Transcription factor OsSNAC1 positively regulates nitrate transporter gene expression in rice.

Nitrogen (N) is a critical factor for crop growth and yield. Improving N use efficiency (NUE) in agricultural systems is crucial for sustainable food production. However, the underlying regulation of N uptake and utilization in crops is not well known. Here, we identified OsSNAC1 (stress-responsive NAC 1) as an upstream regulator of OsNRT2.1 (nitrate transporter 2.1) in rice (Oryza sativa) by yeast 1-hybridization screening. OsSNAC1 was mainly expressed in roots and shoots and induced by N deficiency. We observed similar expression patterns of OsSNAC1, OsNRT2.1/2.2, and OsNRT1.1A/B in response to NO3- supply. Overexpression of OsSNAC1 resulted in increased concentrations of free NO3- in roots and shoots, as well as higher N uptake, higher NUE, and N use index (NUI) in rice plants, which conferred increased plant biomass and grain yield. On the contrary, mutations in OsSNAC1 resulted in decreased N uptake and lower NUI, which inhibited plant growth and yield. OsSNAC1 overexpression significantly upregulated OsNRT2.1/2.2 and OsNRT1.1A/B expression, while the mutation in OsSNAC1 significantly downregulated OsNRT2.1/2.2 and OsNRT1.1A/B expression. Y1H, transient co-expression, and ChIP assays showed OsSNAC1 directly binds to the upstream promoter regions of OsNRT2.1/2.2 and OsNRT1.1A/1.1B. In conclusion, we identified a NAC transcription factor in rice, OsSNAC1, with a positive role in regulating NO3- uptake through direct binding to the upstream promoter regions of OsNRT2.1/2.2 and OsNRT1.1A/1.1B and activating their expression. Our results provide a potential genetic approach for improving crop NUE in agriculture.

Real-time quantum error correction beyond break-even.

The ambition of harnessing the quantum for computation is at odds with the fundamental phenomenon of decoherence. The purpose of quantum error correction (QEC) is to counteract the natural tendency of a complex system to decohere. This cooperative process, which requires participation of multiple quantum and classical components, creates a special type of dissipation that removes the entropy caused by the errors faster than the rate at which these errors corrupt the stored quantum information. Previous experimental attempts to engineer such a process1-7 faced the generation of an excessive number of errors that overwhelmed the error-correcting capability of the process itself. Whether it is practically possible to utilize QEC for extending quantum coherence thus remains an open question. Here we answer it by demonstrating a fully stabilized and error-corrected logical qubit whose quantum coherence is substantially longer than that of all the imperfect quantum components involved in the QEC process, beating the best of them with a coherence gain of G = 2.27 ± 0.07. We achieve this performance by combining innovations in several domains including the fabrication of superconducting quantum circuits and model-free reinforcement learning.

Serum total bilirubin and long-term prognosis of patients with new-onset non-ST elevation myocardial infarction: a cohort study.

BACKGROUND: The potential prognostic role of total bilirubin (TBIL) in patients with new-onset non-ST elevation myocardial infarction (NSTEMI) is not fully understood. This study aims to evaluate the potential predictive value of TBIL for long-term prognosis in patients with new-onset NSTEMI. METHODS: Patients with new-onset NSTEMI that underwent emergency coronary angiography in our department from June 2015 to March 2020 were included. Baseline TBIL was measured at admission. SYNTAX scores were used to indicate the severity of coronary lesions. The association between TBIL and SYNTAX scores was analyzed using multivariate logistic regression. The patients were followed for the incidence of major adverse cardiac and cerebrovascular events (MACCEs). The association between TBIL and MACCEs was analyzed using Kaplan-Meier survival methods. RESULTS: In total 327 patients were included in this study. Patients were divided according to tertiles of TBIL (first tertile < 10.23 µmol/L, n = 109; second tertile 10.23-14.30 µmol/L, n = 109; and third tertile ≥ 14.30 µmol/L, n = 109). TBIL was independently associated with the severity of coronary lesions in patients with NSTEMI, with an adjusted odds ratio (OR) and 95% confidence interval (CI) for the third tertile and the second tertile compared with the first tertile of TBIL of 2.259 (1.197-4.263) and 2.167 (1.157-4.059), respectively (both p < 0.05). After a mean follow-up of 30.33 months, MACCE had occurred in 57 patients. TBIL was independently associated with the increased risk of MACCEs, with an adjusted hazard ratio (HR) and 95% CI for the third tertile and the second tertile compared with the first tertile of TBIL of 2.737 (1.161-6.450) and 3.272 (1.408-7.607), respectively (both p < 0.05). CONCLUSIONS: Higher myocardial infarction admission TBIL might independently predict poor prognosis in patients with NSTEMI.

MZF1 mediates oncogene-induced senescence by promoting the transcription of p16INK4A.

Oncogene induced senescence is a tumor suppressing defense mechanism, in which the cell cycle-dependent protein kinase (CDK) inhibitor p16INK4A (encoded by the CDKN2A gene) plays a key role. We previously reported that a transcriptional co-activator chromodomain helicase DNA binding protein 7 (CHD7) mediates oncogenic ras-induced senescence by inducing transcription of the p16INK4A gene. In the current study, we identified myeloid zinc finger 1 (MZF1) as the transcriptional factor that recruits CHD7 to the p16INK4A promoter, where it mediates oncogenic ras-induced p16INK4A transcription and senescence through CHD7, in primary human cells from multiple origins. Moreover, the expression of MZF1 is induced by oncogenic ras in senescent cells through the c-Jun and Ets1 transcriptional factors upon their activation by the Ras-Raf-1-MEK-ERK signaling pathway. In non-small cell lung cancer (NSCLC) and pancreatic adenocarcinoma (PAAD) where activating ras mutations occur frequently, reduced MZF1 expression is observed in tumors, as compared to corresponding normal tissues, and correlates with poor patient survival. Analysis of single cell RNA-sequencing data from PAAD patients revealed that among the tumor cells with normal RB expression levels, those with reduced levels of MZF1 are more likely to express lower p16INK4A levels. These findings have identified novel signaling components in the pathway that mediates induction of the p16INK4A tumor suppressor and the senescence response, and suggested that MZF1 is a potential tumor suppressor in at least some cancer types, the loss of which contributes to the inactivation of the p16INK4A/RB pathway and disruption of senescence in tumor cells with intact RB.

Size-dependent influence of NOx on the growth rates of organic aerosol particles.

Atmospheric new-particle formation (NPF) affects climate by contributing to a large fraction of the cloud condensation nuclei (CCN). Highly oxygenated organic molecules (HOMs) drive the early particle growth and therefore substantially influence the survival of newly formed particles to CCN. Nitrogen oxide (NOx) is known to suppress the NPF driven by HOMs, but the underlying mechanism remains largely unclear. Here, we examine the response of particle growth to the changes of HOM formation caused by NOx. We show that NOx suppresses particle growth in general, but the suppression is rather nonuniform and size dependent, which can be quantitatively explained by the shifted HOM volatility after adding NOx. By illustrating how NOx affects the early growth of new particles, a critical step of CCN formation, our results help provide a refined assessment of the potential climatic effects caused by the diverse changes of NOx level in forest regions around the globe.

[Implications of EET in renal ischemia/reperfusion by regulating NLRP3 expression and pyroptosis].

Objective: To investigate the mechanism of epoxyeicosatrienoic acids (EET) on renal ischemia/reperfusion (I/R). Methods: Thirty 10-week male C57BL6 mice were randomly divided into five groups: sham goup, I/R group, I/R with EET group, I/R with toll-like receptor 4 (TLR4) inhibitor (TAK242) group, I/R with EET and TAK242 group. Blood urea nitrogen (BUN) and serum creatinine (Scr) as well as renal pathological changes were observed 24 h after reperfusion. The protein expression of NOD-like receptor pyrin domain containing 3 (NLRP3), cysteinyl aspartate specific proteinase 1 (caspase-1), interleukin-1ß (IL-1ß), TLR4 and myeloid differentiation factor 88 (MyD88) were evaluated using Western blot. Results: Severe renal tubular epithelial cell injury and decreased renal function [BUN:(10.37±0.53) vs (6.70±0.82)mmol/L, t=9.17, P<0.001; Scr: (83.67±3.88) vs (32.50±3.51)µmol/L, t=23.96, P<0.001] occurred in I/R group. Compared to the sham group, the relative expression of NLRP3 (1.54±0.10 vs 0.71±0.05, t=13.14, P<0.001), caspase-1 (2.35±0.05 vs 0.62±0.02, t=73.77, P<0.001), IL-1ß (3.11±0.11 vs 1.26±0.05, t=35.97, P<0.001), TLR4 (1.58±0.03 vs 0.39±0.01, t=86.00, P<0.001), MyD88 (0.94±0.02 vs 0.26±0.01, t=72.61, P<0.001) were significantly increased. Mice pretreated with EET analog featured lower kidney damage and diminished levels of above proteins than I/R group (all P<0.001). Besides, the co-administration of TAK242 and EET analog could even markedly reduced the expression levels of each proteins than those in I/R group and I/R with EET group (all P<0.001). Conclusion: EET exerts a protective effect on attenuating renal I/R injury possibly through inhibiting TLR4 pathway to regulate the activation of NLRP3-induced pyroptosis.

Regorafenib and ginsenoside combination therapy: inhibition of HepG2 cell growth through modulating survivin and caspase-3 gene expression.

BACKGROUND: This work aimed to investigate the inhibitory effect of regorafenib in combination with ginsenoside on the growth of HepG2 liver cancer cells. METHODS: HepG2 liver cancer cells were divided into blank control group, regorafenib single-drug group, ginsenoside single-drug group, and regorafenib/ginsenoside combination group. Cells in the regorafenib single-drug group were treated with regorafenib at 0.25 mg/L, 0.5 mg/L, and 1 mg/L, respectively, while cells in the ginsenoside single-drug group were treated with ginsenoside at 5.0 mg/L, 10.0 mg/L, and 20.0 mg/L, respectively. HepG2 cell proliferation, expression of survivin mRNA, and the apoptotic effector caspase-3 in HepG2 liver cancer cells were assessed. RESULTS: An inhibitory effect on the growth of HepG2 liver cancer cells was observed for both the single-drug therapies and the combination therapy. The synergistic inhibitory effect presented by the combination therapy was dependent on the gradient concentration and treatment time. RT-qPCR results showed that both regorafenib and ginsenoside significantly reduced the expression of survivin mRNA in HepG2 liver cancer cells and the expression level of survivin mRNA in the regorafenib/ginsenoside combination group was much lower than those in the regorafenib single-drug group and ginsenoside single-drug group. The two drugs demonstrated synergistic inhibitory effect when used in combination. CONCLUSIONS: The findings in this study offered a theoretical insight into clinical use of regorafenib and ginsenoside for treatment of liver cancer.

ON THE PRIVACY AND UTILITY PROPERTIES OF TRIPLE MATRIX-MASKING.

Privacy protection is an important requirement in many statistical studies. A recently proposed data collection method, triple matrix-masking, retains exact summary statistics without exposing the raw data at any point in the process. In this paper, we provide theoretical formulation and proofs showing that a modified version of the procedure is strong collection obfuscating: no party in the data collection process is able to gain knowledge of the individual level data, even with some partially masked data information in addition to the publicly published data. This provides a theoretical foundation for the usage of such a procedure to collect masked data that allows exact statistical inference for linear models, while preserving a well-defined notion of privacy protection for each individual participant in the study. This paper fits into a line of work tackling the problem of how to create useful synthetic data without having a trustworthy data aggregator. We achieve this by splitting the trust between two parties, the "masking service provider" and the "data collector."

Two-stage adaptive enrichment design for testing an active factor.

We propose an adaptive enrichment approach to test an active factor, which is a factor whose effect is non-zero in at least one subpopulation. We implement a two-stage play-the-winner design where all subjects in the second stage are enrolled from the subpopulation that has the highest observed effect in the first stage. We recommend a weighted Fisher's combination of the most powerful test for each stage, respectively: the first stage Hotelling's test and the second stage noncentral chi-square test. The test is further extended to cover binary outcomes and time-to-event outcomes.

Impact of prenatal and postnatal maternal environment on nephron endowment, renal function and blood pressure in the Lewis polycystic kidney rat.

Maternal insufficiency during fetal development can have long-lasting effects on the offspring, most notably on nephron endowment. In polycystic kidney disease (PKD), variability in severity of disease is observed and maternal environment may be a modifying factor. In this study, we first established that in a rodent model of PKD, the Lewis polycystic kidney (LPK) rat's nephron numbers are 25% lower compared with wildtype animals. We then investigated the effects of prenatal and postnatal maternal environment on phenotype and nephron number. LPK pups born from and raised by homozygous LPK dams (control) were compared with LPK pups cross-fostered onto heterozygous LPK dams to improve postnatal environment; with LPK pups born from and raised by heterozygous LPK dams to improve both prenatal and postnatal environment and with LPK pups born from and raised by Wistar Kyoto-LPK heterozygous dams to improve both prenatal and postnatal environment on a different genetic background. Improvement in both prenatal and postnatal environment improved postnatal growth, renal function and reduced blood pressure, most notably in animals with different genetic background. Animals with improved postnatal environment only showed improved growth and blood pressure, but to a lesser extent. All intervention groups showed increased nephron number compared with control LPK. In summary, prenatal and postnatal environment had significant effect in delaying progression and reducing severity of PKD, including nephron endowment.

MiR-1298 expression correlates with prognosis and inhibits cell proliferation and invasion of gastric cancer.

OBJECTIVE: To explore the association between miR-1298 expression and clinicopathological factors, prognosis of gastric cancer (GC) patients and biological functions underlying the GC progression. PATIENTS AND METHODS: Expression of miR-1298 was examined by qRT-PCR in GC tissues and cells, the adjacent normal tissues and normal gastric cell line GES-1 cells were used as controls. Association of disease-free survival (DFS) and overall survival (OS) time with miR-1298 expression was analyzed by Kaplan-Meier analysis and log-rank test. Univariate and multivariate analysis were also performed to analyze relative prognostic risk factors of GC patients. Cell proliferation and invasion assays were used to examine cell proliferation and invasion capacities in vitro. The relative protein expression was analyzed by Western blot analysis. RESULTS: MiR-1298 expression was lower in GC tissues and cells, compared to adjacent normal tissues and GES-1 cells, respectively. Lower miR-1298 expression levels were associated with lymph node metastasis and TNM stage. Kaplan-Meier analysis showed that lower miR-1298 expression predicted poor DFS and OS of GC patients. Furthermore, we demonstrated that lymph node metastasis, TNM stage, and lower miR-1298 expression were independent risk factors for DFS and OS in GC patients. In vitro, miR-1298 overexpression inhibited cell proliferation and invasion abilities. Additionally, our results revealed that miR-1298 overexpression suppressed PI3K/AKT signaling pathway in GC cells. CONCLUSIONS: Our evidence indicated that miR-1298 may provide a specifically promising target for therapy of GC patients.

Characterization of oligotrophic AnAOB culture: morphological, physiological, and ecological features.

Anaerobic ammonium oxidation (anammox) process is regarded as a promising nitrogen removal technology to treat ammonium wastewaters in a wide concentration range. Oligotrophic anaerobic ammonia oxidation bacteria (O-AnAOB) culture has been successfully achieved from a new anammox system to treat superlow ammonium concentration wastewaters. In this work, the O-AnAOB culture was compared with the eutrophic AnAOB (E-AnAOB) culture to reveal its physiological, morphological, and ecological features. Results showed that the specific anammox activity (SAA) of O-AnAOB culture was 0.07 kgN/(kgVSS·d) with the nitrogen removal rate (NRR) of 0.20 kgN/ (m3 d) in the reactor, while the SAA of E-AnAOB culture was 2.11 kgN/(kgVSS·d) with the NRR of 11.10 kgN/(m3 d). The hzs gene transcription levels (hzs-mRNA) of O-AnAOB and E-AnAOB cultures were 1.32 × 109 copies/gVSS and 1.51 × 1010 copies/gVSS, respectively. Morphologically, the O-AnAOB culture took on the unique brown color rather than the typical red color of E-AnAOB. The O-AnAOB cells lived in a disperse pattern in the culture. The cells were seriously deformed with deep craters on the cell wall. The size of anammoxsome and paryphoplasm compartments inside the O-AnAOB cells was smaller than that inside the E-AnAOB cells. Ecologically, the O-AnAOB culture had special microbial community with a higher bacterial diversity than the E-AnAOB. The most dominant genera in O-AnAOB were Anaerolineaceae (33.7%, fermentative bacteria), Candidatus Kuenenia (17.4%, anammox bacteria), and Nitrospira (7.3%, nitrite oxidizing bacteria). This study provided an insight into the new anammox process for deep nitrogen removal from wastewaters.

Atmospheric gas-to-particle conversion: why NPF events are observed in megacities?

In terms of the global aerosol particle number load, atmospheric new particle formation (NPF) dominates over primary emissions. The key for quantifying the importance of atmospheric NPF is to understand how gas-to-particle conversion (GTP) takes place at sizes below a few nanometers in particle diameter in different environments, and how this nano-GTP affects the survival of small clusters into larger sizes. The survival probability of growing clusters is tied closely to the competition between their growth and scavenging by pre-existing aerosol particles, and the key parameter in this respect is the ratio between the condensation sink (CS) and the cluster growth rate (GR). Here we define their ratio as a dimensionless survival parameter, P, as P = (CS/10-4 s-1)/(GR/nm h-1). Theoretical arguments and observations in clean and moderately-polluted conditions indicate that P needs to be smaller than about 50 for a notable NPF to take place. However, the existing literature shows that in China, NPF occurs frequently in megacities such as in Beijing, Nanjing and Shanghai, and our analysis shows that the calculated values of P are even larger than 200 in these cases. By combining direct observations and conceptual modelling, we explore the variability of the survival parameter P in different environments and probe the reasons for NPF occurrence under highly-polluted conditions.

Genome-wide analysis of TCP family in tobacco.

The TCP family is a transcription factor family, members of which are extensively involved in plant growth and development as well as in signal transduction in the response against many physiological and biochemical stimuli. In the present study, 61 TCP genes were identified in tobacco (Nicotiana tabacum) genome. Bioinformatic methods were employed for predicting and analyzing the gene structure, gene expression, phylogenetic analysis, and conserved domains of TCP proteins in tobacco. The 61 NtTCP genes were divided into three diverse groups, based on the division of TCP genes in tomato and Arabidopsis, and the results of the conserved domain and sequence analyses further confirmed the classification of the NtTCP genes. The expression pattern of NtTCP also demonstrated that majority of these genes play important roles in all the tissues, while some special genes exercise their functions only in specific tissues. In brief, the comprehensive and thorough study of the TCP family in other plants provides sufficient resources for studying the structure and functions of TCPs in tobacco.

Enhanced air pollution via aerosol-boundary layer feedback in China.

Severe air pollution episodes have been frequent in China during the recent years. While high emissions are the primary reason for increasing pollutant concentrations, the ultimate cause for the most severe pollution episodes has remained unclear. Here we show that a high concentration of particulate matter (PM) will enhance the stability of an urban boundary layer, which in turn decreases the boundary layer height and consequently cause further increases in PM concentrations. We estimate the strength of this positive feedback mechanism by combining a new theoretical framework with ambient observations. We show that the feedback remains moderate at fine PM concentrations lower than about 200 µg m(-3), but that it becomes increasingly effective at higher PM loadings resulting from the combined effect of high surface PM emissions and massive secondary PM production within the boundary layer. Our analysis explains why air pollution episodes are particularly serious and severe in megacities and during the days when synoptic weather conditions stay constant.

Effects of inorganic salts on denitrifying granular sludge: The acute toxicity and working mechanisms.

It is highly significant to investigate the toxicity of inorganic salts to denitrifying granular sludge (DGS) and its mechanism since the application of high-rate denitrification is seriously limited in the treatment of saline nitrogen-rich wastewaters. The batch experiments showed that the IC50 (half inhibition concentration) and LC50 (half lethal concentration) of NaCl, Na2SO4 and Na3PO4 on DGS were 11.46, 21.72, 7.46 g/L and 77.35, 100.58, 67.92 g/L respectively. Based on the analysis of specific denitrifying activity, the live cell percentage, the cell structure, and the DNA leakage, the toxicity of low salinity was ascribed to the inhibition of denitrifying activity and the toxicity of high salinity was ascribed to both the inhibition of denitrifying activity and the lethality of denitrifying cell.

Homology-based analysis of the GRAS gene family in tobacco.

Members of the GRAS gene family are important transcriptional regulators. In this study, 21 GRAS genes were identified from tobacco, and were classified into eight subgroups according to the classification of Arabidopsis thaliana. Here, we provide a preliminary overview of this gene family in tobacco, describing the gene structure, gene expression, protein motif organization, phylogenetic analysis, and comparative analysis in tobacco, Arabidopsis, and rice. Using the sequences of 21 GRAS genes in Arabidopsis to search against the American tobacco genome database, 21 homologous GRAS genes in tobacco were identified. Sequence analysis indicates that these GRAS proteins have five conserved domains, which is consistent with their counterparts in other plants. Phylogenetic analyses divided the GRAS gene family into eight subgroups, each of which has distinct conserved domains and biological functions. Furthermore, the expression pattern of these 21 GRAS genes reveals that most are expressed in all six tissues studied; however, some have tissue specificity. Taken together, this comprehensive analysis will provide a rich resource to assist in the study of GRAS protein functions in tobacco.

Computed tomography-guided iodine-125 interstitial implantation as an alternative treatment option for lung cancer.

PURPOSE: The aim was to evaluate the safety, feasibility and efficacy of computed tomography (CT)-guided percutaneous interstitial brachytherapy using radioactive iodine-125 ( 125 I) seeds for the treatment of lung cancer. MATERIALS AND METHODS: Included in this study were 45 male and 35 female patients aged 52-85 years (mean 72-year) who were diagnosed with lung cancer. Of the 80 cases of lung cancer, 38 were pathologically confirmed as squamous cell carcinoma, 29 as adenocarcinoma, 2 as small cell lung cancer, and 11 as metastatic lung cancer. Percutaneous interstitial implantation of radioactive 125 I seeds was performed under CT guidance. The treatment planning system was used to reconstruct three-dimensional images of the tumor to determine the quantity and distribution of 125 I seeds to be implanted. Under CT guidance, 125 I seeds were embedded into the tumor, with the matched peripheral dose set at 100-130 Gy. Follow-up CT scan was done in 2-month to explore the treatment efficacy. RESULTS: The procedure was successful in all patients. No major procedure-associated death occurred. The duration of follow-up was 6-month. Complete response (CR) was seen in 38 cases (47.5%), partial response (PR) in 27 cases (33.75%), stable disease (SD) in 10 cases (12.5%), and progressive disease in 5 cases (6.25%), with a local control rate (CR + PR + SD) of 93.75%. The 2-, 4- and 6-month overall response rate (CR + PR) was 78%, 83% and 81%, respectively. CONCLUSION: Implantation of CT-guided 125 I seeds is a safe and effective alternative option for the treatment of lung cancer.

Optimizing the high-resolution manometry (HRM) study protocol.

BACKGROUND: Intolerance of the esophageal manometry catheter may prolong high-resolution manometry (HRM) studies and increase patient distress. We assessed the impact of obtaining the landmark phase at the end of the study when the patient has acclimatized to the HRM catheter. METHODS: 366 patients (mean age 55.4 ± 0.8 years, 62.0% female) undergoing esophageal HRM over a 1-year period were studied. The standard protocol consisted of the landmark phase, 10 5 mL water swallows 20-30 s apart, and multiple rapid swallows where 4-6 2 mL swallows were administered in rapid succession. The modified protocol consisted of the landmark phase at the end of the study after test swallows. Study duration, technical characteristics, indications, and motor findings were compared between standard and modified protocols. KEY RESULTS: Of the 366 patients, 89.6% underwent the standard protocol (study duration 12.9 ± 0.3 min). In 10.4% with poor catheter tolerance undergoing the modified protocol, study duration was significantly longer (15.6 ± 1.0 min, p = 0.004) despite similar duration of study maneuvers. Only elevated upper esophageal sphincter basal pressures at the beginning of the study segregated modified protocol patients. The 95th percentile time to landmark phase in the standard protocol patients was 6.1 min; as many as 31.4% of modified protocol patients could not obtain their first study maneuver within this period (p = 0.0003). Interpretation was not impacted by shifting the landmark phase to the end of the study. CONCLUSIONS & INFERENCES: Modification of the HRM study protocol with the landmark phase obtained at the end of the study optimizes study duration without compromising quality.