CycC1;1-WRKY75 complex-mediated transcriptional regulation of SOS1 controls salt stress tolerance in Arabidopsis.

SALT OVERLY SENSITIVE1 (SOS1) is a key component of plant salt tolerance. However, how SOS1 transcription is dynamically regulated in plant response to different salinity conditions remains elusive. Here, we report that C-type Cyclin1;1 (CycC1;1) negatively regulates salt tolerance by interfering with WRKY75-mediated transcriptional activation of SOS1 in Arabidopsis (Arabidopsis thaliana). Disruption of CycC1;1 promotes SOS1 expression and salt tolerance in Arabidopsis because CycC1;1 interferes with RNA polymerase II recruitment by occupying the SOS1 promoter. Enhanced salt tolerance of the cycc1;1 mutant was completely compromised by an SOS1 mutation. Moreover, CycC1;1 physically interacts with the transcription factor WRKY75, which can bind to the SOS1 promoter and activate SOS1 expression. In contrast to the cycc1;1 mutant, the wrky75 mutant has attenuated SOS1 expression and salt tolerance, whereas overexpression of SOS1 rescues the salt sensitivity of wrky75. Intriguingly, CycC1;1 inhibits WRKY75-mediated transcriptional activation of SOS1 via their interaction. Thus, increased SOS1 expression and salt tolerance in cycc1;1 were abolished by WRKY75 mutation. Our findings demonstrate that CycC1;1 forms a complex with WRKY75 to inactivate SOS1 transcription under low salinity conditions. By contrast, under high salinity conditions, SOS1 transcription and plant salt tolerance are activated at least partially by increased WRKY75 expression but decreased CycC1;1 expression.

Calcium-induced upregulation of energy metabolism heats neurons during neural activity.

Cellular temperature affects every biochemical reaction, underscoring its critical role in cellular functions. In neurons, temperature not only modulates neurotransmission but is also a key determinant of neurodegenerative diseases. Considering that the brain consumes a disproportionately high amount of energy relative to its weight, neural circuits likely generate a lot of heat, which can increase cytosolic temperature. However, the changes in temperature within neurons and the mechanisms of heat generation during neural excitation remain unclear. In this study, we achieved simultaneous imaging of Ca2+ and temperature using the genetically encoded indicators, B-GECO and B-gTEMP. We then compared the spatiotemporal distributions of Ca2+ responses and temperature. Following neural excitation induced by veratridine, an activator of the voltage-gated Na+ channel, we observed an approximately 2 °C increase in cytosolic temperature occurring 30 s after the Ca2+ response. The temperature elevation was observed in the non-nuclear region, while Ca2+ increased throughout the cell body. Moreover, this temperature increase was suppressed under Ca2+-free conditions and by inhibitors of ATP synthesis. These results indicate that Ca2+-induced upregulation of energy metabolism serves as the heat source during neural excitation.

GSDMD/Drp1 signaling pathway mediates hippocampal synaptic damage and neural oscillation abnormalities in a mouse model of sepsis-associated encephalopathy.

BACKGROUND: Gasdermin D (GSDMD)-mediated pyroptotic cell death is implicated in the pathogenesis of cognitive deficits in sepsis-associated encephalopathy (SAE), yet the underlying mechanisms remain largely unclear. Dynamin-related protein 1 (Drp1) facilitates mitochondrial fission and ensures quality control to maintain cellular homeostasis during infection. This study aimed to investigate the potential role of the GSDMD/Drp1 signaling pathway in cognitive impairments in a mouse model of SAE. METHODS: C57BL/6 male mice were subjected to cecal ligation and puncture (CLP) to establish an animal model of SAE. In the interventional study, mice were treated with the GSDMD inhibitor necrosulfonamide (NSA) or the Drp1 inhibitor mitochondrial division inhibitor-1 (Mdivi-1). Surviving mice underwent behavioral tests, and hippocampal tissues were harvested for histological analysis and biochemical assays at corresponding time points. Haematoxylin-eosin staining and TUNEL assays were used to evaluate neuronal damage. Golgi staining was used to detect synaptic dendritic spine density. Additionally, transmission electron microscopy was performed to assess mitochondrial and synaptic morphology in the hippocampus. Local field potential recordings were conducted to detect network oscillations in the hippocampus. RESULTS: CLP induced the activation of GSDMD, an upregulation of Drp1, leading to associated mitochondrial impairment, neuroinflammation, as well as neuronal and synaptic damage. Consequently, these effects resulted in a reduction in neural oscillations in the hippocampus and significant learning and memory deficits in the mice. Notably, treatment with NSA or Mdivi-1 effectively prevented these GSDMD-mediated abnormalities. CONCLUSIONS: Our data indicate that the GSDMD/Drp1 signaling pathway is involved in cognitive deficits in a mouse model of SAE. Inhibiting GSDMD or Drp1 emerges as a potential therapeutic strategy to alleviate the observed synaptic damages and network oscillations abnormalities in the hippocampus of SAE mice.

BioNet: a large-scale and heterogeneous biological network model for interaction prediction with graph convolution.

MOTIVATION: Understanding chemical-gene interactions (CGIs) is crucial for screening drugs. Wet experiments are usually costly and laborious, which limits relevant studies to a small scale. On the contrary, computational studies enable efficient in-silico exploration. For the CGI prediction problem, a common method is to perform systematic analyses on a heterogeneous network involving various biomedical entities. Recently, graph neural networks become popular in the field of relation prediction. However, the inherent heterogeneous complexity of biological interaction networks and the massive amount of data pose enormous challenges. This paper aims to develop a data-driven model that is capable of learning latent information from the interaction network and making correct predictions. RESULTS: We developed BioNet, a deep biological networkmodel with a graph encoder-decoder architecture. The graph encoder utilizes graph convolution to learn latent information embedded in complex interactions among chemicals, genes, diseases and biological pathways. The learning process is featured by two consecutive steps. Then, embedded information learnt by the encoder is then employed to make multi-type interaction predictions between chemicals and genes with a tensor decomposition decoder based on the RESCAL algorithm. BioNet includes 79 325 entities as nodes, and 34 005 501 relations as edges. To train such a massive deep graph model, BioNet introduces a parallel training algorithm utilizing multiple Graphics Processing Unit (GPUs). The evaluation experiments indicated that BioNet exhibits outstanding prediction performance with a best area under Receiver Operating Characteristic (ROC) curve of 0.952, which significantly surpasses state-of-theart methods. For further validation, top predicted CGIs of cancer and COVID-19 by BioNet were verified by external curated data and published literature.

CCT6A facilitates lung adenocarcinoma progression and glycolysis via STAT1/HK2 axis.

BACKGROUND: Chaperonin Containing TCP1 Subunit 6 A (CCT6A) is a prominent protein involved in the folding and stabilization of newly synthesized proteins. However, its roles and underlying mechanisms in lung adenocarcinoma (LUAD), one of the most aggressive cancers, remain elusive. METHODS: Our study utilized in vitro cell phenotype experiments to assess CCT6A's impact on the proliferation and invasion capabilities of LUAD cell lines. To delve into CCT6A's intrinsic mechanisms affecting glycolysis and proliferation in lung adenocarcinoma, we employed transcriptomic sequencing and liquid chromatography-mass spectrometry analysis. Co-immunoprecipitation (Co-IP) and chromatin immunoprecipitation (CHIP) assays were also conducted to substantiate the mechanism. RESULTS: CCT6A was found to be significantly overexpressed in LUAD and associated with a poorer prognosis. The silencing of CCT6A inhibited the proliferation and migration of LUAD cells and elevated apoptosis rates. Mechanistically, CCT6A interacted with STAT1 protein, forming a complex that enhances the stability of STAT1 by protecting it from ubiquitin-mediated degradation. This, in turn, facilitated the transcription of hexokinase 2 (HK2), a critical enzyme in aerobic glycolysis, thereby stimulating LUAD's aerobic glycolysis and progression. CONCLUSION: Our findings reveal that the CCT6A/STAT1/HK2 axis orchestrated a reprogramming of glucose metabolism and thus promoted LUAD progression. These insights position CCT6A as a promising candidate for therapeutic intervention in LUAD treatment.

LncRNA FOXD1-AS1 regulates pancreatic cancer stem cell properties and 5-FU resistance by regulating the miR-570-3p/SPP1 axis as a ceRNA.

Cancer stem cells (CSCs) play a pivotal role in the pathogenesis of human cancers. Previous studies have highlighted the role of long non-coding RNA (lncRNA) in modulating the stemness of CSCs. In our investigation, we identified an upregulation of lncRNA FOXD1-AS1 in CSCs. The enforced expression of lncRNA FOXD1-AS1 promotes tumorigenesis and self-renewal in pancreatic cancer CSCs. Conversely, the knockdown of lncRNA FOXD1-AS1 inhibits tumorigenesis and self-renewal in pancreatic cancer CSCs. Furthermore, our findings reveal that lncRNA FOXD1-AS1 enhances self-renewal and tumorigenesis in pancreatic cancer CSCs by up-regulating osteopontin/secreted phosphoprotein 1(SPP1) and acting as a ceRNA to sponge miR-570-3p in pancreatic cancer (PC) CSCs. Additionally, lncRNA FOXD1-AS1 depleted pancreatic cancer cells exhibit heightened sensitivity to 5-FU-indued cell growth inhibition and apoptosis. Analysis of patient-derived xenografts (PDX) indicates that a low level of lncRNA FOXD1-AS1 may serve as a predictor of 5-FU benefits in PC patients. Moreover, the introduction of SPP1 can reverse the sensitivity of lncRNA FOXD1-AS1-knockdown PC cells to 5-FU-induced cell apoptosis. Importantly, molecular studies have indicated that the elevated levels of lncRNAFOXD1-AS1 in PC are facilitated through METTL3 and YTHDF1-dependent m6A methylation. In summary, our results underscore the critical functions of lncRNA FOXD1-AS1 in the self-renewal and tumorigenesis of pancreatic cancer CSCs, positioning lncRNA FOXD1-AS1 as a promising therapeutic target for PC.

Rapid Construction of 18F-Triazolyl-tetrazines through the Click Reaction.

Due to the fast reaction rate, 18F-labeled tetrazines have been widely applied in positron emission tomography (PET) imaging in cancer research and drug discovery. In this work, several functional 18F-triazolyl-tetrazines were rapidly obtained through an optimized copper-catalyzed alkyene-azide cycloaddition reaction system in >99% radiochemical conversions. Notably, the commonly used 18F-labeled azides were isolated through cartridges and directly used for cycloadditions, which greatly simplified the labeling procedure. The assembled triazolyl-tetrazines demonstrated high in vitro stability and reaction kinetics, exhibiting considerable potential for the development of PET agents.

Hydroboration and hydrosilylation of alkenes catalyzed by an unsymmetrical magnesium methyl complex.

The hydroboration and hydrosilylation of alkenes catalyzed by the unsymmetrical ß-diketiminate magnesium methyl complex [(DippXylNacnac)MgMe (THF)] (1) have been reported. When complex 1 was employed as a highly efficient catalyst in the hydroboration of various alkenes with HBpin, only the anti-Markovnikov hydroboration products were obtained in high yields and with high regioselectivities under mild reaction conditions (60 °C). To our surprise, it showed different regioselectivities in the hydrosilylation of a range of alkenes with PhSiH3. Aromatic alkene substrates afforded the corresponding branched Markovnikov hydrosilylation products in high yields and with high regioselectivities; conversely, aliphatic alkenes produced the linear anti-Markovnikov products in moderate yields. This is completely consistent with the corresponding density functional theory (DFT) calculations. In addition, the practical utility was demonstrated via scale-up reactions of boronate esters and a preliminary plausible mechanism of hydroboration and hydrosilylation have been investigated as well.

ENPP1 inhibits the transcription activity of the hepatitis B virus pregenomic promoter by upregulating the acetylation of LMNB1.

Current therapies for hepatitis B virus (HBV) infection can slow disease progression but cannot cure the infection, as it is difficult to eliminate or permanently silence HBV covalently closed circular DNA (cccDNA). The interaction between host factors and cccDNA is essential for their formation, stability, and transcriptional activity. Here, we focused on the regulatory role of the host factor ENPP1 and its interacting transcription factor LMNB1 in HBV replication and transcription to better understand the network of host factors that regulate HBV, which may facilitate the development of new antiviral drugs. Overexpression of ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) in Huh7 cells decreased HBV pregenomic RNA (pgRNA) and hepatitis B core antigen (HBcAg) expression levels, whereas knockdown of ENPP1 increased them. A series of HBV promoter and mutant plasmids were constructed, and a luciferase reporter assay showed that overexpression of ENPP1 caused inhibition of the HBV promoter and its mutants. A DNA pull-down assay showed that lamin B1 (LMNB1), but not ENPP1, interacts directly with the HBV enhancer II/ basic core promoter (EnhII/BCP). ZDOCK and PyMOL software were used to predict the interaction of ENPP1 with LMNB1. Overexpression of LMNB1 inhibited the activity of the HBV promoter and its mutant. The acetylation levels at the amino acids 111K, 261K, and 483K of LMNB1 were reduced compared to the control, and an LMNB1 acetylation mutant containing 111R, 261Q, 261R, 483Q, and 483R showed increased promoter activity. In summary, ENPP1 together with LMNB1 increased the acetylation level at 111K and 261K, and LMNB1 inhibited the activity of HBV promoter and downregulated the expression of pregenomic RNA and HBcAg. Our follow-up studies will investigate the expression, clinical significance, and relevance of ENPP1 and LMNB1 in HBV patient tissues, explore the effect of LMNB1 on post-transcriptional progression, and examine whether ENPP1 can reduce cccDNA levels in the nucleus.

Fourteen new 2-benzylbenzofuran glycosides with cardioprotective activity from Heterosmilax yunnanensis.

Fourteen new 2-benzylbenzofuran O-glycosides (1-13, 15) and one new key precursor, diarylacetone (14) were isolated from the roots of Heterosmilax yunnanensis Gagnep, which all have characteristic 2,3,4-O-trisubstituted benzyl. Their structures were elucidated by 1D and 2D NMR, HRESIMS, UV and IR. The isolated compounds were assessed for their cardioprotective activities and compounds 1, 3 and 6 could significantly improve cardiomyocytes viability. Moreover, the mechanistic study revealed that these three compounds could significantly decrease intracellular ROS levels and maintain mitochondrial homeostasis upon hypoxia inducement. Consequently, 1, 3 and 6 might serve as potential lead compounds to prevent myocardial ischemia.

Type 2 Biomarkers and Their Clinical Implications in Bronchiectasis: A Prospective Cohort Study.

PURPOSE: Bronchiectasis is predominantly marked by neutrophilic inflammation. The relevance of type 2 biomarkers in disease severity and exacerbation risk is poorly understood. This study explores the clinical significance of these biomarkers in bronchiectasis patients. METHODS: In a cross-sectional cohort study, bronchiectasis patients, excluding those with asthma or allergic bronchopulmonary aspergillosis, underwent clinical and radiological evaluations. Bronchoalveolar lavage samples were analyzed for cytokines and microbiology. Blood eosinophil count (BEC), serum total immunoglobulin E (IgE), and fractional exhaled nitric oxide (FeNO) were measured during stable disease states. Positive type 2 biomarkers were defined by established thresholds for BEC, total IgE, and FeNO. RESULTS: Among 130 patients, 15.3% demonstrated BEC ≥ 300 cells/µL, 26.1% showed elevated FeNO ≥ 25 ppb, and 36.9% had high serum total IgE ≥ 75 kU/L. Approximately 60% had at least one positive type 2 biomarker. The impact on clinical characteristics and disease severity was variable, highlighting BEC and FeNO as reflective of different facets of disease severity and exacerbation risk. The combination of low BEC with high FeNO appeared to indicate a lower risk of exacerbation. However, Pseudomonas aeruginosa colonization and a high neutrophil-to-lymphocyte ratio (NLR ≥ 3.0) were identified as more significant predictors of exacerbation frequency, independent of type 2 biomarker presence. CONCLUSIONS: Our study underscores the distinct roles of type 2 biomarkers, highlighting BEC and FeNO, in bronchiectasis for assessing disease severity and predicting exacerbation risk. It advocates for a multi-biomarker strategy, incorporating these with microbiological and clinical assessments, for comprehensive patient management.

How multiple air pollutants affect hand, foot, and mouth disease incidence in children: assessing effect modification by geographical context in multicity of Sichuan, southwest China.

BACKGROUND: Several studies have suggested a significant association of hand, foot, and mouth disease (HFMD) with ambient air pollutants. Existing studies have characterized the role of air pollutants on HFMD using only risk ratio measures while ignoring the attributable burden. And whether the geographical context (i.e., diverse topographic features) could modulate the relationships is unclear. METHODS: Daily reported childhood HFMD counts, ambient air pollution, and meteorological data during 2015-2017 were collected for each of 21 cities in Sichuan Province. A multistage analysis was carried out in different populations based on geographical context to assess effect modification by topographic conditions. We first constructed a distributed lag nonlinear model (DLNM) for each city to describe the relationships with risk ratio measures. Then, we applied a multivariate meta-regression to estimate the pooled effects of multiple air pollutants on HFMD from the exposure and lagged dimensions. Finally, attributable risks measures were calculated to quantify HFMD burden by air pollution. RESULTS: Based on 207554 HFMD cases in Sichuan Province, significant associations of HFMD with ambient air pollutants were observed mainly at relatively high exposure ranges. The effects of ambient air pollutants on HFMD are most pronounced on lag0 or around lag7, with relative risks gradually approaching the reference line thereafter. The attributable risks of O3 were much greater than those of other air pollutants, particularly in basin and mountain regions. CONCLUSIONS: This study revealed significant pooled relationships between multiple air pollutants and HFMD incidence from both exposure and lag dimensions. However, the specific effects, including RRs and ARs, differ depending on the air pollution variable and geographical context. These findings provide local authorities with more evidence to determine key air pollutants and regions for devising and implementing targeted interventions.

The RING-Type Domain-Containing Protein GNL44 Is Essential for Grain Size and Quality in Rice (Oryza sativa L.).

Grain size in rice (Oryza sativa L.) shapes yield and quality, but the underlying molecular mechanism is not fully understood. We functionally characterized GRAIN NUMBER AND LARGE GRAIN SIZE 44 (GNL44), encoding a RING-type protein that localizes to the cytoplasm. The gnl44 mutant has fewer but enlarged grains compared to the wild type. GNL44 is mainly expressed in panicles and developing grains. Grain chalkiness was higher in the gnl44 mutant than in the wild type, short-chain amylopectin content was lower, middle-chain amylopectin content was higher, and appearance quality was worse. The amylose content and gel consistency of gnl44 were lower, and protein content was higher compared to the wild type. Rapid Visco Analyzer results showed that the texture of cooked gnl44 rice changed, and that the taste value of gnl44 was lower, making the eating and cooking quality of gnl44 worse than that of the wild type. We used gnl44, qgl3, and gs3 monogenic and two-gene near-isogenic lines to study the effects of different combinations of genes affecting grain size on rice quality-related traits. Our results revealed additive effects for these three genes on grain quality. These findings enrich the genetic resources available for rice breeders.

Abscisic acid facilitates phosphate acquisition through the transcription factor ABA INSENSITIVE5 in Arabidopsis.

Low phosphate (LP) in soil is a common nutrient stress that severely restricts agricultural production, but the role, if any, of the major stress phytohormone abscisic acid (ABA) in plant phosphate (Pi) starvation responses remains elusive. Here, we report that LP-induced ABA accumulation promotes Pi uptake in an ABA INSENSITIVE5 (ABI5)-dependent manner in Arabidopsis thaliana. LP significantly activated plant ABA biosynthesis, metabolism, and stress responses, suggesting a role of ABA in the plant response to Pi availability. LP-induced ABA accumulation and expression of two major high-affinity phosphate transporter genes PHOSPHATE TRANSPORTER1;1/1;4 (PHT1;1/1;4) were severely impaired in a mutant lacking BETA-GLUCOSIDASE1 (BG1), which converts conjugated ABA to active ABA, and the mutant had shorter roots and less Pi content than wild-type plants under LP conditions. Moreover, a mutant of ABI5, which encodes a central transcription factor in ABA signaling, also exhibited suppressed root elongation and had reduced Pi content under LP conditions. ABI5 facilitated Pi acquisition by activating the expression of PHT1;1 by directly binding to its promoter, while overexpression of PHT1;1 completely rescued its Pi content under LP conditions. Together, our findings illustrate a molecular mechanism by which ABA positively modulates phosphate acquisition through ABI5 in the Arabidopsis response to phosphate deficiency.

Anti-inflammatory and analgesic effect of Forsythiaside B on complete Freund's adjuvant-induced inflammatory pain in mice.

Chronic pain is frequently reported in clinical practice. Therefore, it is important to identify effective therapy to relieve pain. In this work, we selected Forsythoside B (FB), a phenylethanoid glycoside isolated from Forsythia suspensa (Thunb.) Vahl, to evaluate its effect in modulating inflammatory pain induced by complete Freund's adjuvant (CFA) and the involved mechanisms. We discovered that FB could attenuate inflammatory pain triggered by CFA injection and exert anti-anxiety effects. In detail, proinflammatory cytokines, consisting of IL-6 and TNF-α, were decreased after FB administration in the CFA-injected mice. Furthermore, the FB application ameliorated the activation of ionized calcium-binding adaptor molecule 1 (Iba-1) and glial fibrillary acidic protein (GFAP), the microglia and astrocytes markers respectively. Therefore, our findings indicate that FB could be a promising treatment for chronic inflammatory pain.

Palaeobotanical evidence reveals the living conditions of Miocene Lufengpithecus in East Asia.

BACKGROUND: Understanding the relationship between human evolution and environmental changes is the key to lifting the veil on human origin. The hypothesis that environmental changes triggered the divergence of humans from apes (ca. 9.3-6.5 million years ago, Ma) has been poorly tested because of limited continuous environmental data from fossil localities. Lufengpithecus (12.5-6.0 Ma) found on the southeastern margin of the Tibetan Plateau (SEMTP) across the ape-human split provides a good chance for testing this hypothesis. RESULTS: Here, we reconstructed the habitats of L. keiyuanensis (12.5-11.6 Ma) with comprehensive vegetation, climate, and potential food web data by palaeobotanical evidence, together with other multidisciplinary data and partly tested the environment-driven hypothesis by revealing the living conditions of Lufengpithecus. CONCLUSION: A detailed comparison of hominoids on different continents reveals their behaviour and fate divergence across the ape-human split against the background of global climate change, i.e., the stable living conditions of SEMTP not only provided a so-called 'refuge' for arboreal Lufengpithecus but also acted as a 'double-edged sword', preventing their further evolution while vegetation shifts in East Africa probably stimulated the emergence of human bipedalism, and the intense climatic changes in Europe possibly prevented those hominoids from surviving that time interval. Our findings provide interesting insight into the environmental impacts on the behavioural evolution of hominoids.

Lyotropic Lamellar Nanostructures Enabled High-Voltage Windows, Efficient Charge Transport, and Thermally Safe Solid-State Electrolytes for Lithium-Ion Batteries.

Developing electrolytes combining solid-like instinct stability and liquid-like conducting performance will be satisfactory for efficient and durable Li-ion batteries. Herein lamellar lyotropic liquid crystals (LLCs) demonstrate high-voltage windows, efficient charge transport, and inherent thermal safety as solid-state electrolytes in lithium-ion batteries. Lamellar LLCs are simply prepared by nanosegregation of [C16 Mim][BF4 ] and LiBF4 /Propylene carbonate (PC) liquid solutions, which induce lamellar assembly of the liquids as dynamic conducting pathways. Broadened liquid conducting pathways will boost the conducting performance of the LLC electrolytes. The lyotropic lamellar nanostructures enable liquid-like ion conductivity of the LLC electrolytes at ambient temperatures, as well as provide solid-like stability for the electrolytes to resist high voltage and flammability overwhelming to LiBF4 /PC liquid electrolytes. Despite minor consumption of PC solvents (34.5 wt.%), the lamellar electrolytes show energy conversion efficiency comparable to the liquid electrolytes (PC wt. 92.8%) in Li/LiFePO4 batteries under ambient temperatures even at a 2 C current density, and exhibit attractively robust stability after 200th cyclic charge/discharge even under 60 °C. The work demonstrates LLC electrolytes have great potential to supersede traditional liquid electrolytes for efficient and durable Lithium-ion (Li-ion) batteries.

CycC1;1 negatively modulates ABA signaling by interacting with and inhibiting ABI5 during seed germination.

Regulation of seed germination is important for plant survival and propagation. ABSCISIC ACID (ABA) INSENSITIVE5 (ABI5), the central transcription factor in the ABA signaling pathway, plays a fundamental role in the regulation of ABA-responsive gene expression during seed germination; however, how ABI5 transcriptional activation activity is regulated remains to be elucidated. Here, we report that C-type Cyclin1;1 (CycC1;1) is an ABI5-interacting partner affecting the ABA response and seed germination in Arabidopsis (Arabidopsis thaliana). The CycC1;1 loss-of-function mutant is hypersensitive to ABA, and this phenotype was rescued by mutation of ABI5. Moreover, CycC1;1 suppresses ABI5 transcriptional activation activity for ABI5-targeted genes including ABI5 itself by occupying their promoters and disrupting RNA polymerase II recruitment; thus the cycc1;1 mutant shows increased expression of ABI5 and genes downstream of ABI5. Furthermore, ABA reduces the interaction between CycC1;1 and ABI5, while phospho-mimic but not phospho-dead mutation of serine-42 in ABI5 abolishes CycC1;1 interaction with ABI5 and relieves CycC1;1 inhibition of ABI5-mediated transcriptional activation of downstream target genes. Together, our study illustrates that CycC1;1 negatively modulates the ABA response by interacting with and inhibiting ABI5, while ABA relieves the CycC1;1 interaction with and inhibition of ABI5 to activate ABI5 activity for the ABA response, thereby inhibiting seed germination.

Plasma transfusion-transmission of Zika virus in mice and macaques.

BACKGROUND: Zika virus (ZIKV) epidemics with infections in pregnant women are associated with severe neurological disease in newborns. Although an arbovirus, ZIKV is also blood transfusion-transmitted (TT). Greater knowledge of the efficiency of ZIKV TT would aid decisions on testing and pathogen reduction technologies (PRT). STUDY DESIGN AND METHODS: Plasma units from ZIKV RNA-reactive blood donors were used to study infectivity in vitro, in mice, and in macaques. Furthermore, plasma units were subjected to PRT using amotosalen/ultraviolet light A (A/UVA) before transfusion. RESULTS: In vitro infectivity of ZIKV RNA-reactive plasma varied between 100 and 1000 international units (IU) of ZIKV RNA. Immunodeficient mice were more sensitive with as low as 32 IU sufficient to infect 50% of mice. 50-5500 IU of RNA led to TT in macaques using dose escalation of three different RNA-positive, seronegative plasma units. In contrast, RNA-reactive units collected postseroconversion were not infectious in macaques, even at a dose of 9 million IU RNA. After A/UVA PRT, transfusion of plasma containing up to 18 million IU was no longer infectious in vitro and did not result in ZIKV TT in macaques. CONCLUSION: Significant risks of ZIKV TT are likely confined to a relatively short viremic window before seroconversion, and that sensitive nucleic acid amplification testing likely identifies the majority of infectious plasma. PRT was demonstrated to be effective at preventing ZIKV TT. Considering that there is no approved ZIKV vaccine, these data are relevant to mitigate the risk of TT during the future ZIKV outbreaks.

A 6-month prognostic nomogram incorporating hemoglobin level for intracerebral hemorrhage in younger adults.

OBJECTIVE: Intracerebral hemorrhage (ICH) is the second most common subtype of stroke, with high mortality and morbidity. At present, there are no effective 6-month prognostic markers, particularly for younger patients. The aim of this research was to construct a new valuable prognostic nomogram model incorporating haemoglobin levels for adult patients with ICH. METHODS: Patients aged between 18 and 50 presenting with intracerebral haemorrhage at the Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology between January 1st 2012 and December 31st 2018 were included in this retrospective study. Independent factors of prognosis were identified by univariate and multivariate logistic regression analyses, and a new nomogram model was constructed and validated. The clinical value of the nomogram model was subsequently explored utilizing decision curve analysis and clinical impact curves. RESULTS: In total, 565 patients were enrolled in this study, 117 (20.7%) of whom developed an unfavourable prognosis. Infratentorial lesion (adjusted odds ratio [aOR] = 3.708, 95% confidence interval [CI], 1.490-9.227; P = 0.005) was the most significant unfavourable outcome. Age ([aOR] = 1.054; 95% CI, 1.014-1.096; P = 0.008), hematoma volume (aOR = 1.014, 95% CI, 1.002-1.027; P = 0.024), haemoglobin (aOR = 0.981, 95% CI, 0.969-0.993; P = 0.002), blood glucose (aOR = 1.135, 95% CI, 1.037-1.241; P = 0.005) and NIHSS (aOR = 1.105, 95% CI, 1.069-1.141; P < 0.001) were independent risk factors. Based on these 6 factors, the nomogram can be employed to predict early functional prognosis with high accuracy (AUC 0.791). Decision curve analysis and clinical impact curves showed an increased net benefit for utilizing the nomogram. CONCLUSION: The haemoglobin level at admission may be an easily overlooked factor in clinical work. This new nomogram model could be a promising and convenient tool to predict the early functional prognosis of adults with ICH. More prospective multicentre studies are needed to validate these findings.