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1.
Plant Cell ; 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38801741

RESUMO

The phytohormone jasmonate (JA) plays a central role in plant defenses against biotic stressors. However, our knowledge of the JA signaling pathway in rice (Oryza sativa) remains incomplete. Here, we integrated multi-omic data from three tissues to characterize the functional modules involved in organizing JA-responsive genes. In the core regulatory sector, MYC2 transcription factor transcriptional cascades are conserved. in different species but with distinct regulators (e.g. bHLH6 in rice)., in which genes are early expressed across all tissues. In the feedback sector, MYC2 also regulates the expression of JA repressor and catabolic genes, providing negative feedback that truncates the duration of JA responses. For example, the MYC2-regulated NAC (NAM, ATAF1/2 and CUC2) transcription factor genes NAC1, NAC3, and NAC4 encode proteins that repress JA signaling and herbivore resistance. In the tissue-specific sector, many late-expressed genes are associated with the biosynthesis of specialized metabolites that mediate particular defensive functions. For example, the terpene synthase gene TPS35 is specifically induced in the leaf sheath and TPS35 functions in defense against oviposition by brown planthoppers and the attraction of this herbivore's natural enemies. Thus, by characterizing core, tissue-specific, and feedback sectors of JA-elicited defense responses, this work provides a valuable resource for future discoveries of key JA components in this important crop.

2.
Nature ; 589(7841): 258-263, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33268894

RESUMO

Animal behaviours that are superficially similar can express different intents in different contexts, but how this flexibility is achieved at the level of neural circuits is not understood. For example, males of many species can exhibit mounting behaviour towards same- or opposite-sex conspecifics1, but it is unclear whether the intent and neural encoding of these behaviours are similar or different. Here we show that female- and male-directed mounting in male laboratory mice are distinguishable by the presence or absence of ultrasonic vocalizations (USVs)2-4, respectively. These and additional behavioural data suggest that most male-directed mounting is aggressive, although in rare cases it can be sexual. We investigated whether USV+ and USV- mounting use the same or distinct hypothalamic neural substrates. Micro-endoscopic imaging of neurons positive for oestrogen receptor 1 (ESR1) in either the medial preoptic area (MPOA) or the ventromedial hypothalamus, ventrolateral subdivision (VMHvl) revealed distinct patterns of neuronal activity during USV+ and USV- mounting, and the type of mounting could be decoded from population activity in either region. Intersectional optogenetic stimulation of MPOA neurons that express ESR1 and vesicular GABA transporter (VGAT) (MPOAESR1∩VGAT neurons) robustly promoted USV+ mounting, and converted male-directed attack to mounting with USVs. By contrast, stimulation of VMHvl neurons that express ESR1 (VMHvlESR1 neurons) promoted USV- mounting, and inhibited the USVs evoked by female urine. Terminal stimulation experiments suggest that these complementary inhibitory effects are mediated by reciprocal projections between the MPOA and VMHvl. Together, these data identify a hypothalamic subpopulation that is genetically enriched for neurons that causally induce a male reproductive behavioural state, and indicate that reproductive and aggressive states are represented by distinct population codes distributed between MPOAESR1 and VMHvlESR1 neurons, respectively. Thus, similar behaviours that express different internal states are encoded by distinct hypothalamic neuronal populations.


Assuntos
Agressão/fisiologia , Hipotálamo/citologia , Hipotálamo/fisiologia , Comportamento Sexual Animal/fisiologia , Animais , Copulação , Receptor alfa de Estrogênio/metabolismo , Feminino , Homossexualidade Masculina , Masculino , Camundongos , Optogenética , Área Pré-Óptica/metabolismo , Proteínas Vesiculares de Transporte de Aminoácidos Inibidores/metabolismo
3.
Proc Natl Acad Sci U S A ; 120(23): e2305007120, 2023 06 06.
Artigo em Inglês | MEDLINE | ID: mdl-37256931

RESUMO

Plants produce chemical defenses that poison insect herbivores or deter their feeding, but herbivores are also accompanied by microbial endosymbionts crucial for their nutrition, reproduction, and fitness. Hence, plant defenses could target a herbivore's beneficial endosymbionts, but this has not yet been demonstrated. Here, we studied flavonoids that are induced when rice is attacked by a phloem-feeding pest, the brown planthopper (BPH), which harbors beneficial yeast-like symbionts (YLS) essential for insect nutrition, such as by remedying deficiencies in sterols. BPH attack dramatically increased sakuranetin accumulations in leaf sheaths and phloem exudates. Sakuranetin is an antifungal phytoalexin derived from the antibacterial precursor, naringenin, via catalysis of naringenin-O-methyltransferase (NOMT). When added to artificial diets, sakuranetin decreased BPH survivorship, suggesting that it functions as an induced defense. Mutation of NOMT abolished sakuranetin accumulation and increased BPH oviposition and hatching rates. High-throughput amplicon sequencing revealed that BPH fed on sakuranetin-deficient nomt lines were enriched in YLS with only minor changes in the bacterial endosymbionts, compared to those feeding on sakuranetin-rich wild-type (WT) plants. In-vitro feeding of sakuranetin suggested that this flavonoid directly inhibited the growth of YLS. BPH feeding on nomt lines accumulated higher cholesterol levels, which might be attributed to increases in the supply of sterol precursors from the YLS, while nomt lines suffered more damage than WT plants did from BPH herbivory. BPH-elicited accumulation of sakuranetin requires intact jasmonate (JA) signaling. This study reveals that rice uses a JA-induced antifungal flavonoid phytoalexin in defense against BPH by inhibiting its beneficial endosymbionts.


Assuntos
Hemípteros , Oryza , Animais , Feminino , Antifúngicos , Flavonoides/farmacologia , Regulação da Expressão Gênica de Plantas , Oryza/genética
4.
EMBO J ; 40(2): e106123, 2021 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-33274785

RESUMO

Identifying and sorting highly tumorigenic and metastatic tumor cells from a heterogeneous cell population is a daunting challenge. Here, we show that microfluidic devices can be used to sort marker-based heterogeneous cancer stem cells (CSC) into mechanically stiff and soft subpopulations. The isolated soft tumor cells (< 400 Pa) but not the stiff ones (> 700 Pa) can form a tumor in immunocompetent mice with 100 cells per inoculation. Notably, only the soft, but not the stiff cells, isolated from CD133+ , ALDH+ , or side population CSCs, are able to form a tumor with only 100 cells in NOD-SCID or immunocompetent mice. The Wnt signaling protein BCL9L is upregulated in soft tumor cells and regulates their stemness and tumorigenicity. Clinically, BCL9L expression is correlated with a worse prognosis. Our findings suggest that the intrinsic softness is a unique marker of highly tumorigenic and metastatic tumor cells.


Assuntos
Carcinogênese/genética , Células-Tronco Neoplásicas/fisiologia , Antígeno AC133/genética , Aldeído Desidrogenase/genética , Animais , Linhagem Celular Tumoral , Proteínas de Ligação a DNA/genética , Feminino , Humanos , Células MCF-7 , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos NOD , Camundongos SCID , Regulação para Cima/genética , Proteínas Wnt/genética
5.
Nano Lett ; 24(21): 6225-6232, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38752702

RESUMO

Magnetic proximity interaction provides a promising route to manipulate the spin and valley degrees of freedom in van der Waals heterostructures. Here, we report a control of valley pseudospin in the WS2/MoSe2 heterostructure by utilizing the magnetic proximity effect of few-layered CrBr3 and, for the first time, observe a substantial difference in valley polarization of intra/interlayer excitons under different circularly polarized laser excitations, referred to as chirality-dependent valley polarization. Theoretical and experimental results reveal that the spin-selective charge transfer between MoSe2 and CrBr3, as well as between MoSe2 and WS2, is mostly responsible for the chiral feature of valley polarization in comparison with the proximity exchange field. This means that a long-distance manipulation of exciton behaviors in multilayer heterostructures can be achieved through spin-selective charge transfer. This work marks a significant advancement in the control of spin and valley pseudospin in multilayer structures.

6.
Plant J ; 115(5): 1277-1297, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37235696

RESUMO

Plant embryogenic calli (ECs) can undergo somatic embryogenesis to regenerate plants. This process is mediated by regulatory factors, such as transcription factors and specifically expressed genes, but the precise molecular mechanisms underlying somatic embryogenesis at the single-cell level remain unclear. In this study, we performed high-resolution single-cell RNA sequencing analysis to determine the cellular changes in the EC of the woody plant species Dimocarpus longan (longan) and clarify the continuous cell differentiation trajectories at the transcriptome level. The highly heterogeneous cells in the EC were divided into 12 putative clusters (e.g., proliferating, meristematic, vascular, and epidermal cell clusters). We determined cluster-enriched expression marker genes and found that overexpression of the epidermal cell marker gene GDSL ESTERASE/LIPASE-1 inhibited the hydrolysis of triacylglycerol. In addition, the stability of autophagy was critical for the somatic embryogenesis of longan. The pseudo-timeline analysis elucidated the continuous cell differentiation trajectories from early embryonic cell division to vascular and epidermal cell differentiation during the somatic embryogenesis of longan. Moreover, key transcriptional regulators associated with cell fates were revealed. We found that ETHYLENE RESPONSIVE FACTOR 6 was characterized as a heat-sensitive factor that negatively regulates longan somatic embryogenesis under high-temperature stress conditions. The results of this study provide new spatiotemporal insights into cell division and differentiation during longan somatic embryogenesis at single-cell resolution.


Assuntos
Sapindaceae , Transcriptoma , Transcriptoma/genética , Sapindaceae/genética , Perfilação da Expressão Gênica , Análise de Sequência de RNA , Desenvolvimento Embrionário , Técnicas de Embriogênese Somática de Plantas , Regulação da Expressão Gênica de Plantas/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
7.
Small ; : e2402725, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38837316

RESUMO

Unveiling the inherent link between polysulfide adsorption and catalytic activity is key to achieving optimal performance in Lithium-sulfur (Li-S) batteries. Current research on the sulfur reaction process mainly relies on the strong adsorption of catalysts to confine lithium polysulfides (LiPSs) to the cathode side, effectively suppressing the shuttle effect of polysulfides. However, is strong adsorption always correlated with high catalysis? The inherent relationship between adsorption and catalytic activity remains unclear, limiting the in-depth exploration and rational design of catalysts. Herein, the correlation between "d-band center-adsorption strength-catalytic activity" in porous carbon nanofiber catalysts embedded with different transition metals (M-PCNF-3, M = Fe, Co, Ni, Cu) is systematically investigated, combining the d-band center theory and the Sabatier principle. Theoretical calculations and experimental analysis results indicate that Co-PCNF-3 electrocatalyst with appropriate d-band center positions exhibits moderate adsorption capability and the highest catalytic conversion activity for LiPSs, validating the Sabatier relationship in Li-S battery electrocatalysts. These findings provide indispensable guidelines for the rational design of more durable cathode catalysts for Li-S batteries.

8.
Plant Physiol ; 193(1): 555-577, 2023 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-37313777

RESUMO

Somatic embryogenesis (SE), like zygotic embryo development, is a progressive process. Early SE is the beginning of a switch from a somatic to an embryogenic state and is an important stage for initiating chromatin reprogramming of SE. Previous studies suggest that changes in chromatin accessibility occur during early SE, although information on the 3D structure of chromatin is not yet available. Here, we present a chromosome-level genome assembly of longan (Dimocarpus longan) using PacBio combined with high-through chromosome conformation capture scaffolding, which resulted in a 446 Mb genome assembly anchored onto 15 scaffolds. During early SE, chromatin was concentrated and then decondensed, and a large number of long terminal repeat retrotransposons (LTR-RTs) were enriched in the local chromatin interaction region, suggesting LTR-RTs were involved in chromatin reorganization. Early SE was accompanied by the transformation from A to B compartments, and the interactions between B compartments were enhanced. Results from chromatin accessibility, monomethylation of histone H3 at lysine 4 (H3K4me1) modification, and transcription analyses further revealed a gene regulatory network for cell wall thickening during SE. Particularly, we found that the H3K4me1 differential peak binding motif showed abnormal activation of ethylene response factor transcription factors and participation in SE. The chromosome-level genomic and multiomics analyses revealed the 3D conformation of chromatin during early SE, providing insight into the molecular mechanisms underlying cell wall thickening and the potential regulatory networks of TFs during early SE in D. longan. These results provide additional clues for revealing the molecular mechanisms of plant SE.


Assuntos
Cromossomos de Plantas , Técnicas de Embriogênese Somática de Plantas , Sapindaceae , Biomarcadores/metabolismo , Parede Celular , Cromatina , Redes Reguladoras de Genes , Genoma de Planta , Código das Histonas , Anotação de Sequência Molecular , Sapindaceae/citologia , Sapindaceae/crescimento & desenvolvimento , Sapindaceae/metabolismo , Transcriptoma
9.
Biomacromolecules ; 25(1): 238-247, 2024 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-38116793

RESUMO

Chitinase plays a vital role in the efficient biotransformation of the chitin substrate. This study aimed to modify and elucidate the contribution of the relatively conserved residues in the active site architecture of a thermophilic chitinase SsChi18A from Streptomyces sp. F-3 in processive catalysis. The enzymatic activity on colloidal chitin increased to 151%, 135%, and 129% in variants Y286W, E287A, and K186A compared with the wild type (WT). Also, the apparent processive parameter G2/G1 was lower in the variants compared to the WT, indicating the essential role of Tyr-286, Glu-287, and Lys-186 in processive catalysis. Additionally, the enzymatic activity on the crystalline chitin of F48W and double mutants F48W/Y209F and F48W/Y286W increased by 35%, 16%, and 36% compared with that for WT. Molecular dynamics simulations revealed that the driving force of processive catalysis might be related to the changes in interaction energy. This study provided a rational design strategy targeting relatively conserved residues to enhance the catalytic activity of GH18 processive chitinases.


Assuntos
Quitinases , Domínio Catalítico , Quitinases/genética , Quitinases/química , Quitinases/metabolismo , Quitina/química , Simulação de Dinâmica Molecular
10.
Dement Geriatr Cogn Disord ; : 1-11, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38776891

RESUMO

INTRODUCTION: The prevalence of cognitive impairment and dementia in the older population is increasing, and thereby, early detection of cognitive decline is essential for effective intervention. METHODS: This study included 2,288 participants with normal cognitive function from the Ma'anshan Healthy Aging Cohort Study. Forty-two potential predictors, including demographic characteristics, chronic diseases, lifestyle factors, anthropometric indices, physical function, and baseline cognitive function, were selected based on clinical importance and previous research. The dataset was partitioned into training, validation, and test sets in a proportion of 60% for training, 20% for validation, and 20% for testing, respectively. Recursive feature elimination was used for feature selection, followed by six machine learning algorithms that were employed for model development. The performance of the models was evaluated using area under the curve (AUC), specificity, sensitivity, and accuracy. Moreover, SHapley Additive exPlanations (SHAP) was conducted to access the interpretability of the final selected model and to gain insights into the impact of features on the prediction outcomes. SHAP force plots were established to vividly show the application of the prediction model at the individual level. RESULTS: The final predictive model based on the Naive Bayes algorithm achieved an AUC of 0.820 (95% CI, 0.773-0.887) on the test set, outperforming other algorithms. The top ten influential features in the model included baseline Mini-Mental State Examination (MMSE), education, self-reported economic status, collective or social activities, Pittsburgh sleep quality index (PSQI), body mass index, systolic blood pressure, diastolic blood pressure, instrumental activities of daily living, and age. The model demonstrated the potential to identify individuals at a higher risk of cognitive impairment within 3 years from older adults. CONCLUSION: The predictive model developed in this study contributes to the early detection of cognitive impairment in older adults by primary healthcare staff in community settings.

11.
Nanomedicine ; : 102764, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38885751

RESUMO

Glucose oxidase (GOx) is often used to starvation therapy. However, only consuming glucose cannot completely block the energy metabolism of tumor cells. Lactate can support tumor cell survival in the absence of glucose. Here, we constructed a nanoplatform (Met@HMnO2-GOx/HA) that can deplete glucose while inhibiting the compensatory use of lactate by cells to enhance the effect of tumor starvation therapy. GOx can catalyze glucose into gluconic acid and H2O2, and then HMnO2 catalyzes H2O2 into O2 to compensate for the oxygen consumed by GOx, allowing the reaction to proceed sustainably. Furthermore, metformin (Met) can inhibit the conversion of lactate to pyruvate in a redox-dependent manner and reduce the utilization of lactate by tumor cells. Met@HMnO2-GOx/HA nanoparticles maximize the efficacy of tumor starvation therapy by simultaneously inhibiting cellular utilization of two carbon sources. Therefore, this platform is expected to provide new strategies for tumor treatment.

12.
BMC Biol ; 21(1): 231, 2023 10 23.
Artigo em Inglês | MEDLINE | ID: mdl-37867192

RESUMO

BACKGROUND: RNA splicing plays significant roles in fundamental biological activities. However, our knowledge about the roles of alternative splicing and underlying mechanisms during spermatogenesis is limited. RESULTS: Here, we report that Serine/arginine-rich splicing factor 2 (SRSF2), also known as SC35, plays critical roles in alternative splicing and male reproduction. Male germ cell-specific deletion of Srsf2 by Stra8-Cre caused complete infertility and defective spermatogenesis. Further analyses revealed that deletion of Srsf2 disrupted differentiation and meiosis initiation of spermatogonia. Mechanistically, by combining RNA-seq data with LACE-seq data, we showed that SRSF2 regulatory networks play critical roles in several major events including reproductive development, spermatogenesis, meiotic cell cycle, synapse organization, DNA recombination, chromosome segregation, and male sex differentiation. Furthermore, SRSF2 affected expression and alternative splicing of Stra8, Stag3 and Atr encoding critical factors for spermatogenesis in a direct manner. CONCLUSIONS: Taken together, our results demonstrate that SRSF2 has important functions in spermatogenesis and male fertility by regulating alternative splicing.


Assuntos
Splicing de RNA , Espermatogênese , Masculino , Humanos , Espermatogênese/genética , Proteínas de Ligação a RNA/genética , Processamento Alternativo , Meiose/genética , RNA Mensageiro
13.
Sensors (Basel) ; 24(10)2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38793816

RESUMO

Quenched Co-based ribbon strips are widely used in the fields of magnetic amplifier, magnetic head material, magnetic shield, electric reactor, inductance core, sensor core, anti-theft system label, and so on. In this study, Co-based composite CoFeNiSiB ribbon strips with a micron width were fabricated by micro-electro-mechanical systems (MEMS) technology. The carbon and FeCoGa nanofilms were deposited for surface modification. The effect of carbon and FeCoGa nanofilm coatings on the crystal structure, surface morphology, magnetic properties, and magnetoimpedance (MI) effect of composite ribbon strips were systematically investigated. The results show that the surface roughness and coercivity of the composite ribbon strips are minimum at a thickness of the carbon coating of 60 nm. The maximum value of MI effect is 41% at 2 MHz, which is approximately 2.4 times greater than plain ribbon and 1.6 times greater than FeCoGa-coated composite ribbon strip. The addition of a carbon layer provides a conductive path for high frequency currents, which effectively reduces the characteristic frequency of the composite ribbon strip. The FeCoGa coating is able to close the flux path and reduce the coercivity, which, in turn, increases the transverse permeability and improves the MI effect. The findings indicate that a successful combination of carbon layer and magnetostrictive FeCoGa nanofilm layer can improve the MI effect and magnetic field sensitivity of the ribbon strips, demonstrating the potential of the composite strips for local and micro area field sensing applications.

14.
Molecules ; 29(9)2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38731653

RESUMO

In pursuit of enhancing the mechanical properties, especially the tensile strength, of 4D-printable consumables derived from waste cooking oil (WCO), we initiated the production of acrylate-modified WCO, which encompasses epoxy waste oil methacrylate (EWOMA) and epoxy waste oil acrylate (EWOA). Subsequently, a series of WCO-based 4D-printable photocurable resins were obtained by introducing a suitable diacrylate molecule as the second monomer, coupled with a composite photoinitiator system comprising Irgacure 819 and p-dimethylaminobenzaldehyde (DMAB). These materials were amenable to molding using an LCD light-curing 3D printer. Our findings underscored the pivotal role of triethylene glycol dimethacrylate (TEGDMA) among the array of diacrylate molecules in enhancing the mechanical properties of WCO-based 4D-printable resins. Notably, the 4D-printable material, composed of EWOA and TEGDMA in an equal mass ratio, exhibited nice mechanical strength comparable to that of mainstream petroleum-based 4D-printable materials, boasting a tensile strength of 9.17 MPa and an elongation at break of 15.39%. These figures significantly outperformed the mechanical characteristics of pure EWOA or TEGDMA resins. Furthermore, the EWOA-TEGDMA resin demonstrated impressive thermally induced shape memory performance, enabling deformation and recovery at room temperature and retaining its shape at -60 °C. This resin also demonstrated favorable biodegradability, with an 8.34% weight loss after 45 days of soil degradation. As a result, this 4D-printable photocurable resin derived from WCO holds immense potential for the creation of a wide spectrum of high-performance intelligent devices, brackets, mold, folding structures, and personalized products.

15.
BMC Plant Biol ; 23(1): 643, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-38097929

RESUMO

BACKGROUND: Bright flower colour assists plants attract insects to complete pollination and provides distinct ornamental values. In some medicinal plants, diverse flower colour variations usually imply differences in active ingredients. Compared to the common bluish purple of Scutellaria baicalensis flower (SB), the natural variants present rose red (SR) and white (SW) flowers were screened out under the same growing conditions in the genuine producing area Shandong Province, China. However, the mechanism of flower colour variation in S. baicalensis was remain unclear. In the present study, we conducted integrated transcriptome and metabolome analyses to uncover the metabolic difference and regulation mechanism in three S. baicalensis flowers. RESULTS: The results showed that 9 anthocyanins were identified. Among which, 4 delphinidin-based anthocyanins were only detected in SB, 4 cyanidin-based anthocyanins (without cyanidin-3-O-glucoside) mainly accumulated in SR, and no anthocyanin but high level of flavanone, naringenin, was detected in SW. The gene expression profile indicated that the key structural genes in the flavonoid and anthocyanin biosynthesis pathway differentially expressed in flowers with different colours. Compared to SB, the down-regulated expression of F3'5'H, ANS, and 3GT gene in SR might influence the anthocyanin composition. Especially the InDel site with deletion of 7 nucleotides (AATAGAG) in F3'5'H in SR might be the determinant for lack of delphinidin-based anthocyanins in rose red flowers. In SW, the lower expression levels of DFR and two F3H genes might reduce the anthocyanin accumulation. Notably the SNP site of G > A mutation in the splicing site of DFR in SW might block anthocyanin biosynthesis from flavanones and thus cause white flowers. In addition, several key transcription factors, including MYB, bHLH, and NAC, which highly correlated with structural gene expression and anthocyanin contents were also identified. CONCLUSIONS: These results provide clues to uncover the molecular regulatory mechanism of flower colour variation in S. baicalensis and promote novel insights into understanding the anthocyanin biosynthesis and regulation.


Assuntos
Antocianinas , Scutellaria baicalensis , Antocianinas/metabolismo , Cor , Scutellaria baicalensis/genética , Scutellaria baicalensis/metabolismo , Perfilação da Expressão Gênica , Flores/metabolismo , Transcriptoma , Metaboloma , Regulação da Expressão Gênica de Plantas , Pigmentação/genética
16.
Mol Genet Genomics ; 298(5): 1007-1021, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37233799

RESUMO

High-altitude adaptation (HAA) was reported to be significantly associated with reduced risks for multiple cardiovascular diseases (CVDs). However, the causality and direction of the associations are largely uncharacterized. We aimed to examine the potential causal relationships between HAA and six types of CVD, including coronary artery disease (CAD), cerebral aneurysm, ischemic stroke, peripheral artery disease, arrhythmia and atrial fibrillation. We obtained the summary data from largest available genome-wide association study of HAA and six types of CVD. Two-sample bidirectional Mendelian randomization (MR) analyses were performed to infer the causality between them. In the sensitivity analyses, MR-Egger regression analyses and MR-Pleiotropy RESidual Sum and Outlier (MR-PRESSO) global analyses were used to assess the pleiotropic effects; Cochran's Q tests were used to test the heterogeneity by inverse variance-weighted (IVW) and MR-Egger methods; and the leave-one-out analyses were used to examine whether some single nucleotide polymorphisms (SNPs) could influence the results independently. The MR main analyses showed that the genetically instrumented HAA was significantly causally associated with the reduced risks of CAD (odds ratio [OR] = 0.029; 95% confidence interval [CI] = 0.004-0.234; P = 8.64 × 10-4). In contrast, there was no statistically significant relationship between CVDs and HAA. Our findings provide evidence for the causal effects of HAA on the reduced risks of CAD. However, there is no causality of CVDs on HAA. These findings might be helpful in developing the prevention and intervention strategies for CAD.


Assuntos
Doenças Cardiovasculares , Doença da Artéria Coronariana , Humanos , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/genética , Altitude , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana
17.
Small ; 19(30): e2300481, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37035992

RESUMO

The damaged endometrium and the formation of fibrosis are key barriers to pregnancy and further lead to infertility. However, how to promote endometrium repair is always a challenge. Here, a bioactive injectable and self-healing hydrogel is developed by physically combination of thiolated polyethylene (PEG), Cu2+ and cell-free fat extract (CEFFE, CF) for endometrial regeneration and fertility. By inheriting the advantages of various active proteins contained in CEFFE, it could induce the overall repair of endometrial microenvironment for intrauterine adhesion (IUA). In vitro, CF@Cu-PEG reduces endometrial cell apoptosis by more than 50%, and increases angiogenesis by 92.8%. In the IUA mouse, injection of CF@Cu-PEG significantly reduces the rate of uterine hydrometra and prevents the formation of endometrial fibrosis. Remarkably, CF@Cu-PEG contributes to the repair of endometrial microstructure, especially increases the number of endometrial pinopodes, significantly improves endometrial receptivity, and increases the pregnancy rate of IUA mice from 7.14% to 66.67%. In summary, through the physically combination of CEFFE and Cu-PEG, the construction of loaded bioactive injectable hydrogel not only inhibits the IUA, but also induces the self-repair of endometrial cells in situ and improves fertility, providing a new strategy for IUA repair in clinical application.


Assuntos
Hidrogéis , Doenças Uterinas , Gravidez , Feminino , Humanos , Camundongos , Animais , Hidrogéis/química , Endométrio , Doenças Uterinas/metabolismo , Doenças Uterinas/patologia , Regeneração , Fibrose
18.
Plant Cell Environ ; 46(5): 1562-1581, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36695201

RESUMO

Low light stress seriously decreased wheat grain number through the formation of aborted spike during the reproductive period and induced new tiller regeneration to offset the loss of grain number. However, the mechanism by which plants coordinate spike aborted growth and the regeneration of new tillers remains unknown. To better understand this coordinated process, morphological, physiological and transcriptomic analyses were performed under low light stress at the young microspore stage. Our findings indicated that leaves exhausted most stored carbohydrates in 1 day of darkness. However, spike and uppermost internode (UI) were converted from sink to source, due to increased abscisic acid (ABA) content and decreased cytokinin content. During this process, genes encoding amylases, Sugars Will Eventually be Exported Transporters (SWEET) and sucrose transporters or sucrose carriers (SUT/SUC) were upregulated in spike and UI, which degraded starch into soluble sugars and loaded them into the phloem. Subsequently, soluble sugars were transported to tiller node (TN) where cytokinin and auxin content increased and ABA content decreased, followed by unloading into TN cells by upregulated cell wall invertase (CWINV) genes and highly expressed H+ /hexose symporter genes. Finally, expansin genes integrated the sugar pathway and hormone pathway, and regulate the formation of new tillers directly.


Assuntos
Carboidratos , Triticum , Triticum/fisiologia , Ácido Abscísico/metabolismo , Proteínas de Membrana Transportadoras/genética , Sacarose/metabolismo , Citocininas , Açúcares , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
19.
Reprod Biomed Online ; 47(2): 103203, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37349244

RESUMO

RESEARCH QUESTION: What is the underlying mechanism of IVF and embryo transfer (IVF-ET) failure in patients with elevated peripheral blood natural killer cell (pNK) counts? DESIGN: Patients undergoing IVF-ET cycles for tubal obstruction or pelvic adhesion (n = 486) were assigned to three groups: high (CD56+CD16+pNK >30% [n = 49]); medium (15< CD56+CD16+pNK ≤30% [n = 211]); and normal pNK groups (5≤ CD56+CD16+pNK ≤15% [n = 226]). Their general condition, previous pregnancy history and IVF outcomes were compared. Uterine fluid and endometrial tissue from patients in the high and normal pNK groups were collected during the mid-secretory phase and studied to elucidate the molecular mechanism underlying impaired endometrial receptivity. RESULTS: The highest incidence of IVF-ET cycles (P < 0.0001) and biochemical pregnancy losses (P < 0.0001), and lowest implantation and clinical pregnancy rates (both P < 0.0001), were observed in patients with pNK over 30%. No significant difference was found in the number of previous miscarriages and rate of spontaneous miscarriage in IVF outcomes. Lower Septin11 (SEPT11) expression in the uterine fluid and endometrial epithelial cells (EEC), and higher endometrial IFN-γ, was observed in patients with high pNK. Ishikawa cell and human endometrial epithelial cell (HEEC) adhesion was inhibited after SEPT11 knock-down. Elevated IFN-γ decreased the SEPT11 protein levels in Ishikawa cells and HEECs. CONCLUSIONS: CD56+CD16+pNK above 30% may be a threshold for adverse IVF-ET outcomes. Low SEPT11 expression in EEC inhibits cell adhesion, which may cause impaired endometrial receptivity in patients with elevated pNK. The level of SEPT11 in mid-secretory uterine fluid could serve as a non-invasive marker to assess endometrial receptivity in these patients.


Assuntos
Aborto Espontâneo , Implantação do Embrião , Septinas , Feminino , Humanos , Gravidez , Regulação para Baixo , Implantação do Embrião/fisiologia , Endométrio/metabolismo , Células Epiteliais , Células Matadoras Naturais , Septinas/genética , Septinas/metabolismo
20.
Angew Chem Int Ed Engl ; 62(10): e202218386, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36637169

RESUMO

Crystallography modulation of zinc (Zn) metal anode is promising to promote Zn reversibility in aqueous electrolytes, but efficiently constructing Zn with specific crystallographic texture remains challenging. Herein, we report a current-controlled electrodeposition strategy to texture the Zn electrodeposits in conventional aqueous electrolytes. Using the electrolytic cell with low-cost Zn(CH3 COO)2 electrolyte and Cu substrate as a model system, the texture of as-deposited Zn gradually transforms from (101) to (002) crystal plane as increasing the current density from 20 to 80 mA cm-2 . Moreover, the high current accelerates the Zn nucleation rate with abundant nuclei, enabling uniform deposition. The (002) texture permits stronger resistance to dendrite growth and interfacial side reactions than the (101) texture. The resultant (002)-textured Zn electrode achieves deep cycling stability and supports the stable operation of full batteries with conventional V/Mn-based oxide cathodes.

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