Increased Expression and Prognostic Significance of BYSL in Melanoma.

We evaluated the BYSL content and underlying mechanism in melanoma (SKCM) overall survival (OS). In this study, we used a comprehensive approach combining bioinformatics tools, including miRNA estimation, quantitative real-time polymerase chain reaction (qRT-PCR) of miRNAs, E3 ligase estimation, STRING analysis, TIMER analysis, examination of associated upstream modulators, protein-protein interaction (PPI) analysis, as well as retrospective and survival analyses, alongside clinical sample validation. These methods were used to investigate the content of BYSL, its methylation status, its relation to patient outcome, and its immunologic significance in tumors. Our findings revealed that BYSL expression is negatively regulated by BYSL methylation. Analysis of 468 cases of SKCM RNA sequencing samples demonstrated that enhanced BYSL expression was associated with higher tumor grade. We identified several miRNAs, namely hsa-miR-146b-3p, hsa-miR-342-3p, hsa-miR-511-5p, hsa-miR-3690, and hsa-miR-193a-5p, which showed a strong association with BYSL levels. Furthermore, we predicted the E3 ubiquitin ligase of BYSL and identified CBL, FBXW7, FZR1, KLHL3, and MARCH1 as potential modulators of BYSL. Through our investigation, we discovered that PNO1, RIOK2, TSR1, WDR3, and NOB1 proteins were strongly associated with BYSL expression. In addition, we found a close association between BYSL levels and certain immune cells, particularly dendritic cells (DCs). Notably, we observed a significant negative correlation between miR-146b-3p and BYSL mRNA expression in SKCM sera samples. Collectively, based on the previously shown evidences, BYSL can serve as a robust bioindicator of SKCM patient prognosis, and it potentially contributes to immune cell invasion in SKCM.

All of whom? Limitations encountered using All of Us Researcher Workbench in a Primary Care residents secondary data analysis research training block.

OBJECTIVES: The goal of this case report is to detail experiences and challenges experienced in the training of Primary Care residents in secondary analysis using All of Us Researcher Workbench. At our large, urban safety net hospital, Primary Care/Internal Medicine residents in their third year undergo a research intensive block, the Research Practicum, where they work as a team to conduct secondary data analysis on a dataset with faculty facilitation. In 2023, this research block focused on use of the All of Us Researcher Workbench for secondary data analysis. MATERIALS AND METHODS: Two groups of 5 residents underwent training to access the All of Us Researcher Workbench, and each group explored available data with a faculty facilitator and generated original research questions. Two blocks of residents successfully completed their research blocks and created original presentations on "social isolation and A1C" levels and "medical discrimination and diabetes management." RESULTS: Departmental faculty were satisfied with the depth of learning and data exploration. In focus groups, some residents noted that for those without interest in performing research, the activity felt extraneous to their career goals, while others were glad for the opportunity to publish. In both blocks, residents highlighted dissatisfaction with the degree to which the All of Us Researcher Workbench was representative of patients they encounter in a large safety net hospital. DISCUSSION: Using the All of Us Researcher Workbench provided residents with an opportunity to explore novel questions in a massive data source. Many residents however noted that because the population described in the All of Us Researcher Workbench appeared to be more highly educated and less racially diverse than patients they encounter in their practice, research may be hard to generalize in a community health context. Additionally, given that the data required knowledge of 1 of 2 code-based data analysis languages (R or Python) and work within an idiosyncratic coding environment, residents were heavily reliant on a faculty facilitator to assist with analysis. CONCLUSION: Using the All of Us Researcher Workbench for research training allowed residents to explore novel questions and gain first-hand exposure to opportunities and challenges in secondary data analysis.

Metagenomic next generation sequencing of bronchoalveolar lavage fluids for the identification of pathogens in patients with pulmonary infection: A retrospective study.

Due to the limitations of traditional laboratory methods (TMs), identification of causative pathogens of numerous pulmonary infections (PIs) remains difficult. This study evaluated the value of metagenomic next generation sequencing (mNGS) in the identification of various respiratory pathogens. A total of 207 patients with TMs and mNGS data were collected for this retrospective study. TMs included sputum culture, blood, and bronchoalveolar lavage fluid (BALF) analysis, or polymerase chain reaction analysis of throat swabs. Otherwise, BALF was collected and analyzed using mNGS. For bacterial pathogens, sensitivities of mNGS as compared to TMs were 76.74 % and 58.14 % (P=0.012). For fungal pathogens, the detection rate of mNGS sensitivity was higher as compared to that of TMs (93.68 % vs 22.11 %; P<0.001). The positive predictive value and negative predictive value were also greater for mNGS. Use of mNGS for BALF analysis offers good specificity and thus facilitates to the clinical diagnosis of PIs.

Asymmetric Total Synthesis of Anti-HBV Drug Entecavir: Catalytic Strategies for the Stereospecific Construction of Densely Substituted Cyclopentene Cores.

We have successfully accomplished a catalytic asymmetric total synthesis of entecavir, a first-line antihepatitis B virus medication. The pivotal aspect of our strategy lies in the utilization of a Pd-catalyzed enyne borylative cyclization reaction, enabling the construction of a highly substituted cyclopentene scaffold with exceptional stereoselectivity. Additionally, we efficiently accessed the crucial 1,3-diol enyne system early in our synthetic route through a diarylprolinol organocatalyzed enantioselective cross-aldol reaction and Re-catalyzed allylic alcohol relocation. By strategically integrating these three catalytic protocols, we established a practical pathway for acquiring valuable densely heteroatom-substituted cyclopentene cores.

Full-Section Deformation Monitoring of High-Altitude Fault Tunnels Based on Three-Dimensional Laser Scanning Technology.

In traditional tunnel monitoring, the characteristic points of an object within a tunnel are measured to obtain information about the object. Considering the limitations of the traditional method in measuring the complex surface structure of tunnels, such as limited monitoring points, a long measurement period, and low precision, this study introduces an approach that uses three-dimensional (3D) laser scanning for monitoring tunnel cross-section deformation. Using this approach, the soft surrounding rock of a high-altitude ultralong tunnel was taken as the monitoring object. The test tunnel was first scanned using a 3D laser scanner, and the collected data were processed. The internal structural data of the tunnel were subsequently compared with its actual contour lines and the data of its primary branch and secondary lining on different dates. The results indicate that the arch roof of the tunnel tended to be stable within a certain time range when the positions of the primary branch and secondary lining were at different measuring points with different pile numbers. The deformation of the pile number on the left and right sides did not generally exceed 0.02 m, except at a few measuring points. A comparison between the actual cross section of the initial branch and that of the designed section showed that the actual elevation of the arch of the initial branch of the tunnel was greater than its designed elevation by no more than 0.3 m. Hence, through this study, a convenient and practical method is presented for monitoring deformation in complex curved tunnel structures.

Identification of superior and rare haplotypes to optimize branch number in soybean.

KEY MESSAGE: Using the integrated approach in the present study, we identified eleven significant SNPs, seven stable QTLs and 20 candidate genes associated with branch number in soybean. Branch number is a key yield-related quantitative trait that directly affects the number of pods and seeds per soybean plant. In this study, an integrated approach with a genome-wide association study (GWAS) and haplotype and candidate gene analyses was used to determine the detailed genetic basis of branch number across a diverse set of soybean accessions. The GWAS revealed a total of eleven SNPs significantly associated with branch number across three environments using the five GWAS models. Based on the consistency of the SNP detection in multiple GWAS models and environments, seven genomic regions within the physical distance of ± 202.4 kb were delineated as stable QTLs. Of these QTLs, six QTLs were novel, viz., qBN7, qBN13, qBN16, qBN18, qBN19 and qBN20, whereas the remaining one, viz., qBN12, has been previously reported. Moreover, 11 haplotype blocks, viz., Hap4, Hap7, Hap12, Hap13A, Hap13B, Hap16, Hap17, Hap18, Hap19A, Hap19B and Hap20, were identified on nine different chromosomes. Haplotype allele number across the identified haplotype blocks varies from two to five, and different branch number phenotype is regulated by these alleles ranging from the lowest to highest through intermediate branching. Furthermore, 20 genes were identified underlying the genomic region of ± 202.4 kb of the identified SNPs as putative candidates; and six of them showed significant differential expression patterns among the soybean cultivars possessing contrasting branch number, which might be the potential candidates regulating branch number in soybean. The findings of this study can assist the soybean breeding programs for developing cultivars with desirable branch numbers.

Design, Synthesis, and Fungicidal Activities of Novel N-(Pyrazol-5-yl)benzamide Derivatives Containing a Diphenylamine Moiety.

To accelerate the development of novel fungicides, a variety of N-(pyrazol-5-yl)benzamide derivatives with a diphenylamine moiety were designed and synthesized using a pharmacophore recombination strategy based on the structure of pyrazol-5-yl-aminophenyl-benzamides. The bioassay results demonstrated that most of the target compounds had excellent in vitro antifungal activities against Sclerotinia sclerotiorum, Valsa mali, and Botrytis cinerea. In particular, compound 5IIIh exhibited remarkable activity against S. sclerotiorum (EC50 = 0.37 mg/L), which was similar to that of fluxapyroxad (EC50 = 0.27 mg/L). In addition, compound 5IIIc (EC50 = 1.32 mg/L) was observed to be more effective against V. mali than fluxapyroxad (EC50 = 12.8 mg/L) and comparable to trifloxystrobin (EC50 = 1.62 mg/L). Furthermore, compound 5IIIh demonstrated remarkable in vivo protective antifungal properties against S. sclerotiorum, with an inhibition rate of 96.8% at 100 mg/L, which was close to that of fluxapyroxad (99.6%). Compounds 5IIIc (66.7%) and 5IIIh (62.9%) exhibited good in vivo antifungal effects against V. mali at 100 mg/L, which were superior to that of fluxapyroxad (11.1%) but lower than that of trifloxystrobin (88.9%). The succinate dehydrogenase (SDH) enzymatic inhibition assay was conducted to confirm the mechanism of action. Molecular docking analysis further revealed that compound 5IIIh has significant hydrogen-bonding, π-π, and p-π conjugation interactions with ARG 43, SER 39, TRP 173, and TYR 58 in the binding site of SDH, and the binding mode was similar to that of the commercial fungicide fluxapyroxad. All of the results suggest that compound 5IIIh could be a potential SDH inhibitor, offering a valuable reference for future studies.

Interaction between Per- and Polyfluorinated Substances (PFAS) and Acetaminophen in Disease Exacerbation-Focusing on Autism and the Gut-Liver-Brain Axis.

This review presents a new perspective on the exacerbation of autism spectrum disorder (ASD) by per- and polyfluoroalkyl substances (PFAS) through the gut-liver-brain axis. We have summarized evidence reported on the involvement of the gut microbiome and liver inflammation that led to the onset and exacerbation of ASD symptoms. As PFAS are toxicants that particularly target liver, this review has comprehensively explored the possible interaction between PFAS and acetaminophen, another liver toxicant, as the chemicals of interest for future toxicology research. Our hypothesis is that, at acute dosages, acetaminophen has the ability to aggravate the impaired conditions of the PFAS-exposed liver, which would further exacerbate neurological symptoms such as lack of social communication and interest, and repetitive behaviors using mechanisms related to the gut-liver-brain axis. This review discusses their potential interactions in terms of the gut-liver-brain axis and signaling pathways that may contribute to neurological diseases.

The regulatory mechanism of physiological sleep-wake / 中国药理学通报

This paper explains the mechanism of the mutual switching between physiological sleep and wakefulness from the aspects of the sleep circadian system and the sleep homeostasis system. In the circadian rhythm system, with the suprachiasmatic nucleus as the core, the anatomical connections between the suprachiasmatic nucleusand various systems that affect sleep are summarized, starting from the suprachiasmatic nucleus, passing through the four pathways of the melatonin system, namely, subventricular area of the hypothalamus, the ventrolateral nucleus of the preoptic area, orexin neurons, and melatonin, then the related mechanisms of their regulation of sleep and wakefulness are expounded. In the sleep homeostasis system, with adenosine and prostaglandin D2 as targets, the role of hypnogen in sleep arousal mechanisms in regulation is also expounded.

Comparison of two novel methods for counting wheat ears in the field with terrestrial LiDAR.

BACKGROUND: The metrics for assessing the yield of crops in the field include the number of ears per unit area, the grain number per ear, and the thousand-grain weight. Typically, the ear number per unit area contributes the most to the yield. However, calculation of the ear number tends to rely on traditional manual counting, which is inefficient, labour intensive, inaccurate, and lacking in objectivity. In this study, two novel extraction algorithms for the estimation of the wheat ear number were developed based on the use of terrestrial laser scanning (TLS) in conjunction with the density-based spatial clustering (DBSC) algorithm based on the normal and the voxel-based regional growth (VBRG) algorithm. The DBSC involves two steps: (1) segmentation of the point clouds using differences in the normal vectors and (2) clustering of the segmented point clouds using a density clustering algorithm to calculate the ear number. The VBRG involves three steps: (1) voxelization of the point clouds, (2) construction of the topological relationships between the voxels as a connected region using the k-dimensional tree, and (3) detection of the wheat ears in the connected areas using a regional growth algorithm. RESULTS: The results demonstrated that DBSC and VBRG were promising in estimating the number of ears for different cultivars, planting densities, N fertilization rates, and growth stages of wheat (RMSE = 76 ~ 114 ears/m2, rRMSE = 18.62 ~ 27.96%, r = 0.76 ~ 0.84). Comparing the performance of the two algorithms, the overall accuracy of the DBSC (RMSE = 76 ears/m2, rRMSE = 18.62%, r = 0.84) was better than that of the VBRG (RMSE = 114 ears/m2, rRMSE = 27.96%, r = 0.76). It was found that with the DBSC, the calculation in points as units permitted more detailed information to be retained, and this method was more suitable for estimation of the wheat ear number in the field. CONCLUSIONS: The algorithms adopted in this study provide new approaches for non-destructive measurement and efficient acquisition of the ear number in the assessment of the wheat yield phenotype.

Dynamic Threshold Cable-Stayed Bridge Health Monitoring System Based on Temperature Effect Correction.

The early health warning of a cable-stayed bridge is of great significance for discovering the abnormal condition of the structure, eliminating the risk factors, and ensuring the normal operation of the bridge in order to set a reasonable safety monitoring threshold to ensure the safety warning and condition assessment of the bridge structure. A method of dynamic early warning by considering the temperature effect is adopted in this paper on the basis of the benchmark threshold. Based on the long-term deflection monitoring data of a bridge in Wuhan, the generalized Pareto distribution (GPD) extreme value analysis theory is used to set the benchmark threshold. Then, by constructing the seasonal autoregressive integrated moving average (SARIMA) long-span bridge temperature effect prediction model, the reference threshold is dynamically adjusted. Finally, it is compared with the traditional fixed threshold monitoring system. The results show that the dynamic threshold has stronger adaptability to the monitoring of cable-stayed bridges and can also achieve effective monitoring of local mutations in other periods. Dynamic threshold early warning can reduce the shortcomings of traditional early warning methods such as underreporting and misreporting. At the same time, the GPD extreme value analysis theory overcomes the disadvantage that the extreme value information is not fully utilized. It has an important application value for bridge health monitoring.

Chronic exposure to nanocellulose altered depression-related behaviors in mice on a western diet: The role of immune modulation and the gut microbiome.

AIMS: To determine if cellulose nanofibrils (CNF) have potential applications as food additives. MATERIALS AND METHODS: Male C57BL/6 mice on a Western diet were exposed to CNF for one month at a dose of 30 mg/kg by gavage. Male NOD mice, a model for type 1 diabetes (T1D), were used in a six-month study. KEY FINDINGS: Sequencing analysis of 16S rRNA genes suggested significant changes in gut microbiome of male C57BL/6 mice exposed to CNF. Analysis of functional metagenomics indicated that many of the functional contents that might be altered following CNF ingestion were associated with lipid and carbohydrate processing. Further studies in NOD mice suggested that there were some decreases in the blood glucose levels during the insulin tolerance test and glucose tolerance test following CNF treatment. However, these small decreases were not considered biologically meaningful as there were no significant changes in either the area under the curve or the first-order rate constant for glucose disappearance. Moreover, serum concentrations of cytokines/chemokines including IL-3, IL-12(p70) and the keratinocyte chemoattractant were increased following chronic exposure to CNF. In addition, behavioral studies suggested that the percentage of immobility time during the tail-suspension test was significantly increased following six months of exposure to CNF in NOD mice, signifying an increase in depression-related behavior. SIGNIFICANCE: Collectively, long-term CNF consumption was associated with changes in the ecology of the gut microbiome, immune homeostasis, and possibly energy metabolism and mental health in male NOD mice on a Western diet.

Genome-wide survey identified superior and rare haplotypes for plant height in the north-eastern soybean germplasm of China.

The proper and efficient utilization of natural genetic diversity can significantly impact crop improvements. Plant height is a quantitative trait governing the plant type as well as the yield and quality of soybean. Here, we used a combined approach including a genome-wide association study (GWAS) and haplotype and candidate gene analyses to explore the genetic basis of plant height in diverse natural soybean populations. For the GWAS analysis, we used the whole-genome resequencing data of 196 diverse soybean cultivars collected from different accumulated temperature zones of north-eastern China to detect the significant single-nucleotide polymorphisms (SNPs) associated with plant height across three environments (E1, E2, and E3). A total of 33 SNPs distributed on four chromosomes, viz., Chr.02, Chr.04, Chr.06, and Chr.19, were identified to be significantly associated with plant height across the three environments. Among them, 23 were consistently detected in two or more environments and the remaining 10 were identified in only one environment. Interestingly, all the significant SNPs detected on the respective chromosomes fell within the physical interval of linkage disequilibrium (LD) decay (± 38.9 kb). Hence, these genomic regions were considered to be four quantitative trait loci (QTLs), viz., qPH2, qPH4, qPH6, and qPH19, regulating plant height. Moreover, the genomic region flanking all significant SNPs on four chromosomes exhibited strong LD. These significant SNPs thus formed four haplotype blocks, viz., Hap-2, Hap-4, Hap-6, and Hap-19. The number of haplotype alleles underlying each block varied from four to six, and these alleles regulate the different phenotypes of plant height ranging from dwarf to extra-tall heights. Nine candidate genes were identified within the four haplotype blocks, and these genes were considered putative candidates regulating soybean plant height. Hence, these stable QTLs, superior haplotypes, and candidate genes (after proper validation) can be deployed for the development of soybean cultivars with desirable plant heights. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-023-01363-7.

Acupuncture for Chronic Prostatitis or Chronic Pelvic Pain Syndrome: An Updated Systematic Review and Meta-Analysis.

Background: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a complex male dysfunction, mostly seen in young and middle-aged men with a history of more than 3 months. As a traditional therapy of Traditional Chinese Medicine, acupuncture has been proven an effective method to treat CP/CPPS in recent years. Though some meta-analyses on acupuncture for chronic prostatitis were published in 2018 and 2019, most of the included studies were low in quality according to the JADAD score (JADAD < 4). The conclusions of acupuncture for CP/CPPS remain indefinite. Purpose: This review aims to evaluate the efficacy of acupuncture for CP/CPPS by including high-quality literature only (JADAD ≥ 4) to provide a reliable basis for clinical applications and research. Method: Nine electronic databases were searched from inception to March 1, 2022, and only randomized controlled trials (RCT) with high-quality (JADAD ≥ 4) were included. Data were analyzed using Review Manager 5.3. and was verified through trial sequential analysis (TSA). We carried out a sensitivity analysis for the heterogeneity (I 2 ≥ 50%). Publication bias was explored using a funnel plot. Result: Ten RCTs (11 trials) of high-quality methodology involving 798 patients were included. Meta-analysis showed that compared to sham acupuncture (SAT) and western medicine (WM), acupuncture (AT) played superior roles for CP/CPPS patients in pain score, NIH-CPSI score, quality of life score, urinary symptom, and efficacy rate. As for the adverse effects, 4 RCTs described mild hematoma and pain in AT and SAT groups, while specific symptoms including nausea, abdominal pain, dizziness, and low blood pressure were reported in WM groups. Conclusion: This meta-analysis indicated that acupuncture has measurable benefits on CP/CPPS, and security has also been ensured. However, this meta-analysis only included 10 RCTs; thus, RCTs with a larger sample size and longer-term observation are required to verify the effectiveness of acupuncture further in the future.

Development and clinical evaluation of an online automated quality control system for improving laboratory quality management.

BACKGROUND: We developed an efficient online automated quality control (AUTO QC) system and tested its feasibility on automatic laboratory assembly lines. METHODS: AUTO QC is based on developed quality control software (Smart QC) and designed adaptable consumables before. We applied the system to two assembly lines in our laboratory. Using third-party quality control samples, we evaluated the impact of the online AUTO QC system on out-of-control rate, biosecurity risk, turnaround time (TAT) and cost. RESULTS: AUTO QC significantly decreased the occurrence rate of the Westgard quality control rules 13S/22S/R4s and 12S, representing out-of-control and warning, respectively. The out-of-control rates were reduced by 58%, and the potential biosecurity risk of the samples decreased by 90%. The AUTO QC implementation also reduced the median TAT (by 7 min), the number of full-time employees and the cost of the quality control samples (by 45%). CONCLUSIONS: The total laboratory AUTO QC system can improve the quality and stability of QC testing and reduce cost.

Effects of king grass and rice straw hay on apparent digestibility and ruminal microorganisms of buffalo.

The purpose of this study was to explore the effects of Rice straw and King grass on apparent digestibility, ruminal bacterial, and fungus composition in buffaloes. Three ruminal fistulated buffaloes were used in a 3 × 2 Latin square design. The dietary treatments were king grass and straw hay. Experimental animals were kept in individual pens and concentrate was offered at 1 kg/d while roughage was fed ad libitum. Each period lasted for 15d, with the first 12d for an adaptation period, followed by a 3-day formal trial period. King grass has higher digestibility of protein. Rice straw has higher digestibility to cellulose. The results showed that when buffaloes were fed king grass and straw, Bacteroidetes were dominant in the rumen normal flora, but firmicutes were not. In addition, the results of this experiment suggest that increasing protein content in diets may be beneficial to increase the relative abundance of Proteobacteria. Similarly, higher dietary fiber content may be beneficial for increasing relative abundance of Prevotella and Staphylococcus. The dominant fungi in ruminal fluid 2 h after ingestion were aerobic fungi. These aerobic fungi most likely entered the rumen with food. Whether and how long aerobic fungi can survive in the rumen needs more research.

Six weeks effect of different nanocellulose on blood lipid level and small intestinal morphology in mice.

AIMS: Cellulose nanofibrils (CNF, or NFC), cellulose nanocrystals (CNC, or NCC), and Tempo (2,2,6,6-tetramethylpiperidine-1-oxyl radical) oxidized CNF (Tempo-CNF) were compared for the short-term effect on mice fed with a high-fat and high-sugar (Western diet, WD) to investigate their effect when combined with a sub-optimal diet. SCOPE: Thirty C57B/C female mice (10 weeks old; 5-6 mice/group) were given water, cellulose, or three types of nanocellulose once daily in a dose of 30 mg/kg body weight by oral gavage. After six weeks, weight changes, fecal output, glucose homeostasis, and gut permeability showed no significant among groups. Serum analysis including triglycerides, cholesterol and total bile acids and small intestinal morphology including villus length, villus width, crypt depth, goblet cell count and goblet cell density were no difference for all groups. Only CNC group had higher excretion of bile acids in the feces. CONCLUSIONS: These results suggest that current treated dose using three types of nanocellulose had no detrimental effects on blood lipid level and small intestinal morphology.

Subacute exposure to dechlorane 602 dysregulates gene expression and immunity in the gut of mice.

Dechlorane 602 (Dec 602) has biomagnification potential. Our previous studies suggested that exposure to Dec 602 for 7 days induced colonic inflammation even after 7 days of recovery. To shed some light on the underlying mechanisms, disturbances of gut immunity and gene expression were further studied. Adult C57BL/6 mice were administered orally with Dec 602 for 7 days, then allowed to recover for another 7 days. Colonic type 3 innate lymphoid cells (ILC3s) in lamina propria lymphocytes (LPLs) and lymphocytes in mesenteric lymph nodes (MLNs) were examined by flow cytometry. Expressions of genes in the gut were determined by RNA-Seq. It was found that Dec 602 exposure up-regulated the percentage of CD4+ T cells in MLNs. The mean fluorescent intensity (MFI) of interleukin (IL)- 22 in LPLs was decreased, while the MFI of IL-17a as well as the percentage of IL-17a+ ILC3s in LPLs were increased after exposure to Dec 602. Genes involved in the formation of blood vessels and epithelial-mesenchymal transition were up-regulated by Dec 602. Ingenuity pathway analysis of differentially expressed genes predicted that exposure to Dec 602 resulted in the activation of liver X receptor/retinoid X receptor (LXR/RXR) and suppression of muscle contractility. Our results, on one hand, verified that the toxic effects of Dec 602 on gut immunity could last for at least 14 days, and on the other hand, these results predicted other adverse effects of Dec 602, such as muscle dysfunction. Overall, our studies provided insights for the further investigation of Dec 602 and other emerging environmental pollutants.

Exposure to dechlorane 602 induces perturbation of gut immunity and microbiota in female mice.

The homeostasis of gut immunity and microbiota are associated with the health of the gut. Dechlorane 602 (Dec 602) with food web magnification potential has been detected in daily food. People who were orally exposed to Dec 602 may encounter increased risk of health problems in the gut. In order to reveal the influence of short-term exposure of Dec 602 on gut immunity and microbiota, adult female C57BL/6 mice were administered orally with Dec 602 (low/high doses: 1.0/10.0 µg/kg body weight per day) for 7 days. Lymphocytes were examined by flow cytometry. Gut microbiota was measured by 16S rRNA gene sequencing. Results showed that fecal IgA was upregulated after exposure to the high dose of Dec 602, suggesting that there might be inflammation in the gut. Then, changes of immune cells in mesenteric lymph nodes and colonic lamina propria were examined. We found that exposure to the high dose of Dec 602 decreased the percentages of the anti-inflammatory T regulatory cells in mesenteric lymph nodes. In colonic lamina propria, the production of gut protective cytokine interleukin-22 by CD4+ T cells was decreased, and a decreased trend of interleukin-22 production was also observed in type 3 innate lymphoid cells in the high dose group. Furthermore, an altered microbiota composition toward inflammation in the gut was observed after exposure to Dec 602. Additionally, the altered microbiota correlated with changes of immune parameters, suggesting that there were interactions between influenced microbiota and immune parameters after exposure to Dec 602. Taken together, short-term exposure to Dec 602 induced gut immunity and microbiota perturbations, and this might be the mechanisms for Dec 602 to elicit inflammation in the gut.

Subacute effects of the chlorinated flame retardant dechlorane 602 on intestinal microenvironment in mice.

BACKGROUND: Chlorinated flame retardant Dechlorane 602 (Dec 602) has been detected in daily food, indicating that it may pose a risk to intestinal health. The intestinal microenvironment plays an important role in intestinal health. Intestinal microbiota and metabolites are two important factors for maintaining the microenvironment. However, little is known about the effects of Dec 602 on intestinal microbiota and metabolites. OBJECTIVES: We aimed to probe the effects of Dec 602 on the intestine by revealing the changes that Dec 602 caused to the intestinal microbiota and metabolites. METHODS: Adult female C57BL/6 mice were exposed to Dec 602 (low/high doses: 1.0/10.0 µg/kg body weight per day) orally for 7 consecutive days, and sacrificed after 7 days of recovery. The composition of colonic microbiota was measured by 16S rRNA gene sequencing, and the colonic metabolites were determined by LC-ESI-MS/MS. Finally, the effects of Dec 602 on the colon were validated by histopathological analysis. RESULTS: The intestinal microbiota composition was altered toward a pro-inflammatory status after exposure to Dec 602. Dec 602 exposure also up-regulated oxidative metabolites (glutathione disulfide, taurine and retinoic acid) and pro-inflammatory metabolites (prostaglandin E2). On the other hand, antioxidative metabolites (s-adenosylmethionine and 11-cis-retinol) and anti-inflammatory metabolites (alpha-linolenic acid, eicosapentaenoic acid and docosahexaenoic acid) were down-regulated after exposure to Dec 602. Infiltration of lymphocytes in the colonic lamina propria was observed in the mice treated with Dec 602 for 7 days, and it was not recovered after another 7 days without further treatment. CONCLUSION: Dec 602 interfered with the colonic microbiota and metabolome, and exhibited inflammatory features. Histopathological studies confirmed that Dec 602 exposure did induce colonic inflammation.