Pear genomes display significant genetic diversity and provide novel insights into the fruit quality traits differentiation

The pear(Pyrus spp.)is well known for diverse flavors,textures,and global horticultural importance.However,the genetic diversity responsible for its extensive phenotypic variations remains largely unexplored.Here,we de novo assembled and annotated the genomes of the maternal(PsbM)and paternal(PsbF)lines of the hybrid‘Yuluxiang'pear and constructed the pear pangenome of 1.15 Gb by combining these two genomes with five previously published pear genomes representing cultivated and wild germplasm.Using the constructed pangenome,we identified 21224 gene PAVs(Presence-absence variation)and 1158812 SNPs(Single Nucleotide Polymorphism)in the non-reference genome that were absent in the PsbM reference genome.Compared with SNP markers,PAV-based analysis provides additional insights into the pear population structure.In addition,some genes associated with pear fruit quality traits have differential occurrence frequencies and differential gene expression between Asian and European populations.Moreover,our analysis of the pear pangenome revealed a mutated SNP and an insertion in the promoter region of the gene PsbMGH3.1 potentially enhance sepal shedding in‘Xuehuali'which is vital for pear quality.PsbMGH3.1 may play a role in the IAA pathway,contributing to a distinct low-auxin phenotype observed in plants by heterologously overexpressing this gene.This research helps capture the genetic diversity of pear populations and provides genomic resources for accelerating breeding.

Induced Th2 dominant immune response in APPswe, PSEN1dE9 transgenic mice after nasal immunization with an adenoviral vector encoding 10 tandem repeats of beta-amyloid 3-10

Immunotherapy for Alzheimer＇s disease （AD） is effective in improving cognitive function in transgenic mouse models of AD. Because the AN1792 [beta-amyloid （Aβ） 1-42] vaccine was halted because of T cell mediated meningoencephalitis, many scientists are searching for a nove） vaccine to avoid the T cell mediated immune response caused by the Aβ1-42. Importantly, the time when the immunization is begun can influence the immune effect. In this study, an adenovirus vaccine was constructed containing 10 x Aβ3-10 repeats and gene adjuvant CpG DNA. Transgenic AD mice were immunized intranasally for 3 months. After 10 × Aβ3-10 vaccine immunization, high titers of anti-Aβ42 IgG1 predominant antibodies were induced. In spatial learning ability and probe tests, the 10 × Aβ3-10 immunized mice showed significantly improved memories compared to control mice. The 10 × Aβ3-10 vaccine resulted in a robust Th2 dominant humoral immune response and reduced learning deficits in AD mice. In addition, the 10 × Aβ3-10 vaccine might be more efficient if administered before Aβ aggregation at an early stage in the AD mouse brain. Thus, the adenovirus vector encoding 10 × Aβ-10 is a promising vaccine for AD.

Removal of the main inflorescence to induce reflowering of loquat

Loquat(Eriobotrya japonica Lindl.)is an evergreen fruit tree species of the Rosaceae,and its unique flowering time greatly hinders its production.To explore the artificial regulation of loquat flowering time,we removed the main inflorescence(by cutting it)to induce reflowering.For different loquat tree cultivars with different stages,the inflorescence was removed by cutting the main floral axis at two alternative positions:the upper or the lower position beneath the inflorescence,and it was found that the proportion of reflowering resulting from removing the upper position of the main floral axis of yellow-flesh loquat cultivars during the full-bloom stage was the highest.In addition,compared with those of the normal-growing panicles,the number of flower buds and branch axes of the reflowering panicles decreased significantly after cutting.Importantly,these newly produced inflorescences flowered 2–4 months later than normal-growing inflorescences did,effectively prolonging both the flowering and fruiting time.In addition,qRT-PCR results showed that EjFT1,EjFT2,EjAP1–1 and EjAP1–2 were highly expressed in the floral axis.These findings highlighted a new method for extending the production cycle of loquat and provided a reference for the flowering regulation of loquat and other economically important fruit tree species.

Ipsilateral versus bilateral limb-training in promoting the proliferation and differentiation of endogenous neural stem cells following cerebral infarction in rats

We investigated the effects of ipsilateral versus bilateral limb-training on promotion of endogenous neural stem cells in the peripheral infarct zone and the corresponding cerebral region in the unaffected hemisphere of rats with cerebral infarction. Middle cerebral artery occlusion was induced in Wistar rats. The rat forelimb on the unaffected side was either wrapped up with tape to force the use of the paretic forelimb in rats or not braked to allow bilateral forelimbs to participate in training. Daily training consisted of mesh drum training, balance beam training, and stick rolling training for a total of 40 minutes, once per day. Control rats received no training. At 14 days after functional training, rats receiving bilateral limb-training exhibited milder neurological impairment than that in the ipsilateral limb-training group or the control group. The number of nestin/glial fibrillary acidic protein-positive and nestin/microtubule-associated protein 2-positive cells in the peripheral infarct zone and in the corresponding cerebral region in the unaffected hemisphere was significantly higher in rats receiving bilateral limb-training than in rats receiving ipsilateral limb-training. These data suggest that bilateral limb-training can promote the proliferation and differentiation of endogenous neural stem cells in the bilateral hemispheres after cerebral infarction and accelerate the recovery of neurologic function. In addition, bilateral limb-training produces better therapeutic effects than ipsilateral limb-training.

A Strong Tracking Filtering Approach for Health Estimation of Marine Gas Turbine Engine

Monitoring and evaluating the health parameters of marine gas turbine engine help in developing predictive control techniques and maintenance schedules.Because the health parameters are unmeasurable,researchers estimate them only based on the available measurement parameters.Kalman filter-based approaches are the most commonly used estimation approaches;how-ever,the conventional Kalman filter-based approaches have a poor robustness to the model uncertainty,and their ability to track the mutation condition is influenced by historical data.Therefore,in this paper,an improved Kalman filter-based algorithm called the strong tracking extended Kalman filter(STEKF)approach is proposed to estimate the gas turbine health parameters.The analytical expressions of Jacobian matrixes are deduced by non-equilibrium point analytical linearization to address the problem of the conventional approaches.The proposed approach was used to estimate the health parameters of a two-shaft marine gas turbine engine in the simulation environment and was compared with the extended Kalman filter(EKF)and the unscented Kalman filter(UKF).The results show that the STEKF approach not only has a computation cost similar to that of the EKF approach but also outperforms the EKF approach when the health parameters change abruptly and the noise mean value is not zero.

A new DNA vaccine fused with the C3d-p28 induces a Th2 immune response against amyloid-beta

To enhance anti-amyloid-beta （Aβ） antibody generation and induce a Th2 immune response, we constructed a new DNA vaccine p（Aβ3-10 ）10-C3d-p28.3 encoding ten repeats of Aβ3-10 and three copies of C3d-p28 as a molecular adjuvant. In this study, we administered this adjuvant intramus-cularly to female C57BL/6J mice at 8-10 weeks of age. Enzyme linked immunosorbent assay was used to detect the titer of serum anti-Aβ antibody, isotypes, and cytokines in splenic T cel s. A 3-（4,5-cimethylthiazol-2-yl）-2,5-diphenyl tetrazolium bromide assay was used to detect the prolifera-tion rate of splenic T cel s. Brain sections from a 12-month-old APP/PS1 transgenic mouse were used for detecting the binding capacities of anti-Aβ antibodies to Aβ plaques. The p（Aβ3-10）10-C3d-p28.3 vaccine induced high titers of anti-amyloid-βantibodies, which bound to Aβplaques in APP/PS1 transgenic mouse brain tissue, demonstrating that the vaccine is effective against plaques in a mouse model of Alzheimer’s disease. Moreover, the vaccine elicited a pre-dominantly IgG1 humoral response and low levels of interferon-γ in ex vivo cultured splenocytes, indicating that the vaccine could shift the cel ular immune response towards a Th2 phenotype. This indicated that the vaccine did not elicit a detrimental immune response and had a favorable safety profile. Our results indicate that the p（Aβ3-10）10-C3d-p28.3 vaccine is a promising immunothera-peutic option for Aβvaccination in Alzheimer’s disease.

What is the new target inhibiting the progression of Alzheimer's disease?

To stop the progression of Alzheimer＇s disease in the early stage, it is necessary to identify new therapeutic targets. We examined striatal-enriched phosphatase 61 expression in the brain tissues of 12-month-old APPswe/PSEN1dE9 transgenic mice. Immunohistochemistry showed that striatal-enriched phosphatase 61 protein expression was significantly increased but phosphorylated N-methyl-D-aspartate receptor 2B levels were significantly decreased in the cortex and hippocampus of APPswe/PSEN1dE9 transgenic mice. Western blotting of a cell model of Alzheimer＇s disease consisting of amyloid-beta peptide （1-42）-treated C57BL/6 mouse cortical neurons in vitro showed that valeric acid （AP5）, an N-methyl-D-aspartate receptor antagonist, significantly inhibited amyloidbeta 1-42-induced increased activity of striatal-enriched phosphatase 61. In addition, the phosphorylation of N-methyl-D-aspartate receptor 2B at Tyr1472 was impaired in amyloid-beta 1-42-treated cortical neurons, but knockdown of striatal-enriched phosphatase 61 enhanced the phosphorylation of N-methyl-D-aspartate receptor 2B. Collectively, these findings indicate that striatal-enriched phosphatase 61 can disturb N-methyl-D-aspartate receptor transport and inhibit the progression of learning and study disturbances induced by Alzheimer＇s disease. Thus, striatal-enriched phosphatase 61 may represent a new target for inhibiting the progression of Alzheimer＇s disease.

Nasal mucosal inhalation of amyloid-beta peptide 3–10 defective adenovirus attenuates cytotoxicity induced by beta-amyloid(1–42)

Three-month-old Alzheimer＇s disease model transgenic mice were immunized with Aβ1-42, Plp-Adenovirus [Ad]-X-CMV-（Aβ3-10）lo-CpG [AdCpG-（Aβ3-10）1] or AdCpG virus fluid via na- sal mucosal inhalation, respectively. ELISA analysis of serum showed Aβ42 antibody titers were significantly increased in mice immunized with Aβ1-42 and AdCpG-（Aβ3-10）10. Concanavalin A and AdCpG-（Aβ3-10）10 stimulation significantly increased the number of proliferating spleen cells cultured from AdCpG（Aβ3-10）Io and Aβ42 groups compared with the control group. In the AdCp- G（Aβ3-10）10 group, levels of interleukin （IL）-4 and IL-10 were increased, while those of IL-2 and interferon-y were decreased. In the A[342 group, levels of IL-4, IL-10, IL-2 and interferon-y were all increased. Experimental findings indicate that AdCpG-（Aβ3-10）10 vaccine can produce strong T helper 2 （Th2） humoral immune responses in addition to the production of Aβ42 antibody. The cellular immunologic response was weak and avoided Aβ1-42-mediated cytotoxicity.

Comprehensive Management of Daily Living Activities,behavioral and Psychological Symptoms,and Cognitive Function in Patients with Alzheimer's Disease:A Chinese Consensus on Alzheimer's Disease

Alzheimer's disease(AD)is the most common cognitive disorder in the elderly.Its main clinical manifestations are cognitive decline(C),behavioral and psychological symptoms(B),and a decline in the activities of daily living(A),also known as ABC symptoms.Early identification and evaluation of ABC symptoms are helpful for establishing the accurate diagnosis,comprehensive treatment,and prognosis of AD.To guide Chinese clinical practice for optimization of the comprehensive management of AD,in 2018,The Academy of Cognitive Disorder of China gathered 22 neurologists and gerontologists in China to build a consensus on the comprehensive management of AD.Based on a review of the evidence,the consensus summarizes the pathogenesis,pathological changes,clinical manifestations,evaluation,diagnosis,drug and non-drug treatment,and patient care for AD.Focus group discussion was used to establish a flowchart of comprehensive ABC management for AD patients.The new consensus provides a feasible AD management process for clinicians.

Correction to:Comprehensive Management of Daily Living Activities,behavioral and Psychological Symptoms,and Cognitive Function in Patients with Alzheimer’s Disease:A Chinese Consensus on the Comprehensive Management of Alzheimer’s Disease

The article‘Comprehensive Management of Daily Living Activities,behavioral and Psychological Symptoms,and Cognitive Function in Patients with Alzheimer’s Disease:A Chinese Consensus on the Comprehensive Management of Alzheimer’s Disease’,written by Jun Xu,Jun Liu,Yongjun Wang,Yanjiang Wang,Yunpeng Cao,Qihao Guo,Qiuming Qu,Cuibai Wei,Wenshi Wei,Junjian Zhang&Enyan Yu,was originally published electronically on the publisher’s internet portal on 29th May 2021 without open access.With the author(s)’decision to opt for Open Choice the copyright of the article changed on 11th June 2021 to©The Author(s)2021 and the article is forthwith distributed under a Creative Commons Attribution 4.0 International License,which permits use,sharing,adaptation,distribution and reproduction in any medium or format,as long as you give appropriate credit to the original author(s)and the source,provide a link to the Creative Commons licence,and indicate if changes were made.The original article has been corrected.

A PpEIL2/3–PpNAC1–PpWRKY14 module regulates fruit ripening by modulating ethylene production in peach

WRKY transcription factors play key roles in plant resistance to various stresses,but their roles in fruit ripening remain largely unknown.Here,we report a WRKY gene PpWRKY14 involved in the regulation of fruit ripening in peach.The expression of PpWRKY14 showed an increasing trend throughout fruit development.PpWRKY14was a target gene of PpNAC1,a master regulator of peach fruit ripening.PpWRKY14 could directly bind to the promoters of PpACS1 and PpACO1 to induce their expression,and this induction was greatly enhanced when PpWRKY14 formed a dimer with PpNAC1.However,the transcription of PpNAC1 could be directly suppressed by two EIN3/EIL1 genes,PpEIL2 and PpEIL3.The PpEIL2/3 genes were highly expressed at the early stages of fruit development,but their expression was programmed to decrease significantly during the ripening stage,thus derepressing the expression of PpNAC1.These results suggested a PpEIL2/3–PpNAC1–PpWRKY14 module that regulates fruit ripening by modulating ethylene production in peach.Our results provided an insight into the regulatory roles of EIN3/EIL1 and WRKY genes in fruit ripening.