Cellular response toβ-amyloid neurotoxicity in Alzheimer's disease and implications in new therapeutics

β-Amyloid(Aβ)is a specific pathological hallmark of Alzheimer's disease(AD).Because of its neurotoxicity,AD patients exhibit multiple brain dysfunctions.Disease-modifying therapy(DMT)is the central concept in the development of AD thera-peutics today,and most DMT drugs that are currently in clinical trials are anti-Aβdrugs,such as aducanumab and lecanemab.Therefore,understanding Aβ's neurotoxic mechanism is crucial for Aβ-targeted drug development.Despite its total length of only a few dozen amino acids,Aβis incredibly diverse.In addition to the well-known Aβ_(1-42),N-terminally truncated,glutaminyl cyclase(QC)catalyzed,and pyroglutamate-modified Aβ(pEAβ)is also highly amyloidogenic and far more cytotoxic.The extracel-lular monomeric Aβ_(x-42)(x=1-11)initiates the aggregation to form fibrils and plaques and causes many abnormal cellular responses through cell membrane receptors and receptor-coupled signal pathways.These signal cascades further influence many cel-lular metabolism-related processes,such as gene expression,cell cycle,and cell fate,and ultimately cause severe neural cell damage.However,endogenous cellular anti-Aβdefense processes always accompany the Aβ-induced microenvironment alterations.Aβ-cleaving endopeptidases,Aβ-degrading ubiquitin-proteasome system(UPS),and Aβ-engulfing glial cell immune responses are all essential self-defense mechanisms that we can leverage to develop new drugs.This review discusses some of the most recent advances in understanding Aβ-centric AD mechanisms and suggests prospects for promising anti-Aβstrategies.

Analysis on Sustainable Development of Tire Industry Cluster based on Life Cycle Theory

The research on the tire industry cluster based on life cycle theory can be carried out by a four stage periods,namely initial period,growth period,maturity period,and recession period.This paper analyzes on the possible risks taken in each life cycle period as well as proposes corresponding suggestions to strengthen the research by looking into the conditions and factors of the continuous sustainable development process in a tire industry.

Electricity-Carbon Interactive Optimal Dispatch of Multi-Virtual Power Plant Considering Integrated Demand Response

As new power systems and dual carbon policies develop,virtual power plant cluster(VPPC)provides another reliable way to promote the efficient utilization of energy and solve environmental pollution problems.To solve the coordinated optimal operation and low-carbon economic operation problem in multi-virtual power plant,a multi-virtual power plant(VPP)electricity-carbon interaction optimal scheduling model considering integrated demand response(IDR)is proposed.Firstly,a multi-VPP electricity-carbon interaction framework is established.The interaction of electric energy and carbon quotas can realize energy complementarity,reduce energy waste and promote low-carbon operation.Secondly,in order to coordinate the multiple types of energy and load in VPPC to further achieve low-carbon operation,the IDR mechanism based on the user comprehensive satisfaction(UCS)of electricity,heat as well as hydrogen is designed,which can effectively maintain the UCS in the cluster within a relatively high range.Finally,the unit output scheme is formulated to minimize the total cost of VPPC and the model is solved using theCPLEX solver.The simulation results showthat the proposed method effectively promotes the coordinated operation among multi-VPP,increases the consumption rate of renewable energy sources and the economics of VPPC and reduces carbon emissions.

The genetic basis and process of inbreeding depression in an elite hybrid rice

Inbreeding depression refers to the reduced performance arising from increased homozygosity,a phenomenon that is the reverse of heterosis and exists among plants and animals.As a natural self-pollinated crop with strong heterosis,the mechanism of inbreeding depression in rice is largely unknown.To understand the genetic basis of inbreeding depression,we constructed a successive inbreeding population from the F_(2)to F_(4)generation and observed inbreeding depression of all heterotic traits in the progeny along with the decay of heterozygosity in each generation.The expected depression effect was largely explained by 13 QTLs showing dominant effects for spikelets per panicle,11 for primary branches,and 12 for secondary branches,and these loci constitute the main correlation between heterosis and inbreeding depression.However,the genetic basis of inbreeding depression is also distinct from that of heterosis,such that a biased transmission ratio of alleles for QTLs with either dominant or additive effects in four segregation distortion regions would result in minor effects in expected depression.Noticeably,two-locus interactions may change the extent and direction of the depression effects of the target loci,and overall interactions would promote inbreeding depression among generations.Using an F_(2:3)variation population,the actual performance of the loci showing expected depression was evaluated considering the heterozygosity decay in the background after inbreeding.We found inconsistent or various degrees of background depression from the F_(2)to F_(3)generation assuming different genotypes of the target locus,which may affect the actual depression effect of the locus due to epistasis.The results suggest that the genetic architecture of inbreeding depression and heterosis is closely linked but also differs in their intrinsic mechanisms,which expand our understanding of the whole-genome architecture of inbreeding depression.

RNA-Directed DNA Methylation Is Involved in Regulating Photoperiod-Sensitive Male Sterility in Rice

Photoperiod-sensitive male sterility （PSMS） is a valuable germplasm for hybrid rice breeding. Recently, we cloned pros3, a locus controlling PSMS, which encodes a long non-coding RNA called LDMAR required for normal male fertility of the rice plant under long-day conditions. Increased methylation in the promoter of LDMAR in the PSMS rice （Nongken 58S） relative to the wild-type （Nongken 58） reduced expression of LDMAR leading to male sterility under long-day conditions. In this study, we identified a siRNA named Psi-LDMAR in the LDMAR promoter region that was more abundant in Nongken 58S than in Nongken 58. We showed that Psi-LDMAR was likely derived from AKl11270, a transcript obtained from the sense strand of the LDMAR promoter with its 3＇-end having a 110-base overlap with the 5＇-end of LDMAR. Overexpressing AKl11270 in Nongken 58S greatly enriched Psi-LDMAR, which induced RNA-directed DNA methylation in the LDMAR promoter and repressed the expression of LDMAR. Reduction of LDMAR in Nongken 58S changed the critical day length for fertility recovery and delayed the fertility recovery under short-day conditions. This result added to our understanding of the molecular mechanism for PSMS.

Reversible Histone H2B Monoubiquitination Fine-Tunes Abscisic Acid Signaling and Drought Response in Rice

Histone H2B monoubiquitination (H2Bub1) plays important roles in several physiological and developmental processes, but its roles in the regulation of plant stress responses remain elusive. Here, we report that H2Bub1 is crucially involved in abscisic acid (ABA) signaling and drought response in rice. We found that rice HISTONE MONOUBIQUITINATION2 (OsHUB2), an E3 ligase for H2Bub1, in teracted with OsbZIP46, a key transcription factor regulating ABA signaling and drought response in rice. Genetic analyses suggest that OsHUB2, upregulated by drought and ABA, positively modulates ABA sensitivity and drought resistance. The H2Bub1 levels were in creased in the target genes of OsbZIP46 under the drought stress and ABA treat- merits, which were positively correlated with their increased expression levels. Interestingly, MODD, a reported suppressor of ABA signaling and drought resistance by mediating OsbZIP46 deactivation and degradation, could reduce the H2Bub1 levels in the target genes of OsbZIP46 by recruiting a putative deubiquitinase OsOTLD1 . Suppression of OsOTLD1in vivo resulted in increased H2Bub1 levels and expression of OsbZIP46 target genes. Collectively, these fin dings established an elaborate mecha nism of histone monoubiquitination in the fine-turning of ABA signaling and drought response by balancing H2Bub1 deposition and removal.

Rice MtN3/saliva/SWEET gene family: Evolution,expression profiling, and sugar transport

The rice MtN3/saliva/SWEET gene family consists of 21 paralogs. However, their functions in physiological processes are largely unknown, although at least three of the 21 paralogs are used by pathogenic bacteria to infect rice. Here, we report the evolutionary features, transcriptional characteristics, and putative functions in sugar transport of this gene family. The wild rice accessions in this study included those with AA, BB, CC, BBCC, CCDD, EE, and GG genomes, which appeared approximately 0.58-14.6 million years ago. The structures, chromosomal locations, phylogenetic relationships, and homologous distribution among the accessions suggest that the number of rice MtN3/saliva/SWEET paralogs gradual y increased as the Oryza genus evolved, and one third of the paralogs may have originated recently. These paralogs are differentially expressed in vegetative and reproductive tissues, in the leaf senescence process, and in signaling dependent on gibberel ic acid, cytokinin, or 1-naphthalene acetic acid （an analog of auxin）, suggesting that they may be associated with multiple physiological processes. Four paralogs could transport galactose in yeast, which suggests that they may have a similar function in rice. These results will help to elucidate their roles and biochemical functions in rice development, adaptation to environment, host-pathogen interaction, and so forth.

The origin of Wx^(la) provides new insights into the improvement of grain quality in rice

Appearance and taste are important factors in rice(Oryza sativa) grain quality. Here, we investigated the taste scores and related eating-quality traits of533 diverse cultivars to assess the relationships between—and genetic basis of—rice taste and eating-quality. A genome-wide association study highlighted the Wx gene as the major factor underlying variation in taste and eating quality. Notably, a novel waxy(Wx) allele, Wx^(la), which combined two mutations from Wx^(b) and Wx^(in), exhibited a unique phenotype. Reduced GBSSI activity conferred Wx^(la) rice with both a transparent appearance and good eating quality. Haplotype analysis revealed that Wx^(la) was derived from intragenic recombination. In fact,the recombination rate at the Wx locus was estimated to be 3.34 kb/c M, which was about 75-fold higher than the genome-wide mean, indicating that intragenic recombination is a major force driving diversity at the Wx locus. Based on our results, we propose a new network for Wx evolution, noting that new Wx alleles could easily be generated by crossing genotypes with different Wx alleles. This study thus provides insights into the evolution of the Wx locus and facilitates molecular breeding for quality in rice.

Genetic architecture and key genes controlling the diversity of oil composition in rice grains

Rice grain oil is a valuable nutrient source.However,the genetic basis of oil biosynthesis in rice grains remains unclear.In this study,we performed a genome-wide association study on oil composition and oil concentration in a diverse panel of 533 cultivated rice accessions.High variation for 11 oil-related traits was observed,and the oil composition of rice grains showed differentiation among the subpopulations.We identified 46 loci that are significantly associated with grain oil concentration or composition,16 of which were detected in three recombinant inbred line populations.Twenty-six candidate genes encoding enzymes involved in oil metabolism were identified from these 46 loci,four of which(PAL6,LIN6,MYR2,and ARA6)were found to contribute to natural variation in oil composition and to show differentiation among the subpopulations.Interestingly,population genetic analyses revealed that specific haplotypes of PAL6 and LIN6 have been selected in japonica rice.Based on these results,we propose a possible oil biosynthetic pathway in rice grains.Collectively,our results provide new insights into the genetic basis of oil biosynthesis in rice grains and can facilitate marker-based breeding of rice varieties with enhanced oil and grain quality.

The rice Raf-like MAPKKK OsILA1 confers broad-spectrum resistance to bacterial blight by suppressing the OsMAPKK4-OsMAPK6 cascade

Mitogen-activated protein kinase kinase kinase(MAPKKK)are the first components of MAPK cascades,which play pivotal roles in signaling during plant development and physiological processes.The genome of rice encodes 75 MAPKKKs,of which 43 are Raf-like MAPKKKs.The functions and action modes of most of the Raf-like MAPKKKs,whether they function as bona fide MAPKKKs and which are their downstream MAPKKs,are largely unknown.Here,we identified the osmapkkk43 mutant,which conferred broad-spectrum resistance to Xanthomonas oryzae pv.oryzae(Xoo),the destructive bacterial pathogen of rice.Oryza sativa(Os)MAPKKK43 encoding a Raf-like MAPKKK was previously known as Increased Leaf Angle 1(OsILA1).Genetic analysis indicated that OsILA1 functioned as a negative regulator and acted upstream of the OsMAPKK4-OsMAPK6 cascade in rice-Xoo interactions.Unlike classical MAPKKKs,OsILA1 mainly phosphorylated the threonine 34 site at the N-terminal domain of OsMAPKK4,which possibly influenced the stability of OsMAPKK4.The N-terminal domain of OsILA1 is required for its homodimer formation and its full phosphorylation capacity.Taken together,our findings reveal that OsILA1 acts as a negative regulator of the OsMAPKK4-OsMAPK6 cascade and is involved in rice-Xoo interactions.

Characterization of a disease susceptibility locus for exploring an efficient way to improve rice resistance against bacterial blight

Bacterial blight caused by Xanthomonas oryzae pv.oryzae(Xoo) is the most harmful bacterial disease of rice worldwide.Previously,we characterized major disease resistance(MR) gene xa25,which confers race-specific resistance to Xoo strain PXO339.The xa25 is a recessive allele of the SWEET13 locus,but SWEET13's interaction with PXO339 and how efficiently using this locus for rice breeding still need to be defined.Here we show that the SWEET 13 allele from rice Zhenshan 97 is a susceptibility gene to PXO339.Using this allele's promoter to regulate xa25 resulted in disease,suggesting that the promoter is a key determinant in SWEET13 caused disease in Zhanshan 97 after PXO339 infection.PXO339 transcriptionally induces SWEET13 to cause disease.Partial suppressing SWEET13 expression leads to a high level of resistance to PXO339.Thus,the transcriptionally suppressed SWEET13 functions as xa25 in resistance to PXO339.Hybrid rice is widely grown in many countries.However,recessive MR genes have not been efficiently used for disease resistance breeding in hybrid rice production for both parents of the hybrid have to carry the same recessive gene.However,the suppressed SWEET 13 functions dominantly,which will have advantage to improve the resistance of hybrid rice to xa25-incomptible Xoo.

Origination and Establishment of a Trigenic Reproductive Isolation System in Rice

Dear Editor,Reproductive isolation is both the indicator and a primary force of speciation, and plays a key role in maintaining species identity. Understanding the origin and mechanisms of reproductive isola- tion is of fundamental importance in evolutionary biology. In recent years, a number of genes that induce reproductive barriers have been identified in several model organisms such as Drosophila, rodents, yeast, Arabidopsis.

正念减压疗法对阿尔茨海默病居家照顾者疾病负担的影响

目的:探讨正念减压疗法对阿尔茨海默病(AD)主要照顾者疾病负担的影响。方法:选取2019年5月至2022年10月AD主要照顾者78例为研究对象,随机分为观察组和对照组,各39例。观察组使用正念减压疗法进行干预,对照组采用常规健康教育干预。通过独立样本t检验、重复检测方差分析和χ2检验对比两组的疾病负担的改善情况。结果:对干预前、干预4周和干预12周3个时间点观察组和对照组疾病负担得分进行独立样本t检验分析,结果显示,干预前两组差异无统计学意义(P>0.05),干预4周和干预12周观察组疾病负担明显低于对照组,差异有统计学意义(P<0.01)。利用重复测量方差分析对两组干预前、干预4周和干预12周3个时间点疾病负担得分进行对比显示,两组照顾者接受的干预方式不同,疾病负担存在明显差异(P<0.05);随干预时间增长,两组照顾者疾病负担出现明显下降(P<0.01);时间因素和分组因素交互作用表明,不同的组内,时间因素作用是不同的(P<0.01)。结论:正念减压疗法能够降低AD主要照顾者疾病负担。

Integrative Regulation of Drought Escape through ABA-Dependent and -Independent Pathways in Rice

Many plants have evolved a drought escape （DE） mechanism to shorten their life cycle when facing water- deficit conditions. While drought tolerance has been intensively investigated, the genetic and molecular mechanisms of DE remain elusive. In this study, we found that low water-deficit treatment （LWT） at the early stage of rice development can trigger early flowering and reduced tiller numbers. LWT induced the accu- mulation of abscisic acid （ABA）, which in turn has feed-back effects on light perception and circadian clock by synchronously regulating many flowering-related genes to promote early flowering. Moreover, some of light receptors, circadian components, and flowering-related genes including OsTOC1, Ghd7, and PhyB were found to be involved in LWT in an ABA-dependent manner, whereas some of the other flowering- related genes including OsGI, OsELF3, OsPRR37, and OsMADS50 were involved in the regulation of DE independent of ABA. In addition, we found that strigolactones and OsTB1 are involved in the tillering inhibition under LWT, which is independent of the flowering pathway in rice. Taken together, our.findings provide compelling evidence that DE in rice is coordinately regulated by multiple pathways during the reproduction （flowering） switch.

Bract suppression regulated by the miR156/529-SPLs-NL1-PLA1 module is required for the transition from vegetative to reproductive branching in rice

Reproductive transition of grasses is characterized by switching the pattern of lateral branches,featuring the suppression of outgrowth of the subtending leaves(bracts)and rapid formation of higher-order branches in the inflorescence(panicle).However,the molecular mechanisms underlying such changes remain largely unknown.Here,we show that bract suppression is required for the reproductive branching in rice.We identified a pathway involving the intrinsic time ruler microRNAI56/529,their targets SQUAMOSA PROMOTER BINDING PROTEIN LIKE(SPL)genes,NECK LEAF1(NL1),and PLASTOCHRON1(PLA1),which regulates the bract outgrowth and thus affects the pattern switch between vegetative and reproductive branching.Suppression of the bract results in global reprogramming of transcriptome and chromatin accessibility following the reproductive transition,while these processes are largely dysregu-lated in the mutants of these genes.These discoveries contribute to our understanding of the dynamic plant architecture and provide novel insights for improving crop yields.

Artificial Selection in Domestication and Breeding Prevents Speciation in Rice

Speciation has long been regarded as an irreversible process once the reproductive barriers had been established.However,unlike in natural populations,artificial selection might either accelerate or prevent speciation processes in domesticated species.Asian cultivated rice is a target crop for both domestication and artificial breeding;it contains two subspecies of indica and japonica,which usually produce sterile inter-subspecific hybrids due to reproductive barriers.In this study,we constructed the evolutionary trajectory of a reproductive isolation system S5,which regulates fertility in indica-japonica hybrids via three adjacent genes,based on the data of 606 accessions including two cultivated and 11 wild rice species.Although hybrid sterility haplotypes at S5 lead to establishment of a killer-protector reproductive barrier,origin of wide-compatibility haplotypes by complex hybridization and recombination provides an opposing force to reproductive isolation and thus prevents speciation during domestication.Analysis in a diallel set of 209 crosses involving 21 parents showed that the wide-compatibility genotypes largely rescued fertility of indica-japonica hybrids,indicating that the wide-compatibility gene would enable gene flow to maintain species coherence.This counteracting system indicates that combined effects of natural evolution and artificial selection may result in reversible processes of speciation in rice,which may also have implications for genetic improvement of rice.

Multiple Alleles Encoding Atypical NLRs with Unique Central Tandem Repeats in Rice Confer Resistance to Xanthomonas oryzae pv. oryzae

Plants have developed various mechanisms for avoiding pathogen invasion,including resistance(R)genes.Most R genes encode nucleotide-binding domain and leucine-rich repeat containing proteins(NLRs).Here,we report the isolation of three new bacterial blight R genes in rice,Xa1-2,Xa14,and Xa31(t),which were allelic to Xa1 and encoded atypical NLRs with unique central tandem repeats(CTRs).We also found that Xa31(t)was the same gene as Xa1-2.Although Xa1-2 and Xa14 conferred different resistance spectra,their performance could be attenuated by iTALEs,as has previously been reported for Xa1.XA1,XA1-2,XA14,and non-resistant RGAF differed mainly in the substructure of the leucine-rich repeat domain.They all contained unique CTRs and belonged to the CTR-NLRs,which existed only in Gramineae.We also found that interactions among these genes led to differing resistance performance.In conclusion,our results uncover a unique locus in rice consisting of at least three multiple alleles(Xa1,Xa1-2,and Xa14)that encode CTRNLRs and confer resistance to Xanthomonas oryzae pv.oryzae(Xoo).

The tRNA 3'-end Processing Enzyme tRNase Z2Contributes to Chloroplast Biogenesis in Rice

tRNase Z （TRZ） is a ubiquitous endonuclease that removes the 3＇-trailer from precursor tRNAs during maturation. In yeast and animals, TRZ regulates the cell cycle via its （t）RNA processing activity; however, its physiological function in higher plants has not been well characterized. This study describes the identification of a rice （Oryza sativa） TRZ2 mutant; plants homozygous for the osatrz2 mutation were albinos with deficient chlorophyll content. A microscopic analysis of the mutant plants revealed that the transition of proplastids to chloroplasts was arrested at an early stage, and the number and size of the plastids in callus cells was substantially decreased. A genetic complementation test and an RNA interference analysis confirmed that disruption of OsaTRZ2 was responsible for the mutant phenotype. OsaTRZ2 is expressed in all rice tissues, but is preferentially expressed in leaves, sheathes, and calli. OsaTRZ2 was subcellularly localized in chloroplasts, and displayed tRNA 3＇-end processing activity in both in vitro and in vivo assays. In the osatrz2 mutants, transcription of plastid-encoded and nucleus- encoded RNA polymerases was severely reduced and moderately increased, respectively. These results suggest that the tRNA 3＇ processing activity of OsaTRZ2 contributes to chloroplast biogenesis.