Effects of aripiprazole on prolactin levels and differences in effectiveness in patients with schizophrenia: a post-hoc analysis of the real-world data of a multicenter study.

Objectives: To investigate the effect of aripiprazole on prolactin levels in patients with schizophrenia and analyze whether varying baseline prolactin levels affect the effectiveness and safety of aripiprazole, in a real-life diagnostic and therapeutic setting in a post-hoc analysis. Methods: In this post-hoc analysis, patients with schizophrenia in the acute phase were divided into an elevated-prolactin group and a normal-prolactin group. After 8 weeks of aripiprazole treatment, changes in the proportion of patients with an abnormal prolactin level were analyzed in both groups, and the efficacy and safety of aripiprazole were compared between the two groups. Results: The elevated-prolactin group had more women, a longer duration of disease, and lower Positive and Negative Syndrome Scale (PANSS) total and subscale scores at baseline compared with the normal-prolactin group (all P < 0.05), and there was no significant difference in the proportion of patients with prior use of antipsychotic medication between the two groups. Regardless of previous antipsychotic use, patients in both groups developed hyperprolactinemia (23/168 [13.7%] in those who had taken antipsychotics vs. 43/375 [11.4%] in those who had not). After 8 weeks of aripiprazole treatment, the proportion of patients with abnormal prolactin in the elevated-prolactin group significantly decreased with prolonged treatment (P < 0.001), and aripiprazole had no significant effect on the normal-prolactin group (P = 0.250). Normal-prolactin group showed better efficacy than the elevated-prolactin group, and the differences in efficacy between the two groups was observed from week 4 to the endpoint (all p<0.05). In total, 87.2% (68/78) patients experienced mild to moderate adverse events in the elevated-prolactin group, which was significantly more frequent compared with the normal-prolactin group 71.0% (365/514). Conclusions: In this real-world study, for patients with acute schizophrenia, aripiprazole was effective in lowering the proportion of patients with abnormal prolactin levels, while it had no significant effect on patients with normal baseline prolactin. After adjusting for factors such as sex, age, prior antipsychotic drugs use history and disease severity, effectiveness and safety of aripiprazole in patients with normal baseline prolactin was significantly better than that in patients with elevated baseline prolactin.

An ABC transporter-mediated transport and metabolism of the pesticide bentazone in rice (Oryza sativa L.).

INTRODUCTION: Bentazon (BNTZ) is a selective contact herbicide widely used to control field weeds for crop production. Excessive use of BNTZ leads to its accumulation in soils and crops, becoming an environmental contaminant. Therefore, investigation of the mechanisms for BNTZ detoxification and degradation in crops is fundamentally important to reduce crop contamination and ensure food safety. OBJECTIVES: This study aims to elucidate the mechanism of detoxification and degradation pathways of the BNTZ complex in rice by creating transgenic lines expressing a rice ATP-binding cassette (OsABC) transporter gene through genetic engineering techniques combined with chemical analytical techniques and metabolomics approaches. METHODS: We established the rice transgenic lines overexpressing (OE) a rice OsABC transporter and its knockout lines by CRISPR-Cas9 to characterize the gene function and measured the accumulation of BNTZ residues in rice. The metabolites of BNTZ were characterized by LC/Q-TOF-HRMS/MS (Liquid chromatography/time of flight-high resolution mass spectrometry). RESULTS: Overexpression of OsABC significantly conferred rice resistance to BNTZ toxicity by increasing plant elongation, dry weight, and chlorophyll content, and significantly reducing cell membrane damage and BNTZ accumulation in rice tissues. Six different metabolites and ten conjugates were well defined in chemical structures. The reduced BNTZ levels and degradation products in the grains of the OE lines supported the robust activity of the OsABC gene function. Using UPLC-Q-TOF/MS, we further identified accumulated basic metabolites of various carbohydrates, amino acids, hormones, and flavonoids, and found that these metabolites involved in BNTZ degradation were increased more in OE lines than in wild-type (WT) rice. CONCLUSIONS: Our work demonstrates that the OsABC transporter plays a critical role in regulating the mobility and degradative metabolism of BNTZ in rice, thus revealing a regulatory mechanism underlying rice resistance to BNTZ toxicity and adaptation to the environmental stress.

Childhood maltreatment predicts poor sleep quality in Chinese adults: The influence of coping style tendencies.

BACKGROUND: This longitudinal study assessed the prospective link between childhood maltreatment and sleep quality in adulthood, with a specific focus on examining whether different coping style tendencies influence these associations. METHODS: The baseline sample included 1600 adult participants, with 1140 participants successfully followed up 5 years later. The key variables were measured using the Childhood Trauma Questionnaire (CTQ), Simplified Coping Style Questionnaire (SCSQ), and Pittsburgh Sleep Quality Index (PSQI). Generalized linear mixed models were employed to estimate unstandardized ß estimates and 95 % confidence intervals (95%CIs). Structural equation modeling was used to test the mediation model. RESULTS: Individuals reported childhood maltreatment at baseline were at an increased risk for sleep disturbances at follow-up. Childhood maltreatment negatively predicted the baseline coping style tendency (ß = -0.29, P < 0.001), the baseline coping style tendencies negatively predicted the follow-up sleep quality (ß = -0.10, P < 0.001), and childhood maltreatment positively predicted the follow-up sleep quality (ß = 0.42, P < 0.01). The mediating effect of baseline coping style tendencies between childhood maltreatment and the follow-up sleep quality was significant, with an effect value of 0.03. LIMITATIONS: First, the sample was from a single province (Shandong), which limits the generalizability of the findings. Second, recall bias was unavoidable in this adult sample study. CONCLUSIONS: Developing positive coping strategies is an important way to reduce the risk of sleep problems in adults with a history of childhood maltreatment.

Triple modal aptasensor arrays driven by CHA-mediated DNAzyme for signal-amplified atrazine pesticide accumulation monitoring in agricultural crops.

Developing sensors with high selectivity and sensitivity is of great significance for pesticide analysis in environmental assessment. Herein, a versatile three-way sensor array was designed for the detection of the pesticide atrazine, based on the integration of catalytic hairpin assembly (CHA) amplification and three-mode signal transducers. With atrazine, CHA was triggered to generate abundant G-quadruplex. The produced G-quadruplex hybrid could assemble with thioflavin T (TFT) or hemin to mimic enzyme and induce the fluorescence enhancement by TFT, or the colorimetric increase by the oxidized chromogenic substrate and the naked-eye color change by inhibiting the L-cysteine-mediated aggregation of gold nanoparticles. A distinctive three-mode array was successfully constructed with convenience, on-site accessibility and high sensitivity for enzyme-free practical analysis of atrazine. It is also effective and reliable for analyzing real samples including paddy water, paddy soil and polished rice. The detection limits for atrazine were as low as 7.4 pg/mL by colorimetric observation and 0.25 pg/mL by fluorescent detection. Furthermore, the array was exploited to monitor the residue, distribution and bioaccumulation of atrazine in maize and rice for food security and environmental assessment. Hence, this work presented a versatile example for sensitive and on-site all-in-one pesticide analysis arrays with multiple signal report modes.

High plasma nesfatin-1 level in Chinese adolescents with depression.

Depression is a common psychiatric disorder with high prevalence and mortality rates as well as high risk of serious harm in adolescents that have significant negative impact on families and society. The feeding inhibitor Nesfatin-1 contributes to the regulation of stress and emotion. The purpose of this project was to compare the differences in the levels of Nesfatin-1 between adolescents with depression and healthy adolescents, and verify the association between the levels of Nesfatin-1 and severity of depression in adolescents. Adolescents with depression (n = 61) and healthy adolescents (n = 30) were evaluated. The Hamilton Depression Rating Scale (HAMD-17) was used to classify the adolescents with depression. Thirty-one and thirty-two was assigned to the mild-to-moderate (HAMD-17 ≤ 24) depression group and severe group (HAMD-17 > 24). Plasma Levels of Nesfatin-1 were measured by human ELISA Kit and differences among groups evaluated. Data were analyzed using the statistical software SPSS 23. HAMD-17 score was significantly higher in adolescents with depression than that in the healthy adolescents (P < 0.001). Median plasma Nesfatin-1 levels in adolescents with depression and healthy adolescents differed significantly at 37.3 pg/ml (22.1 pg/ml, 63.6 pg/ml) and 18.1 pg/ml (10.0 pg/ml, 25.7 pg/ml) (p < 0.001). A multivariate logistic regression analysis showed high plasma Nesfatin-1 concentrations were associated with increased risk of depression (OR = 0.914, 95% CI 0.87-0.96, P < 0.001). The receiver operating characteristic curve showed that the area under curve were 0.808 (95% CI 0.722-0.894, P < 0.001). Plasma Nesfatin-1 cut-off point of 32.45 pg/mL showed 59% sensitivity and 100% specificity. Median plasma Nesfatin-1 levels in the severe depression group (n = 30), mild-to-moderate depression group (n = 31), and control group (n = 30) were 53.4 pg/ml (28.2 pg/ml, 149.1 pg/ml), 29.9 pg/ml (14.5 pg/ml, 48.5 pg/ml) and 18.1 pg/ml (10.0 pg/ml, 25.7 pg/ml), and differed significantly among the three groups (P < 0.001). Median plasma level of Nesfatin-1 in males (n = 20) was 38.6 pg/ml (23.5 pg/ml, 70.1 pg/ml), while that in females (n = 41) was 37.3 pg/ml (22.0 pg/ml, 63.6 pg/ml), which was not a significant difference (P > 0.05). Plasma levels of Nesfatin-1 increased with severity of depression in adolescents and may be useful as a biomarker of depression severity. Further studies are needed in future projects.

Hypoxia Primes Human ISCs for Interleukin-Dependent Rescue of Stem Cell Activity.

BACKGROUND AND AIMS: Hypoxia in the intestinal epithelium can be caused by acute ischemic events or chronic inflammation in which immune cell infiltration produces inflammatory hypoxia starving the mucosa of oxygen. The epithelium has the capacity to regenerate after some ischemic and inflammatory conditions suggesting that intestinal stem cells (ISCs) are highly tolerant to acute and chronic hypoxia; however, the impact of hypoxia on human ISC (hISC) function has not been reported. Here we present a new microphysiological system (MPS) to investigate how hypoxia affects hISCs from healthy donors and test the hypothesis that prolonged hypoxia modulates how hISCs respond to inflammation-associated interleukins (ILs). METHODS: hISCs were exposed to <1.0% oxygen in the MPS for 6, 24, 48, and 72 hours. Viability, hypoxia-inducible factor 1a (HIF1a) response, transcriptomics, cell cycle dynamics, and response to cytokines were evaluated in hISCs under hypoxia. HIF stabilizers and inhibitors were screened to evaluate HIF-dependent responses. RESULTS: The MPS enables precise, real-time control and monitoring of oxygen levels at the cell surface. Under hypoxia, hISCs maintain viability until 72 hours and exhibit peak HIF1a at 24 hours. hISC activity was reduced at 24 hours but recovered at 48 hours. Hypoxia induced increases in the proportion of hISCs in G1 and expression changes in 16 IL receptors. Prolyl hydroxylase inhibition failed to reproduce hypoxia-dependent IL-receptor expression patterns. hISC activity increased when treated IL1ß, IL2, IL4, IL6, IL10, IL13, and IL25 and rescued hISC activity caused by 24 hours of hypoxia. CONCLUSIONS: Hypoxia pushes hISCs into a dormant but reversible proliferative state and primes hISCs to respond to a subset of ILs that preserves hISC activity. These findings have important implications for understanding intestinal epithelial regeneration mechanisms caused by inflammatory hypoxia.

An All-Arthroscopic Simple Double 360° Lasso Loop Technique for Supraopectoral Biceps Tenodesis.

In many shoulder joint diseases, there is often a combination of long head biceps tendon（LHBT）pathology. Biceps pathology is one of the main causes of shoulder pain, and it is effectively managed with tenodesis. Biceps tenodesis can be performed in a variety of ways with different fixation and at different locations. This article introduces an all-arthroscopic suprapectoral biceps tenodesis technique with a 2-suture anchor. Double 360° Lasso Loop is used to fix the biceps tendon, and only one puncture of the biceps tendon was required, which caused little damage to the tendon and was not easy for the suture to slip and fail.

Multiple Metabolism Pathways of Bentazone Potentially Regulated by Metabolic Enzymes in Rice.

Bentazone (BNTZ) is a selective and efficient herbicide used in crop production worldwide. However, the persistence of BNTZ residues in the environment has led to their increasing accumulation in farmland and crops, posing a high risk to human health. To evaluate its impact on crop growth and environmental safety, a comprehensive study was conducted on BNTZ toxicity, metabolic mechanism, and resultant pathways in rice. The rice growth was compromised to the treatment with BNTZ at 0.2-0.8 mg/L (529.95-1060.05 g a.i./ha), while the activities of enzymes including SOD, POD, CAT, GST, GT, and CYP450 were elevated under BNTZ stress. A genome-wide RNA-sequencing (RNA-Seq) was performed to dissect the variation of transcriptomes and metabolic mechanisms in rice exposed to BNTZ. The degradative pathways of BNTZ in rice are involved in glycosylation, hydrolysis, acetylation, and conjugation processes catalyzed by the enzymes. Our data provided evidence that helps understand the BNTZ metabolic and detoxic mechanisms.

Detection of Antibiotic Resistance in Feline-Origin ESBL Escherichia coli from Different Areas of China and the Resistance Elimination of Garlic Oil to Cefquinome on ESBL E. coli.

The development of drug-resistance in the opportunistic pathogen Escherichia coli has become a global public health concern. Due to the share of similar flora between pets and their owners, the detection of pet-origin antibiotic-resistant E. coli is necessary. This study aimed to detect the prevalence of feline-origin ESBL E. coli in China and to explore the resistance elimination effect of garlic oil to cefquinome on ESBL E. coli. Cat fecal samples were collected from animal hospitals. The E. coli isolates were separated and purified by indicator media and polymerase chain reaction (PCR). ESBL genes were detected by PCR and Sanger sequencing. The MICs were determined. The synergistic effect of garlic oil and cefquinome against ESBL E. coli was investigated by checkerboard assays, time-kill and growth curves, drug-resistance curves, PI and NPN staining, and a scanning electronic microscope. A total of 80 E. coli strains were isolated from 101 fecal samples. The rate of ESBL E. coli was 52.5% (42/80). The prevailing ESBL genotypes in China were CTX-M-1, CTX-M-14, and TEM-116. In ESBL E. coli, garlic oil increased the susceptibility to cefquinome with FICIs from 0.2 to 0.7 and enhanced the killing effect of cefquinome with membrane destruction. Resistance to cefquinome decreased with treatment of garlic oil after 15 generations. Our study indicates that ESBL E. coli has been detected in cats kept as pets. The sensitivity of ESBL E. coli to cefquinome was enhanced by garlic oil, indicating that garlic oil may be a potential antibiotic enhancer.

An ABCG-type transporter intensifies ametryn catabolism by Phase III reaction mechanism in rice.

Pesticide residues in food crops are one of the seriously environmental contaminants that risk food safety and human health. Understanding the mechanism for pesticide catabolism is critical to develop effective biotechniques for rapid eliminating the residues in food crops. In this study we characterized a novel ABC transporter family gene ABCG52 (PDR18) in regulating rice response to pesticide ametryn (AME) widely used in the farmland. Efficient biodegradation of AME was evaluated by measuring its biotoxicity, accumulation, and metabolites in rice plants. OsPDR18 was localized to the plasma membrane and strongly induced under AME exposure. Transgenic rice overexpressing OsPDR18 (OE) conferred rice resistance and detoxification to AME by increasing chlorophyll contents, improving growth phenotypes, and reducing AME accumulation in plants. The AME concentrations in OE plants were only 71.8-78.1% (shoots) and 75.0-83.3% (roots) of the wild type. Mutation of OsPDR18 by CRISPR/Cas9 protocol led to the compromised growth and enhanced AME accumulation in rice. Five AME metabolites for Phase I and 13 conjugates for Phase II reactions in rice were characterized by HPLC/Q-TOF-HRMS/MS. Relative content analysis revealed that the AME metabolic products in OE plants were significantly reduced compared with wild-type. Importantly, the OE plants accumulated less AME metabolites and conjugates in rice grains, suggesting that OsPDR18 expression may actively facilitate the transport of AME for catabolism. These data unveil a AME catabolic mechanism by which OsPDR18 contributes to the AME detoxification and degradation in rice crops.

Target-Responsive Metal-Organic Framework Nanosystem with Synergetic Sensitive Detection and Controllable Degradation against the Pesticide Triazophos in Contaminated Samples for Environment Assessment and Food Safety.

Developing sensitive practical sensors for monitoring pesticide residues in edible foods and environmental samples is vital for food safety and environmental protection. Enzyme-inhibited biosensors offer effective alternative sensing strategies by using the inherent characteristics of pesticides. To further improve the degradation function of pesticide sensors, here, a target-triggered porphyrin metal-organic framework (MOF)-based nanosystem was designed with the synergetic bifunction of sensitive detection and controllable degradation of the triazophos pesticide. As a result of triazophos-inhibited glutathione consumption, the MOF collapsed and released the ligand porphyrin, leading to the recovery of fluorescence and photosensitization of the free porphyrin. The fluorescence recovery resulted in a sensitive detection limit of 0.6 ng mL-1 for triazophos, which was also applied for the determination of contaminated samples and bioaccumulation in rice. Furthermore, the target-activated photocatalytic ability of porphyrin endowed the system with the ability to effectively generate reactive oxygen species for degrading triazophos with a removal rate of ∼85%, achieving eco-friendly synergetic detection and photodegradation in a controllable way. Therefore, the intelligent multifunctional MOF system demonstrated the potential of programmable systems for jointly controllable tracking and elimination of pesticide residues in the environment and opened a new avenue for designing a precise mechanism for stimulus-triggered degradation of pesticide residues accompanied by sensitive detection for environmental friendliness and food safety.

Associations between frequent nightmares, nightmare distress and depressive symptoms in adolescent psychiatric patients.

BACKGROUND: Nightmares are common in patients with psychiatric disorders. Patients with psychiatric disorders often experience depressive symptoms. Nightmares have been associated with depressive symptoms among adolescents. Previous studies have explored the mediating role of nightmare distress in the relationship between frequent nightmares and depressive symptoms in the general adolescent population. We aimed to explore the associations between frequent nightmares, nightmare distress, and depressive symptoms in Chinese adolescent patients with psychiatric disorders. METHODS: A total of 408 adolescents participated in this study. A self-administered questionnaire was used to measure nightmare frequency, nightmare distress, depressive symptoms, and covariates. Linear regressions and mediation analyses were performed to examine the associations between nightmare frequency, nightmare distress, and depressive symptoms. RESULTS: The mean age of participants was 15.31 ± 1.88 years, and 152 (37.3%) were boys. The prevalence of frequent nightmares in adolescent patients with psychosis was 49.3%. Girls reported more frequent nightmares and had significantly higher scores of depressive symptoms and nightmare distress. Patients with frequent nightmares had higher scores of nightmare distress and depressive symptoms. Frequent nightmares and nightmare distress were significantly associated with depressive symptoms. Nightmare distress had a full mediating effect on the correlation between frequent nightmares and depressive symptoms. CONCLUSIONS: In Chinese adolescent patients with psychiatric disorders, frequent nightmares and nightmare distress were associated with depressive symptoms, whereas the association between frequent nightmares and depressive symptoms was mediated by nightmare distress. Interventions for nightmare distress may be more useful in reducing depressive symptoms in adolescent patients with psychiatric disorders.

Spatial-Temporal Variations in of Soil Conservation Service and Its Influencing Factors under the Background of Ecological Engineering in the Taihang Mountain Area, China.

Soil conservation (SC) plays an important role in maintaining regional land productivity and sustainable development. Ecological engineering (EE) is being implemented in different countries to effectively alleviate the damage to the ecological environment and effectively protect soil and food security. It is important to determine whether or not the SC capacity becomes stronger after the implementation of EE and whether or not EE has a notable impact on SC in different altitude zones. The exploration of the influencing mechanism and identification of the dominate influencing factors in different geographical regions needs to be improved. In this study, the soil conservation services (SCSs) from 1980 to 2020 in the Taihang Mountain area was assessed using the integrated valuation of ecosystem services and trade-offs (InVEST) model, and the spatial and temporal distributions and influencing factors were explored. The results showed the following: (1) the average SCSs exhibited an increasing trend from 1980 to 2020 on the whole, and the rate of increase reached 50.53% during the 41-year period. The rate of increase of the SCSs varied in the different EE implementation regions, and it was significantly higher than that of the entire study area. (2) The spatial distribution of the SCSs was highly heterogeneous, and the high SCS value areas were coincident with the high-altitude areas where forest and grassland occupied a large proportion. The low value areas were mainly located in the hilly zone or some of the basin regions where the proportion of construction land was relatively high. (3) The distribution pattern of the SCSs was the result of multiple factors. The EE intensity had the strongest explanatory power for the SCSs in the hilly zone, explaining 34.63%. The slope was the most critical factor affecting the SCSs in the mid-mountain and sub-alpine zones. The slope and normalized difference vegetation index (NDVI) had the greatest interactions with the other factors in the three altitude zones, especially in the high-altitude regions. The quantitative analysis of the SCSs and the influences of EE and natural factors on the SCSs revealed the heterogeneity in the mountainous areas. These results also provide a scientific basis for the reasonable implementation of EE and sustainable management of SCSs in the Taihang Mountain area.

A leaky human colon model reveals uncoupled apical/basal cytotoxicity in early Clostridioides difficile toxin exposure.

Clostridioides difficile (C. difficile) toxins A (TcdA) and B (TcdB) cause antibiotic-associated colitis in part by disrupting epithelial barrier function. Accurate in vitro models are necessary to detect early toxicity kinetics, investigate disease etiology, and develop preclinical models for new therapies. Properties of cancer cell lines and organoids inherently limit these efforts. We developed adult stem cell-derived monolayers of differentiated human colonic epithelium (hCE) with barrier function, investigated the impact of toxins on apical/basal aspects of monolayers, and evaluated whether a leaky epithelial barrier enhances toxicity. Single-cell RNA-sequencing (scRNAseq) mapped C. difficile-relevant genes to human lineages. Transcriptomics compared hCE to Caco-2, informed timing of in vitro stem cell differentiation, and revealed transcriptional responses to TcdA. Transepithelial electrical resistance (TEER) and fluorescent permeability assays measured cytotoxicity. Contribution of TcdB toxicity was evaluated in a diclofenac-induced leaky gut model. scRNAseq demonstrated broad and variable toxin receptor expression. Absorptive colonocytes in vivo displayed increased toxin receptor, Rho GTPase, and cell junction gene expression. Advanced TcdA toxicity generally decreased cytokine/chemokine and increased tight junction and death receptor genes. Differentiated Caco-2 cells remained immature whereas hCE monolayers were similar to mature colonocytes in vivo. Basal exposure of TcdA/B caused greater toxicity and apoptosis than apical exposure. Apical exposure to toxins was enhanced by diclofenac. Apical/basal toxicities are uncoupled with more rapid onset and increased magnitude postbasal toxin exposure. Leaky junctions enhance toxicity of apical TcdB exposure. hCE monolayers represent a physiologically relevant and sensitive system to evaluate the impact of microbial toxins on gut epithelium.NEW & NOTEWORTHY Novel human colonocyte monolayer cultures, benchmarked by transcriptomics for physiological relevance, detect early cytopathic impacts of Clostridioides difficile toxins TcdA and TcdB. A fluorescent ZO-1 reporter in primary human colonocytes is used to track epithelial barrier disruption in response to TcdA. Basal TcdA/B exposure generally caused more rapid onset and cytotoxicity than apical exposure. Transcriptomics demonstrate changes in tight junction, chemokine, and cytokine receptor gene expression post-TcdA exposure. Diclofenac-induced leaky epithelium enhanced apical exposure toxicity.

Transport and Environmental Risks of Propachlor Within the Soil-Plant-Water Phase as Affected by Dissolved Organic Matter as a Nonionic Surfactant.

Propachlor is a widely used acylaniline herbicide for weeding annual gramineous and dicot plants in farmland. As a toxic agricultural chemical, it is overused in crop production and has become one of the most serious environmental pollutants. Yet, understanding the impact of environmental factors on its behavior in farmland soils is critically important for healthy crop production and food safety. In this study, we characterized the effect of dissolved organic matter (DOM) extracted from rice straw on the mobility behavior of propachlor in farmland soil using comprehensive approaches such as the batch equilibrium experiment, soil thin-layer chromatography, soil column leaching, and wheat bioaccumulation with Triton X-100 (TX-100) as a reference surfactant. The application of DOM at 60 and 120 mg DOC L-1 and TX-100 at 96, 192, and 288 mg L-1 reduced the sorption and increased the desorption of propachlor in soil. Freundlich constant K f values (sorption) of propachlor declined with the expansion of DOM and TX-100 concentrations. The addition of DOM and TX-100 increased the mobility of propachlor and the total concentration of propachlor in the leachate of soil columns. The retention factors (R f) were evaluated in the soil thin-layer chromatography as 0.741 and 0.772 (for DOM) and 0.731, 0.763, and 0.791 (for TX-100), all of which were greater than the control (0.710) under the treatment. The application of DOM or TX-100 reduced root growth (biomass) and increased bioaccumulation of propachlor in the roots and shoots of wheat. The outcome of the study can provide important references for the rational use of propachlor and help agronomic management to minimize pesticide contamination in realistic crop production.

A new microphysiological system shows hypoxia primes human ISCs for interleukin-dependent rescue of stem cell activity.

Background & Aims: Hypoxia in the intestinal epithelium can be caused by acute ischemic events or conditions like Inflammatory Bowel Disease (IBD) where immune cell infiltration produces 'inflammatory hypoxia', a chronic condition that starves the mucosa of oxygen. Epithelial regeneration after ischemia and IBD suggests intestinal stem cells (ISCs) are highly tolerant to acute and chronic hypoxia; however, the impact of acute and chronic hypoxia on human ISC (hISC) properties have not been reported. Here we present a new microphysiological system (MPS) to investigate how hypoxia affects hISCs isolated from healthy human tissues. We then test the hypothesis that some inflammation-associated interleukins protect hISCs during prolonged hypoxia. Methods: hISCs were exposed to <1.0% oxygen in the MPS for 6-, 24-, 48- & 72hrs. Viability, HIF1α response, transcriptomics, cell cycle dynamics, and hISC response to cytokines were evaluated. Results: The novel MPS enables precise, real-time control and monitoring of oxygen levels at the cell surface. Under hypoxia, hISCs remain viable until 72hrs and exhibit peak HIF1α at 24hrs. hISCs lose stem cell activity at 24hrs that recovers at 48hrs of hypoxia. Hypoxia increases the proportion of hISCs in G1 and regulates hISC capacity to respond to multiple inflammatory signals. Hypoxia induces hISCs to upregulate many interleukin receptors and hISCs demonstrate hypoxia-dependent cell cycle regulation and increased organoid forming efficiency when treated with specific interleukins. Conclusions: Hypoxia primes hISCs to respond differently to interleukins than hISCs in normoxia through a transcriptional response. hISCs slow cell cycle progression and increase hISC activity when treated with hypoxia and specific interleukins. These findings have important implications for epithelial regeneration in the gut during inflammatory events.

Acetyltransferase OsACE2 acts as a regulator to reduce the environmental risk of oxyfluorfen to rice production.

The constant use of the pesticide oxyfluorfen (OFF) in farmland contaminates the soil, posing threats to crop growth and human health. To avoid the contamination of food crops with OFF, it is critically important to understand its absorption and degradation mechanisms. In this study, we characterized a new functional locus encoding an acetyltransferase (OsACE2) that can facilitate OFF degradation in rice. OsACE2 was drastically induced by OFF at 0.04-0.2 mg L-1 for 6 days and the rice growth was significantly inhibited. To demonstrate the regulatory role of OsACE2 in resistance to OFF toxicity, we generated OsACE2 overexpression (OE) and knockout mutant using genetic transformation and gene-editing technologies (CRISPR/Cas9). The OE plants grown in the hydroponic medium showed improved growth (plant elongation and biomass), increased chlorophyll content, and reduced OFF-induced oxidative stress. The OsACE2-improved growth phenotypes of rice were attributed to the significantly lower OFF accumulation in OE plants. Conversely, knocking out OsACE2 resulted in compromised growth phenotypes compared to the wild-type (WT). Using LC-LTQ-HRMS/MS, five mono-metabolites and eleven conjugates of OFF were characterized through various canonical pathways, such as hydrolysis, oxidation, reduction, glycosylation, acetylation, malonylation, and interaction with amino acids. These metabolites increased in the OE plants, and five acetylated conjugates were reported for the first time. Collectively, OsACE2 plays a primary role in catabolizing OFF residues in rice through multiple degradation pathways and reducing OFF in its growth environment.

Interpretation of ametryn biodegradation in rice based on joint analyses of transcriptome, metabolome and chemo-characterization.

Agrochemicals such as pesticide residues become environmental contaminants due to their ecotoxic risks to plant, animal and human health. Ametryn (AME) is a widely used farmland pesticide and its residues are widespread in soils, surface stream and groundwater. However, its toxicological and degradative mechanisms in plants and food crops are largely unknown. This study comprehensively investigated AME toxicology and degradation mechanisms in a paddy crop. AME was freely absorbed by rice roots, translocated to the above-ground and thus repressed plant elongation, and reduced dry weight and chlorophyll concentration, but increased oxidative injury and subcellular electrolyte permeability. Analysis of the transcriptome and metabolome revealed that exposure to AME evoked global AME-responsive genes and step-wise catabolism of AME. We detected 995 (roots) and 136 (shoots) upregulated and differentially expressed genes (DEGs) in response to AME. Metabolomic profiling revealed that many basal metabolites such as carbohydrates, amino acids, glutathione, hormones and phenylpropanoids involved in AME catabolism were accordingly accumulated in rice. Eight metabolites and twelve conjugates of AME were characterized by HPLC-Q-TOF-HRMS/MS. These AME metabolites and conjugates are closely related to DEGs, differentially accumulated metabolites (DAMs) and activities of antioxidative enzymes. Collectively, our work highlights the specific mechanisms for AME degradative metabolism through Phase I and II reactive pathways (e.g. hydroxylation and dealkylation), with will help develop genetically engineered rice used to bioremediate AME-contaminated paddy soils and minimize AME accumulation rice crops.

Detoxification and catabolism of mesotrione and fomesafen facilitated by a Phase II reaction acetyltransferase in rice.

INTRODUCTION: The excessive dosage of pesticides required for agronomic reality results in growing contamination of pesticide residues in environment, thus bringing high risks to crop production and human health. OBJECTIVES: This study aims to unveil a novel mechanism for catabolism of two pesticides MTR and FSA facilitated by an uncharacterized Phase II reaction enzyme termed acetyltransferase-1 (ACE1) in rice and to make assessment of its potential for bioremediation to minimize the risks to crop production and food safety. METHODS: We developed genetically improved cultivars overexpressing OsACE1 (OE) and knockout mutant lines by CRISPR-Cas9 technology to identify the MTR and FSA detoxic and metabolic functions and characterized their metabolites and conjugates by HPLC-LTQ-MS/MS. RESULTS: OsACE1 overexpression conferred rice resistance to toxicity of MTR/FSA compared to wild-type, manifested by improved plant elongation and biomass, attenuated cellular injury, and increased chlorophyll accumulation. The OE plants accumulated significantly less parent MTR/FSA and more degradative metabolites, and removed MTR/FSA from their growth medium by 1.38 and 1.61 folds over the wild-type. In contrast, knocking out OsACE1 led to compromised growth fitness and intensified toxic symptoms under MTR/FSA stress and accumulation of more toxic MTR and FSA in rice. The reduced metabolites of MTR and FSA detected in the Cas9 plants suggest the impaired capability of OsACE1 function. CONCLUSIONS: These results signified that OsACE1 expression is required for detoxifying the two poisoning chemicals in rice and plays a critical role in accelerating breakdown of the pesticides mainly through Phase II reaction mechanism pathways.