Phosphorylation regulation of nitrogen,phosphorus,and potassium uptake systems in plants

The uptake of ammonium,nitrate,phosphorus,and potassium ions by roots is mediated by specific ion transporter or channel proteins,and protein phosphorylation regulation events occurring on these proteins and their regulators determine their ultimate activity.Elucidating the mechanism by which protein phosphorylation modification regulates nutrient uptake will advance plant breeding for high nutrientuse efficiency.In this review,it is concluded that the root nutrient absorption system is composed of several,but not all,members of a specific ion transporter or channel family.Under nutrient-starvation conditions,protein phosphorylation-based regulation of these proteins and associated transcription factors increases ion transporter-or channel-mediated nutrient uptake capacity via direct function activity enhancement,allowing more protein trafficking to the plasma membrane,by strengthening the interaction of transporters and channels with partner proteins,by increasing their protein stability,and by transcriptional activation.Under excessive nutrient conditions,protein phosphorylation-based regulation suppresses nutrient uptake by reversing these processes.Strengthening phosphorylation regulation items that increase nutrient absorption and weakening phosphorylation modification items that are not conducive to nutrient absorption show potential as strategies for increasing nutrient use efficiency.

The pentatricopeptide repeat protein EMP601 functions in maize seed development by affecting RNA editing of mitochondrial transcript ccmC

Although several pentatricopeptide repeat(PPR) proteins are involved in post-transcriptional processing of mitochondrial RNA, it is unclear which specific protein is involved in the RNA editing of ccmC in maize(Zea mays). Here we report the identification of the maize empty pericarp 601(emp601) mutant and the map-based cloning of the Emp601 gene, which encodes an E2-type PPR protein that is targeted to mitochondria. A single-nucleotide deletion in the emp601 mutant caused a frameshift and introduced a premature stop codon into the predicted EMP601. This mutation was associated with reduced accumulation of mitochondrial complex Ⅲ as well as with inhibition of growth and differentiation of basal endosperm transfer layer cells, leading to final degeneration of the embryo and endosperm. We determine that loss of EMP601 function prevents the C-to-U RNA editing of the mitochondrial transcript ccmC at position 358.EMP601 binds to the ccmC transcript and directly interacts with Multiple organellar RNA editing factor 8and may be a component of the plant mitochondrial editosome. We conclude that EMP601 functions in RNA editing of mitochondrial ccmC transcripts and influences mitochondrial function and seed development.

Comparative DNA-methylome and transcriptome analysis reveals heterosis-and polyploidy-associated epigenetic changes in rice

Heterosis and polyploidy have an overwhelming influence on plant evolution.Recently,polyploid rice hybrids have been used to breed new rice varieties because they combine the advantages of both heterosis and polyploidy.In this study,we generated six rice lines:autotetraploid rice hybrids and their autotetraploid parents,diploid donors,and hybrids of the diploid donors.To investigate the molecular mechanism controlling the effects of both hybridization and polyploidization,we performed bisulfite and RNA sequencing on young panicles at the pollen meiosis stage to compare the DNA metabolomes and transcriptomes among the six rice lines.The hybrids lines were hypermethylated compared to their corresponding parents and the autotetraploid lines showed globally increased DNA methylation of their transposable elements compared to the diploid donors.The alteration in DNA methylation level corresponded to the differential gene expressions among the rice genotypes,suggesting that methylation changes induced by polyploidization and hybridization may affect gene expression.Groups of gene candidates were identified that may be associated with heterosis and polyploidy.Our results provide DNA information that can be used to investigate epigenetic modification during heterosis and polyploidy in rice.

A novel PTEN gene promoter mutation and untypical Cowden syndrome

Cowden syndrome （CS）, an autosomal dominant disorder, is one of a spectrum of clinical disorders that have been linked to germline mutations in the phosphatase and tensin homolog （PTEN） gene. Although 70-80% of patients with CS have an identifiable germline PTEN mutation, the clinical diagnosis presents many challenges because of the phenotypic and genotypic variations. In the present study, we sequenced the exons and the promoter of PTEN gene, mutations and variations in the promoter and exons were identified, and a PTEN protein expression negative region was determined by immunohistochemistry （IHC）. In conclusion, a novel promoter mutation we found in PTEN gene may turn off PTEN protein expression occasionally, leading to the disorder of PTEN and untypical CS manifestations.

A high-quality chromosome-scale assembly of the centipedegrass[Eremochloa ophiuroides(Munro)Hack.]genome provides in sights into chromosomal structural evolution and prostrate growth habit

Centipedegrass[Eremochloa ophiuroides(Munro)Hack.],a member of the Panicoideae subfamily,is one of the most important warm-season turfgrasses originating from China.This grass has an extremely developed prostrate growth habit and has been widely used in transitional and warm climatic regions.To better understand the genetic basis of important biological characteristics,such as prostrate growth and seed yield,in warm-season turfgrasses,we present a high-quality reference genome for centipedegrass and use PacBio,BioNano,and Hi-C technologies to anchor the 867.43 Mb genome assembly into nine pseudochromosomes,with a scaffold N50 of 86.05 Mb and 36,572 annotated genes.Centipedegrass was most closely related to sorghum and diverged from their common ancestor~16.8 Mya.We detected a novel chromosome reshuf fling event in centipedegrass,namely,the nest chromosome fusion event in which fusion of chromosomes 8 and 10 of sorghum into chromosome 3 of centipedegrass likely occurred after the divergence of centipedegrass from sorghum.The typical prostrate growth trait in centipedegrass may be linked to the expansion of candidate PROSTRATE GROWTH 1(PROG1)genes on chromosome 2.Two orthologous genes of OsPROGl,EoPROGl,and EoPROG2,were con firmed to increase the stem number and decrease the stem angle in Arabidopsis.Collectively,our assembled reference genome of centipedegrass offers new knowledge and resources to dissect the genome evolution of Panicoideae and accelerate genome-assisted breeding and improvement of plant architecture in turf plants.

In-situ growth of CNTs encapsulating P-doped NiSe_(2) nanoparticles on carbon framework as efficient bifunctional electrocatalyst for overall water splitting

Nickel diselenide(NiSe_(2)) is a promising low-cost catalyst for both hydrogen evolution reaction(HER) and oxygen evolution reaction(OER),due to its suitable d-electron configuration and high electrical conductivity.Several representative elements,e.g.,Co,Fe and P,have been utilized as cation or anion to promote the electrocatalytic activity of NiSe_(2) by modulating the interaction with Se element,whilst the catalyst stability is less concerned.In this work,the catalytic Ni nanoparticles were in-situ encapsulated in carbon nanotubes grown on three-dimensional conducting carbon framework.Subsequent phosphorization and selenization yield dispersed P-doped NiSe_(2) nanoparticles protected by carbon shell with highly exposed yet stable active sides,resulting in significantly promoted HER and OER activities as well as accelerated kinetics.In detail,the P-NiSe_(2)@N-CNTs/NC hybrid catalyst deliver low overpotentials of 95 and 306 mV at10 mA cm^(-2) for HER and OER in alkaline media,respectively.DFT calculations reveal that P doping reduces the electron density surrounding Ni atoms while accumulates the charges to Se, respectively,which in turn reduces the energy barriers for both water dissociation and intermediates adsorption for both HER and OER.As a concept of proof,a cell assembled by P-NiSe_(2)@N-CNTs/NC hybrid catalystbased anode and cathode performs a low applied voltage of 1.609 V to reach 10 mA cm^(-2),and outstanding long-term stability.

小学高年级儿童认知共情对第三方惩罚群体偏好的影响

儿童作为第三方在公平规范执行过程中存在群体偏好现象,即对内外群体的惩罚不同.儿童后期公平规范意识提升,儿童面临的人际情境更加复杂.然而,儿童后期第三方惩罚群体偏好的发展趋势尚不明确.认知共情可能是影响儿童后期第三方惩罚群体偏好的潜在因素.为探究小学高年级儿童认知共情能力对第三方惩罚行为群体偏好的影响,共招募320名小学四~六年级儿童,采用改编自独裁者博弈的第三方惩罚任务,被试观看不公平分配方案(90/10)后对分配者实施有代价的惩罚.分别对分配者和接受者的群体身份进行操纵(任务一和任务二),均为2(群体身份:内群体,外群体)×3(年级:四、五、六年级)的混合实验设计,并测量儿童的认知共情能力.研究发现:(1)小学高年级儿童第三方惩罚行为存在群体偏好,3个年级的儿童均对内群体违规者更包容,对内群体受害者更偏袒,并且六年级儿童对内群体分配者的惩罚高于四年级和五年级,表明群体偏好随年级升高减弱.(2)儿童的认知共情能力影响第三方惩罚的群体偏好,并受到年级调节,具体表现为四年级和五年级儿童的认知共情能力能够预测对分配者的群体偏好和对内群体的惩罚,而当接受者是外群体成员时,四年级儿童的认知共情能力能够预测对分配者的惩罚.本研究揭示了小学高年级儿童的群体偏好随年级升高而减弱的现象以及共情的预测作用.研究结果从发展的角度为共情对第三方惩罚群体偏好的影响提供了证据,为深入理解儿童在社会交互过程中道德认知与情感发展之间的关系提供了新的视角.

Endoplasmic reticulum-targeted delivery of celastrol and PD-L1 siRNA for reinforcing immunogenic cell death and potentiating cancer immunotherapy

The prospect of employing chemoimmunotherapy targeted towards the endoplasmic reticulum(ER)presents an opportunity to amplify the synergistic effects of chemotherapy and immunotherapy.In this study,we initially validated celastrol(CEL)as an inducer of immunogenic cell death(ICD)by promoting ER stress and autophagy in colorectal cancer(CRC)cells.Subsequently,an ER-targeted strategy was posited,involving the codelivery of CEL with PD-L1 small interfering RNAs(siRNA)using KDEL peptide-modified exosomes derived from milk(KME),to enhance chemoimmunotherapy outcomes.Our findings demonstrate the efficient transportation of KME to the ER via the Golgi-to-ER pathway.Compared to their non-targeting counterparts,KME exhibited a significant augmentation of the CEL-induced ICD effect.Additionally,it facilitated the release of danger signaling molecules(DAMPs),thereby stimulating the antigen-presenting function of dendritic cells and promoting the infiltration of T cells into the tumor.Concurrently,the ER-targeted delivery of PD-L1 siRNA resulted in the downregulation of both intracellular and membrane PD-L1 protein expression,consequently fostering the proliferation and activity of CD8^(+)T cells.Ultimately,the ER-targeted formulation exhibited enhanced anti-tumor efficacy and provoked anti-tumor immune responses against orthotopic colorectal tumors in vivo.Collectively,a robust ER-targeted delivery strategy provides an encouraging approach for achieving potent cancer chemoimmunotherapy.

Evaluation of molecular residual disease in operable non-small cell lung cancer with gene fusions,MET exon skipping or de novo MET amplification

Gene fusions and MET alterations are rare and difficult to detect in plasma samples.The clinical detection efficacy of molecular residual disease(MRD)based on circulating tumor DNA(ctDNA)in patients with non-small cell lung cancer(NSCLC)with these mutations remains unknown.This prospective,non-intervention study recruited 49 patients with operable NSCLC with actionable gene fusions(ALK,ROS1,RET,and FGFR1),MET exon 14 skipping or de novo MET amplification.We analyzed 43 tumor tissues and 111 serial perioperative plasma samples using 1021-and 338-gene panels,respectively.Detectable MRD correlated with a significantly higher recurrence rate(P<0.001),yielding positive predictive values of 100%and 90.9%,and negative predictive values of 82.4%and 86.4%at landmark and longitudinal time points,respectively.Patients with detectable MRD showed reduced disease-free survival(DFS)compared to those with undetectable MRD(P<0.001).Patients who harbored tissue-derived fusion/MET alterations in their MRD had reduced DFS compared to those who did not(P=0.05).To our knowledge,this is the first comprehensive study on ctDNA-MRD clinical detection efficacy in operable NSCLC patients with gene fusions and MET alterations.Patients with detectable tissue-derived fusion/MET alterations in postoperative MRD had worse clinical outcomes.

早产儿先天性长QT综合征1例

本文报告1例早产儿先天性长QT综合征,患儿于胎儿期即发现胎心不齐,生后出现严重心律失常,心率55~110次/min,24 h动态心电图示QT间期延长、尖端扭转型心律失常、二度Ⅱ型房室传导阻滞,基因检测发现KCNH2基因变异,生后10 d家长放弃治疗后死亡。

Adding Fuel to the Fire by Increased GABAergic Inhibition:A Seizure-Amplifying Nigra-Parafascicular Pathway

Epilepsy is a common neurological disorder characterized by recurrent seizures.Most anti epileptic drugs (AEDs)work by regulating the balance of the excitatory glutamatergic and inhibitory GABAergic transmission.However,the current AEDs cannot successfully control seizures in most (>70%) patients with temporal lobe epilepsy (TLE)[1],in whom seizures typically begin in the hippocampus.This may be caused by changes in the synaptic efficacy and remodeling of neural circuits,such as alterations in the distribution/expression of GABA_A receptor subunits and mossy-fiber sprouting.Since Dr.Karen Gale and colleagues originally described the seizure-modulating effects of nigral GABAergic transmission in the early 1980s [2]。

Digital Karyotyping with Whole Genomic Sequencing for Complex Congenital Disorder

Complex congenital disorders may be caused by multiple genetic alterations and/or environmental hazards. Diagnosis and management of these diseases are usually difficult. Robust next-generation sequencing （NGS） technologies provide unprecedented opportunities to maximize mutation detection and improve genetic counseling and clinical management. Targeted or whole exome sequencing （WES） mainly detects protein-coding DNA sequence aberrations and is the major DNA sequencing technology that is entering clinical practice （Liu et al., 2014）.

Use of Whole-Exome Sequencing for the Diagnosis of Atypical Birte-Hogge-Dubé Syndrome

Destruction of the lung parenchyma may result in the forma- tion of cysts, cavities and bullae. Definition of the type of destructive lesion is best achieved by high-resolution computed tomography （HRCT） scans of the chest （Trotman- Dickenson, 2014）. The loss of lung parenchyma may result in respiratory compromise and pneumothoraces. In the case of cystic lung destruction, multiple causes have been identified, with the cysts being a manifestation of inherited and non- inherited diseases （Sahn and Heffner, 2000）. Compared with sporadic cases, familial lung cysts/spontaneous pneumothorax are rare and are manifestation of some Mendelian genetic diseases.