively. This increase in plant biomass corresponded to the enrichment of four plant growth-promoting rhizobacteria (PGPR) in the rhizospheric soil, namely, Chitinophagaceae bacterium 4GSH07, Paraburkholderia soli, Sinomonas atrocyanea, and Aquincola tertiaricarbonis. For Al-sensitive soybean, AMF addition increased the fresh shoot and root biomass by 112%/64% and 30%/217%, respectively, with/without rhizobial addition. Interestingly, this significant increase coincided with a decrease in the pathogenic fungus Nigrospora oryzae as well as an increase in S. atrocyanea, A. tertiaricarbonis, and Talaromyces verruculosus (a P-solubilizing fungus) in the rhizospheric soil. Lastly, the compartment niche along the soil-plant continuum shaped microbiome assembly, with pathogenic/saprotrophic microbes accumulating in the rhizospheric soil and PGPR related to nitrogen fixation or stress resistance (e.g., Rhizobium leguminosarum and Sphingomonas azotifigens) accumulating in the endospheric layer. IMPORTANCE Taken together, this study examined the effects of arbuscular mycorrhizal fungi (AMF) and rhizobial combinations on the growth of Al-tolerant and Al-sensitive soybeans as well as their associated microbial communities in acidic soils and concluded that AMF enhances soybean growth and Al stress tolerance by recruiting PGPR and altering the root-associated microbiome assembly in a host-dependent manner. In the future, these findings will help us better understand the impacts of AMF on rhizosphere microbiome assembly and will contribute to the development of soybean breeding techniques for the comprehensive use of PGPR in sustainable agriculture.

SbNAC9 Improves Drought Tolerance by Enhancing Scavenging Ability of Reactive Oxygen Species and Activating Stress-Responsive Genes of Sorghum.

Drought stress severely threatens the yield of cereal crops. Therefore, understanding the molecular mechanism of drought stress response of plants is crucial for developing drought-tolerant cultivars. NAC transcription factors (TFs) play important roles in abiotic stress of plants, but the functions of NAC TFs in sorghum are largely unknown. Here, we characterized a sorghum NAC gene, SbNAC9, and found that SbNAC9 can be highly induced by polyethylene glycol (PEG)-simulated dehydration treatments. We therefore investigated the function of SbNAC9 in drought stress response. Sorghum seedlings overexpressing SbNAC9 showed enhanced drought-stress tolerance with higher chlorophyll content and photochemical efficiency of PSII, stronger root systems, and higher reactive oxygen species (ROS) scavenging capability than wild-type. In contrast, sorghum seedlings with silenced SbNAC9 by virus-induced gene silencing (VIGS) showed weakened drought stress tolerance. Furthermore, SbNAC9 can directly activate a putative peroxidase gene SbC5YQ75 and a putative ABA biosynthesis gene SbNCED3. Silencing SbC5YQ75 and SbNCED3 led to compromised drought tolerance and reduced ABA content of sorghum seedlings, respectively. Therefore, our findings revealed the important role of SbNAC9 in response to drought stress in sorghum and may shed light on genetic improvement of other crop species under drought-stress conditions.

PKM2/PDK1 dual-targeted shikonin derivatives restore the sensitivity of EGFR-mutated NSCLC cells to gefitinib by remodeling glucose metabolism.

Pyruvate kinase 2 (PKM2) and pyruvate dehydrogenase kinase 1 (PDK1) are two key enzymes in tumor glucose metabolism pathway that not only promote tumor growth and proliferation through accelerating aerobic glycolysis, but also contribute to drug resistance of non-small cell lung cancer (NSCLC). Considering that targeting PKM2 or PDK1 alone seems insufficient to remodel abnormal glucose metabolism to achieve significant antitumor activity, we proposed a "two-step approach" that regulates PKM2 and PDK1 synchronously. Firstly, we found that the combination of ML265 (PKM2 activator) and AZD7545 (PDK1 inhibitor) could synergistically inhibit proliferation and induce apoptosis in H1299 cells. Base on this, we designed a series of novel shikonin (SK) thioether derivatives as PKM2/PDK1 dual-target agents, among which the most potent compound E5 featuring a 2-methyl substitution on the benzene ring exerted significantly increased inhibitory activity toward EGFR mutant NSCLC cell H1975 (IC50 = 1.51 µmol/L), which was 3 and 17-fold more active than the lead compound SK (IC50 = 4.56 µmol/L) and the positive control gefitinib (IC50 = 25.56 µmol/L), respectively. Additionally, E5 also showed good anti-tumor activity in xenografted mouse models, with significantly lower toxicity side effects than SK. Moreover, E5 also inhibited the entry of PKM2 into nucleus to regulate the transcriptional activation of oncogenes, thus restoring the sensitivity of H1975 cell to gefitinib. Collectively, these data demonstrate that E5, a dual inhibitor of PKM2/PDK1, may be a promising adjunct to gefitinib in the treatment of EGFR-TKIs resistant NSCLC, deserving further investigation.

Discrepancies in rhizobacterial assembly caused by glyphosate application and herbicide-tolerant soybean Co-expressing GAT and EPSPS.

There are concerns that the innovation of genetically modified herbicide-tolerant (GMHT) plants, as well as the application of herbicide to such GMHT plants, could have an impact on ecological interactions and unintentionally harm non-targeted organisms. Consequently, we intend to use full-length 16 S rDNA amplicon sequencing to examine changes in the bacterial community in the rhizosphere of GMHT soybean (Z106) harboring 5-enolpyruvylshikimate-3-phosphate synthase and Glyphosate N-acetyltransferase genes and GMHT soybean treated with glyphosate (Z106G). Glyphosate application significantly impacted bacterial alpha diversity (species richness, and Shannon diversity). Permutational multivariate analysis of variance of beta diversity demonstrated that soil compartments and growth stages had a substantial impact on soybean rhizobacterial communities (soil compartments, growth stages, P = 0.001). Community composition revealed that Z106G soils were abundant in Taibaiella and Arthrobacter pascens at maturity, while Chryseobacterium joostei and Stenotrophomonas maltophilia predominated in Z106 soils during flowering. Nitrogen-fixing and phosphate-solubilizing microbes were found in higher proportions in the rhizosphere than in bulk soil, with Sinorhizobium being more abundant in Z106 and Bacillus and Stenotrophomonas being more prevalent in Z106G rhizosphere soils. Collectively, our findings suggest glyphosate application and glyphosate-tolerant soybean as potential regulators of soybean rhizobacterial composition.

Ethylene-responsive SbWRKY50 suppresses leaf senescence by inhibition of chlorophyll degradation in sorghum.

The onset of leaf de-greening and senescence is governed by a complex regulatory network including environmental cues and internal factors such as transcription factors (TFs) and phytohormones, in which ethylene (ET) is one key inducer. However, the detailed mechanism of ET signalling for senescence regulation is still largely unknown. Here, we found that the WRKY TF SbWRKY50 from Sorghum bicolor L., a direct target of the key component ETHYLENE INSENSITIVE 3 in ET signalling, functioned for leaf senescence repression. The clustered regularly interspaced short palindromic repeats/CRISPR-associated protein9-edited SbWRKY50 mutant (SbWRKY5O-KO) of sorghum displayed precocious senescent phenotypes, while SbWRKY50 overexpression delayed age-dependent and dark-induced senescence in sorghum. SbWRKY50 negatively regulated chlorophyll degradation through direct binding to the promoters of several chlorophyll catabolic genes. In addition, SbWRKY50 recruited the Polycomb repressive complex 1 through direct interaction with SbBMI1A, to induce histone 2A mono-ubiquitination accumulation on the chlorophyll catabolic genes for epigenetic silencing and thus delayed leaf senescence. Especially, SbWRKY50 can suppress early steps of chlorophyll catabolic pathway via directly repressing SbNYC1 (NON-YELLOW COLORING 1). Other senescence-related hormones could also influence leaf senescence through repression of SbWRKY50. Hence, our work shows that SbWRKY50 is an essential regulator downstream of ET and SbWRKY50 also responds to other phytohormones for senescence regulation in sorghum.

Efficacy and safety of perampanel for the treatment of epilepsy in adolescents: a meta-analysis.

BACKGROUND: In the present meta-analysis, the efficacy and safety of perampanel (PER) for the treatment of adolescents with epilepsy were assessed. METHODS: Keyword searches were performed in Embase, PubMed, Cochrane Library, Web of Science, EBSCO and CNKI from 1 January 2020 to 10 October 2020. The randomized controlled trials (RCTs) and case-control studies in which PER was compared with other Anti-seizure drugs (ASDs) and/or placebo in children with epilepsy, were considered eligible studies. Odds ratio (OR) with 95% confidence interval (95% CI) for the dichotomous outcome statistic was calculated using a fixed-effects or random-effects model. RESULTS: Three RCTs with a total of 372 adolescents' patients were included in this meta-analysis. Placebo was used as a control in these studies. Compared with placebo, PER showed better efficacy in median seizure frequency reduction from baseline per 28 days (OR = 2.49, 95% CI: 1.25-4.96, p = 0.009) and in responder rate (OR = 1.87, 95% CI: 1.15-3.05, p = 0.01); both were considered statistically increased in PER group. Regarding adverse effects (AEs), significant differences between PER and placebo (OR = 1.47, 95% CI: 0.92-2.41, p = 0.11) were not found, and the most common AEs of PER were dizziness (24.0%), somnolence (15.9%), headache (11.2%), nasopharyngitis (9.7%), upper respiratory tract infection (7.0%) and aggression (7.0%). CONCLUSION: Based on the results in this study, PER showed better efficacy than placebo therapy in children with epilepsy and the AEs were similar in PER group and placebo group. PER showed good efficacy and a low risk of AEs, and might be a promising medication for the treatment of pediatric epilepsy. In the future, well-designed and large-scale RCTs are necessary to validate the present findings.

Ginsenoside Rg1 inhibits nucleus pulposus cell apoptosis, inflammation and extracellular matrix degradation via the YAP1/TAZ pathway in rats with intervertebral disc degeneration.

PURPOSE: Intervertebral disc degeneration (IDD) is one of the main causes of low back pain, which not only affects patients' life quality, but also places a great burden on the public health system. Recently, ginsenoside Rg1 has been found to act in IDD; however, the mechanism is still unclear. The purpose of this study is to explore the function of ginsenoside Rg1 and its molecular mechanism in IDD. METHODS: The rat model of IDD and nucleus pulposus (NP) experimental groups treated with ginsenoside Rg1 was constructed for investing the role of ginsenoside Rg1 in IDD rats. In the in vitro and in vivo study, the histological morphological changes, motor threshold (MT), inflammatory factors, oxidative stress, apoptosis and expression of the YAP1/TAZ signaling pathway-related proteins of the intervertebral discs (IVD) were measured by histological staining, mechanical and thermal stimulation, ELISA, qRT-PCR, flow cytometry, and western blot, respectively. RESULTS: Ginsenoside Rg1 significantly increased the threshold for mechanical and thermal stimulation and alleviated histological changes in IDD rats. Ginsenoside Rg1 had a significant inhibitory effect on the secretion level of inflammatory factors, redox activity, extracellular matrix (ECM) degradation in IVD tissue and NP cells, and apoptosis in NP cells. Further investigation revealed that ginsenoside Rg1 significantly inhibited the expression of YAP1/TAZ signaling pathway-related proteins. Additionally, the above inhibitory effect of ginsenoside Rg1 on IDD progression was concentration-dependent, that is, the highest concentration of ginsenoside Rg1 was most effective. CONCLUSION: Ginsenoside Rg1 inhibits IDD progression by suppressing the activation of YAP1/TAZ signaling pathway. This means that ginsenoside Rg1 has the potential to treat IDD.

Root-associated fungal microbiota of the perennial sweet sorghum cultivar under field growth.

Root-associated fungal microbiota, which inhabit the rhizosphere, rhizoplane and endosphere, have a profound impact on plant growth and development. Sorghum bicolor (L.) Moench, also called broomcorn or sweet sorghum, is a multipurpose crop. The comparison between annual and perennial sweet sorghum cultivars in terms of plant growth, as well as their interactions with belowground fungal microbiota, is still poorly understood, although there has been growing interest in the mutualism between annual sweet sorghum and soil bacteria or bacterial endophytes. In this study, the perennial sweet sorghum cultivar N778 (N778 simply) and its control lines TP213 and TP60 were designed to grow under natural field conditions. Bulk soil, rhizosphere soil and sorghum roots were collected at the blooming and maturity stages, and then the fungal microbiota of those samples were characterized by high-throughput sequencing of the fungal ITS1 amplicon. Our results revealed that the alpha diversity of the fungal microbiota in rhizosphere soil and root samples was significantly different between N778 and the two control lines TP213 and TP60 at the blooming or maturity stage. Moreover, beta diversity in rhizosphere soil of N778 was distinct from those of TP213 and TP60, while beta diversity in root samples of N778 was distinct from those of TP213 but not TP60 by PCoA based on Bray-Curtis and WUF distance metrics. Furthermore, linear discriminant analysis (LDA) and multiple group comparisons revealed that OTU4372, a completely unclassified taxon but with symbiotroph mode, was enriched in sorghum roots, especially in N778 aerial roots at the blooming stage. Our results indicate that Cladosporium and Alternaria, two fungal genera in the rhizosphere soil, may also be dominant indicators of sorghum yield and protein content in addition to Fusarium at the maturity stage and imply that the perennial sweet sorghum N778 can primarily recruit dominant psychrotolerant bacterial taxa but not dominant cold-tolerant fungal taxa into its rhizosphere to support its survival below the freezing point.

The host niches of soybean rather than genetic modification or glyphosate application drive the assembly of root-associated microbial communities.

Plant roots significantly influence soil microbial diversity, and soil microorganisms play significant roles in both natural and agricultural ecosystems. Although the genetically modified (GM) crops with enhanced insect and herbicide resistance are thought to have unmatched yield and stress resistance advantages, thorough and in-depth case studies still need to be carried out in a real-world setting due to the potential effects of GM plants on soil microbial communities. In this study, three treatments were used: a recipient soybean variety Jack, a triple transgenic soybean line JD321, and the glyphosate-treated JD321 (JD321G). Three sampling stages (flowering, seed filling and maturing), as well as three host niches of soybean rhizosphere [intact roots (RT), rhizospheric soil (RS) and surrounding soil (SS)] were established. In comparison to Jack, the rhizospheric soil of JD321G had higher urease activity and lower nitrite reductase at the flowering stage. Different treatments and different sampling stages existed no significant effects on the compositions of microbial communities at different taxonomic levels. However, at the genus level, the relative abundance of three plant growth-promoting fungal genera (i.e. Mortierella, Chaetomium and Pseudombrophila) increased while endophytic bacteria Chryseobacterium and pathogenic bacteria Streptomyces decreased from the inside to the outside of the roots (i.e. RT → RS → SS). Moreover, two bacterial genera, Bradyrhizobium and Ensifer were more abundant in RT than in RS and SS, as well as three species, Agrobacterium radiobacter, Ensifer fredii and Ensifer meliloti, which are closely related to nitrogen-fixation. Furthermore, five clusters of orthologous groups (COGs) associated to nitrogen-fixation genes were higher in RT than in RS, whereas only one COG annotated as dinitrogenase iron-molybdenum cofactor biosynthesis protein was lower. Overall, the results imply that the rhizosphere host niches throughout the soil-plant continuum largely control the composition and function of the root-associated microbiome of triple transgenic soybean.