Elevation of Serum Prostate-Specific Antigen Levels in Males With Pulmonary Embolism.

Hypoxemia is a clinical characteristic of pulmonary embolism (PE). Hypoxemia is associated with variations in serum prostate-specific antigen (PSA) levels. Thus, the present study aimed to determine serum PSA levels in patients with PE, which may be helpful in improving clinical evaluation in screening for prostate diseases in those with PE. Clinical data from 61 consecutive male patients with PE and 113 age-matched healthy male controls were retrospectively analyzed. The pulmonary artery obstruction index (PAOI) was used to evaluate the pulmonary embolic burden. Compared with healthy controls, serum total PSA (tPSA) levels were significantly increased (P = .003), and free PSA (fPSA)/tPSA ratio was significantly decreased in patients with PE (P < .001). There was no significantly difference in serum fPSA levels between patients with PE and healthy controls (P = .253). A significant positive association was observed between serum tPSA levels and PAOI in patients with PE (ß = .270, P = .036). Multivariable linear regression analysis revealed that serum tPSA levels were independently associated with PAOI in patients with PE (ß = .347, P = .003). Serum tPSA levels were higher in male patients with PE than those in healthy controls, but fPSA was not affected. These findings highlight that PE may elevate serum tPSA levels, and that measures of tPSA should be interpreted with caution in screening for prostate diseases in patients with PE.

[Differential diagnosis of autism spectrum disorder and global developmental delay based on machine learning and Children Neuropsychological and Behavioral Scale]. / åŸºäºŽæœºå™¨å­¦ä¹ å’Œå„¿ç«¥ç¥žç»å¿ƒç†è¡Œä¸ºæ£€æŸ¥é‡è¡¨é‰´åˆ«å­¤ç‹¬ç—‡è°±ç³»éšœç¢å’Œå ¨é¢å‘è‚²è¿Ÿç¼“å„¿ç«¥çš„ç ”ç©¶.

OBJECTIVES: To investigate the efficacy and required indicators of Children Neuropsychological and Behavioral Scale-Revision 2016 (CNBS-R2016) in the differential diagnosis of autism spectrum disorder (ASD) and global developmental delay (GDD). METHODS: A total of 277 children with ASD and 415 children with GDD, aged 18-48 months, were enrolled as subjects. CNBS-R2016 was used to assess the developmental levels of six domains, i.e., gross motor, fine motor, adaptive ability, language, social behavior, and warning behavior, and a total of 13 indicators on intelligence age and developmental quotient (DQ) were obtained as the input features. Five commonly used machine learning classifiers were used for training to calculate the classification accuracy, sensitivity, and specificity of each classifier. RESULTS: DQ of warning behavior was selected as the first feature in all five classifiers, and the use of this indicator alone had a classification accuracy of 78.90%. When the DQ of warning behavior was used in combination with the intelligence age of warning behavior, gross motor, and language, it had the highest classification accuracy of 86.71%. CONCLUSIONS: Machine learning combined with CNBS-R2016 can effectively distinguish children with ASD from those with GDD. The DQ of warning behavior plays an important role in machine learning, and its combination with other features can improve classification accuracy, providing a basis for the efficient and accurate differential diagnosis of ASD and GDD in clinical practice.

Serum bilirubin levels in primary Sjögren's syndrome: an association with interstitial lung disease.

OBJECTIVE: We aimed to assess the association between serum bilirubin levels and interstitial lung disease (ILD) in patients with Primary Sjögren's syndrome (pSS). MATERIALS AND METHODS: The retrospectively analysis included 89 consecutive patients with pSS, we collected the clinical materials of pSS patients from the electronic medical records, and all pSS patients were divide into pSS with ILD group and pSS without ILD group. RESULTS: Serum bilirubin levels were significantly lower in pSS patients with ILD than those without ILD (p = 0.010). Serum bilirubin levels showed a significant negative correlation with erythrocyte sedimentation rate (ESR) (r = -0.321, p = 0.002) in patients with pSS. A multivariable logistic regression analysis confirmed that serum bilirubin presented an independent association with ILD in patients with pSS (OR = 0.841, 95%CI:0.728-0.972, p = 0.019). CONCLUSION: Serum bilirubin is independently associated with ILD and therefore may be a promising marker of ILD in patients with pSS.

[Research hotspots in post-discharge follow-up management of preterm infants]. / æ—©äº§å„¿å‡ºé™¢åŽéšè®¿ç ”ç©¶çƒ­ç‚¹.

Preterm infants, especially those born extremely or very prematurely, are at high risk for growth retardation and neurodevelopmental disorders. Regular follow-up after discharge, early intervention, and timely catch-up growth are important guarantees for improving the quality of life of preterm infants and improving the quality of the population. This article provides an overview of the research hotspots in follow-up management of preterm infants after discharge over the past two years, including follow-up modes, nutritional metabolism and body composition follow-up, growth pattern follow-up, neurodevelopmental follow-up, early intervention, etc., in order to provide clinical guidance and research ideas for domestic peers.

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.

The Role of G3BP1 Gene Mediates P38 MAPK/JNK Pathway in Testicular Spermatogenic Dysfunction Caused by Cyfluthrin.

In recent years, male infertility has received global attention and seriously affected the quality of human fertility, and pyrethroids (type II pyrethroids), as recognized environmental endocrine disruptors, may threaten male reproductive health. Therefore, in this study, we established an in vivo model for the development of testicular and germ cell toxicity induced by cyfluthrin and explored the role and mechanism of the G3BP1 gene-mediated P38 MAPK/JNK pathway in testicular and germ cell damage caused by cyfluthrin to find early and sensitive indicators and new therapeutic targets for the development of testicular damage. Firstly, 40 male Wistar rats (about 260 g) were divided into a control group (corn oil), low dose group (6.25 mg/kg), middle dose group (12.5 mg/kg) and high dose group (25 mg/kg). The rats were anesthetized and executed after 28 days of poisoning on alternate days. Then, HE staining, transmission electron microscopy, ELISA, q-PCR, Western blot, immunohistochemistry, double-immunofluorescence and TUNEL were used to observe the pathology, androgen levels, oxidative damage and altered expression of the key factors of the G3BP1 and MAPK pathways in rat testes. The results showed that, compared with the control group, the testicular tissue and spermatocytes were superficially damaged with an increasing dose of cyfluthrin; furthermore, it could interfere with the normal secretion of the hypothalamic-pituitary-gonadal axis (serum GnRH, FSH, T and LH levels) and cause hypergonadal dysfunction. A dose-dependent increase in MDA and a dose-dependent decrease in T-AOC indicated that the oxidative-antioxidative homeostatic balance was disrupted. The Western blot and qPCR analysis revealed that G3BP1, p-JNK1/2/3, P38 MAPK, p-ERK, COX1 and COX4 proteins and mRNA expression were decreased, and p-JNK1/2/3, p-P38MAPK, caspase 3/8/9 proteins and mRNA expression were significantly increased. The double-immunofluorescence and immunohistochemistry results showed that the protein expression of G3BP1 decreased with an increasing dose of staining, while the expression of JNK1/2/3 and P38 MAPK were increased significantly. The positive expressions of G3BP1 were mainly located in the testicular germinal epithelium and germ cell layer, and the positive expressions of JNK1/2/3 were mainly located in the testicular germinal epithelium and sperm cells, while the positive expressions of P38 MAPK were located in all levels of the germ cells and spermatozoa. Our results demonstrated that exposure to cyfluthrin caused testicular and spermatocyte damage in rats, which could cause pathomorphology, altered androgen levels and a decreased antioxidant capacity. When the intracellular antioxidant capacity was impaired, G3BP1 expression and activity were inhibited, causing activation of the P38 MAPK/JNK pathway and activation of the intracellular apoptotic pathway, which, in turn, led to germ cell apoptosis.

[Physical growth and neurodevelopment of preterm infants at the corrected age of 18-24 months]. / æ—©äº§å„¿æ ¡æ­£18~24æœˆé¾„ä½“æ ¼ç”Ÿé•¿å’Œç¥žç»å‘è‚²æ°´å¹³ç ”ç©¶.

OBJECTIVES: To investigate the levels of physical growth and neurodevelopment in preterm infants at the corrected age of 18-24 months. METHODS: The physical growth data and neurodevelopment data of 484 preterm infants at corrected age of 18-24 months were prospectively collected by a post-discharge follow-up system for preterm infants. The infants were regularly followed up in Shenzhen Bao'an Maternal and Child Health Hospital Affiliated to Jinan University from April 2018 to December 2021. The neurodevelopment was evaluated by the Children Neuropsychological and Behavioral Scale-Revision 2016. A total of 219 full-term infants served as controls. The infants were divided into groups (extremely preterm, very preterm, moderate late preterm, and full-term) based on gestational age, and the groups were compared in the levels of physical growth and neurodevelopment. RESULTS: Except that the moderate preterm group had a higher length-for-age Z-score than the full-term group (P=0.038), there was no significant difference in physical growth indicators between the preterm groups and the full-term group (P>0.05). Each preterm group had a significantly lower total developmental quotient (DQ) than the full-term group (P<0.05). Except for the social behavior domain, the DQ of other domains in the extremely preterm and very preterm groups was significantly lower than that in the full-term group (P<0.05). The <32 weeks preterm group had a significantly higher incidence rate of global developmental delay than the full-term group (16.7% vs 6.4%, P=0.012), and the incidence rate of global developmental delay tended to increase with the reduction in gestational age (P=0.026). CONCLUSIONS: Preterm infants can catch up with full-term infants in terms of physical growth at the corrected age of 18-24 months, but with a lower neurodevelopmental level than full-term infants. Neurodevelopment monitoring and early intervention should be taken seriously for preterm infants with a gestational age of <32 weeks.

The role of stimulator of interferon genes-mediated AMPK/mTOR/P70S6K autophagy pathway in cyfluthrin-induced testicular injury.

Cyfluthrin is widely used in the field of sanitary pest control by its wide insecticidal spectrum, high efficiency and low toxicity, low residue, and good biodegradability. But, as a double-edged sword, a large amount of cyfluthrin remains are still in the environment. The residual cyfluthrin is absorbed into the food chain through vegetation and then poses a risk to soil organisms and human health. Several studies have suggested that cyfluthrin is one of the main factors causing testicular damage, but the mechanism remains unclear. In this study, we established in vivo and in vitro models of testicular injury in rats and GC-2 cells exposed to cyfluthrin to explore whether stimulator of interferon genes (STING) gene mediates the regulation of AMPK/mTOR/p70S6K autophagy pathway, which lays a foundation for further study of the mechanism of testicular injury induced by cyfluthrin. The results showed that the activity of super oxide dismutase in testis decreased and the activity of malonic dialdehyde increased with the increase of concentration in vivo and in vitro. At the same time, the levels of mitochondrial damage and inflammation in the testis also increased, which further activated autophagy. In this process, the increased level of inflammation is related to the increased expression of STING gene, and AMPK/mTOR/p70S6K autophagy pathway is also involved. To sum up, cyfluthrin has certain reproductive toxicity, and long-term exposure can induce testicular cell damage. STING gene can participate in cyfluthrin-induced testicular injury through AMPK/mTOR/P70S6K autophagy pathway.

Insights into the accumulation, distribution and toxicity of pyrene associated with microplastics in rice (Oryza sativa L.) seedlings.

Microplastic and polycyclic aromatic hydrocarbons (PAHs) can be introduced into agroecosystems through various agricultural activities and may threaten food safety and human health. However, little research has focused on the behavior of microplastics-associated PAHs and their toxicity effects in agroecosystems, especially in crops. In the present study, we investigated the accumulation, distribution and toxicity of pyrene associated with polyethylene (PE) microplastics in rice (Oryza sativa L.). With quantitative analysis using 14C isotope labelling, the total accumulation efficiency of 14C-pyrene in rice seedlings was 22.4 ± 1.2% and 14.5 ± 0.3% when exposed to freely dissolved pyrene and PE-associated pyrene, respectively. The translocation of 14C-pyrene was significantly decreased by microplastics adsorption even when the amount of pyrene in the rice roots had no significant difference. Subcellular distribution of 14C-pyrene in rice suggested that PE microplastics-associated pyrene located more on cell walls than free dissolved pyrene. Furthermore, results showed free pyrene, but not PE-associated pyrene, significantly decreased the length and biomass of rice roots as well as increased the activities of antioxidant enzymes (superoxide dismutase and catalase). It indicated that the association with microplastics alleviated the phytotoxicity of pyrene in rice seedlings. These findings shed new light on the environmental behavior and effects of PAHs associated with microplastics in crops and will be helpful to its comprehensive risks assessment.

Comprehensive analysis of M2 macrophage-derived exosomes facilitating osteogenic differentiation of human periodontal ligament stem cells.

BACKGROUND: The role of periodontal ligament stem cells (PDLSCs) and macrophage polarization in periodontal tissue regeneration and bone remodeling during orthodontic tooth movement (OTM) has been well documented. Nevertheless, the interactions between macrophages and PDLSCs in OTM remain to be investigated. Consequently, the present study was proposed to explore the effect of different polarization states of macrophages on the osteogenic differentiation of PDLSCs. METHODS: After M0, M1 and M2 macrophage-derived exosomes (M0-exo, M1-exo and M2-exo) treatment of primary cultured human PDLSCs, respectively, mineralized nodules were observed by Alizarin red S staining, and the expression of ALP and OCN mRNA and protein were detected by RT-qPCR and Western blotting, correspondingly. Identification of differentially expressed microRNAs (DE-miRNA) in M0-exo and M2-exo by miRNA microarray, and GO and KEGG enrichment analysis of DE-miRNA targets, and construction of protein-protein interaction networks. RESULTS: M2-exo augmented mineralized nodule formation and upregulated ALP and OCN expression in PDLSCs, while M0-exo had no significant effect. Compared to M0-exo, a total of 52 DE-miRNAs were identified in M2-exo. The expression of hsa-miR-6507-3p, hsa-miR-4731-3p, hsa-miR-4728-3p, hsa-miR-3614-5p and hsa-miR-6785-3p was significantly down-regulated, and the expression of hsa-miR-6085, hsa-miR-4800-5p, hsa-miR-4778-5p, hsa-miR-6780b-5p and hsa-miR-1227-5p was significantly up-regulated in M2-exo compared to M0-exo. GO and KEGG enrichment analysis revealed that the downstream targets of DE-miRNAs were mainly involved in the differentiation and migration of multiple cells. CONCLUSIONS: In summary, we have indicated for the first time that M2-exo can promote osteogenic differentiation of human PDLSCs, and have revealed the functions and pathways involved in the DE-miRNAs of M0-exo and M2-exo and their downstream targets.

OsBR6ox, a member in the brassinosteroid synthetic pathway facilitates degradation of pesticides in rice through a specific DNA demethylation mechanism.

This manuscript described a comprehensive study on a pesticide degradation factor OsBR6ox that promoted the degradation of pesticides atrazine (ATZ) and acetochlor (ACT) in rice tissues and grains through an epigenetic mechanism. OsBR6ox was transcriptionally induced under ATZ and ACT stress. Genetic disruption of OsBR6ox increased rice sensitivity and led to more accumulation of ATZ and ACT, whereas transgenic rice overexpressing OsBR6ox lines (OEs) showed opposite effects with improved growth and lower ATZ and ACT accumulation in various tissues, including grains. OsBR6ox-mediated detoxification of ATZ and ACT was associated with the increased abundance of brassinolide (one of the brassinosteroids, BRs), a plant growth regulator for stress responses. Some Phase I-II reaction protein genes for pesticide detoxification such as genes encoding laccase, O-methyltransferase and glycosyltransferases were transcriptionally upregulated in OE lines under ATZ and ACT stress. HPLC-Q-TOF-MS/MS analysis revealed an enhanced ATZ/ATC metabolism in OE plants, which removed 1.21-1.49 fold ATZ and 1.31-1.44 fold ACT from the growth medium but accumulated only 83.1-87.1 % (shoot) and 71.7-84.1 % (root) of ATZ and 69.4-83.4 % of ACT of the wild-type. Importantly, an ATZ-responsive demethylated region in the upstream of OsBR6ox was detected. Such an epigenetic modification marker was responsible for the increased OsBR6ox expression and consequent detoxification of ATZ/ACT in rice and environment. Overall, this work uncovered a new model showing that plants utilize two mechanisms to co-regulate the detoxification and metabolism of pesticides in rice and provided a new approach for building up cleaner crops and eliminating residual pesticides in environments.

Serum Levels of Mitochondrial Fission- and Fusion-Related Genes of Coal Workers' Pneumoconiosis and Risk Factor Analysis Based on a Generalized Linear Model.

Objective: We aimed to explore the risk factors for coal workers' pneumoconiosis and to further explore the significance of mitochondrial fission and fusion factors in CWP and verify the feasibility of mitochondrial fission and fusion factors as diagnostic and therapeutic targets. Methods: The data of 168 cases were collected, and they were divided into a healthy control group (40 cases), dust exposure control group (61 cases), and CWP group (67 cases) and entered into SPSS 24.0. The statistical data were analyzed by the chi-square test or Fisher's exact probability method. The variables with statistically significant differences of the univariate analysis results were included in the generalized linear model. Test level was α = 0.05. Blood samples were collected to detect the ROS content, MDA content, and SOD activity. The mRNA expression levels of OPA1, Drp1, MFN2, Fis1, Col I, Col III, and α-SMA were determined by q-PCR. The protein expression levels of OPA1, Drp1, MFN2, Fis1, Col I, Col III, and α-SMA were detected by western blot. Results: Generalized linear regression analysis showed that lower school education, no respiratory protective measures, the working age beyond 15 years, and the type of work like coal mine drillers were the risk factors for CWP. With the aggravation of CWP, the degree of fibrosis and inflammation increased oxidative damage, increased mitochondrion division, and decreased fusion, which were more sensitive in the second and third stages of CWP. Conclusion: The results in this found that mitochondria are injured by fission and fusion in the CWP patients. Detection of the mitochondria fission and fusion factors provides the application value to evaluate the injury degree and progress of CWP and the clues for finding the real and effective screening and diagnosis biomarkers.

Sleep initiation patterns and their influence on sleep quality in infants and young children. / å©´å¹¼å„¿å ¥ç¡æ–¹å¼åŠå ¶å¯¹ç¡çœ è´¨é‡çš„å½±å“.

OBJECTIVES: To investigate the current status of sleep initiation patterns, influencing factors for sleep initiation patterns, and the influence of sleep initiation patterns on sleep quality in infants and young children. METHODS: A total of 521 infants and young children, aged 0-35 months, who underwent physical examination at the outpatient service of the Department of Growth and Development in Shenzhen Bao'an Women's and Children's Hospital Affiliated to Jinan University were enrolled as subjects. A self-designed questionnaire and Brief Infant Sleep Questionnaire were used to collect the information on family background, parenting behaviors, and sleep quality in the past one week. A multivariate logistic regression analysis was used to evaluate the influencing factors for sleep initiation patterns. A multiple linear regression analysis was used to evaluate the influence of sleep initiation patterns on the number of nighttime awakenings. RESULTS: Among the 521 infants and young children, 258 (49.5%) were breastfed/bottle fed to initiate sleep, 62 (11.9%) were rocked/held to initiate sleep, 39 (7.5%) slept independently, and 162 (31.1%) initiated sleep accompanied by parents. The multivariate logistic regression analysis showed that the children with breastfeeding and a younger age were more likely to be breastfed/bottle fed to initiate sleep (P<0.05) and that the children with a younger age were also more likely to be rocked/held to initiate sleep (P<0.05). The multiple linear regression analysis showed that sleep initiation with breastfeeding/bottle feeding significantly increased the number of nighttime awakenings (P<0.05). CONCLUSIONS: Most infants and young children initiate sleep by being breastfed/bottle fed, rocked/held, or accompanied. The sleep initiation pattern is associated with the age of children and whether they are still breastfeeding. Sleep initiation with breastfeeding/bottle feeding can increase the number of nighttime awakenings. io.

Minimized Atrazine Risks to Crop Security and Its Residue in the Environment by a Rice Methyltransferase as a Regulation Factor.

Atrazine (ATZ) is an agricultural pesticide for controlling field weeds. ATZ accumulates in many crops, posing high risks to crop production and food safety. Characterizing one of the novel rice MT genes named Oryza sativa atrazine-responsive methyltransferase (OsARM) showed that the expression of OsARM was associated with DNA demethylation (hypomethylation) in its promoter region. The enhancement of OsARM expression was manifested by the attenuated symptoms of ATZ toxicity including better growth and lower ATZ accumulation in plants. The promoted capacity of detoxification was confirmed by transgenic rice overexpression OsARM lines and also functionally proved by CRISPR-Cas9 knockout mutants. The transgenic lines accumulate more ATZ metabolites in rice and lower concentrations in the growth environment, pointing out that ATZ metabolism or degradation can be intensified. The ATZ-induced DNA demethylation is an important hallmark representing the epigenetic mechanism, which is required for the extra OsARM expression to facilitate ATZ disappearance in rice and the environment.

Assessment of growth pattern of preterm infants up to a corrected age of 24 months. / æ—©äº§å„¿æ ¡æ­£24æœˆé¾„å† ç”Ÿé•¿è½¨è¿¹ç ”ç©¶.

OBJECTIVES: To assess the growth of preterm infants up to a corrected age of 24 months, and to understand the growth trend and pattern of preterm infants. METHODS: A preterm infant follow-up database was established based on the Internet Plus follow-up system. A total of 3 188 preterm infants who were born from April 2018 to April 2021 were enrolled. Their length, weight, and head circumference were recorded at birth and at the corrected ages of 1, 3, 6, 12, 18, and 24 months. The preterm infants were grouped by perinatal factors. The growth curves of these infants were plotted and compared with the International Fetal and Newborn Growth Consortium for the 21st Century (INTERGROWTH-21st) standard and World Health Organization (WHO) standard. RESULTS: The weight, length, and head circumference curves of each group of preterm infants grouped by various perinatal factors all rose rapidly within the corrected age of 6 months, but the growth rate slowed down after the corrected age of 6 months. Based on the actual age for the groups of preterm infants with different gestational ages (<28 weeks, 28-31+6 weeks, 32-33+6 weeks, and 34-36+6 weeks), the length curve gradually coincided with the WHO curve after the actual age of 9 months (P=0.082), while for the preterm infants with a gestational age of <32 weeks, the weight and head circumference curves were significantly lower than the WHO curves (P<0.001). Based on the corrected age, the physical growth curve of preterm infants with different gestational ages (<28 weeks, 28-31+6 weeks, 32-33+6 weeks, and 34-36+6 weeks) basically coincided with each other (P>0.05). For the infants with extremely low birth weight and the small-for-gestational-age infants, the length, weight, and head circumference curves were significantly lower than those of the INTERGROWTH-21st standard and the WHO standard (P<0.05). CONCLUSIONS: The physical growth rate of preterm infants is faster within the corrected age of 6 months, and the growth rate slows down after the corrected age of 6 months. Preterm infants with a smaller gestational age need longer time to catch up in weight and head circumference. More attention should be paid to the physical growth of extremely preterm infants, extremely low birth weight infants, and small-for-gestational-age infants.

Residues of Reduced Herbicides Terbuthylazine, Ametryn, and Atrazine and Toxicology to Maize and the Environment through Salicylic Acid.

Terbuthylazine (TBA), ametryn (AME), and atrazine (ATZ) are triazine family herbicides. They are dominantly used in the field of cereal crops like wheat and maize for prevention of upland from annual gramineous and broad-leaved weeds, with attributes of weed efficiency broad spectrum and good market performance. Salicylic acid (SA) is a kind of natural plant growth regulator existing widely in the plant kingdom and participating in many physiological and defense processes. In this study, the effects of SA on the detoxification and degradation of herbicides TBA, AME, and ATZ in maize were investigated. When maize plants were exposed to 6 mg kg-1 of the triazine herbicides, the growth and chlorophyll concentration were reduced, while the membrane permeability increased. After maize was sprayed with 5 mg kg-1 SA, the herbicide-induced phytotoxicity was significantly assuaged, with the increased content of chlorophyll and decreased cellular damage in plants. Activities of several biomarker enzymes such as SOD, POD, and GST were repressed in the presence of SA. The concentration of the triazine herbicides in maize and the soil determined by high-performance liquid chromatography was drastically reduced by spraying SA. Using LC/Q-TOF-MS/MS, six metabolites and nine conjugates of AME in maize and soil were characterized. The relative contents of AME metabolites and conjugates in maize with SA were higher than those without SA. These results suggest that SA is able to promote the detoxification and decay of these triazine herbicides in maize and soil.

Hyperthermia Selectively Destabilizes Oncogenic Fusion Proteins.

The PML/RARα fusion protein is the oncogenic driver in acute promyelocytic leukemia (APL). Although most APL cases are cured by PML/RARα-targeting therapy, relapse and resistance can occur due to drug-resistant mutations. Here we report that thermal stress destabilizes the PML/RARα protein, including clinically identified drug-resistant mutants. AML1/ETO and TEL/AML1 oncofusions show similar heat shock susceptibility. Mechanistically, mild hyperthermia stimulates aggregation of PML/RARα in complex with nuclear receptor corepressors leading to ubiquitin-mediated degradation via the SIAH2 E3 ligase. Hyperthermia and arsenic therapy destabilize PML/RARα via distinct mechanisms and are synergistic in primary patient samples and in vivo, including three refractory APL cases. Collectively, our results suggest that by taking advantage of a biophysical vulnerability of PML/RARα, thermal therapy may improve prognosis in drug-resistant or otherwise refractory APL. These findings serve as a paradigm for therapeutic targeting of fusion oncoprotein-associated cancers by hyperthermia. SIGNIFICANCE: Hyperthermia destabilizes oncofusion proteins including PML/RARα and acts synergistically with standard arsenic therapy in relapsed and refractory APL. The results open up the possibility that heat shock sensitivity may be an easily targetable vulnerability of oncofusion-driven cancers.See related commentary by Wu et al., p. 300.

Cytotoxicity of mesoporous silica modified by amino and carboxyl groups on vascular endothelial cells.

Mesoporous silica is widely used because of its unique and excellent properties, especially it can be used as a drug carrier and gene carrier in the biomedical field. After the mesoporous silica is put into clinical use, it is more likely to be exposed in human body. Therefore, the effect of mesoporous silica on human body cannot be ignored. The injury of vascular endothelial cells is a prerequisite for the occurrence of many cardiovascular diseases. As a drug and gene carrier, mesoporous silica increases its contact with vascular endothelial cells, so its toxic effect on cardiovascular system cannot be ignored. In this study, amino (NH2 ) and carboxyl (COOH) were modified on mesoporous silica SBA-15 by post-grafting. The results showed that it still maintained the one-dimensional hexagonal mesoporous structure of SBA-15 and had typical mesoporous structure. Then human umbilical vein endothelial cells (HUVECs) were infected with SBA-15, NH2 -SBA-15, and COOH-SBA-15. The results showed that the functionalized mesoporous silica SBA-15 had cytotoxicity to HUVECs and damaged the cell membrane, but compared with the unmodified mesoporous silica SBA-15 the cytotoxicity of functionalized mesoporous silica SBA-15 was lower and the toxicity of carboxyl modified group was the lowest. By comparing the cell inhibition rate and the expression level of lactate dehydrogenate and reactive oxygen species induced by the three materials, oxidative damage and cell membrane damage may be two mechanisms of cytotoxicity. Mesoporous silica SBA-15 has an effect on cardiovascular system by inducing the high expression of nitric oxide, intercellular adhesive molecule-1 and vascular cell adhesive molecule-1 in HUVECs. In summary, our results show that mesoporous silica is toxic to vascular endothelial cells.

Identification of a novel function of a component in the jasmonate signaling pathway for intensive pesticide degradation in rice and environment through an epigenetic mechanism.

Developing a biotechnical system with rapid degradation of pesticide is critical for reducing environmental, food security and health risks. Here, we investigated a novel epigenetic mechanism responsible for the degradation of the pesticide atrazine (ATZ) in rice crops mediated by the key component CORONATINE INSENSITIVE 1a (OsCOI1a) in the jasmonate-signaling pathway. OsCOI1a protein was localized to the nucleus and strongly induced by ATZ exposure. Overexpression of OsCOI1a (OE) significantly conferred resistance to ATZ toxicity, leading to the improved growth and reduced ATZ accumulation (particularly in grains) in rice crops. HPLC/Q-TOF-MS/MS analysis revealed increased ATZ-degraded products in the OE plants, suggesting the occurrence of vigorous ATZ catabolism. Bisulfite-sequencing and chromatin immunoprecipitation assays showed that ATZ exposure drastically reduced DNA methylation at CpG context and histone H3K9me2 marks in the upstream of OsCOI1a. The causal relationships between the DNA demethylation (hypomethylatioin), OsCOI1a expression and subsequent detoxification and degradation of ATZ in rice and environment were well established by several lines of biological, genetic and chemical evidence. Our work uncovered a novel regulatory mechanism implicated in the defense linked to the epigenetic modification and jasmonate signaling pathway. It also provided a modus operandi that can be used for metabolic engineering of rice to minimize amounts of ATZ in the crop and environment.