野生田头菇菌株的驯化及其子实体营养成分分析

采自湖南洞庭湖大通湖区芦苇湿地的野生菌株,经鉴定为田头菇Agrocybe praecox。通过驯化实现人工栽培,栽培原料以芦苇屑为主,使用液体菌种和覆土栽培方式,初潮菇平均生物转化率为45.6%。营养成分分析表明：以芦苇屑为栽培培养基,子实体中矿物元素含量分别为K（2 190mg/kg）、Fe（16.2mg/kg）、Mg（59.7mg/kg）、Ca（33.4mg/kg）,必需氨基酸含量占比高达44.85%,谷氨酸、蛋氨酸、天冬氨酸含量高,是一种高蛋白、低脂肪、高钾低钠的食用菌。     

Soybean AP1 homologs control flowering time and plant height

Flowering time and plant height are key agronomic traits that directly affect soybean (Glycine max) yield. APETALA1 (AP1) functions as a class A gene in the ABCE model for floral organ development, helping to specify carpel, stamen, petal, and sepal identities. There are four AP1 homologs in soybean, all of which are mainly expressed in the shoot apex. Here, we used clustered regularly interspaced short palindromic repeats (CRISPR) – CRISPR‐associated protein 9 technology to generate a homozygous quadruple mutant, gmap1, with loss‐of‐function mutations in all four GmAP1 genes. Under short‐day (SD) conditions, the gmap1 quadruple mutant exhibited delayed flowering, changes in flower morphology, and increased node number and internode length, resulting in plants that were taller than the wild type. Conversely, overexpression of GmAP1a resulted in early flowering and reduced plant height compared to the wild type under SD conditions. The gmap1 mutant and the overexpression lines also exhibited altered expression of several genes related to flowering and gibberellic acid metabolism, thereby providing insight into the role of GmAP1 in the regulatory networks controlling flowering time and plant height in soybean. Increased node number is the trait with the most promise for enhancing soybean pod number and grain yield. Therefore, the mutant alleles of the four AP1 homologs described here will be invaluable for molecular breeding of improved soybean yield.     

Induction of γ-aminobutyric acid plays a positive role to Arabidopsis resistance against Pseudomonas syringae

Gamma‐aminobutyric acid (GABA) is an important metabolite which functions in plant growth, development, and stress responses. However, its role in plant defense and how it is regulated are largely unknown. Here, we report a detailed analysis of GABA induction during the resistance response to Pseudomonas syringae in Arabidopsis thaliana. While searching for the mechanism underlying the pathogen‐responsive mitogen‐activated protein kinase (MPK)3/MPK6 signaling cascade in plant immunity, we found that activation of MPK3/MPK6 greatly induced GABA biosynthesis, which is dependent on the glutamate decarboxylase genes GAD1 and GAD4. Inoculation with Pseudomonas syringae pv tomato DC3000 (Pst) and Pst‐avrRpt2 expressing the avrRpt2 effector gene induced GAD1 and GAD4 gene expression and increased the levels of GABA. Genetic evidence revealed that GAD1, GAD2, and GAD4 play important roles in both GABA biosynthesis and plant resistance in response to Pst‐avrRpt2 infection. The gad1/2/4 triple and gad1/2/4/5 quadruple mutants, in which the GABA levels were extremely low, were more susceptible to both Pst and Pst‐avrRpt2. Functional loss of MPK3/MPK6, or their upstream MKK4/MKK5, or their downstream substrate WRKY33 suppressed the induction of GAD1 and GAD4 expression after Pst‐avrRpt2 treatment. Our findings shed light on both the regulation and role of GABA in the plant immunity to a bacterial pathogen.     

Achieving stable myocardial regeneration after apical resection in neonatal mice

The neonatal heart completely regenerates after apical resection (AR), providing a desirable research model to study the mechanism of cardiac regeneration and cardiomyocyte proliferation. However, AR-induced neonatal heart regenerative phenomenon is controversial due to the variation of operative details in different laboratories. Here, we provide an optimized AR operation procedure with stable regeneration and high survival rate by achieving heart exposure, normalizing myocardium cut-offs, and reducing operation duration. We also established a whole-heart-slice approach to estimate the myocardial regeneration after the AR operation, which ensures no false-negative/positive results. The combination of the optimized AR operation and the whole-heart-slice analysis provides a stable system to study neonatal heart regeneration and cardiomyocyte proliferation in situ.     

Genome‐wide association study of word reading: Overlap with risk genes for neurodevelopmental disorders

Reading disabilities (RD) are the most common neurocognitive disorder, affecting 5% to 17% of children in North America. These children often have comorbid neurodevelopmental/psychiatric disorders, such as attention deficit/hyperactivity disorder (ADHD). The genetics of RD and their overlap with other disorders is incompletely understood. To contribute to this, we performed a genome‐wide association study (GWAS) for word reading. Then, using summary statistics from neurodevelopmental/psychiatric disorders, we computed polygenic risk scores (PRS) and used them to predict reading ability in our samples. This enabled us to test the shared aetiology between RD and other disorders. The GWAS consisted of 5.3 million single nucleotide polymorphisms (SNPs) and two samples; a family‐based sample recruited for reading difficulties in Toronto (n = 624) and a population‐based sample recruited in Philadelphia [Philadelphia Neurodevelopmental Cohort (PNC)] (n = 4430). The Toronto sample SNP‐based analysis identified suggestive SNPs (P ~ 5 × 10^?7) in the ARHGAP23 gene, which is implicated in neuronal migration/axon pathfinding. The PNC gene‐based analysis identified significant associations (P < 2.72 × 10^?6) for LINC00935 and CCNT1, located in the region of the KANSL2/CCNT1/LINC00935/SNORA2B/SNORA34/MIR4701/ADCY6 genes on chromosome 12q, with near significant SNP‐based analysis. PRS identified significant overlap between word reading and intelligence (R² = 0.18, P = 7.25 × 10^?181), word reading and educational attainment (R² = 0.07, P = 4.91 × 10^?48) and word reading and ADHD (R² = 0.02, P = 8.70 × 10^?6; threshold for significance = 7.14 × 10^?3). Overlap was also found between RD and autism spectrum disorder (ASD) as top‐ranked genes were previously implicated in autism by rare and copy number variant analyses. These findings support shared risk between word reading, cognitive measures, educational outcomes and neurodevelopmental disorders, including ASD.     

A novel prognostic signature of immune‐related genes for patients with colorectal cancer

Colorectal cancer (CRC) is one of the most commonly diagnosed cancers with an estimated 1.8 million new cases worldwide and associated with high mortality rates of 881 000 CRC‐related deaths in 2018. Screening programs and new therapies have only marginally improved the survival of CRC patients. Immune‐related genes (IRGs) have attracted attention in recent years as therapeutic targets. The aim of this study was to identify an immune‐related prognostic signature for CRC. To this end, we combined gene expression and clinical data from the CRC data sets of The Cancer Genome Atlas (TCGA) into an integrated immune landscape profile. We identified a total of 476 IRGs that were differentially expressed in CRC vs normal tissues, of which 18 were survival related according to univariate Cox analysis. Stepwise multivariate Cox proportional hazards analysis established an immune‐related prognostic signature consisting of SLC10A2, FGF2, CCL28, NDRG1, ESM1, UCN, UTS2 and TRDC. The predictive ability of this signature for 3‐ and 5‐year overall survival was determined using receiver operating characteristics (ROC), and the respective areas under the curve (AUC) were 79.2% and 76.6%. The signature showed moderate predictive accuracy in the validation and GSE38832 data sets as well. Furthermore, the 8‐IRG signature correlated significantly with tumour stage, invasion, lymph node metastasis and distant metastasis by univariate Cox analysis, and was established an independent prognostic factor by multivariate Cox regression analysis for CRC. Gene set enrichment analysis (GSEA) revealed a relationship between the IRG prognostic signature and various biological pathways. Focal adhesions and ECM‐receptor interactions were positively correlated with the risk scores, while cytosolic DNA sensing and metabolism‐related pathways were negatively correlated. Finally, the bioinformatics results were validated by real‐time RT?qPCR. In conclusion, we identified and validated a novel, immune‐related prognostic signature for patients with CRC, and this signature reflects the dysregulated tumour immune microenvironment and has a potential for better CRC patient management.     

Triptolide prevents bone loss via suppressing osteoclastogenesis through inhibiting PI3K-AKT-NFATc1 pathway

Bone loss (osteopenia) is a common complication in human solid tumour. In addition, after surgical treatment of gynaecological tumour, osteoporosis often occurs due to the withdrawal of oestrogen. The major characteristic of osteoporosis is the low bone mass with micro-architectural deteriorated bone tissue. And the main cause is the overactivation of osteoclastogenesis, which is one of the most important therapeutic targets. Inflammation could induce the interaction of RANKL/RANK, which is the promoter of osteoclastogenesis. Triptolide is derived from the traditional Chinese herb lei gong teng, presented multiple biological effects, including anti-cancer, anti-inflammation and immunosuppression. We hypothesized that triptolide could inhibits osteoclastogenesis by suppressing inflammation activation. In this study, we confirmed that triptolide could suppress RANKL-induced osteoclastogenesis in bone marrow mononuclear cells (BMMCs) and RAW264.7 cells and inhibited the osteoclast bone resorption functions. PI3K-AKT-NFATc1 pathway is one of the most important downstream pathways of RANKL-induced osteogenesis. The experiments in vitro indicated that triptolide suppresses the activation of PI3K-AKT-NFATc1 pathway and the target point located at the upstream of AKT because both NFATc1 overexpression and AKT phosphorylation could ameliorate the triptolide suppression effects. The expression of MDM2 was elevated, which demonstrated the MDM-p53-induced cell death might contribute to the osteoclastogenesis suppression. Ovariectomy-induced bone loss and inflammation activation were also found to be ameliorated in the experiments in vivo. In summary, the new effect of anti-cancer drug triptolide was demonstrated to be anti-osteoclastogenesis, and we demonstrated triptolide might be a promising therapy for bone loss caused by tumour.     

Cytisine attenuates bone loss of ovariectomy mouse by preventing RANKL‐induced osteoclastogenesis

Postmenopausal Osteoporosis (PMOP) is oestrogen withdrawal characterized of much production and activation by osteoclast in the elderly female. Cytisine is a quinolizidine alkaloid that comes from seeds or other plants of the Leguminosae (Fabaceae) family. Cytisine has been shown several potential pharmacological functions. However, its effects on PMOP remain unknown. This study designed to explore whether Cytisine is able to suppress RANKL‐induced osteoclastogenesis and prevent the bone loss induced by oestrogen deficiency in ovariectomized (OVX) mice. In this study, we investigated the effect of Cytisine on RAW 264.7 cells and bone marrow monocytes (BMMs) derived osteoclast culture system in vitro and observed the effect of Cytisine on ovariectomized (OVX) mice model to imitate postmenopausal osteoporosis in vivo. We found that Cytisine inhibited F‐actin ring formation and tartrate‐resistant acid phosphatase (TRAP) staining in dose‐dependent ways, as well as bone resorption by pit formation assays. For molecular mechanism, Cytisine suppressed RANK‐related trigger RANKL by phosphorylation JNK/ERK/p38‐MAPK, IκBα/p65‐NF‐κB, and PI3K/AKT axis and significantly inhibited these signalling pathways. However, the suppression of PI3K‐AKT‐NFATc1 axis was rescued by AKT activator SC79. Meanwhile, Cytisine inhibited RANKL‐induced RANK‐TRAF6 association and RANKL‐related gene and protein markers such as NFATc1, Cathepsin K, MMP‐9 and TRAP. Our study indicated that Cytisine could suppress bone loss in OVX mouse through inhibited osteoclastogenesis. All data provide the evidence that Cytisine may be a promising agent in the treatment of osteoclast‐related diseases such as osteoporosis.