Rewiring of the Fruit Metabolome in Tomato Breeding.

Humans heavily rely on dozens of domesticated plant species that have been further improved through intensive breeding. To evaluate how breeding changed the tomato fruit metabolome, we have generated and analyzed a dataset encompassing genomes, transcriptomes, and metabolomes from hundreds of tomato genotypes. The combined results illustrate how breeding globally altered fruit metabolite content. Selection for alleles of genes associated with larger fruits altered metabolite profiles as a consequence of linkage with nearby genes. Selection of five major loci reduced the accumulation of anti-nutritional steroidal glycoalkaloids in ripened fruits, rendering the fruit more edible. Breeding for pink tomatoes modified the content of over 100 metabolites. The introgression of resistance genes from wild relatives in cultivars also resulted in major and unexpected metabolic changes. The study reveals a multi-omics view of the metabolic breeding history of tomato, as well as provides insights into metabolome-assisted breeding and plant biology.

MicroRNAs inhibit the translation of target mRNAs on the endoplasmic reticulum in Arabidopsis.

Translation inhibition is a major but poorly understood mode of action of microRNAs (miRNAs) in plants and animals. In particular, the subcellular location where this process takes place is unknown. Here, we show that the translation inhibition, but not the mRNA cleavage activity, of Arabidopsis miRNAs requires ALTERED MERISTEM PROGRAM1 (AMP1). AMP1 encodes an integral membrane protein associated with endoplasmic reticulum (ER) and ARGONAUTE1, the miRNA effector and a peripheral ER membrane protein. Large differences in polysome association of miRNA target RNAs are found between wild-type and the amp1 mutant for membrane-bound, but not total, polysomes. This, together with AMP1-independent recruitment of miRNA target transcripts to membrane fractions, shows that miRNAs inhibit the translation of target RNAs on the ER. This study demonstrates that translation inhibition is an important activity of plant miRNAs, reveals the subcellular location of this activity, and uncovers a previously unknown function of the ER.

Antagonistic regulation of target genes by the SISTER OF TM3-JOINTLESS2 complex in tomato inflorescence branching.

Inflorescence branch number is a yield-related trait controlled by cell fate determination in meristems. Two MADS-box transcription factors (TFs)-SISTER OF TM3 (STM3) and JOINTLESS 2 (J2)-have opposing regulatory roles in inflorescence branching. However, the mechanisms underlying their regulatory functions in inflorescence determinacy remain unclear. Here, we characterized the functions of these TFs in tomato (Solanum lycopersicum) floral meristem and inflorescence meristem (IM) through chromatin immunoprecipitation and sequencing analysis of their genome-wide occupancy. STM3 and J2 activate or repress the transcription of a set of common putative target genes, respectively, through recognition and binding to CArG box motifs. FRUITFULL1 (FUL1) is a shared putative target of STM3 and J2 and these TFs antagonistically regulate FUL1 in inflorescence branching. Moreover, STM3 physically interacts with J2 to mediate its cytosolic redistribution and restricts J2 repressor activity by reducing its binding to target genes. Conversely, J2 limits STM3 regulation of target genes by transcriptional repression of the STM3 promoter and reducing STM3-binding activity. Our study thus reveals an antagonistic regulatory relationship in which STM3 and J2 control tomato IM determinacy and branch number.

Heterozygous variants in USP25 cause genetic generalized epilepsy.

USP25 encodes ubiquitin-specific proteases 25, a key member of deubiquitinating enzyme family and is involved in neural fate determination. Although abnormal expression in Down's syndrome was reported previously, the specific role of USP25 in human diseases has not been defined. In this study, we performed trio-based whole exome sequencing in a cohort of 319 cases (families) with generalized epilepsy of unknown etiology. Five heterozygous USP25 variants including two de novo and three co-segregated variants were determined in eight individuals affected by generalized seizures and/or febrile seizures from five unrelated families. The frequency of USP25 variants showed a significantly high aggregation in this cohort compared to the East Asian population and all populations in the gnomAD database. The mean onset ages of febrile and afebrile seizures were 10 months (infancy) and 11.8 years (juvenile), respectively. The patients achieved seizure freedom except one had occasional nocturnal seizures at the last follow-up. Two patients exhibited intellectual disability. Usp25 was ubiquitously expressed in mouse brain with two peaks on embryonic days (E14‒E16) and postnatal day 21, respectively. Similarly, USP25 expressed in fetus/early childhood stage with a second peak at approximately 12‒20 years old in human brain, consistent with the seizure onset age at infancy and juvenile in the patients. To investigate the functional impact of USP25 deficiency in vivo, we established Usp25 knock-out mice, which showed increased seizure susceptibility compared to wild-type mice in pentylenetetrazol-induced seizure test. To explore the impact of USP25 variants, we employed multiple functional detections. In HEK293T cells, the severe phenotype associated variant (p.Gln889Ter) led to a significant reduction of mRNA and protein expressions but formed a stable truncated dimers with increment of deubiquitinating enzyme activities and abnormal cellular aggregations, indicating a gain-of-function effect. The p.Gln889Ter and p.Leu1045del increased neuronal excitability in mice brain, with a higher firing ability in p.Gln889Ter. These functional impairments align with the severity of the observed phenotypes, suggesting a genotype-phenotype correlation. Hence, a moderate association between USP25 and epilepsy was noted, indicating USP25 is potentially a predisposing gene for epilepsy. Our results from Usp25 null mice and the patient-derived variants indicated that USP25 would play epileptogenic role via loss-of-function or gain-of-function effects. The truncated variant p.Gln889Ter would have profoundly different effect on epilepsy. Together, our results underscore the significance of USP25 heterozygous variants in epilepsy, thereby highlighting the critical role of USP25 in the brain.

ASYMMETRIC LEAVES 2 and ASYMMETRIC LEAVES 2-LIKE are partially redundant genes and essential for fruit development in tomato.

Fruit size and shape are controlled by genes expressed during the early developmental stages of fruit. Although the function of ASYMMETRIC LEAVES 2 (AS2) in promoting leaf adaxial cell fates has been well characterized in Arabidopsis thaliana, the molecular mechanisms conferring freshy fruit development as a spatial-temporal expression gene in tomato pericarp remain unclear. In the present study, we verified the transcription of SlAS2 and SlAS2L, two homologs of AS2, in the pericarp during early fruit development. Disruption of SlAS2 or SlAS2L caused a significant decrease in pericarp thickness as a result of a reduction in the number of pericarp cell layers and cell area, leading to smaller tomato fruit size, which revealed their critical roles in tomato fruit development. In addition, leaves and stamens exhibited severe morphological defects in slas2 and slas2l single mutants, as well as in the double mutants. These results demonstrated the redundant and pleiotropic functions of SlAS2 and SlAS2L in tomato fruit development. Yeast two-hybrid and split-luciferase complementation assays showed that both SlAS2 and SlAS2L physically interact with SlAS1. Molecular analyses further indicated that SlAS2 and SlAS2L regulate various downstream genes in leaf and fruit development, and that some genes participating in the regulation of cell division and cell differentiation in the tomato pericarp are affected by these genes. Our findings demonstrate that SlAS2 and SlAS2L are vital transcription factors required for tomato fruit development.

Genome-wide analysis and expression profiling of the HD-ZIP gene family in kiwifruit.

The homeodomain-leucine zipper (HD-Zip) gene family plays a pivotal role in plant development and stress responses. Nevertheless, a comprehensive characterization of the HD-Zip gene family in kiwifruit has been lacking. In this study, we have systematically identified 70 HD-Zip genes in the Actinidia chinensis (Ac) genome and 55 in the Actinidia eriantha (Ae) genome. These genes have been categorized into four subfamilies (HD-Zip I, II, III, and IV) through rigorous phylogenetic analysis. Analysis of synteny patterns and selection pressures has provided insights into how whole-genome duplication (WGD) or segmental may have contributed to the divergence in gene numbers between these two kiwifruit species, with duplicated gene pairs undergoing purifying selection. Furthermore, our study has unveiled tissue-specific expression patterns among kiwifruit HD-Zip genes, with some genes identified as key regulators of kiwifruit responses to bacterial canker disease and postharvest processes. These findings not only offer valuable insights into the evolutionary and functional characteristics of kiwifruit HD-Zips but also shed light on their potential roles in plant growth and development.

Tomato APETALA2 family member SlTOE1 regulates inflorescence branching by repressing SISTER OF TM3.

Inflorescence architecture directly impacts yield potential in most crops. As a model of sympodial plants, tomato (Solanum lycopersicum) inflorescence exhibits highly structural plasticity. However, the genetic regulatory network of inflorescence architecture in tomato remains unclear. Here, we investigated a modulator of inflorescence branching in tomato, TARGET OF EAT1 (SlTOE1), an APETALA2 (AP2) family member found to be predominantly expressed in the floral meristem (FM) of tomato. sltoe1 knockout mutants displayed highly branched inflorescences and defective floral organs. Transcriptome analysis revealed that SISTER OF TM3 (STM3) and certain floral development-related genes were upregulated in the flower meristem of sltoe1. SlTOE1 could directly bind the promoters of STM3 and Tomato MADS-box gene 3 (TM3) to repress their transcription. Simultaneous mutation of STM3 and TM3 partially restored the inflorescence branching of the sltoe1cr mutants, suggesting that SlTOE1 regulates inflorescence development, at least in part through an SlTOE1STM3/TM3 module. Genetic analysis showed that SlTOE1 and ENHANCER OF JOINTLESS 2 (EJ2) additively regulate tomato inflorescence branching; their double mutants showed more extensive inflorescence branching. Our findings uncover a pathway controlling tomato inflorescence branching and offer deeper insight into the functions of AP2 subfamily members.

[Determination of 21 organophosphate esters and their metabolites in drinking water by automatic solid phase extraction-liquid chromatography-tandem mass spectrometry].

OBJECTIVE: To establish a method for simultaneous determination of 21 organophosphate esters(OPEs) and their metabolites in drinking water by automatic solid phase extraction-liquid chromatography-tandem mass spectrometry. METHODS: The drinking water was purified by automatic solid phase extraction with HLB column, eluted by methanol, determined by liquid chromatography tandem mass spectrometry with ACQUITY UPLC BEH(100 mm×2.1mm, 1.7 µm) column, and quantified by internal standard method. RESULTS: The optimized method could simultaneously detect 21 organophosphate esters and their metabolites in drinking water. The detection limit was 0.01-0.24 ng/L, the quantitation limit was 0.03-0.77 ng/L. The recovery range was 57.6%-121.2% and the relative standard deviation is 1.2%-11.1% when the concentration was 0.8-20 ng/L. Senventeen tap water and 30 packaged drinking water collected by the supermarket were measured. The ΣOPEs range was 16.8-177 ng/L, and the Σdi-OPEs range was 0.328-16.3ng/L, indicating the exposure risk of organophosphates and their metabolites in water. CONCLUSION: The pretreatment of the method is simple, automatic and sensitive, and is suitable for simultaneous high-throughput determination of organophosphate esters and their metabolites in large quantities of drinking water.

Differential airway resistome and its correlations with clinical characteristics in Haemophilus- or Pseudomonas-predominant microbial subtypes of bronchiectasis.

The prevalence and clinical correlates of antibiotic resistance genes (ARGs) in bronchiectasis are not entirely clear. We aimed to profile the ARGs in sputum from adults with bronchiectasis, and explore the association with airway microbiome and disease severity and subtypes. In this longitudinal study, we prospectively collected 118 sputum samples from stable and exacerbation visits of 82 bronchiectasis patients and 19 healthy subjects. We profiled ARGs with shotgun metagenomic sequencing, and linked these to sputum microbiome and clinical characteristics, followed by validation in an international cohort. We compared ARG profiles in bronchiectasis according to disease severity, blood and sputum inflammatory subtypes. Unsupervised clustering revealed a Pseudomonas predominant subgroup (n = 16), Haemophilus predominant subgroup (n = 48), and balanced microbiome subgroup (N = 54). ARGs of multi-drug resistance were over-dominant in the Pseudomonas-predominant subgroup, while ARGs of beta-lactam resistance were most abundant in the Haemophilus-predominant subgroup. Pseudomonas-predominant subgroup yielded the highest ARG diversity and total abundance, while Haemophilus-predominant subgroup and balanced microbiota subgroup were lowest in ARG diversity and total abundance. PBP-1A, ksgA and emrB (multidrug) were most significantly enriched in Haemophilus-predominant subtype. ARGs generally correlated positively with Bronchiectasis Severity Index, fluoroquinolone use, and modified Reiff score. 68.6% of the ARG-clinical correlations could be validated in an independent international cohort. In conclusion, ARGs are differentially associated with the dominant microbiome and clinical characteristics in bronchiectasis.

Characterization of natural rubber concerning its components and molecular weight in Taraxacum kok-saghyz Rodin using pyrolysis gas chromatography-mass spectrometry.

Taraxacum kok-saghyz Rodin (TKS) has abundant natural rubber in its root and the molecular weight of its natural rubber is higher than that in Hevea brasiliensis. Thus, TKS is an excellent alternative for the commercial production of natural rubber. The content and molecular weight of natural rubber are two qualitative indicators. Efficient determination for both indicators is still a challenge. In this study, we developed a method to simultaneously determine the content and molecular weight of natural rubber in TKS with pyrolysis－gas chromatography-mass spectrometry. The content of natural rubber was quantified by internal standard method. We optimized the pyrolysis temperature and chromatographic method during content determination. The limits of detection and quantification were 0.47 and 1.56 µg, respectively. In addition, the arachidonic acid methyl ester, an unsaturated fatty acid proposed from the α-end group of natural rubber, was quantified to obtain the number of natural rubber polymers. Based on the content and the polymer number, we also quantified the molecular weight of natural rubber. Thus, the content and molecular weight of natural rubber were simultaneously determined in TKS. Our study provides a new perspective for the high throughput analysis of natural rubber.

Effects of Tea Polyphenols and Theaflavins on Three Oral Cariogenic Bacteria.

In order to investigate the antibacterial mechanism of tea polyphenols and theaflavins against oral cariogenic bacteria, the pH value of the culture medium, the number of bacteria adhering to the smooth glass tube wall, and the electrical conductivity value within 10 h were measured, respectively. The effects of four concentrations of tea polyphenols and theaflavins below the MIC value were studied on acid production, adhesion, and electrical conductivity of oral cariogenic bacteria. The live/dead staining method was used to observe the effects of four concentrations of tea polyphenols and theaflavins below the MIC value on the biofilm formation of oral cariogenic bacteria under a laser scanning confocal microscope. With the increase in concentrations of tea polyphenols and theaflavins, the acid production and adhesion of the cariogenic bacteria gradually decreased, and the conductivity gradually increased. However, the conductivity increase was not significant (p < 0.05). Compared with the control group, the 1/2MIC and 1/4MIC tea polyphenols and theaflavins treatments significantly reduced the biomass of the cariogenic biofilm (p < 0.05). The confocal laser scanning microscope showed that the integrated optical density of green fluorescence of the cariogenic biofilm gradually decreased with the increase in agent concentration after the action of tea polyphenols and theaflavins.

[Rapid confirmation method of food poisoning caused by Bacillus cereus cereulide in rice and flour products].

OBJECTIVE: To develop a method for rapid determination of Bacillus cereus cereulide in rice and flour products by ultra-performance liquid chromatography-tandem mass spectrometry, providing emergency measures for food poisoning caused by cereulide. METHODS: Single rice and flour samples were extracted with acetonitrile aqueous solution, salting out, after centrifuged and filmed, the organic phase was directly determined. The complex matrix samples fried rice and noodles were extracted with acetonitrile aqueous solution, cleaned up with HLB column, a ACQUITY UPLC Peptide BEH C_(18) 300Å column(2.1 mm×100 mm, 1.7 µm)was used for liquid chromatography separation, multiple reaction monitoring(MRM) mode was used for detection in electrospray ionization with positive ion mode, and quantified by the solvent standard curve method. RESULTS: At the spiked level of 0.5, 1.0 and 5.0 µg/kg, the recoveries of cereulide in negative steamed rice, steamed bread and noodles samples were 87.4%-98.3%, and the relative standard deviations were 1.4%-4.2%. At the spiking levels of 1.0, 2.0 and 5.0 µg/kg, the recoveries of cereulide in the negative samples such as fried steamed rice and fried noodles were 89.5%-99.3% with the relative standard deviations of 1.1%-7.5%(n=6). The detection limit of cereulide was 0.2-0.3 µg/kg, and the quantification limit was 0.5-1.0 µg/kg. The established method was applied to the detection of the actual samples causing food poisoning in a certain place in Beijing. The content of cereulide in poisoned food samples was 1287-7398 µg/kg, the content of cereulide in two raw materials cold noodles was 0.4 and 9.4 µg/kg. CONCLUSION: The method is simple, rapid, high sensitivity and accurate, and can realize the rapid treatment of food poisoning caused by cereulide.

Imbalance of alveolar epithelial type I and type â ¡ cells in lipopolysaccharide-induced chronic lung injury young mouse model.

Children are susceptible to pneumonia, which affects their growth and development. Immune disorders and unrepaired alveolar mucosal epithelium following pneumonia cause chronic lung injury. The mechanism of chronic lung injury is unknown and lacks animal models for reference. Therefore, we developed a chronic lung injury young mouse model to simulate the pathological process of children. 3-week-old mice were intratracheal instillation of lipopolysaccharide (LPS) every other day for six weeks. Consequently, the histopathology showed damaged integrity of lung tissue, fibrosis, and abnormally distributed alveolar epithelial cells. The total protein concentration in bronchoalveolar lavage fluid (BALF) was increased, alveolar epithelial type (AT) I cells were abnormal distribution, and AT II cells were reduced. The phosphorylation levels of IKBα and the expression levels of NF-κB p65 in lung tissue were up-regulated. In serum and BALF, the IL-6 was oversecretion, nitric oxide (NO) and superoxide dismutase (SOD) were perturbed secretion, oxidative stress imbalance. In addition, blood viscosity, plasma viscosity, and erythrocyte sedimentation rate (ESR) indexes in hemorheology were increased. In conclusion, it is feasible to construct the mouse model of chronic lung injury, and AT I and AT Ⅱ cells were imbalanced, which paves the way for further investigations on the pathogenesis of chronic lung injury and the efficacy of novel treatments.

TNF antagonizes CCN1 in apoptosis in esophageal adenocarcinoma.

TNF signaling mostly supports cell growth by activating NFκB and only induces cell death when NFκB activation fails. CCN1 is a matricellular protein that has been reported capable to convert TNF from a pro-survival factor into a stimulus for cell death without interfering with NFκB signaling. In this study, we examined the relationship between CCN1 and TNF in the context of esophageal adenocarcinoma and found that CCN1 did not help TNF to induce cell death when they were together, instead, it inhibited TNF expression, as well as TNF-induced JNK activation and apoptosis. CCN1 induced apoptosis in the cancer cells by itself through upregulation of TRAIL and its death receptors. The presence of TNF significantly lowered CCN1 expression and its capability in apoptosis induction. Furthermore, we found that CCN1 boosted ADAM17-mediated cleavage of TNF receptors through ITGA11 and the soluble decoy receptors generated by this action neutralized TNF activity. Taken together, CCN1 and TNF antagonize each other in esophageal cancer cells.

TNF upregulates peptidoglycan recognition protein 1 in esophageal cancer cells to clear the path to its signaling: Making the "enemy" a friend.

TNF, CCN1, and peptidoglycan recognition protein 1 (PGLYRP1) are often found together in the inflammatory tissue. While TNF and CCN1 promote tissue regeneration, PGLYRP1 protects it from bacterial infection. In fibroblasts, CCN1 was reported to support TNF in apoptosis induction while PGLYRP1 was found to compete with TNF for binding to TNFR1. When PGLYRP1 binds to TNFR1 by itself, it silences the receptor, but if HSP70 joins them, it leads to cell death. In cancer cells, however, CCN1 was found to antagonize TNF signaling by increasing the extracellular pool of TNFR1. In this study, we assessed their relationship in the esophageal cancer cells and found a more complex liaison among them. At first, TNF highly upregulated PGLYRP1 expression but downregulated CCN1. Secondly, PGLYRP1 bound TNFR1 and HSP70 both intracellularly and extracellularly, but TNF only promoted their extracellular interaction. Lastly, the knockdown of PGLYRP1 impaired TNF signaling. Taken together, this study shows that CCN1 interrupts TNF signaling by increasing the extracellular TNFR1 species while TNF fights back by upregulating PGLYRP1 to absorb them.

Recent advances in the structure, synthesis, and applications of natural polymeric hydrogels.

Hydrogels, polymeric network materials, are capable of swelling and holding the bulk of water in their three-dimensional structures upon swelling. In recent years, hydrogels have witnessed increased attention in food and biomedical applications. In this paper, the available literature related to the design concepts, types, functionalities, and applications of hydrogels with special emphasis on food applications was reviewed. Hydrogels from natural polymers are preferred over synthetic hydrogels. They are predominantly used in diverse food applications for example in encapsulation, drug delivery, packaging, and more recently for the fabrication of structured foods. Natural polymeric hydrogels offer immense benefits due to their extraordinary biocompatible nature. Hydrogels based on natural/edible polymers, for example, those from polysaccharides and proteins, can serve as prospective alternatives to synthetic polymer-based hydrogels. The utilization of hydrogels has so far been limited, despite their prospects to address various issues in the food industries. More research is needed to develop biomimetic hydrogels, which can imitate the biological characteristics in addition to the physicochemical properties of natural materials for different food applications.

Spatial Pattern of Endophytic Fungi and the Symbiotic Germination of Tulasnella Fungi from Wild Cymbidium goeringii (Orchidaceae) in China.

The endophytic microbiome in orchid plants is rich and diverse; however, few studies have analyzed the endophytic microbiome of Cymbidium plants in different tissues and soils. This study implemented the Illumina Miseq technology to investigate the diversity of endophytic fungi in different tissues of wild Cymbidium goeringii. The results demonstrated that different tissue samples harbor a rich fungal endophytic community, and those fungi could be classified into 4 phyla, at least 145 families, and 185 genera. The endophytic fungal community diversity differed among the orchid tissues and soils, and some fungal taxa were clearly concentrated in certain orchid tissues, with more operational taxonomic units (OTUs) being detected. Investigation of mycorrhizal associations showed that 43 (about 3.8%) of the total 1137 OTUs could be assigned as Orchidaceae mycorrhizal fungi (OMF), while about 96.2% the OTUs were non-mycorrhizal fungi. Among the OMFs, OTUs of the ectomycorrhizal fungi Russulaceae and Thelephoraceae families were the most abundant, with different richness in the soil, followed by Tulasnellaceae and Ceratobasidiaceae, which were dominant in the root communities of C. goeringii. In the seeds, the absolutely dominant family was Nectriaceae, and the common OMFs Ceratobasidiaceae (five OTUs) and Tulasnellaceae (one OTU) were also detected in the seeds. Two Tulasnella spp. isolates from the roots of wild C. goeringii could effectively promote seed germination and rhizome formation of wild C. goeringii, and these strains might be particularly important in the practice of conservation for many endangered C. goeringii in China.

Comparative study of the efficacy of dexmedetomidine and fentanyl on anxiety and pain of parturients with different COMTva1158met genotypes.

OBJECTIVE: This study investigates the effects of COMTval158met gene polymorphism on maternal anxiety and pain during delivery and on the analgesic and anxiety efficacy of dexmedetomidine during delivery. METHODS: Sixty-one pregnant women, who were hospitalized in our hospital from January to November of 2016 were recruited and randomly divided into two groups, F and D groups. The pregnant women in the F group were given labor analgesia with ropivacaine combined with fentanyl. The pregnant women in the D group were given labor analgesia with ropivacaine combined with dexmedetomidine. Before and after labor analgesia, the genotype of COMT in the blood from two groups was detected, and the situation of labor anxiety and analgesia was analyzed. Then, the relationship between labor anxiety, analgesia, and COMT polymorphism was analyzed. RESULTS: In the 61 pregnant women, there were 30 women of wild homozygotes (GG) of COMT, 22 women of mutant heterozygotes (GA), and nine women of mutant homozygotes (AA), the mutation rate of allele A was 23.77%. The anxiety status score, anxiety trait score, and pain score in the AA genotype were significantly higher than those in the GG and GA genotype (p < 0.05). There was a significant difference in the efficacy of GG and AA genotypes between groups D and F for treating labor anxiety (p < 0.05), the efficacy of group D was better than that of group F in treating delivery anxiety, there was no significant difference in anxiety scores between the two groups in GA genotypes (p > 0.05); there was no significant difference in pain between group D and F in GG, GA, and AA genotypes (p > 0.05). There was no significant difference in pain and anxiety scores between the three genotypes in group D (p > 0.05), there was significant difference in pain scores among the three genotypes in group F (p < 0.05), but there was no significant difference in anxiety (p > 0.05). CONCLUSIONS: The mutation of the COMTval158met gene leads to increased anxiety and pain during childbirth. The effect of dexmedetomidine on the anxiety of GG and AA genotypes is better than that of fentanyl, and the mutation of the COMTval158met gene has no impact on dexmedetomidine effect.

Anti-Cancer Effects of Auranofin in Human Lung Cancer Cells by Increasing Intracellular ROS Levels and Depleting GSH Levels.

Auranofin, as a thioredoxin reductase (TrxR) inhibitor, has promising anti-cancer activity in several cancer types. However, little is known about the inhibitory effect of auranofin on lung cancer cell growth. We, therefore, investigated the antigrowth effects of auranofin in various lung cancer cells with respect to cell death, reactive oxygen species (ROS), and glutathione (GSH) levels. Treatment with 0~5 µM auranofin decreased cell proliferation and induced cell death in Calu-6, A549, SK-LU-1, NCI-H460, and NCI-H1299 lung cancer cells at 24 h. In addition, 0~5 µM auranofin increased ROS levels, including O2•-, and depleted GSH levels in these cells. N-acetyl cysteine (NAC) prevented growth inhibition and mitochondrial membrane potential (MMP, ∆Ψm) loss in 3 and 5 µM auranofin-treated Calu-6 and A549 cells at 24 h, respectively, and decreased ROS levels and GSH depletion in these cells. In contrast, L-buthionine sulfoximine (BSO) enhanced cell death, MMP (∆Ψm) loss, ROS levels, and GSH depletion in auranofin-treated Calu-6 and A549 cells. Treatment with 3 and 5 µM auranofin induced caspase-3 activation and poly (ADP ribose) polymerase (PARP) cleavage in Calu-6 and A549 cells, respectively. Both were prevented by NAC, but enhanced by BSO. Moreover, TrxR activity was reduced in auranofin-treated Calu-6 and A549 cells. That activity was decreased by BSO, but increased by NAC. In conclusion, these findings demonstrate that auranofin-induced cell death is closely related to oxidative stress resulted from increased ROS levels and GSH depletion in lung cancer cells.

[Contamination characteristics and preliminaery exposure risk assessment of chloropropanol esters and glycidyl esters in infant formula sold in Beijing in 2021].

OBJECTIVE: To explore the contamination characteristics of chloropropanol esters and glycidyl esters in infant formulas sold in Beijing in 2021, and to evaluate the exposure risk of chloropropanol esters and glycidyl esters for infants and toldders aged 0-36 months old. METHODS: The contents of chloropropanol esters and glycidyl esters in infant formula samples were determined using gas chromatography-mass spectrometry with deuterated internal standards. Combined with the recommended consumption of infant formulas, the exposure level of chloropropanol esters and glycidyl esters in infants and toddlers aged 0-36 months was calculated. RESULTS: The detection rate of 3-chloropropane-1, 2-diol esters(3-MCPDE), 2-chloropropane-1, 3-diol esters(2-MCPDE) and glycidyl esters in infant formulas were 98.6%, 97.1% and 95.7%, respectively. The average contents of 3-MCPDE, 2-MCPDE and glycidyl esters were 44.54, 15.65 and 12.65 µg/kg. For infant of each age groups, the daily intakes of 3-MCPDE via infant formulas by each infant groups were 0.28-0.90 µg/(kg BW), which were all lower than the tolerable daily intake(TDI, 2 µg/(kg BW));the daily intakes of 2-MCPDE via infant formulas by each infant groups were 0.10-0.29 µg/(kg BW);the exposure levels of glycidyl were 0.08-0.22 µg/(kg BW), and the margin of exposure(MOE) values were all higher than 25 000. CONCLUSION: Chloropropanol esters and glycidyl esters in infant formulas sold in Beijing from 2021 were less polluted and their intake was within the safe range.