查看更多>>摘要：Transposable elements(TEs)are ubiquitous genomic components and hard to study due to being highly repetitive.Here we assembled 232 chromosome-level genomes based on long-read sequencing data.Coupling the 232 genomes with 15 existing assemblies,we developed a pan-TE map comprising both cultivated and wild Asian rice.We detected 177 084 high-quality TE variations and inferred their derived state using outgroups.We found TEs were one source of phenotypic variation during rice domestication and differentiation.We identified 1246 genes whose expression variation was associated with TEs but not single-nucleotide polymorphisms(SNPs),such as OsRbohB,and validated OsRbohB's relative expression activity using a dual-Luciferase(LUC)reporter assays system.Our pan-TE map allowed us to detect multiple novel loci associated with agronomic traits.Collectively,our findings highlight the contributions of TEs to domestication,differentiation and agronomic traits in rice,and there is massive potential for gene cloning and molecular breeding by the high-quality Asian pan-TE map we generated.
查看更多>>摘要：Accumulation of aggregated α-synuclein(α-syn)in Lewy bodies is the pathological hallmark of Parkinson's disease(PD).Genetic mutations in lipid metabolism are causative for a subset of patients with Parkinsonism.The role of α-syn's lipid interactions in its function and aggregation is recognized,yet the specific lipids involved and how lipid metabolism issues trigger α-syn aggregation and neurodegeneration remain unclear.Here,we found that α-syn shows a preference for binding to lysophospholipids(LPLs),particularly targeting lysophosphatidylcholine(LPC)without relying on electrostatic interactions.LPC is capable of maintaining α-syn in a compact conformation,significantly reducing its propensity to aggregate both in vitro and within cellular environments.Conversely,a reduction in the production of cellular LPLs is associated with an increase in α-syn accumulation.Our work underscores the critical role of LPLs in preserving the natural conformation of α-syn to inhibit improper aggregation,and establishes a potential connection between lipid metabolic dysfunction and α-syn aggregation in PD.
查看更多>>摘要：Decidual natural killer(dNK)cells are the most abundant immune cells at the maternal-fetal interface during early pregnancy in both mice and humans,and emerging single-cell transcriptomic studies have uncovered various human dNK subsets that are disrupted in patients experiencing recurrent early pregnancy loss(RPL)at early gestational stage,suggesting a connection between abnormal proportions or characteristics of dNK subsets and RPL pathogenesis.However,the functional mechanisms underlying this association remain unclear.Here,we established a mouse model by adoptively transferring human dNK cells into pregnant NOG(NOD/Shi-scid/IL-2Rynul1)mice,where human dNK cells predominantly homed into the uteri of recipients.Using this model,we observed a strong correlation between the properties of human dNK cells and pregnancy outcome.The transfer of dNK cells from RPL patients(dNK-RPL)remarkably worsened early pregnancy loss and impaired placental trophoblast cell differentiation in the recipients.These adverse effects were effectively reversed by transferring CD56+CD39+dNK cells.Mechanistic studies revealed that CD56+CD39+dNK subset facilitates early differentiation of mouse trophoblast stem cells(mTSCs)towards both invasive and syncytial pathways through secreting macrophage colony-stimulating factor(M-CSF).Administration of recombinant M-CSF to NOG mice transferred with dNK-RPL efficiently rescued the exacerbated pregnancy outcomes and fetal/placental development.Collectively,this study established a novel humanized mouse model featuring functional human dNK cells homing into the uteri of recipients and uncovered the pivotal role of M-CSF in fetal-supporting function of CD56+CD39+dNK cells during early pregnancy,highlighting that M-CSF may be a previously unappreciated therapeutic target for intervening RPL.
查看更多>>摘要：Our understanding of pre-Cretaceous dinosaur reproduction is hindered by a scarcity of evidence within fossil records.Here we report three adult skeletons and five clutches of embryo-containing eggs of a new sauropodomorph from the Lower Jurassic of southwestern China,displaying several significant reproductive features that are either unknown or unlike other early-diverging sauropodomorphs,such as relatively large eggs with a relatively thick calcareous shell formed by prominent mammillary cones,synchronous hatching and a transitional prehatching posture between the crocodilians and living birds.Most significantly,these Early Jurassic fossils provide strong evidence for the earliest known leathery eggs.Our comprehensive quantitative analyses demonstrate that the first dinosaur eggs were probably leathery,elliptical and relatively small,but with relatively long eggshell units,and that along the line to living birds,the most significant change in reptilian egg morphology occurred early in theropod evolution rather than near the origin of Aves.
查看更多>>摘要：High intraocular pressure(IOP)is one of the high-risk pathogenic factors of glaucoma.Existing methods of IOP measurement are based on the direct interaction with the cornea.Commercial ophthalmic tonometers based on snapshot measurements are expensive,bulky,and their operation requires trained personnel.Theranostic contact lenses are easy to use,but they may block vision and cause infection.Here,we report a sensory system for IOP assessment that uses a soft indentor with two asymmetrically deployed iontronic flexible pressure sensors to interact with the eyelid-eyeball in an eye-closed situation.Inspired by human fingertip assessment of softness,the sensory system extracts displacement-pressure information for soft evaluation,achieving high accuracy IOP monitoring(＞96％).We further design and custom-make a portable and wearable ophthalmic tonometer based on the sensory system and demonstrate its high efficacy in IOP screening.This sensory system paves a way towards cost-effective,robust,and reliable IOP monitoring.
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