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Efficient red-green-blue primary luminescence with an extraordinarily narrow band and durability is crucial for advanced display applications. Recently, the emergence of multiple-resonance (MR) from short-range atomic interactions has been shown to induce extremely narrow spectral widths in pure organic emitters. However, achieving wide-range color tuning without compromising color purity remains a persistent challenge for MR emitters. Herein, the concept of electronic donor/acceptor "core-shell" modulation is proposed within a boron/nitrogen (B/N) MR skeleton, enabling the rational utilization of intramolecular charge transfer to facilitate wavelength shift. The dense B atoms localized at the center of the molecule effectively compress the electron density and stabilize the lowest unoccupied molecular orbital wave function. This electron-withdrawing core is embedded with peripheral electron-donating atoms. Consequently, doping a single B atom into a deep-blue MR framework led to a profound bathochromic shift from 447 to 624 nm (â¼0.8 eV) while maintaining a narrow spectral width of 0.10 eV in this pure-red emitter. Notably, organic light-emitting diodes assisted by thermally activated delayed fluorescence molecules achieved superb electroluminescent stability, with an LT99 (99% of the initial luminance) exceeding 400 h at an initial luminance of 1000 cd m-2, approaching commercial-level performance without the assistance of phosphors.
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BACKGROUND: Drug resistance, including Adriamycin-based therapeutic resistance, remains a challenge in breast cancer (BC) treatment. Studies have revealed that macrophages could play a pivotal role in mediating the chemoresistance of cancer cells. Accumulating evidence suggests that tRNA-Derived small RNAs (tDRs) are associated the physiological and pathological processes in multiple cancers. However, the underlying mechanisms of tDRs on chemoresistance of BC in tumor-associated macrophages remain largely unknown. METHODS: The high-throughput sequencing technique was used to screen tDRs expression profile in BC cells. Gain- and loss-of-function experiments and xenograft models were performed to verify the biological function of 3'tRF-Ala-AGC in BC cells. The CIBERSORT algorithm was used to investigate immune cell infiltration in BC tissues. To explore the role of 3'tRF-Ala-AGC in macrophages, M2 macrophages transfected with 3'tRF-Ala-AGC mimic or inhibitor were co-cultured with BC cells. Effects on Nuclear factor-κb (NF-κb) pathway were investigated by NF-κb nuclear translocation assay and western blot analysis. RNA pull-down assay was performed to identify 3'tRF-Ala-AGC interacting proteins. RESULTS: A 3'tRF fragment of 3'tRF-AlaAGC was screened, which is significantly overexpressed in BC specimens and Adriamycin-resistant cells. 3'tRF-AlaAGC could promote cell malignant activity and facilitate M2 polarization of macrophages in vitro and in vivo. Higher expression of M2 macrophages were more likely to have lymph node metastasis and deeper invasion in BC patients. Mechanistically, 3'tRF-AlaAGC binds Type 1-associated death domain protein (TRADD) in BC cells, and suppression of TRADD partially abolished the enhanced effect of 3'tRF-AlaAGC mimic on phenotype of M2. The NF-κb signaling pathway was activated in BC cells co-cultured with M2 macrophages transfected with 3'tRF-AlaAGC mimic. CONCLUSIONS: 3'tRF-AlaAGC might modulate macrophage polarization via binding to TRADD and increase the effect of M2 on promoting the chemoresistance in BC cells through NF-κb signaling pathway.
Subject(s)
Breast Neoplasms , Drug Resistance, Neoplasm , Macrophages , NF-kappa B , Breast Neoplasms/pathology , Breast Neoplasms/genetics , Breast Neoplasms/metabolism , Humans , Drug Resistance, Neoplasm/genetics , Female , Macrophages/metabolism , Animals , Cell Line, Tumor , NF-kappa B/metabolism , Protein Binding/drug effects , RNA, Transfer/metabolism , RNA, Transfer/genetics , Cell Polarity/drug effects , Mice , Signal Transduction , Mice, Nude , Doxorubicin/pharmacology , Mice, Inbred BALB CABSTRACT
Limited research has reported the association between MTNR1B gene polymorphisms and ischemic stroke (IS), and there is insufficient evidence on whether adopting a healthy lifestyle can mitigate genetic risks in this context. This study aimed to investigate the associations between MTNR1B gene variants (rs10830963 and rs1387153) and IS, examining the potential effect of gene-lifestyle interactions on IS risk. Conducted in northern China, this family-based cohort study involved 5116 initially IS-free subjects. Genotype data for rs10830963 and rs1387153 in MTNR1B were collected. Eight modifiable lifestyle factors, including body mass index (BMI), smoking, alcohol consumption, dietary habits, physical activity, sedentary time, sleep duration, and chronotype, were considered in calculating healthy lifestyle scores. Multilevel Cox models were used to examine the associations between MTNR1B variants and IS. Participants carrying the rs10830963-G and rs1387153-T alleles exhibited an elevated IS risk. Each additional rs10830963-G allele and rs1387153-T allele increased the IS risk by 36% (HR = 1.36, 95% CI, 1.12-1.65) and 32% (HR = 1.32, 95% CI, 1.09-1.60), respectively. Participants were stratified into low, medium, and high healthy lifestyle score groups (1537, 2188, and 1391 participants, respectively). Genetic-lifestyle interactions were observed for rs10830963 and rs1387153 (p for interaction < 0.001). Notably, as the healthy lifestyle score increased, the effect of MTNR1B gene variants on IS risk diminished (p for trend < 0.001). This study underscores the association between the MTNR1B gene and IS, emphasizing that adherence to a healthy lifestyle can mitigate the genetic predisposition to IS.
Subject(s)
Healthy Lifestyle , Ischemic Stroke , Receptor, Melatonin, MT2 , Humans , Receptor, Melatonin, MT2/genetics , Male , Female , Middle Aged , China/epidemiology , Ischemic Stroke/genetics , Ischemic Stroke/epidemiology , Cohort Studies , Polymorphism, Single Nucleotide , Genetic Predisposition to Disease , Adult , AgedABSTRACT
Plants often experience abiotic stress, which severely affects their growth. With the advent of global warming, drought stress has become a pivotal factor affecting crop yield and quality. Increasing numbers of studies have focused on elucidating the molecular mechanisms underlying plant responses to drought stress. As molecular switches, transcription factors (TFs) are key participants in drought-resistance regulatory networks in crops. TFs regulate the transcription of downstream genes and are regulated by various upstream regulatory factors. Therefore, understanding the mechanisms of action of TFs in regulating drought stress can help enhance the adaptive capacity of crops under drought conditions. In this review, we summarize the structural characteristics of several common TFs, their multiple drought-response pathways, and recently employed research strategies. We describe the application of new technologies such as analysis of stress granule dynamics and function, multi-omics data, gene editing, and molecular crosstalk between TFs in drought resistance. This review aims to familiarize readers with the regulatory network of TFs in drought resistance and to provide a reference for examining the molecular mechanisms of drought resistance in plants and improving agronomic traits.
Subject(s)
Droughts , Gene Expression Regulation, Plant , Stress, Physiological , Transcription Factors , Transcription Factors/metabolism , Transcription Factors/genetics , Stress, Physiological/genetics , Plant Proteins/genetics , Plant Proteins/metabolism , Crops, Agricultural/genetics , Crops, Agricultural/physiology , Plants/genetics , Plants/metabolismABSTRACT
Potato (Solanum tuberosum L.) is a major global food crop, and oxidative stress can significantly impact its growth. Previous studies have shown that its resistance to oxidative stress is mainly related to transcription factors, post-translational modifications, and antioxidant enzymes in vivo, but the specific molecular mechanisms remain unclear. In this study, we analyzed the transcriptome data from potato leaves treated with H2O2 and Methyl viologen (MV), and a control group, for 12 h. We enriched 8334 (CK vs. H2O2) and 4445 (CK vs. MV) differentially expressed genes (DEGs), respectively, and randomly selected 15 DEGs to verify the sequencing data by qRT-PCR. Gene ontology (GO) enrichment analysis showed that the DEGs were mainly concentrated in cellular components and related to molecular function, and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis indicated that most of the DEGs were related to metabolic pathways, plant hormone signal transduction, MAPK-signaling pathway, and plant-pathogen interactions. In addition, several candidate transcription factors, mainly including MYB, WRKY, and genes associated with Ca2+-mediated signal transduction, were also found to be differentially expressed. Among them, the plant hormone genes Soltu.DM.03G022780 and Soltu.DM.06G019360, the CNGC gene Soltu.DM.06G006320, the MYB transcription factors Soltu.DM.06G004450 and Soltu.DM.09G002130, and the WRKY transcription factor Soltu.DM.06G020440 were noticeably highly expressed, which indicates that these are likely to be the key genes in the regulation of oxidative stress tolerance. Overall, these findings lay the foundation for further studies on the molecular mechanisms of potato leaves in response to oxidative stress.
Subject(s)
Gene Expression Profiling , Gene Expression Regulation, Plant , Oxidative Stress , Plant Leaves , Solanum tuberosum , Transcriptome , Solanum tuberosum/genetics , Solanum tuberosum/metabolism , Plant Leaves/genetics , Plant Leaves/metabolism , Gene Expression Regulation, Plant/drug effects , Gene Expression Profiling/methods , Gene Ontology , Hydrogen Peroxide/metabolism , Hydrogen Peroxide/pharmacology , Plant Proteins/genetics , Plant Proteins/metabolism , Transcription Factors/genetics , Transcription Factors/metabolismABSTRACT
OBJECTIVE: To evaluate the health benefits and intervention efficiency of different strategies of initiating antihypertensive therapy for the primary prevention of cardiovascular diseases in a community-based Chinese population from the Chinese electronic health records research in Yinzhou (CHERRY) study. METHODS: A decision-analytic Markov model was used to simulate and compare different antihypertensive initiation strategies, including: Strategy 1, initiation of antihypertensive therapy for Chinese adults with systolic blood pressure (SBP) ≥140 mmHg (2020 Chinese guideline on the primary prevention of cardiovascular diseases); Strategy 2, initiation of antihypertensive therapy for Chinese adults with SBP ≥130 mmHg; Strategy 3, initiation of antihypertensive therapy for Chinese adults with SBP≥140 mmHg, or with SBP between 130 and 140 mmHg and at high risk of cardiovascular diseases (2017 American College of Cardiology/American Heart Association guideline for the prevention, detection, evaluation, and management of high blood pressure in adults); Strategy 4, initiation of antihypertensive therapy for Chinese adults with SBP≥160 mmHg, or with SBP between 140 and 160 mmHg and at high risk of cardiovascular diseases (2019 United Kingdom National Institute for Health and Care Excellence guideline for the hypertension in adults: Diagnosis and management). The high 10-year cardiovascular risk was defined as the predicted risk over 10% based on the 2019 World Health Organization cardiovascular disease risk charts. Different strategies were simulated by the Markov model for ten years (cycles), with parameters mainly from the CHERRY study or published literature. After ten cycles of simulation, the numbers of quality-adjusted life years (QALY), cardiovascular events and all-cause deaths were calculated to evaluate the health benefits of each strategy, and the numbers needed to treat (NNT) for each cardiovascular event or all-cause death could be prevented were calculated to assess the intervention efficiency. One-way sensitivity analysis on the uncertainty of incidence rates of cardiovascular disease and probabilistic sensitivity analysis on the uncertainty of hazard ratios of interventions were conducted. RESULTS: A total of 213 987 Chinese adults aged 35-79 years without cardiovascular diseases were included. Compared with strategy 1, the number of cardiovascular events that could be prevented in strategy 2 increased by 666 (95% UI: 334-975), while the NNT per cardiovascular event prevented increased by 10 (95% UI: 7-20). In contrast to strategy 1, the number of cardiovascular events that could be prevented in strategy 3 increased by 388 (95% UI: 194-569), and the NNT per cardiovascular event prevented decreased by 6 (95% UI: 4-12), suggesting that strategy 3 had better health benefits and intervention efficiency. Compared to strategy 1, although the number of cardiovascular events that could be prevented decreased by 193 (95% UI: 98-281) in strategy 4, the NNT per cardiovascular event prevented decreased by 18 (95% UI: 13-37) with better efficiency. The results were consistent in the sensitivity analyses. CONCLUSION: When initiating antihypertensive therapy in an economically developed area of China, the strategy combined with cardiovascular risk assessment is more efficient than those purely based on the SBP threshold. The cardiovascular risk assessment strategy with different SBP thresholds is suggested to balance health benefits and intervention efficiency in diverse populations.
Subject(s)
Antihypertensive Agents , Cardiovascular Diseases , Hypertension , Markov Chains , Primary Prevention , Humans , Cardiovascular Diseases/prevention & control , Antihypertensive Agents/therapeutic use , Hypertension/drug therapy , China/epidemiology , Blood Pressure/drug effects , Female , Male , Middle Aged , Decision Support Techniques , Adult , Quality-Adjusted Life Years , AgedABSTRACT
OBJECTIVE: To explore the effects of short-term particulate matter (PM) exposure and the melatonin receptor 1B (MTNR1B) gene on triglyceride-glucose (TyG) index utilizing data from Fang-shan Family-based Ischemic Stroke Study in China (FISSIC). METHODS: Probands and their relatives from 9 rural areas in Fangshan District, Beijing, were included in the study. PM data were obtained from fixed monitoring stations of the National Air Pollution Monitoring System. TyG index was calculated by fasting triglyceride and glucose concentrations. The associations of short-term PM exposure and rs10830963 polymorphism of the MTNR1B gene with the TyG index were assessed using mixed linear models, in which covariates such as age, sex, and lifestyles were adjusted for. Gene-environment inter-action analysis was furtherly performed using the maximum likelihood methods to explore the potential effect modifier role of rs10830963 polymorphism in the association of PM with TyG index. RESULTS: A total of 4 395 participants from 2 084 families were included in the study, and the mean age of the study participants was (58.98±8.68) years, with 53. 90% females. The results of association analyses showed that for every 10 µg/m3 increase in PM2.5 concentration, TyG index increased by 0.017 (95%CI: 0.007-0.027), while for per 10 µg/m3 increment in PM10, TyG index increased by 0.010 (95%CI: 0.003-0.017). And the associations all had lagged effects. In addition, there was a positive association between the rs10830963 polymorphism and the TyG index. For per increase in risk allele G, TyG index was elevated by 0.040 (95%CI: 0.004-0.076). The TyG index was 0.079 (95%CI: 0.005-0.152) higher in carriers of the GG genotype compared with carriers of the CC genotype. The interaction of rs10830963 polymorphism with PM exposure had not been found to be statistically significant in the present study. CONCLUSION: Short-term exposure to PM2.5 and PM10 were associated with higher TyG index. The G allele of rs10830963 polymorphism in the MTNR1B gene was associated with the elevated TyG index.
Subject(s)
Particulate Matter , Receptor, Melatonin, MT2 , Triglycerides , Humans , Female , Male , Middle Aged , Receptor, Melatonin, MT2/genetics , Triglycerides/blood , Blood Glucose , Environmental Exposure/adverse effects , Air Pollutants , Gene-Environment Interaction , China , Polymorphism, Single Nucleotide , Ischemic Stroke/genetics , Ischemic Stroke/blood , Genotype , Air Pollution/adverse effectsABSTRACT
The investigation of organic light-emitting diodes (OLEDs) and organic laser devices with thermally activated delayed fluorescence (TADF) molecules is emerging due to the potential of harnessing triplets. In this work, a boron/nitrogen multiple-resonance TADF polycyclic framework fusing carbazole units (CzBNPh) was proposed. CzBNPh exhibited a narrowband emission (<30â nm), a unity photoluminescence quantum yield, and a fast radiative rate. Consequently, CzBNPh demonstrated a low distributed feedback (DFB) lasing threshold of 0.68â µJ cm-2 . Furthermore, the stimulated emission zone of CzBNPh was effectively separated from its singlet and triplet absorption, thereby minimizing the singlet-triplet annihilation under long-pulsed excitation ranging from 20â µs to 2.5â ms. Significantly, the enhanced rigid molecular conformation, thermal stability, and photo-stability resulted in improved lasing and electroluminescence stability compared to that of 5,9-diphenyl-5,9-diaza-13b-boranaphtho[3,2,1-de]anthracene (DABNA)-core. These findings indicate the potential of CzBN-core as a promising framework for achieving long-pulsed wave and electrically-pumped lasing in the future.
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BACKGROUND: A global plan has been set to end human deaths from dog-mediated rabies by 2030 ("Zero-by-30"), but whether it could be achieved in some countries, such as China, remains unclear. Although elimination strategies through post-exposure prophylaxis (PEP) use, dog vaccination, and patient risk assessments with integrated bite case management (IBCM) were proposed to be cost-effective, evidence is still lacking in China. We aim to evaluate the future burdens of dog-mediated human rabies deaths in the next decade and provide quantitative evidence on the cost-effectiveness of different rabies-control strategies in China. METHODS: Based on data from China's national human rabies surveillance system, we used decision-analytic modelling to estimate dog-mediated human rabies death trends in China till 2035. We simulated and compared the expected consequences and costs of different combination strategies of the status quo, improved access to PEP, mass dog vaccination, and use of IBCM. RESULTS: The predicted human rabies deaths in 2030 in China will be 308 (95%UI: 214-411) and remain stable in the next decade under the status quo. The strategy of improved PEP access alone could only decrease deaths to 212 (95%UI: 147-284) in 2028, remaining unchanged till 2035. In contrast, scaling up dog vaccination to coverage of 70% could eliminate rabies deaths by 2033 and prevent approximately 3,265 (95%UI: 2,477-3,687) extra deaths compared to the status quo during 2024-2035. Moreover, with the addition of IBCM, the "One Health" approach through mass dog vaccination could avoid unnecessary PEP use and substantially reduce total cost from 12.53 (95%UI: 11.71-13.34) to 8.73 (95%UI: 8.09-9.85) billion US dollars. Even if increasing the total costs of IBCM from 100 thousand to 652.10 million US dollars during 2024-2035, the combined strategy of mass dog vaccination and use of IBCM will still dominate, suggesting the robustness of our results. CONCLUSIONS: The combined strategy of mass dog vaccination and IBCM requires collaboration between health and livestock/veterinary sectors, and it could eliminate Chinese rabies deaths as early as 2033, with more deaths averted and less cost, indicating that adding IBCM could reduce unnecessary use of PEP and make the "One Health" rabies-control strategy most cost-effective.
Subject(s)
Bites and Stings , Rabies , Humans , Dogs , Animals , Rabies/epidemiology , Rabies/prevention & control , Rabies/veterinary , Goals , Vaccination , Post-Exposure Prophylaxis/methodsABSTRACT
Chronic kidney disease (CKD), a disease involving damage to the kidney structure and function, is a global public health problem. Tubulointerstitial fibrosis (TIF) is both an inevitable pathological change in individuals with CKD and a driving force in the progression of renal fibrosis. Nicotinamide N-methyltransferase (NNMT) and its metabolite 1-methylnicotinamide (MNAM) have been shown to protect against lipotoxicity-induced kidney tubular injury. However, the biological roles of NNMT and MNAM in regulating TIF remain elusive. This study aimed to investigate the protective effect of NNMT and MNAM on TIF and the mechanisms involved. We explored the functions and mechanisms of NNMT and MNAM in TIF, as well as the interaction between NNMT and MNAM, using unilateral ureteral obstruction (UUO) mice and cultured mouse tubular epithelial cells (mTECs) stimulated with transforming growth factor-ß1 (TGF-ß1). Several important findings were obtained as follows: (1) NNMT expression was upregulated in the kidneys of UUO mice and TGF-ß1-induced mTECs, and this upregulation was proposed to be a protective compensatory response to TIF. (2) MNAM was a potentially effective antifibrotic and anti-inflammatory medication in UUO mice. (3) The antifibrotic effect of NNMT overexpression was exerted by increasing the concentration of MNAM. (4) The renoprotective role of MNAM depended on the selective blockade of the interaction of Smad3 with TGFß receptor I. Overall, our study shows that NNMT is involved in the development and progression of CKD and that its metabolite MNAM may be a novel inhibitor of the TGF-ß1/Smad3 pathway with great therapeutic potential for CKD.
Subject(s)
Fibrosis/metabolism , Niacinamide/analogs & derivatives , Nicotinamide N-Methyltransferase/metabolism , Renal Insufficiency, Chronic/metabolism , Signal Transduction/physiology , Smad3 Protein/metabolism , Transforming Growth Factor beta1/metabolism , Animals , Cells, Cultured , Kidney/metabolism , Male , Mice , Mice, Inbred C57BL , Niacinamide/metabolism , Ureteral Obstruction/metabolismABSTRACT
Colloidal self-assembly is a viable solution to making advanced metamaterials. While the physicochemical properties of the particles affect the properties of the assembled structures, particle configuration is also a critical determinant factor. Colloidal self-assembly state classification is typically achieved with order parameters, which are aggregate variables normally defined with nontrivial exploration and validation. Here, we present an image-based framework to classify the state of a 2-D colloidal self-assembly system. The framework leverages deep learning algorithms with unsupervised learning for state classification and a supervised learning-based convolutional neural network for state prediction. The neural network models are developed using data from an experimentally validated Brownian dynamics simulation. Our results demonstrate that the proposed approach gives a satisfying performance, comparable and even outperforming the commonly used order parameters in distinguishing void defective states from ordered states. Given the data-based nature of the approach, we anticipate its general applicability and potential automatability to different and complex systems where image or particle coordination acquisition is feasible.
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INTRODUCTION: The clinical significance of hemoglobin level and blood transfusion therapy in elderly sepsis patients remains controversial. The study investigated the relationship between mortality, hemoglobin levels, and blood transfusion in elderly sepsis patients. METHODS: Elderly sepsis patients were included in the Marketplace for Medical Information in Intensive Care (MIMIC-IV) database. A multivariate regression model analyzed the relationship between the Hb level and the 28-day mortality risk. Logistic Multivariate analysis, Propensity Matching (PSM) analysis, an Inverse Probabilities Weighting (IPW) model and doubly robust estimation were applied to analyze the 28-day mortality risk between transfused and non-transfused patients in Hb at 7-8 g/dL, 8-9 g/dL, 9-10 g/dL, and 10-11 g/dL groups. RESULTS: 7473 elderly sepsis patients were enrolled in the study. The Hb level in the ICU and the 28-day mortality risk of patients with sepsis shared a non-linear relationship. The patients with Hb levels of <10 g/dL(p < 0.05) and > 15 g/dL(p < 0.05) within 24 h had a high mortality risk in multivariate analysis. In the Hb level 7-8 g/dL and 8-9 g/dL subgroup, the Multivariate analysis (p < 0.05), PSM (p < 0.05), IPW (p < 0.05) and doubly robust estimation (p < 0.05) suggested that blood transfusion could reduce the mortality risk. In the subgroup with a Hb level of 10-11 g/dL, IPW (p < 0.05) and doubly robust estimation (p < 0.05) suggested that blood transfusion could increase the mortality risk of elderly sepsis patients. CONCLUSION: A non-linear relationship between the Hb level and the 28-day mortality risk and Hb levels of <10 g/dL and > 15 g/dL may increase the mortality risk, and blood transfusion with a Hb level of <9 g/dL may minimize mortality risk in elderly sepsis patients.
Subject(s)
Clinical Relevance , Sepsis , Humans , Aged , Retrospective Studies , Hemoglobins/analysis , Blood Transfusion , Sepsis/therapyABSTRACT
Soil salinity has become an increasingly serious problem worldwide, greatly limiting crop development and yield, and posing a major challenge to plant breeding. Basic leucine zipper (bZIP) transcription factors are the most widely distributed and conserved transcription factors and are the main regulators controlling various plant response processes against external stimuli. The bZIP protein contains two domains: a highly conserved, DNA-binding alkaline region, and a diverse leucine zipper, which is one of the largest transcription factor families in plants. Plant bZIP is involved in many biological processes, such as flower development, seed maturation, dormancy, and senescence, and plays an important role in abiotic stresses such as salt damage, drought, cold damage, osmotic stress, mechanical damage, and ABA signal response. In addition, bZIP is involved in the regulation of plant response to biological stresses such as insect pests and pathogen infection through salicylic acid, jasmonic acid, and ABA signal transduction pathways. This review summarizes and discusses the structural characteristics and functional characterization of the bZIP transcription factor group, the bZIP transcription factor complex and its molecular regulation mechanisms related to salt stress resistance, and the regulation of transcription factors in plant salt stress resistance. This review provides a theoretical basis and research ideas for further exploration of the salt stress-related functions of bZIP transcription factors. It also provides a theoretical basis for crop genetic improvement and green production in agriculture.
Subject(s)
Basic-Leucine Zipper Transcription Factors , Plant Proteins , Basic-Leucine Zipper Transcription Factors/metabolism , Plant Proteins/genetics , Plant Proteins/metabolism , Plant Breeding , Plants/metabolism , Salt Stress/genetics , Stress, Physiological/genetics , Gene Expression Regulation, Plant , PhylogenyABSTRACT
Ubiquitin-conjugating enzymes (E2s/UBC) are components of the ubiquitin proteasome system (UPS), and the ubiquitin-conjugating enzyme variant (UEV) is one of E2s (ubiquitin-conjugating enzymes, UBC) subfamily. The UEVs and UBC13 play an auxiliary role in mediating Lys63-linked polyUb chain assembly, which is correlated with target protein non-proteolytic functions, such as DNA repair or response to stress. However, the collaborative mechanism of StUBC13 (homologue of AtUBC13) and StUEVs (the UEVs in potato) involved in potato are not fully understood understood. Here, we identified two StUBC13 and seven StUEVs from potato genome. We analyzed protein motif and conserved domain, gene structure, phylogenetic features, cis-acting elements of StUBC13 and StUEVs. Subsequently, we screened StUBC13 partners protein and verified interaction between StUBC13 and StUEVs using yeast two-hybrid, split luciferase complementation (SLC) and bimolecular fluorescence complementation (BiFC) approach. The expression profile and qRT-PCR analysis suggested that StUBC13 and StUEVs gene exhibited a tissue-specific expression and were induced by different stress. Overall, this investigative study provides a comprehensive reference and view for further functional research on StUBC13 and StUEV1s in potato.
Subject(s)
Solanum tuberosum , Ubiquitin-Conjugating Enzymes , Ubiquitin-Conjugating Enzymes/metabolism , Ubiquitin/metabolism , Solanum tuberosum/genetics , Solanum tuberosum/metabolism , Phylogeny , Amino Acid Sequence , Saccharomyces cerevisiae/metabolismABSTRACT
Mental disorders are characterized by high incidence and high recurrence rates, and only part of patients responded to drug medication. In this case, substantial preclinical investigations are needed. Most antipsychotics taken daily orally in clinics are administered through injection, oral gavage, or minipum implant in rodents, which may induce stress and affect the results of behavioral tests. How drug administrations on behaviors and drug efficacy remains an unsolved problem. In this study, we compared the intraperitoneal injection (IP), intragastric administration (IG), and tail vein injection (TVI) on behaviors, as well as the difference between administration-induced stress and chronic unpredictable mild stress (CUMS). Next, we studied the effects of IG on CUMS model and drug efficacy. We found that IP, IG, and TVI, especially IG, induced a behavior-like phenotype of depression and anxiety, which we call the "CUMS-like behaviors". However, such behaviors were not equal to depression. When treated CUMS mice with saline by gavage, they didn't show any aggravated phenotype compared with CUMS alone. We observed that fluoxetine by intraperitoneal injection was more effective than intragastric administration. Our study confirmed that repeated administrations lead to CUMS-like behaviors. Although these behaviors are not depression, they have adverse effects on drug efficacy.
Subject(s)
Depression , Fluoxetine , Animals , Anxiety/drug therapy , Behavior, Animal , Depression/drug therapy , Depression/etiology , Disease Models, Animal , Fluoxetine/pharmacology , Fluoxetine/therapeutic use , Hippocampus , Humans , Mice , Stress, Psychological/drug therapyABSTRACT
Brain aneurysm ruptured subarachnoid hemorrhages (SAH) are extremely rare except in humans. This study described a SAH caused by a ruptured anterior communication artery aneurysm and concurrent myocardial infarction, along with pneumonia and intestinal obstruction in a rhesus monkey, which is rather rare in animal experiments.
Subject(s)
Aneurysm, Ruptured , Intracranial Aneurysm , Myocardial Infarction , Subarachnoid Hemorrhage , Aneurysm, Ruptured/complications , Aneurysm, Ruptured/veterinary , Animals , Intracranial Aneurysm/complications , Macaca mulatta , Myocardial Infarction/complications , Subarachnoid Hemorrhage/complications , Subarachnoid Hemorrhage/veterinaryABSTRACT
Protein ubiquitination is one of the most important posttranslational modifications in eukaryotic cells, and it is involved in a variety of biological processes, including abiotic stress response. The ubiquitination modification is highly specific, which depends on the accurate recognition of substrate proteins by ubiquitin ligase. Plant U-box (PUB) proteins are a class of ubiquitin ligases, multiple members of which have shown to participate in water-deficit stress in Arabidopsis and rice. U-box gene family and large-scale profiling of the ubiquitome in potato has not been reported to date, although it is one of the most important food crops. The identified 66 U-box genes from the potato genome database were unevenly distributed on 10 chromosomes. These StPUBs have a large number of tandem repeat sequences. Analysis of gene expression characteristics revealed that many StPUBs responded to abiotic stress. Three hundred and fourteen lys modification sites were identified under PEG-induced drought stress, which were distributed on 200 proteins, with 25 differential ubiquitination modification sites, most of which were up-regulated. The ubiquitination modification in potato protein was enhanced under PEG-induced drought stress, and U-box ubiquitin ligase was involved. This study provides an overall strategy and rich data set to clarify the effects of ubiquitination on potatoes under PEG-induced drought stress and the ubiquitination modification involved in potato U-box genes in response to PEG-induced drought stress.
Subject(s)
Droughts , Solanum tuberosum , Gene Expression Regulation, Plant , Phylogeny , Plant Proteins/genetics , Plant Proteins/metabolism , Solanum tuberosum/genetics , Solanum tuberosum/metabolism , Stress, Physiological/genetics , Ubiquitin-Protein Ligases/genetics , Ubiquitin-Protein Ligases/metabolism , UbiquitinationABSTRACT
Previous studies showed different risk effects on exposure of fine particulate matter (PM2.5) mass for cardiovascular disease (CVD) globally, which is likely due to different constituents of PM2.5. This study aimed to investigate the association between short-term exposure of PM2.5 constituents and hospital admissions of CVD. Daily counts of city-specific hospital admissions for CVD in 18 cities in China between 2014 and 2017 were extracted from the national Urban Employee Basic Medical Insurance database and the Beijing Municipal Commission of Health and Family Planning Information Center database. Directly measured PM2.5 constituents, including ions and polycyclic aromatic hydrocarbons, were collected by the Chinese Environmental Public Health Tracking system. We used the time-stratified case-crossover design to estimate the association between PM2.5 constituents and hospital admissions of CVD. Concentrations of ions accounted for the majority of the detected constituents. Excess risk (ER) of average ions concentrations for CVD was highest as 2.30% (95% CI: 1.62-2.99%) for NH4+, whose major sources are residential and agricultural emissions. This was followed by 1.85% (1.30-2.41%) for NO3- (generally from vehicles), 0.95% (0.28-1.63%) for SO42- (often from fossil fuel burning) respectively. The association for ions were generally consistent with ischemic heart disease (IHD) and ischemic stroke, e.g., NH4+ was associated with IHD (2.50%; 1.52-3.48%) and ischemic stroke (1.77%; 0.65-2.9%). For polycyclic aromatic hydrocarbons (PAHs), mainly from coal and vehicle-related oil combustion, the constituents were all associated with ischemic stroke but not for IHD. The ER for ischemic stroke was highest at 1.69% (0.99-2.39%) for indeno (123-cd) pyrene. Thus, in terms of the subtypes of CVD, the risks of hospital admissions varied with exposure to different PM2.5 constituents. Exposed to NH4+ had the highest risk to IHD and ischemic stroke, whereas PAHs were predominately associated with ischemic stroke only.
Subject(s)
Air Pollutants , Air Pollution , Cardiovascular Diseases , Ischemic Stroke , Polycyclic Aromatic Hydrocarbons , Humans , Cities , Air Pollution/adverse effects , Air Pollution/analysis , Cardiovascular Diseases/epidemiology , Air Pollutants/analysis , Particulate Matter/analysis , Hospitals , China/epidemiology , Environmental Exposure/adverse effectsABSTRACT
Fragrant woodfern (Dryopteris fragrans) is a medicinal plant rich in terpenoids. Ultraviolet-B (UV-B) light could increase concentration of terpenoids. The aim of this study was to analyze how UV-B regulates the terpenoid synthesis of the molecular regulatory mechanism in fragrant woodfern. In this study, compared with the control group, the content of the terpenes was significantly higher in fragrant woodfern leaves under UV-B treatment for 4 days (d). In order to identify how UV-B regulates the terpenoid metabolic mechanism in fragrant woodfern, we examined the mRNAs and small RNAs in fragrant woodfern leaves under UV-B treatment. mRNA and miRNA-seq identified 4533 DEGs and 17 DEMs in the control group compared with fragrant woodfern leaves under UV-B treatment for 4 d. mRNA-miRNA analysis identified miRNA target gene pairs consisting of 8 DEMs and 115 miRNAs. The target genes were subjected to GO and KEGG analyses. The results showed that the target genes were mainly enriched in diterpene biosynthesis, terpenoid backbone biosynthesis, plant hormone signal transduction, MEP pathway and MVA pathway, in which miR156 and miR160 regulate these pathways by targeting DfSPL and DfARF, respectively. The mRNA and miRNA datasets identified a subset of candidate genes. It provides the theoretical basis that UV-B regulates the terpenoid synthesis of the molecular regulatory mechanism in fragrant woodfern.
Subject(s)
Dryopteris , MicroRNAs , Perfume , Dryopteris/genetics , Gene Expression Profiling , MicroRNAs/genetics , MicroRNAs/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , Terpenes/metabolismABSTRACT
Stomata are specialized portals in plant leaves to modulate water loss from plants to the atmosphere by control of the transpiration, thereby determining the water-use efficiency and drought resistance of plants. Despite that the stomata developmental progression is well-understood at the molecular level, the experimental evidence that miRNA regulates stomata development is still lacking, and the underlying mechanism remains elusive. This study demonstrates the involvement of stu-miR827 in regulating the drought tolerance of potato due to its control over the leaf stomatal density. The expression analysis showed that stu-miR827 was obviously repressed by drought stresses and then rapidly increased after rewatering. Suppressing the expression of stu-miR827 transgenic potato lines showed an increase in stomatal density, correlating with a weaker drought resistance compared with wildtype potato lines. In addition, StWRKY48 was identified as the target gene of stu-miR827, and the expression of StWRKY48 was obviously induced by drought stresses and was greatly upregulated in stu-miR827 knockdown transgenic potato lines, suggesting its involvement in the drought stress response. Importantly, the expression of genes associated with stomata development, such as SDD (stomatal density and distribution) and TMM (too many mouths), was seriously suppressed in transgenic lines. Altogether, these observations demonstrated that suppression of stu-miR827 might lead to overexpression of StWRKY48, which may contribute to negatively regulating the drought adaptation of potato by increasing the stomatal density. The results may facilitate functional studies of miRNAs in the process of drought tolerance in plants.