The only species of Calvisia (Phasmatodea, Necrosciinae) from China, with a new synonymy and additional descriptions.

Calvisia is a colorful winged stick insect genus consisting of 6 subgenera and 44 species widely distributed in temperate and tropical Asia. C. medogensis syn. nov. was discovered in Mdog, Xizang (Tibet), China and is so far the only species recorded from China. We here propose that C. medogensis syn. nov. is a synonym of C. fuscoalata after checking type specimens of both species. New materials studied are deposited in Yunnan Agricultural University, China (YNAU).

Design, synthesis and anti-oomycete activity of 2-acyloxyhinokitiol derivatives.

In order to explore novel natural product-based anti-oomycete agent, ten 2-acyloxyhinokitiol derivatives (5a-j) were designed and synthesised, and structurally confirmed by 1H NMR,13C NMR, HRMS, and melting point. The stereochemical configuration of compound 5f was unambiguously confirmed by single-crystal X-ray diffraction. Furthermore, we evaluated the target compounds 5a-j as anti-oomycete activity against a serious agricultural disease of Phytophthora capsici. Among the ten hinokitiol ester derivatives tested, four compounds 5d, 5g, 5h and 5j had anti-oomycete activity higher than the positive control zoxamide (EC50 = 23.59 mg/L), and the EC50 values of 18.90, 20.62, 13.61 and 21.29 mg/L, respectively. Especially compound 5h exhibited the best anti-oomycete activity against P. capsici with EC50 value of 13.61 mg/L. Overall, the anti-oomycete activities of 2-acyloxyhinokitiol derivatives is higher than that of 2-sulfonyloxyhinokitiol derivatives. The results laid a good foundation for the subsequent synthesis of hinokitiol ester derivatives with significant anti-oomycete activity.

Assessment of reproductive toxicity in adult zebrafish (Danio rerio) following sublethal exposure to penthiopyrad.

Penthiopyrad (PO), a succinate dehydrogenase inhibitor (SDHI) fungicide, poses a potential risk to fish. Here, we investigated the adverse effects of PO on endocrine regulation and reproductive capacity in zebrafish during a 21-d sublethal exposure to PO concentrations ranging from 0.02 to 2.00 mg/L. Following exposure to PO (0.20 and 2.00 mg/L), female-specific effects including follicle necrosis, structural disturbance of the yolk follicle, fusion of cortical follicles appeared in ovarian tissue of adult females, which led to a significant reduction in fertility. Correspondingly, 0.20 and 2.00 mg/L PO led to a marked reduction in the GSI values of females, and 2.00 mg/L PO caused a 31% decline in the proportion of perinucleolar oocytes (PCO) in oocytes. In addition, testosterone (T) level was obviously suppressed and 17ß-estradiol (E2) level was increased in females after exposure to 2.00 mg/L PO. Male zebrafish treated with 0.20 and 2.00 mg/L of PO exhibited significant interstitial enlargement, edema in the testes, and reduced diameter of seminiferous tubules, along with a thinner basement membrane. The effects of PO on males were associated with significant increase in E2 level, suggesting that PO has an estrogenic effect on male fish. Greater E2 levels in serum were further supported by increased transcription levels of genes linked to the hypothalamic-pituitary-gonad-liver (HPGL) axis. Notably, transcription levels of cyp19a, er2b, era, and cyp19b was remarkably increased, exhibiting a clear link with variations in E2 levels. Overall, the present study demonstrates that PO induces reproductive impairment in zebrafish by promoting steroidogenesis.

Male refractory hypospadias with sexual reversal: a case report.

BACKGROUND: Hypospadias is one of the most prevalent urogenital malformations in clinic. However, some hypospadias may have a more complex disorder of sex development. Usually, hypospadias in these patients is severe. Among them, the 46,XX male sex reversal syndrome is a rare disorder of sex development, and this may be the main reason for this type of hypospadias being difficult to repair. CASE PRESENTATION: We present a Han nationality 19-year-old male with failure of repeated repair of hypospadias. No sperm was found on semen analysis. Lingual mucosal graft was carried out for this patient. It still did not succeed after using lingual mucosal graft repair. Karyotype analysis of this patient confirmed 46,XX karyotype. CONCLUSION: Hypospadias with 46,XX male sex reversal syndrome is hard to repair. Chromosome karyotype examination in patients with hypospadias is suggested. Genetic testing is recommended. In the future, further research is needed on the pathogenesis of disease and how to treat and prevent it.

Synthesis of novel 18ß-glycyrrhetinic acid sulfonate derivatives displaying significant anti-oomycete activity against Phytophthora capsici.

Using 18ß-glycyrrhetinic acid (GA) as the lead compound, fourteen GA sulphonate derivatives (3a-n) were prepared by modifying its C-3 OH group, and their structures were well confirmed by 1H NMR, 13C NMR, HRMS and melting points. Moreover, we screened the anti-oomycete activity of these compounds against Phytophthora capsici by using the mycelial growth rate method. Among the fourteen GA sulphonate derivatives evaluated, four compounds 3f, 3j, 3k and 3l exhibited more potent anti-oomycete activity than that of the positive control zoxamide (EC50 = 25.17 mg/L), and had the median effective concentration (EC50) values of 23.04, 16.16, 22.55, and 13.93 mg/L, respectively. Especially compound 3l showed the best anti-oomycete activity against P. capsici with EC50 value of 13.93 mg/L. Overall, the introduction of sulfonyloxy groups at the C-3 position of GA has a significant impact on its anti-oomycete activity, and the corresponding derivative activity varies significantly with different substituents R.

Construction and Validation of the Postgraduate Research Innovation Ability Scale (PRIAS): A Three-Dimensional Structural Model Based on Componential Theory of Creativity.

Purpose: To explore the structure of postgraduate research innovation ability and verify the Postgraduate Research Innovation Ability Scale. Patients and Methods: This study was based on the componential theory of creativity. First, we drafted an item pool from the literature review, semi-structured interviews, and group discussions. A total of 125 postgraduates were selected for the pre-test. After item selection and exploratory factor analysis, an 11-item, 3-factor postgraduate research innovation ability scale was formed. The scale was applied to a sample of 330 postgraduates from various domestic universities. Exploratory factor analysis and confirmatory factor analysis were used to examine the factor structure of the scales. Results: The results support a three-factor model including creativity-relevant processes, domain-relevant skills, and intrinsic motivation for the Postgraduate Research Innovation Ability Scale. The scale showed good internal consistency (α =0.89) and test-retest reliability (r=0.86). Exploratory factor analysis showed that the KMO value was 0.87, and the Bartlett's sphericity test results were significant. Confirmatory factor analysis confirmed that the three-factor construct demonstrated a good model fit (χ2/df=1.945, GFI=0.916, CFI=0.950, RMSEA=0.076). Conclusion: The Postgraduate Research Innovation Ability Scale has good reliability and validity, and it can be used for future research in related fields.

Transcriptomic Profiling of Fusarium pseudograminearum in Response to Carbendazim, Pyraclostrobin, Tebuconazole, and Phenamacril.

Fusarium pseudograminearum has been identified as a significant pathogen. It causes Fusarium crown rot (FCR), which occurs in several major wheat-producing areas in China. Chemical control is the primary measure with which to control this disease. In this study, transcriptome sequencing (RNA-Seq) was used to determine the different mechanisms of action of four frequently used fungicides including carbendazim, pyraclostrobin, tebuconazole, and phenamacril on F. pseudograminearum. In brief, 381, 1896, 842, and 814 differentially expressed genes (DEGs) were identified under the carbendazim, pyraclostrobin, tebuconazole, and phenamacril treatments, respectively. After the joint analysis, 67 common DEGs were obtained, and further functional analysis showed that the ABC transported pathway was significantly enriched. Moreover, FPSE_04130 (FER6) and FPSE_11895 (MDR1), two important ABC multidrug transporter genes whose expression levels simultaneously increased, were mined under the different treatments, which unambiguously demonstrated the common effects. In addition, Mfuzz clustering analysis and WGCNA analysis revealed that the core DEGs are involved in several critical pathways in each of the four treatment groups. Taken together, these genes may play a crucial function in the mechanisms of F. pseudograminearum's response to the fungicides stress.

Resistance risk assessment of Fusarium pseudograminearum from wheat to prothioconazole.

Fusarium crown rot (FCR), primarily caused by Fusarium pseudograminearum, poses significant threats to cereal crops worldwide. Prothioconazole is a demethylation inhibitor (DMI) fungicide used to control FCR. However, the risk of resistance in F. pseudograminearum to prothioconazole has not yet been evaluated. In this study, the sensitivity of a total of 255 F. pseudograminearum strains obtained from Henan Province, China to prothioconazole were determined by the mycelial growth inhibition. The results showed that the effective concentration to 50% growth inhibition (EC50) of these strains ranged from 0.4228 µg/mL to 2.5284 µg/mL, with a mean EC50 value of 1.0692 ± 0.4527 µg/mL (mean ± SD). Thirty prothioconazole-resistant mutants were obtained out of six selected sensitive parental strains by means of fungicide taming. The resistant mutants exhibited defects in vegetative growth, conidia production, and pathogenicity on wheat seedlings compared to their parental strains. Under ion, cell wall, and temperature stress conditions but not osmotic stress, all the mutants exhibited decreased growth rates compared with their parental strains, which was consistent with the control treatment. Cross-resistance test showed that there was a cross-resistance relationship between prothioconazole and four DMI fungicides, including prochloraz, metconazole, tebuconazole and hexaconazole, but no cross-resistance was observed between prothioconazole and carbendazim, phenamacril, fludioxonil, or azoxystrobin. Although no site mutation occurred on Cyp51a and Cyp51b genes, the constitutive expression level of the Cyp51a gene was significantly increased in all mutants. After being treated with prothioconazole, the Cyp51a and Cyp51b genes were significantly increased in both the resistant mutants and their parents. These results suggested that the resistance to prothioconazole of the mutants may be attributed to the changes of the relative expression level of Cyp51a and Cyp51b genes. Taken together, these results could provide a theoretical basis for the scientific use of prothioconazole in the field and fungicide resistance management strategies.

Transcriptomic profiling of miR-203a inhibitor and miR-34b-injected zebrafish (Danio rerio) validates oil-induced neurological, cardiovascular and eye toxicity response pathways.

The global sequencing of microRNA (miRNA; miR) and integration to downstream mRNA expression profiles in early life stages (ELS) of fish following exposure to crude oil determined consistently dysregulated miRNAs regardless of the oil source or fish species. The overlay of differentially expressed miRNAs and mRNAs into in silico software determined that the key roles of these miRNAs were predicted to be involved in cardiovascular, neurological and visually-mediated pathways. Of these, altered expression of miRNAs, miR-203a and miR-34b were predicted to be primary targets of crude oil. To better characterize the effect of these miRNAs to downstream transcript changes, zebrafish embryos were microinjected at 1 h post fertilization (hpf) with either a miR-203a inhibitor or miR-34b. Since both miRs have been shown to be associated with aryl hydrocarbon receptor (AhR) function, benzo(a)pyrene (BaP), a potent AhR agonist, was used as a potential positive control. Transcriptomic profiling was conducted on injected and exposed larvae at 7 and 72 hpf, and eye morphology assessed following exposure at 72 hpf. The top predicted physiological system disease and functions between differentially expressed genes (DEGs) shared with miR-203a inhibitor-injected and miR-34b-injected embryos were involved in brain formation, and the development of the central nervous system and neurons. When DEGs of miR-203a inhibitor-injected embryos were compared with BaP-exposed DEGs, alterations in nervous system development and function, and abnormal morphology of the neurosensory retina, eye and nervous tissue were predicted, consistent with both AhR and non-AhR pathways. When assessed morphologically, the eye area of miR-203a inhibitor and miR-34b-injected and BaP-exposed embryos were significantly reduced. These results suggest that miR-203a inhibition and miR-34b overexpression contribute to neurological, cardiovascular and eye toxicity responses that are caused by oil and PAH exposure in ELS fish, and are likely mediated through both AhR and non-AhR pathways.

Physiological and transcriptomic analysis dissects the molecular mechanism governing meat quality during postmortem aging in Hu sheep (Ovis aries).

Introduction: Hu sheep, known for its high quality and productivity, lack fundamental scientific research in China. Methods: This study focused on the effects of 24 h postmortem aging on the meat physiological and transcriptomic alteration in Hu sheep. Results: The results showed that the 24 h aging process exerts a substantial influence on the mutton color, texture, and water content as compared to untreated group. Transcriptomic analysis identified 1,668 differentially expressed genes. Functional enrichment analysis highlighted the importance of glycolysis metabolism, protein processing in endoplasmic reticulum, and the FcγR-mediated phagocytosis pathway in mediating meat quality modification following postmortem aging. Furthermore, protein-protein interaction analysis uncovered complex regulatory networks involving glycolysis, the MAPK signaling pathway, protein metabolism, and the immune response. Discussion: Collectively, these findings offer valuable insights into the molecular mechanisms underlying meat quality changes during postmortem aging in Hu sheep, emphasizing the potential for improving quality control strategies in mutton production.

Deep Learning Prediction of Ovarian Malignancy at US Compared with O-RADS and Expert Assessment.

Background Deep learning (DL) algorithms could improve the classification of ovarian tumors assessed with multimodal US. Purpose To develop DL algorithms for the automated classification of benign versus malignant ovarian tumors assessed with US and to compare algorithm performance to Ovarian-Adnexal Reporting and Data System (O-RADS) and subjective expert assessment for malignancy. Materials and Methods This retrospective study included consecutive women with ovarian tumors undergoing gray scale and color Doppler US from January 2019 to November 2019. Histopathologic analysis was the reference standard. The data set was divided into training (70%), validation (10%), and test (20%) sets. Algorithms modified from residual network (ResNet) with two fusion strategies (feature fusion [hereafter, DLfeature] or decision fusion [hereafter, DLdecision]) were developed. DL prediction of malignancy was compared with O-RADS risk categorization and expert assessment by area under the receiver operating characteristic curve (AUC) analysis in the test set. Results A total of 422 women (mean age, 46.4 years ± 14.8 [SD]) with 304 benign and 118 malignant tumors were included; there were 337 women in the training and validation data set and 85 women in the test data set. DLfeature had an AUC of 0.93 (95% CI: 0.85, 0.97) for classifying malignant from benign ovarian tumors, comparable with O-RADS (AUC, 0.92; 95% CI: 0.85, 0.97; P = .88) and expert assessment (AUC, 0.97; 95% CI: 0.91, 0.99; P = .07), and similar to DLdecision (AUC, 0.90; 95% CI: 0.82, 0.96; P = .29). DLdecision, DLfeature, O-RADS, and expert assessment achieved sensitivities of 92%, 92%, 92%, and 96%, respectively, and specificities of 80%, 85%, 89%, and 87%, respectively, for malignancy. Conclusion Deep learning algorithms developed by using multimodal US images may distinguish malignant from benign ovarian tumors with diagnostic performance comparable to expert subjective and Ovarian-Adnexal Reporting and Data System assessment. © RSNA, 2022 Online supplemental material is available for this article.

Relationship between miR-203a inhibition and oil-induced toxicity in early life stage zebrafish (Danio rerio).

Dysregulation of microRNA (miRNA, miR) by environmental stressors influences the transcription of mRNA which may impair organism development and/or lead to adverse physiological outcomes. Early studies evaluating the effects of oil on developmental toxicity in early life stages of fish showed that reductions in expression of miR-203a were associated with enhanced expression of downstream mRNAs that predicted altered eye development, cardiovascular disease, and improper fin development. To better understand the effects of miR-203a inhibition as an outcome of oil-induced toxicity in early life stage (ELS) fish, embryonic zebrafish were injected with an miR-203a inhibitor or treated with 3.5 µM phenanthrene (Phe) as a positive control for morphological alterations of cardiovascular and eye development caused by oil. Embryos treated with Phe had diminished levels of miR-203a at 7 and 72 h after injection. Embryos treated with the miR-203a inhibitor and Phe exhibited a reduced heart rate by 48 h post fertilization (hpf), with an increased incidence of developmental deformities (including pericardial edema, altered eye development, and spinal deformities) and reduced caudal fin length by 72 hpf. There were significant reductions in lens and eye diameters in 120 hpf miR-203a-inhibitor and Phe-treated fish, as well as a significantly reduced number of eye saccades, determined by an optokinetic response (OKR) behavioral assay. The expression of vegfa, which is an important activator during neovascularization, was significantly upregulated in embryos receiving miR-203a inhibitor injections by 7 and 72 hpf with increased trends in vegfa expression in 72 hpf larvae treated with Phe. There were decreasing trends in crx, neurod1, and pde6h expression by 72 hpf in miR-203a inhibitor and Phe treatments, which are involved in photoreceptor function in developing eyes and regulated by miR-203a. These results suggest that an inhibition of miR-203a in ELS fish exhibits an oil-induced toxic response that is consistent with Phe treatment and specifically impacts retinal, cardiac, and fin development in ELS fish.

Sensitivity and Resistance Risk Assessment of Fusarium graminearum from Wheat to Prothioconazole.

Fusarium head blight (FHB), caused mainly by Fusarium graminearum, is one of the most devastating diseases of wheat. Prothioconazole is a broad-spectrum demethylation inhibitor fungicide with excellent efficacy against FHB. In this study, 235 strains of F. graminearum collected from different regions of Henan Province of China in 2016, 2017, and 2018 were randomly selected. The sensitivity of F. graminearum to prothioconazole was determined by the mycelial growth inhibition method. The results showed that the half maximal effective concentration (EC50) values of F. graminearum to prothioconazole ranged from 0.4742 to 3.4403 µg/ml, and the average EC50 value was 1.7758 ± 0.6667 µg/ml. The sensitivity frequency distribution presented a consequent unimodal curve, and thus the average EC50 value can be established as the baseline sensitivity of F. graminearum to prothioconazole. Ten strains of prothioconazole-resistant mutants were obtained by fungicide taming, and the resistance factor of the mutants ranged from 5.71 to 12.32. The genetic stability assay showed that resistance can be inherited stably for 10 generations. All mutants displayed different degrees of defects in vegetative growth, conidia formation, and pathogenicity compared with the parental strain. These results indicated that F. graminearum has a low risk of resistance to prothioconazole. Cross-resistance assay showed that no cross-resistance was found between prothioconazole and carbendazim, tebuconazole, phenamacril, and pydiflumetofen. Among all mutants, sequence analysis showed that no mutation site was found in cyp51A and cyp51B. Real-time PCR assays showed that the expression levels of cyp51A and cyp51B of the mutants were significantly increased after prothioconazole treatment for 24 h. In summary, our study provided a theoretical basis for the resistance risk assessment of F. graminearum to prothioconazole and scientific application of prothioconazole in controlling FHB.

Environmental level of bisphenol F induced reproductive toxicity toward zebrafish.

Bisphenol F (BPF), as an important bisphenol A substitute, is being increasingly used for industrial production. Here we performed large scale fecundity test for zebrafish that are continuous exposed to environmental levels of BPF (0.5, 5 and 50 µg/L) from embryonic stage, and identified suppressed spawning capacity of females and reduced fertility rate of males in adulthood. Although pathological change is only observed in female gonads, the transcriptional change in the hypothalamic-pituitary-gonad axis genes occurred in the gonads of both female and male fish at 150 days post-exposure. F1 generation embryos showed abnormal developmental outcomes including decreased heart rate, reduced body length, and inhibition of spontaneous movement after parental exposure to BPF. RNA-sequencing showed that the genes involved in skeletal/cardiac muscle development were significantly altered in F1 embryos spawned by BPF-treated zebrafish. The advanced pathway analysis showed that cancer and tumour formation were the most enriched pathways in the offspring of 0.5 and 5.0 µg/L groups; organismal development and cardiovascular system development were mainly affected after parental exposure to 50 µg/L of BPF; these changes were mediated by several involved regulators such as GATA4, MYF6, and MEF2C. These findings confirmed that long-term exposure to BPF at environment relevant concentration would result in reproductive toxicity among zebrafish indicating the urgent demand for the control of BPA substitutes.

Tralopyril affects locomotor activity of zebrafish (Danio rerio) by impairing tail muscle tissue, the nervous system, and energy metabolism.

Tralopyril (TP), an antifouling biocide, is widely used to prevent heavy biofouling, and can have potential risks to aquatic organisms. In this study, the effect of TP on locomotor activity and related mechanisms were evaluated in zebrafish (Danio rerio) larvae. TP significantly reduced locomotor activity after 168 -h exposure. Adverse modifications in tail muscle tissue, the nervous system, and energy metabolism were also observed in larvae. TP caused thinning of the muscle bundle in the tail of larvae. In conjunction with the metabolomics results, changes in dopamine (DA) and acetylcholine (ACh), acetylcholinesterase (AChE) activity, and the expression of genes involved in neurodevelopment, indicate that TP may disrupt the nervous system in zebrafish larvae. The change in metabolites (e.g., glucose 6-phosphate, cis-Aconitic acid, acetoacetyl-CoA, coenzyme-A and 3-Oxohexanoyl-CoA) involved in carbohydrate and lipid metabolism indicates that TP may disrupt energy metabolism. TP exposure may inhibit the locomotor activity of zebrafish larvae by impairing tail muscle tissue, the nervous system, and energy metabolism.

miR133b Microinjection during Early Development Targets Transcripts of Cardiomyocyte Ion Channels and Induces Oil-like Cardiotoxicity in Zebrafish (Danio rerio) Embryos.

Previous studies have shown that altered expression of a family of small noncoding RNAs (microRNAs, or miRs) regulates the expression of downstream mRNAs and is associated with diseases and developmental disorders. miR133b is highly expressed in mammalian cardiac and skeletal muscle, and aberrant expression is associated with cardiac disorders and electrophysiological changes in cardiomyocytes. Similarly, cardiac dysfunction has been observed in early life-stage mahi-mahi (Coryphaena hippurus) exposed to crude oil, a phenotype that has been associated with an upregulation of miR133b as well as subsequent downregulation of a delayed rectifier potassium channel (IKr) and calcium signaling genes that are important for proper heart development during embryogenesis. To examine the potential role of miR133b in oil-induced early life-stage cardiotoxicity in fish, cleavage-stage zebrafish (Danio rerio) embryos were either (1) microinjected with ∼3 nL of negative control miR (75 µM) or miR133b (75 µM) or (2) exposed to a treatment solution containing 5 µM benzo(a)pyrene (BaP), a model polycyclic aromatic hydrocarbon, as a positive control. At 72 h post fertilization (hpf), miR133b-injected fish exhibited BaP-like cardiovascular malformations, including a significantly increased pericardial area relative to negative control miR-injected embryos, as well as a significantly reduced eye area. qPCR revealed that miR133b microinjection decreased the abundance of cardiac-specific IKr kcnh6 at 5 hpf, which may contribute to action potential elongation in oil-exposed cardiomyocytes. Additionally, ryanodine receptor 2, a crucial calcium receptor in the sarcoplasmic reticulum, was also downregulated by miR133b. These results indicate that an oil-induced increase in miR133b may contribute to cardiac abnormalities in oil-exposed fish by targeting cardiac-specific genes essential for proper heart development.

Environmentally relevant concentrations of tralopyril affect carbohydrate metabolism and lipid metabolism of zebrafish (Danio rerio) by disrupting mitochondrial function.

Tralopyril (TP), an antifouling biocide, is widely used to prevent heavy biofouling, and can have potential risks to aquatic organisms. However, there is little information available on the toxicity of tralopyril to aquatic organisms. In this study, the effect of TP on carbohydrate and lipid metabolism, and related mechanisms were evaluated in zebrafish (Danio rerio) larvae. Adverse modifications in carbohydrate metabolism were observed in larvae: hexokinase (HK) activity, succinate dehydrogenase (SDH) activity, and adenosine triphosphate (ATP) content were significantly decreased; and transcript expression of genes (GK, HK1, and PCK1) was also significantly changed. Changes of TG content, FAS activity and transcript expression of genes (ACO, ehhadh, and fas) indicate that TP disrupt lipid metabolism in zebrafish larvae. The change in expression of genes (ndufs4, Sdhα, and uqcrc2) involved in the mitochondrial respiratory complexes, and genes (polg1 and tk2) involved in the mitochondrial DNA replication and transcription indicates that these adverse effects on carbohydrate and lipid metabolism are caused by mitochondrial dysfunction.

Silencing of AHNAK2 restricts thyroid carcinoma progression by inhibiting the Wnt/ß-catenin pathway.

AHNAK nucleoprotein 2 (AHNAK2) has been proposed to have an oncogenic role in various human cancers. However, the functional role of AHNAK2 in thyroid carcinoma (TC) progression has never been explored. In this study, quantitative real-time polymerase chain reaction and western blot were conducted to evaluate the expression of genes. The functional role of AHNAK2 was elucidated by cell count kit-8, colony-forming assay, wound-healing assay, and Transwell invasion assay. We found that AHNAK2 was highly expressed in thyroid carcinoma, and it was tightly correlated with the pathological stage in TC. The mRNA and protein levels of AHNAK2 were increased in TC cells. Silencing of AHNAK2 restricted the proliferation, metastasis, and epithelial-mesenchymal transition (EMT) of TC cells. AHNAK2 silencing inhibited the protein expression of ß-catenin and cyclin D1, and AHNAK2 overexpression had the opposite effects. Moreover, LiCl or ICG-001 exposure counteracted the effects of AHNAK2 silencing or upregulation on malignant phenotypes of TC cells. In conclusion, the knockdown of AHNAK2 restrained the proliferation, metastasis, and EMT of TC cells by inhibiting the Wnt/ß-catenin pathway, providing a new potential mechanism of AHNAK2 in understanding the oncogenesis and progression of TC.

Bioaccumulation, Metabolism and the Toxic Effects of Chlorfenapyr in Zebrafish (Danio rerio).

Chlorfenapyr is widely used as an insecticide/miticide. Tralopyril, the active metabolite of chlorfenapyr, is used as an antifouling biocide in antifouling systems, and negatively affects aquatic environments. However, it is unclear whether tralopyril is a metabolite of chlorfenapyr in aquatic vertebrates, and there is little data on the bioaccumulation and toxicity of chlorfenapyr to aquatic vertebrates. In this study, the bioaccumulation and elimination of chlorfenapyr in zebrafish were assessed, and tralopyril, the active metabolite of chlorfenapyr, was determined. The effects of chronic exposure to chlorfenapyr on zebrafish liver and brain oxidative damage, apoptosis, immune response, and metabolome were investigated. These results showed that chlorfenapyr has a high bioaccumulation in zebrafish, with bioaccumulation factors of 864.6 and 1321.9 after exposure to 1.0 and 10 µg/L chlorfenapyr for 21 days, respectively. Chlorfenapyr at these concentrations also rapidly accumulated in zebrafish, reaching 615.5 and 10336 µg/kg on the second and third days of exposure, respectively. Chlorfenapyr was degraded to tralopyril in zebrafish; therefore, both chlorfenapyr and tralopyril should be considered when evaluating the risk of chlorfenapyr to aquatic organisms. In addition, chronic exposure caused oxidative damage, apoptosis, and immune disorders in zebrafish liver. Chronic exposure also altered the levels of endogenous metabolites in liver and brain. After 9 days of depuration, some indicators of oxidative damage, apoptosis, and immunity returned to normal levels, but the concentration of endogenous metabolites in zebrafish liver was still altered. Overall, these results provide useful information for evaluating the toxicity and environmental fate of chlorfenapyr in aquatic vertebrates.

Comparison of the Diagnostic Performances of Ultrasound-Based Models for Predicting Malignancy in Patients With Adnexal Masses.

AIM: This study aimed to compare different ultrasound-based International Ovarian Tumor Analysis (IOTA) prediction models, namely, the Simple Rules (SRs) the Assessment of Different NEoplasias in the adneXa (ADNEX) models, and the Risk of Malignancy Index (RMI), for the pre-operative diagnosis of adnexal mass. METHODS: This single-centre diagnostic accuracy study involved 486 patients. All ultrasound examinations were analyzed and the prediction models were applied. Pathology was the clinical reference standard. The diagnostic performances of prediction models were measured by evaluating receiver-operating characteristic curves, sensitivities, specificities, positive and negative predictive values, positive and negative likelihood ratios, and diagnostic odds ratios. RESULTS: To discriminate benign and malignant tumors, areas under the ROC curves (AUCs) for ADNEX models were 0.94 (95% CI: 0.92-0.96) with CA125 and 0.94 (95% CI: 0.91-0.96) without CA125, which were significantly higher than the AUCs for RMI I-III: 0.87 (95% CI: 0.83-0.90), 0.83 (95% CI: 0.80-0.86), and 0.82 (95% CI: 0.78-0.86), (all P < 0.0001). At a cut-off of 10%, the ADNEX model with CA125 had the highest sensitivity (0.93; 95% CI: 0.87-0.97) compared with the other models. The SRs model achieved a sensitivity of 0.93 (95% CI: 0.86-0.97) and a specificity of 0.86 (95% CI: 0.82-0.89) when inconclusive diagnoses (11.7%) were classified as malignant. CONCLUSION: ADNEX and SRs models were excellent at characterising adnexal masses which were superior to the RMI in Chinese patients.