Kinetic and Thermodynamic Control of Supramolecular Aggregation of Near Infrared Pyrrolopyrrole Cyanine Fluorophores Confined in Colloidal Nanoparticles.

Control of the intermolecular aggregation of organic π-conjugated molecules as chromophores is crucial for tuning their physical properties such as light absorption/emission, and energy and charge transfer. Lots of advances have been achieved in control of intermolecular aggregation of organic chromophores in solid states where an indefinitely large number of molecules are involved. However, much less understanding has been gained at a mesoscale of aggregates formed by well-defined organization of a deterministic number of chromophores, which has been realized in natural photosynthetic systems but still remains rare in manmade materials. Here, we report both the kinetic and the thermodynamic control of the supramolecular aggregation of a near-infrared cyanine dye, PPcy, and its derivatives confined in colloidal nanoparticles stabilized by surfactants in aqueous media. Our results demonstrate that both the aggregation number, the aggregation state and the optical properties of the PPcy chromophores are controllable through optimization of the alkyl and polymer chains tethered from PPcy, the effective concentration of the chromophore inside each particle, and the surfactants utilized to stabilize the colloids in water.

Mussel-Inspired Surface Coating to Stabilize and Functionalize Supramolecular J-Aggregate Nanotubes Composed of Amphiphilic Cyanine Dyes.

We report a mussel-inspired strategy of polydopamine (PDA) coating to stabilize and functionalize J-aggregate nanotubes (NTs) formed by supramolecular self-assembly of an amphiphilic cyanine dye called C8S3 in aqueous media. Optimization of the coating condition by changing the incubation time in a slightly basic media of dopamine with different concentrations leads to conformal wrapping of the PDA layer with controllable thickness on the surface of the NTs. Compared to noncoated pristine C8S3 NTs, these PDA-coated NTs show enhanced stability against dilution, heating, and photobleaching. Moreover, the PDA layer wrapping around the NTs serves as an adhesive for the adsorption of a variety of metal ions and electroless deposition of the metal nanoparticles. Such stabilized and functionalized NT composites may offer a robust synthetic J-aggregate system to mimic the structure and function of light-harvesting complexes and reaction centers in photosynthetic systems.

Comparison of ARIMA model, DNN model and LSTM model in predicting disease burden of occupational pneumoconiosis in Tianjin, China.

BACKGROUND: This study aims to explore appropriate model for predicting the disease burden of pneumoconiosis in Tianjin by comparing the prediction effects of Autoregressive Integrated Moving Average (ARIMA) model, Deep Neural Networks (DNN) model and multivariate Long Short-Term Memory Neural Network (LSTM) models. METHODS: Disability adjusted life year (DALY) was used to evaluate the disease burden of occupational pneumoconiosis. ARIMA model, DNN model and multivariate LSTM model were used to establish prediction model. Three performance evaluation metrics including Root Mean Squared Error (RMSE), Mean Absolute Error (MAE) and Mean Absolute Percentage Error (MAPE) were used to compare the prediction effects of the three models. RESULTS: From 1990 to 2021, there were 10,694 cases of pneumoconiosis patients in Tianjin, resulting in a total of 112,725.52 person-years of DALY. During this period, the annual DALY showed a fluctuating trend, but it had a strong correlation with the number of pneumoconiosis patients, the average age of onset, the average age of receiving dust and the gross industrial product, and had a significant nonlinear relationship with them. The comparison of prediction results showed that the performance of multivariate LSTM model and DNN model is much better than that of traditional ARIMA model. Compared with the DNN model, the multivariate LSTM model performed better in the training set, showing lower RMES (42.30 vs. 380.96), MAE (29.53 vs. 231.20) and MAPE (1.63% vs. 2.93%), but performed less stable than the DNN on the test set, showing slightly higher RMSE (1309.14 vs. 656.44), MAE (886.98 vs. 594.47) and MAPE (36.86% vs. 22.43%). CONCLUSION: The machine learning techniques of DNN and LSTM are an innovative method to accurately and efficiently predict the burden of pneumoconiosis with the simplest data. It has great application prospects in the monitoring and early warning system of occupational disease burden.

Abscisic acid-dependent PMT1 expression regulates salt tolerance by alleviating abscisic acid-mediated reactive oxygen species production in Arabidopsis.

Phosphocholine (PCho) is an intermediate metabolite of nonplastid plant membranes that is essential for salt tolerance. However, how PCho metabolism modulates response to salt stress remains unknown. Here, we characterize the role of phosphoethanolamine N-methyltransferase 1 (PMT1) in salt stress tolerance in Arabidopsis thaliana using a T-DNA insertional mutant, gene-editing alleles, and complemented lines. The pmt1 mutants showed a severe inhibition of root elongation when exposed to salt stress, but exogenous ChoCl or lecithin rescued this defect. pmt1 also displayed altered glycerolipid metabolism under salt stress, suggesting that glycerolipids contribute to salt tolerance. Moreover, pmt1 mutants exhibited altered reactive oxygen species (ROS) accumulation and distribution, reduced cell division activity, and disturbed auxin distribution in the primary root compared with wild-type seedlings. We show that PMT1 expression is induced by salt stress and relies on the abscisic acid (ABA) signaling pathway, as this induction was abolished in the aba2-1 and pyl112458 mutants. However, ABA aggravated the salt sensitivity of the pmt1 mutants by perturbing ROS distribution in the root tip. Taken together, we propose that PMT1 is an important phosphoethanolamine N-methyltransferase participating in root development of primary root elongation under salt stress conditions by balancing ROS production and distribution through ABA signaling.

A NAC-type transcription factor confers aluminium resistance by regulating cell wall-associated receptor kinase 1 and cell wall pectin.

Transcriptional regulation is important for plants to respond to toxic effects of aluminium (Al). However, our current knowledge to these events is confined to a few transcription factors. Here, we functionally characterized a rice bean (Vigna umbellata) NAC-type transcription factor, VuNAR1, in terms of Al stress response. We demonstrated that rice bean VuNAR1 is a nuclear-localized transcriptional activator, whose expression was specifically upregulated by Al in roots but not in shoot. VuNAR1 overexpressing Arabidopsis plants exhibit improved Al resistance via Al exclusion. However, VuNAR1-mediated Al exclusion is independent of the function of known Al-resistant genes. Comparative transcriptomic analysis revealed that VuNAR1 specifically regulates the expression of genes associated with protein phosphorylation and cell wall modification in Arabidopsis. Transient expression assay demonstrated the direct transcriptional activation of cell wall-associated receptor kinase 1 (WAK1) by VuNAR1. Moreover, yeast one-hybrid assays and MEME motif searches identified a new VuNAR1-specific binding motif in the promoter of WAK1. Compared with wild-type Arabidopsis plants, VuNAR1 overexpressing plants have higher WAK1 expression and less pectin content. Taken together, our results suggest that VuNAR1 regulates Al resistance by regulating cell wall pectin metabolism via directly binding to the promoter of WAK1 and induce its expression.

Alleviation by abscisic acid of Al toxicity in rice bean is not associated with citrate efflux but depends on ABI5-mediated signal transduction pathways.

Under conditions of aluminum (Al) toxicity, which severely inhibits root growth in acidic soils, plants rapidly alter their gene expression to optimize physiological fitness for survival. Abscisic acid (ABA) has been suggested as a mediator between Al stress and gene expression, but the underlying mechanisms remain largely unknown. Here, we investigated ABA-mediated Al-stress responses, using integrated physiological and molecular biology approaches. We demonstrate that Al stress caused ABA accumulation in the root apex of rice bean (Vigna umbellata [Thunb.] Ohwi & Ohashi), which positively regulated Al tolerance. However, this was not associated with known Al-tolerance mechanisms. Transcriptomic analysis revealed that nearly one-third of the responsive genes were shared between the Al-stress and ABA treatments. We further identified a transcription factor, ABI5, as being positively involved in Al tolerance. Arabidopsis abi5 mutants displayed increased sensitivity to Al, which was not related to the regulation of AtALMT1 and AtMATE expression. Functional categorization of ABI5-mediated genes revealed the importance of cell wall modification and osmoregulation in Al tolerance, a finding supported by osmotic stress treatment on Al tolerance. Our results suggest that ABA signal transduction pathways provide an additional layer of regulatory control over Al tolerance in plants.

LeSPL-CNR negatively regulates Cd acquisition through repressing nitrate reductase-mediated nitric oxide production in tomato.

MAIN CONCLUSION: An SPL-type transcription factor, LeSPL-CNR, is negatively involved in NO production by modulating SlNR expression and nitrate reductase activity, which contributes to Cd tolerance. Cadmium (Cd) is a highly toxic pollutant. Identifying factors affecting Cd accumulation in plants is a prerequisite for minimizing dietary uptake of Cd from crops grown with contaminated soil. Here, we report the involvement of a SQUAMOSA PROMOTER-BINDING PROTEIN-LIKE (SPL) transcription factor LeSPL-CNR in Cd tolerance in tomato (Solanum lycopersicum). In comparison with the wild-type Ailsa Craig (AC) plants, the Colourless non-ripening (Cnr) epimutant displayed increased Cd accumulation and enhanced sensitivity to Cd, which was in well accordance with the repression of LeSPL-CNR expression. Cd stress-induced NO production was inhibited by nitrate reductase (NR) inhibitor, but not NO synthase-like enzyme inhibitor. Expression of LeSPL-CNR was negatively correlated with SlNR expression and the NR activity. We also demonstrated that LeSPL-CNR inhibited the SlNR promoter activity in vivo and bound to SlNR promoter sequence that does not contain a known SBP-binding motif. In addition, expression of an IRON-REGULATED TRANSPORTER1, SlIRT1, was more abundant in Cnr roots than AC roots under Cd stress. LeSPL-CNR may thus provide a molecular mechanism linking Cd stress response to regulation of NR-dependent NO production, which then contributes to Cd uptake via SlIRT1 expression in tomato.

Two citrate transporters coordinately regulate citrate secretion from rice bean root tip under aluminum stress.

Aluminum (Al)-induced organic acid secretion from the root apex is an important Al resistance mechanism. However, it remains unclear how plants fine-tune root organic acid secretion which can contribute significantly to the loss of fixed carbon from the plant. Here, we demonstrate that Al-induced citrate secretion from the rice bean root apex is biphasic, consisting of an early phase with low secretion and a later phase of large citrate secretion. We isolated and characterized VuMATE2 as a possible second citrate transporter in rice bean functioning in tandem with VuMATE1, which we previously identified. The time-dependent kinetics of VuMATE2 expression correlates well with the kinetics of early phase root citrate secretion. Ectopic expression of VuMATE2 in Arabidopsis resulted in increased root citrate secretion and Al resistance. Electrophysiological analysis of Xenopus oocytes expressing VuMATE2 indicated VuMATE2 mediates anion efflux. However, the expression regulation of VuMATE2 differs from VuMATE1. While a protein translation inhibitor suppressed Al-induced VuMATE1 expression, it releases VuMATE2 expression. Yeast one-hybrid assays demonstrated that a previously identified transcription factor, VuSTOP1, interacts with the VuMATE2 promoter at a GGGAGG cis-acting motif. Thus, we demonstrate that plants adapt to Al toxicity by fine-tuning root citrate secretion with two separate root citrate transport systems.

A Formate Dehydrogenase Confers Tolerance to Aluminum and Low pH.

Formate dehydrogenase (FDH) is involved in various higher plant abiotic stress responses. Here, we investigated the role of rice bean (Vigna umbellata) VuFDH in Al and low pH (H(+)) tolerance. Screening of various potential substrates for the VuFDH protein demonstrated that it functions as a formate dehydrogenase. Quantitative reverse transcription-PCR and histochemical analysis showed that the expression of VuFDH is induced in rice bean root tips by Al or H(+) stresses. Fluorescence microscopic observation of VuFDH-GFP in transgenic Arabidopsis plants indicated that VuFDH is localized in the mitochondria. Accumulation of formate is induced by Al and H(+) stress in rice bean root tips, and exogenous application of formate increases internal formate content that results in the inhibition of root elongation and induction of VuFDH expression, suggesting that formate accumulation is involved in both H(+)- and Al-induced root growth inhibition. Over-expression of VuFDH in tobacco (Nicotiana tabacum) results in decreased sensitivity to Al and H(+) stress due to less production of formate in the transgenic tobacco lines under Al and H(+) stresses. Moreover, NtMATE and NtALS3 expression showed no changes versus wild type in these over-expression lines, suggesting that herein known Al-resistant mechanisms are not involved. Thus, the increased Al tolerance of VuFDH over-expression lines is likely attributable to their decreased Al-induced formate production. Taken together, our findings advance understanding of higher plant Al toxicity mechanisms, and suggest a possible new route toward the improvement of plant performance in acidic soils, where Al toxicity and H(+) stress coexist.

An Oxalyl-CoA Synthetase Is Involved in Oxalate Degradation and Aluminum Tolerance.

Acyl Activating Enzyme3 (AAE3) was identified to be involved in the catabolism of oxalate, which is critical for seed development and defense against fungal pathogens. However, the role of AAE3 protein in abiotic stress responses is unknown. Here, we investigated the role of rice bean (Vigna umbellata) VuAAE3 in Al tolerance. Recombinant VuAAE3 protein has specific activity against oxalate, with Km = 121 ± 8.2 µm and Vmax of 7.7 ± 0.88 µmol min-1 mg-1 protein, indicating it functions as an oxalyl-CoA synthetase. VuAAE3-GFP localization suggested that this enzyme is a soluble protein with no specific subcellular localization. Quantitative reverse transcription-PCR and VuAAE3 promoter-GUS reporter analysis showed that the expression induction of VuAAE3 is mainly confined to rice bean root tips. Accumulation of oxalate was induced rapidly by Al stress in rice bean root tips, and exogenous application of oxalate resulted in the inhibition of root elongation and VuAAE3 expression induction, suggesting that oxalate accumulation is involved in Al-induced root growth inhibition. Furthermore, overexpression of VuAAE3 in tobacco (Nicotiana tabacum) resulted in the increase of Al tolerance, which was associated with the decrease of oxalate accumulation. In addition, NtMATE and NtALS3 expression showed no difference between transgenic lines and wild-type plants. Taken together, our results suggest that VuAAE3-dependent turnover of oxalate plays a critical role in Al tolerance mechanisms.

Genome-Wide Transcriptome Analysis Reveals Conserved and Distinct Molecular Mechanisms of Al Resistance in Buckwheat (Fagopyrum esculentum Moench) Leaves.

Being an Al-accumulating crop, buckwheat detoxifies and tolerates Al not only in roots but also in leaves. While much progress has recently been made toward Al toxicity and resistance mechanisms in roots, little is known about the molecular basis responsible for detoxification and tolerance processes in leaves. Here, we carried out transcriptome analysis of buckwheat leaves in response to Al stress (20 µM, 24 h). We obtained 33,931 unigenes with 26,300 unigenes annotated in the NCBI database, and identified 1063 upregulated and 944 downregulated genes under Al stress. Functional category analysis revealed that genes related to protein translation, processing, degradation and metabolism comprised the biological processes most affected by Al, suggesting that buckwheat leaves maintain flexibility under Al stress by rapidly reprogramming their physiology and metabolism. Analysis of genes related to transcription regulation revealed that a large proportion of chromatin-regulation genes are specifically downregulated by Al stress, whereas transcription factor genes are overwhelmingly upregulated. Furthermore, we identified 78 upregulated and 22 downregulated genes that encode transporters. Intriguingly, only a few genes were overlapped with root Al-regulated transporter genes, which include homologs of AtMATE, ALS1, STAR1, ALS3 and a divalent ion symporter. In addition, we identified a subset of genes involved in development, in which genes associated with flowering regulation were important. Based on these data, it is proposed that buckwheat leaves develop conserved and distinct mechanisms to cope with Al toxicity.

Application of Gemstone Spectral Computed Tomography Imaging in the Characterization of Solitary Pulmonary Nodules: Preliminary Result.

OBJECTIVE: This study aimed to observe the value of computed tomography (CT) spectral imaging parameters in the diagnosis of solitary pulmonary nodules, during the contrast-enhanced early phase and late phase. MATERIALS AND METHODS: This study was approved by the institutional review board and written informed consent was obtained from all patients. One hundred thirty-nine patients with solitary pulmonary nodules proved by pathology underwent double-phase enhanced CT scan using gemstone spectral imaging mode on a Discovery CT750 HD, and were divided into an active inflammatory group (43 cases), a malignant group (65 cases), and a tuberculosis group (31 cases). The slope rate was calculated from the spectral curve. Iodine concentrations (ICs) were derived from iodine-based material decomposition CT images and normalized to the IC in the aorta. The Kruskal-Wallis test and Nemenyi test were performed to compare quantitative parameters among the 3 groups or between each of the 2 groups. RESULTS: There were significant differences in the slope rate, IC, and normalized IC (NIC) among the 3 groups. In the active inflammatory group, malignant group, and tuberculosis group, the mean slope rate were 3.03 ± 0.71 (SD), 1.96 ± 0.91, and 1.37 ± 0.43, respectively, during the early phase and 3.28 ± 0.67, 2.24 ± 0.82, and 1.67 ± 0.64, respectively, during the late phase. The ICs were 2.68 mg/mL ± 0.56, 1.65 mg/mL ± 0.76, and 1.10 mg/mL ± 0.34, respectively, during the early phase and 2.79 mg/mL ± 0.57, 1.90 mg/mL ± 0.71, and 1.29 mg/mL ± 0.44, respectively, during the late phase. The NIC were 0.24 ± 0.06, 0.16 ± 0.04, and 0.10 ± 0.04, respectively, during the early phase and 0.57 ± 0.10, 0.43 ± 0.11, and 0.25 ± 0.09, respectively, during the late phase. The mean slope rate, IC, and NIC for the active inflammatory group were significantly higher than these parameters for the malignant group (P < 0.05), and the parameters for malignant group were significantly higher than the tuberculosis group (P < 0.05). CONCLUSIONS: Dual-energy CT gemstone spectral imaging provides a novel method to better characterize pulmonary nodules in double-phase contrast-enhanced scanning.

Physiological and Molecular Analysis of Aluminium-Induced Organic Acid Anion Secretion from Grain Amaranth (Amaranthus hypochondriacus L.) Roots.

Grain amaranth (Amaranthus hypochondriacus L.) is abundant in oxalate and can secrete oxalate under aluminium (Al) stress. However, the features of Al-induced secretion of organic acid anions (OA) and potential genes responsible for OA secretion are poorly understood. Here, Al-induced OA secretion in grain amaranth roots was characterized by ion charomatography and enzymology methods, and suppression subtractive hybridization (SSH) together with quantitative real-time PCR (qRT-PCR) was used to identify up-regulated genes that are potentially involved in OA secretion. The results showed that grain amaranth roots secrete both oxalate and citrate in response to Al stress. The secretion pattern, however, differs between oxalate and citrate. Neither lanthanum chloride (La) nor cadmium chloride (Cd) induced OA secretion. A total of 84 genes were identified as up-regulated by Al, in which six genes were considered as being potentially involved in OA secretion. The expression pattern of a gene belonging to multidrug and toxic compound extrusion (MATE) family, AhMATE1, was in close agreement with that of citrate secretion. The expression of a gene encoding tonoplast dicarboxylate transporter and four genes encoding ATP-binding cassette transporters was differentially regulated by Al stress, but the expression pattern was not correlated well with that of oxalate secretion. Our results not only reveal the secretion pattern of oxalate and citrate from grain amaranth roots under Al stress, but also provide some genetic information that will be useful for further characterization of genes involved in Al toxicity and tolerance mechanisms.

Characterization of an inducible C2 H2 -type zinc finger transcription factor VuSTOP1 in rice bean (Vigna umbellata) reveals differential regulation between low pH and aluminum tolerance mechanisms.

The rice bean (Vigna umbellata) root apex specifically secretes citrate through expression activation of Vigna umbellata Multidrug and Toxic Compound Extrusion 1 (VuMATE1) under aluminum (Al(3+) ) stress. However, the underlying mechanisms regulating VuMATE1 expression remain unknown. We isolated and characterized a gene encoding Sensitive to Proton Rhizotoxicity1 (STOP1)-like protein, VuSTOP1, from rice bean. The role of VuSTOP1 in regulating VuMATE1 expression was investigated using the yeast one-hybrid assay. We characterized the function of VuSTOP1 in Al(3)  (+)  - and H(+) -tolerance using in planta complementation assays. We demonstrated that VuSTOP1 has transactivation potential. We found that VuSTOP1 expression is inducible by Al(3+) and H(+) stress. However, although VuSTOP1 binds to the promoter of VuMATE1, the inconsistent tissue localization patterns of VuSTOP1 and VuMATE1 preclude VuSTOP1 as the major factor regulating VuMATE1 expression. In addition, when a protein translation inhibitor increased expression of VuSTOP1, VuMATE1 expression was inhibited. In planta complementation assay demonstrated that VuSTOP1 could fully restore expression of genes involved in H(+) tolerance, but could only partially restore expression of AtMATE. We conclude that VuSTOP1 plays a major role in H(+) tolerance, but only a minor role in Al(3+) tolerance. The differential transcriptional regulation of VuSTOP1 and VuMATE1 reveals a complex regulatory system controlling VuMATE1 expression.

Water-Induced Shape-Locking Magnetic Robots.

Untethered magnetic soft robots capable of performing adaptive locomotion and shape reconfiguration open up possibilities for various applications owing to their flexibility. However, magnetic soft robots are typically composed of soft materials with fixed modulus, making them unable to exert or withstand substantial forces, which limits the exploration of their new functionalities. Here, water-induced, shape-locking magnetic robots with magnetically controlled shape change and water-induced shape-locking are introduced. The water-induced phase separation enables these robots to undergo a modulus transition from 1.78 MPa in the dry state to 410 MPa after hydration. Moreover, the body material's inherent self-healing property enables the direct assembly of morphing structures and magnetic soft robots with complicated structures and magnetization profiles. These robots can be delivered through magnetic actuation and perform programmed tasks including supporting, blocking, and grasping by on-demand deformation and subsequent water-induced stiffening. Moreover, a water-stiffening magnetic stent is developed, and its precise delivery and water-induced shape-locking are demonstrated in a vascular phantom. The combination of untethered delivery, on-demand shape change, and water-induced stiffening properties makes the proposed magnetic robots promising for biomedical applications.

Maternal exposure to E 551 during pregnancy leads to genome-wide DNA methylation changes and metabolic disorders in the livers of pregnant mice and their fetuses.

The widespread use of nanoparticles in the food industry has raised concerns regarding their potential adverse effects on human health, particularly in vulnerable populations, including pregnant mothers and fetuses. However, studies evaluating the reproductive and developmental toxicity of food-grade nanomaterials are limited. This study investigated the potential risks of prenatal dietary exposure to food-grade silica nanoparticles (E 551) on maternal health and fetal growth using conventional toxicological and epigenetic methods. The results showed that prenatal exposure to a high-dose of E 551 induces fetal resorption. Moreover, E 551 significantly accumulates in maternal and fetal livers, triggering a hepatic inflammatory response. At the epigenetic level, global DNA methylation is markedly altered in the maternal and fetal livers. Genome-wide DNA methylation sequencing revealed affected mCG, mCHG, and mCHH methylation landscapes. Subsequent bioinformatic analysis of the differentially methylated genes suggests that E 551 poses a risk of inducing metabolic disorders in maternal and fetal livers. This is further evidenced by impaired glucose tolerance in pregnant mice and altered expression of key metabolism-related genes and proteins in maternal and fetal livers. Collectively, the results of this study highlighted the importance of epigenetics in characterizing the potential toxicity of maternal exposure to food-grade nanomaterials during pregnancy.

miR-106b-5p protects against drug-induced liver injury by targeting vimentin to stimulate liver regeneration.

Understanding the endogenous mechanism of adaptive response to drug-induced liver injury (arDILI) may discover innovative strategies to manage DILI. To gain mechanistic insight into arDILI, we investigated exosomal miRNAs in the adaptive response to toosendanin-induced liver injury (TILI) of mice. Exosomal miR-106b-5p was identified as a specific regulator of arDILI by comprehensive miRNA profiling. Outstandingly, miR-106b-5p agomir treatment alleviated TILI and other DILI by inhibiting apoptosis and promoting hepatocyte proliferation. Conversely, antagomir treatments had opposite effects, indicating that miR-106b-5p protects mice from liver injury. Injured hepatocytes released miR-106b-5p-enriched exosomes taken up by surrounding hepatocytes. Vim (encodes vimentin) was identified as an important target of miR-106b-5p by dual luciferase reporter and siRNA assays. Furthermore, single-cell RNA-sequencing analysis of toosendanin-injured mouse liver revealed a cluster of Vim + hepatocytes; nonetheless declined following miR-106b-5p cotreatment. More importantly, Vim knockout protected mice from acetaminophen poisoning and TILI. In the clinic, serum miR-106b-5p expression levels correlated with the severity of DILI. Indeed, liver biopsies of clinical cases exposed to different DILI causing drugs revealed marked vimentin expression among harmed hepatocytes, confirming clinical relevance. Together, we report mechanisms of arDILI whereby miR-106b-5p safeguards restorative tissue repair by targeting vimentin.

Estimating the Impacts of Plant Internal Nitrogen Deficit at Key Top Dressing Stages on Corn Productivity and Intercepted Photosynthetic Active Radiation.

Accurate and timely appraisal of plant nitrogen (N) demand is imperative to regulate the canopy structure and corn production. The strength and time of plant N deficit can be quantified by critical N concentration. The study was aimed to analyze nitrogen nutrition index (NNI), nitrogen deficit content (NDC), plant nitrogen productivity (PNP), and a fraction of intercepted photosynthetic active radiation (FIPAR) across different N treatments and to develop NNI-NDC, NNI-PNP, NNI-FIPAR, NDC-PNP, and NDC-FIPAR relationships from V6 to V12 stages of corn to quantify the suitable PNP and FIPAR values under the optimal plant N condition. Four multi-N rates (0, 75, 90, 150, 180, 225, 270, and 300 kg N ha-1) field experiments were conducted with two cultivars of corn in Henan province of China. Results indicated that N fertilization affected yield, plant biomass, plant N content, and leaf area index. The values of NNI and NDC were from 0.54 to 1.28 kg ha-1 and from -28.13 to 21.99 kg ha-1 under the different treatments of N rate, respectively. The NDC and NNI showed significantly negative relationships from V6 to V12 stages. The values of PNP and FIPAR increased gradually with the crop growth process. The PNP values gradually declined while the FIPAR values of every leaf layer increased with the increase of N supply. The NDC-PNP and NNI-FIPAR relationships were significantly positive; however, the relationships between NNI-PNP and NDC-FIPAR were significantly negative during the vegetative period of corn. The coefficient of determination (R 2) based on NNI was better than that on NDC. The FIPAR values were ~0.35, 0.67, and 0.76% at the upper, middle, and bottom of leaf layers, respectively, and PNP values were ~39, 44, and 51 kg kg-1 at V6, V9, and V12 stages, respectively, when NNI and NDC values were equal to 1 and 0 kg ha-1, respectively. This study described the quantitative information about the effect of a plant's internal N deficit on plant N productivity and canopy light intercept. The projected results would assist in predicting the appropriate plant growth status during key N top-dressing stages of corn, which can optimize N application and improve N use efficiency.

Genome-Wide DNA Methylation Alterations and Potential Risk Induced by Subacute and Subchronic Exposure to Food-Grade Nanosilica in Mice.

The intensive application of nanomaterials in the food industry has raised concerns about their potential risks to human health. However, limited data are available on the biological safety of nanomaterials in food, especially at the epigenetic level. This study examined the implications of two types of synthetic amorphous silica (SAS), food-grade precipitated silica (S200) and fumed silica Aerosil 200F (A200F), which are nanorange food additives. After 28-day continuous and intermittent subacute exposure to these SAS via diet, whole-genome methylation levels in mouse peripheral leukocytes and liver were significantly altered in a dose- and SAS type-dependent manner, with minimal toxicity detected by conventional toxicological assessments, especially at a human-relevant dose (HRD). The 84-day continuous subchronic exposure to all doses of S200 and A200F induced liver steatosis where S200 accumulated in the liver even at HRD. Genome-wide DNA methylation sequencing revealed that the differentially methylated regions induced by both SAS were mainly located in the intron, intergenic, and promoter regions after 84-day high-dose continuous exposure. Bioinformatics analysis of differentially methylated genes indicated that exposure to S200 or A200F may lead to lipid metabolism disorders and cancer development. Pathway validation experiments indicated both SAS types as potentially carcinogenic. While S200 inhibited the p53-mediated apoptotic pathway in mouse liver, A200F activated the HRAS-mediated MAPK signaling pathway, which is a key driver of hepatocarcinogenesis. Thus, caution must be paid to the risk of long-term exposure to food-grade SAS, and epigenetic parameters should be included as end points during the risk assessment of food-grade nanomaterials.

Reduning injection and its effective constituent luteoloside protect against sepsis partly via inhibition of HMGB1/TLR4/NF-κB/MAPKs signaling pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Reduning injection (RDN), a popular traditional Chinese medicine, formulated by three herbs (i.e., Artemisia carvifolia Buch.-Ham. ex Roxb., Lonicera japonica Thunb., and Gardenia jasminoides J. Ellis), has been widely used to treat upper respiratory infectious diseases in China. AIM OF THE STUDY: To investigate the protective effect of RDN on both lipopolysaccharides (LPS)- and cecal ligation and puncture (CLP)-induced septic mice. To identify the potentially effective constituent, and to determine its protective effect and underlying mechanism in vivo and in vitro. MATERIALS AND METHODS: Male C57BL/6 mice were used to establish septic model by tail intravenous injection of 4 mg/kg LPS or CLP surgery. After modeling, mice were administered by tail intravenous injection of RDN in the dose of 16 or 8 mL/kg/day. The mortality, histopathology, plasma levels of inflammatory cytokines were evaluated respectively. In addition, we screened the potentially effective substances of RDN against sepsis by detecting the nitric oxide (NO) production in LPS-stimulated Raw 264.7 cells and verified the effect of luteoloside in CLP-induced septic mice subsequently. Finally, the underlying mechanisms of RDN and luteoloside were investigated in the inflammatory model in vitro. RESULTS: Administration of RDN significantly reduced the mortality and increased the survival rate in both LPS- and CLP-induced septic mice. Meanwhile, RDN reduced the release of inflammatory cytokines accompanied by alleviating the organs damage of lung, liver, and kidney in CLP-induced septic mice. Moreover, several components from Gardenia jasminoides J. Ellis extract (ZZ) or Lonicera japonica Thunb and Artemisia carvifolia Buch.-Ham. ex Roxb extract (JQ) as well as the constituents of luteoloside, quercetin, and caffeic acid were screened out to have obvious anti-inflammatory activity, which may be the potentially effective substances of RDN against sepsis. We further verified the protective role of luteoloside in CLP-induced septic mice. In addition, RDN and luteoloside significantly inhibited both the secretion and translocation of mobility group box (HMGB)1, and HMGB1-mediated activation of TLR4/NF-κB/MAPKs signaling pathways. CONCLUSION: RDN and its effective constituent luteoloside exhibited a significant protective effect against sepsis, which were potential candidate drugs for treatment of sepsis. The mechanism of antisepsis partly was related to inhibition of HMGB1/TLR4/NF-κB/MAPKs signaling pathways. The results provide an evidence base for the follow-up clinical application of RDN in treatment of sepsis.