Genome-wide association analysis of intra-specific QTL associated with the resistance for enteric septicemia of catfish.

Disease resistance is one of the most important traits for aquaculture industry. For catfish industry, enteric septicemia of catfish (ESC), caused by the bacterial pathogen Edwardsiella ictaluri, is the most severe disease, causing enormous economic losses every year. In this study, we used three channel catfish families with 900 individuals (300 fish per family) and the 690K catfish SNP array, and conducted a genome-wide association study to detect the quantitative trait loci (QTL) associated with ESC resistance. Three significant QTL, with two of located on LG1 and one on LG26, and three suggestive QTL located on LG1, LG3, and LG21, respectively, were identified to be associated with ESC resistance. With a well-assembled- and -annotated reference genome sequence, genes around the involved QTL regions were identified. Among these genes, 37 genes had known functions in immunity, which may be involved in ESC resistance. Notably, nlrc3 and nlrp12 identified here were also found in QTL regions of ESC resistance in the channel catfish × blue catfish interspecific hybrid system, suggesting this QTL was operating within both intra-specific channel catfish populations and interspecific hybrid backcross populations. Many of the genes of the Class I MHC pathway, for mediated antigen processing and presentation, were found in the QTL regions. The positional correlation found in this study and the expressional correlation found in previous studies indicated that Class I MHC pathway was significantly associated with ESC resistance. This study validated one QTL previously identified using the second and fourth generation of the interspecific hybrid backcross progenies, and identified five additional QTL among channel catfish families. Taken together, it appears that there are only a few major QTL for ESC disease resistance, making marker-assisted selection an effective approach for genetic improvements of ESC resistance.

Multiple across-strain and within-strain QTLs suggest highly complex genetic architecture for hypoxia tolerance in channel catfish.

The ability to survive hypoxic conditions is important for various organisms, especially for aquatic animals. Teleost fish, representing more than 50 % of vertebrate species, are extremely efficient in utilizing low levels of dissolved oxygen in water. However, huge variations exist among various taxa of fish in their ability to tolerate hypoxia. In aquaculture, hypoxia tolerance is among the most important traits because hypoxia can cause major economic losses. Genetic enhancement for hypoxia tolerance in catfish is of great interest, but little was done with analysis of the genetic architecture of hypoxia tolerance. The objective of this study was to conduct a genome-wide association study to identify QTLs for hypoxia tolerance using the catfish 250K SNP array with channel catfish families from six strains. Multiple significant and suggestive QTLs were identified across and within strains. One significant QTL and four suggestive QTLs were identified across strains. Six significant QTLs and many suggestive QTLs were identified within strains. There were rare overlaps among the QTLs identified within the six strains, suggesting a complex genetic architecture of hypoxia tolerance. Overall, within-strain QTLs explained larger proportion of phenotypic variation than across-strain QTLs. Many of genes within these identified QTLs have known functions for regulation of oxygen metabolism and involvement in hypoxia responses. Pathway analysis indicated that most of these genes were involved in MAPK or PI3K/AKT/mTOR signaling pathways that were known to be important for hypoxia-mediated angiogenesis, cell proliferation, apoptosis and survival.

[Aripiprazole for drug-induced sexual dysfunction in schizophrenic males].

OBJECTIVE: To investigate the clinical effects of aripiprazole on sexual dysfunction induced by amisulpride or risperidone in male patients with schizophrenia. METHODS: This study included 75 male patients with drug-induced secondary sexual dysfunction after treated with amisulpride or risperidone for first-episode schizophrenia between October 2014 and October 2016. We substituted aripiprazole for amisulpride or risperidone, gradually increased the dose from 10 to 30 mg/d within 2 weeks, and maintained 30 mg/d from the 3rd week. At 4 and 8 weeks after medication, we evaluated the sexual function of the patients, measured the levels of serum prolactin (PRL) and testosterone (T), obtained the scores of the Positive and Negative Symptoms Scale (PANSS), recorded adverse reactions, and compared the parameters with those before aripiprazole administration. RESULTS: Compared with pre-aripiprazole administration, the patients showed significant increases after 4 weeks of medication in the sexual function score (24.3 ± 2.1 vs 32.6 ± 3.6, P <0.05) and T level (ï¼»13.3 ± 2.7ï¼½ vs ï¼»17.4±3.0ï¼½ mmol/L, P <0.05) but a decreased level of PRL (ï¼»38.5 ± 10.5ï¼½ vs ï¼»27.9 ± 8.2ï¼½ ng/ml, P <0.05). At 8 weeks, the sexual function score and serum PRL were both restored to the baseline levels at admission, and the erectile function score, ejaculation score, total score, and serum T level even exceeded the baseline, though with no statistically significant differences (P >0.05). In comparison with pre-aripiprazole administration, the PANSS score was significantly decreased at 4 weeks after medication (62.1 ± 4.9 vs 57.2 ± 5.5, P <0.05) and even lower at 8 weeks (51.2 ± 5.2) (P <0.05). The incidence rates of medication-related excitation, dizziness, insomnia, and loss of appetite were 6.7%, 5.3%, 4.0% and 1.3% respectively, and no other serious adverse reactions were observed. CONCLUSIONS: Aripiprazole is effective for the treatment of drug-induced sexual dysfunction in schizophrenic men by continuously alleviating their positive and negative symptoms and meanwhile improving their sexual function and restoring their sexual hormone levels.

Continuous warming shifts the community pattern of periphytic protozoan fauna in marine environments.

Protozoan fauna is playing an important role in the functioning of microbial food webs by transferring the flux of material and energy from low to high tropic levels in marine ecosystems. To assess effects of elevated temperature on the marine ecosystem, periphytic protozoan communities were used as the test microbial fauna, and were incubated in a temperature-controlled circulation system in a successive temperature gradient of 22 (control), 25, 28, 31 and 34 °C. The results showed that: (1) the test microbial fauna was shifted in both species composition and community structure; (2) the average taxonomic distinctness represented a clear decreasing trend, (3) while the variation in taxonomic distinctness significantly increased with increase of water temperature; and (4) the community pattern was significantly departed from an expectation when temperature increased by 12 °C. These results suggested that Protozoa may be used as a useful bioindicator of global warming in marine ecosystems.

Microplastics drive community dynamics of periphytic protozoan fauna in marine environments.

The pollution of microplastics (MPs) to the marine environment has become a widespread focus of attention. To assess MP-induced ecotoxicity on marine ecosystems, periphytic protozoan communities were used as test organisms and exposed to five concentrations of MPs: 0, 1, 5, 25, and 125 mg l-1. Protozoan samples were collected using microscope slides from coastal waters of the Yellow Sea, northern China. A total of 13 protozoan species were identified and represented different tolerance to MP-induced ecotoxicity. Inhibition effects of MPs on the test protozoan communities were clearly shown in terms of both the species richness and individual abundance and followed linear relationships to MP concentrations. The community patterns were driven by MPs and significantly shifted at concentrations over 5 mg l-1. Our findings demonstrated that MPs may induce the community-level ecotoxic response of periphytic protozoan fauna and followed significant community dynamics. Thus, it is suggested that periphytic protozoan fauna may be used as useful community-based test model organisms for evaluating MP-induced ecotoxicity in marine environments.

Colonization dynamics in body-size spectrum of protozoan periphytons for marine bioassessment using two modified sampling systems.

The body-size spectrum of microperiphytons has been proved to be a powerful tool for bioassessment. To explore colonization dynamics in body-size spectrum of periphytic protozoa in two modified sampling systems of both glass slide (mGS) and polyurethane foam unit (mPFU), a 28-day colonization survey was conducted in coastal waters of the Yellow Sea, China. A total of 7 body-size ranks were identified from 62 species, with 7 ranks (60 species) in the mGS and 6 ranks (37 species) in the mPFU system. The stable pattern with similar body-size spectra was found earlier in the mGS system than mPFU system during the colonization period. Both the trajectory and bootstrapped average analyses revealed that the colonization dynamics were significantly different in the body-size spectrum between the two methods. Based on our data, it suggests that the mGS system might be a better choice than the mPFU system for bioassessment in marine ecosystems.

Interpretable machine learning model based on the systemic inflammation response index and ultrasound features can predict central lymph node metastasis in cN0T1-T2 papillary thyroid carcinoma.

Background: It is arguable whether individuals with T1-T2 papillary thyroid cancer (PTC) who have a clinically negative (cN0) diagnosis should undergo prophylactic central lymph node dissection (pCLND) on a routine basis. Many inflammatory indices, including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), and systemic immune-inflammatory index (SII), have been reported in PTC. However, the associations between the systemic inflammation response index (SIRI) and the risk of central lymph node metastasis (CLNM) remain unclear. Methods: Retrospective research involving 1,394 individuals with cN0T1-T2 PTC was carried out, and the included patients were randomly allocated into training (70%) and testing (30%) subgroups. The preoperative inflammatory indices and ultrasound (US) features were used to train the models. To assess the forecasting factors as well as drawing nomograms, the least absolute shrinkage and selection operator (LASSO) and multivariate logistic regression were utilized. Then eight interpretable models based on machine learning (ML) algorithms were constructed, including decision tree (DT), K-nearest neighbor (KNN), support vector machine (SVM), artificial neural network (ANN), random forest (RF), extreme gradient boosting (XGBoost), light gradient boosting machine (LightGBM), and categorical boosting (CatBoost). The performance of the models was evaluated by incorporating the area under the precision-recall curve (auPR) and the area under the receiver operating characteristic curve (auROC), as well as other conventional metrics. The interpretability of the optimum model was illustrated via the shapley additive explanations (SHAP) approach. Results: Younger age, larger tumor size, capsular invasion, location (lower and isthmus), unclear margin, microcalcifications, color Doppler flow imaging (CDFI) blood flow, and higher SIRI (≥0.77) were independent positive predictors of CLNM, whereas female sex and Hashimoto thyroiditis were independent negative predictors, and nomograms were subsequently constructed. Taking into account both the auROC and auPR, the RF algorithm showed the best performance, and superiority to XGBoost, CatBoost and ANN. In addition, the role of key variables was visualized in the SHAP plot. Conclusions: An interpretable ML model based on the SIRI and US features can be used to predict CLNM in individuals with cN0T1-T2 PTC.

Targeting survivin with Tanshinone IIA inhibits tumor growth and overcomes chemoresistance in colorectal cancer.

The inhibitor of apoptosis protein survivin has a critical regulatory role in carcinogenesis and treatment tolerance in colorectal cancer (CRC). However, the targeted drugs for survivin protein are extremely limited. In the present research, we discovered that Tanshinone IIA (Tan IIA) played a dual regulatory role in inhibiting tumorigenesis and reversing 5-Fu tolerance via modulating the expression and phosphorylation of survivin in CRC cells. Mechanistically, Tan IIA suppressed the Akt/WEE1/CDK1 signaling pathway, which led to the downregulation of survivin Thr34 phosphorylation and destruction of the interaction between USP1 and survivin to promote survivin ubiquitination and degradation. Furthermore, Tan IIA significantly facilitated chemoresistant CRC cells to 5-Fu sensitivity. These results revealed that Tan IIA possessed a strong antitumor activity against CRC cells and could act as an up-and-coming agent for treating CRC and overcoming chemotherapy resistance.

Can tidal events influence analysis on colonization dynamics in body-size spectrum of periphytic ciliates for marine bioassessment?

The tidal influence on body-size spectrum of the protozoan periphytons was explored by using the conventional slide system (CS) and the polyurethane foam enveloped slide system (PFES) in coastal waters during a 1-month study. During the colonization process, clear temporal patterns of the body-size spectrum were observed using the two sampling methods. In terms of relative species number and frequency of occurrence, the rank S4 represented a more stable temporal variability in the PFES system than the CS system during the colonization. Additionally, the small forms (e.g., S1, S2, and S3) were more abundant in the PFES system. The clustering and bootstrapped average analyses demonstrated differences in body-size spectrum of protozoans between the two sampling systems. Our results imply that the body-size spectrum of protozoan periphytons may be impacted by tidal events during colonization process in marine waters.

Insights into the ecotoxicity of nitrofurazone in marine ecosystems based on body-size spectra of periphytic ciliates.

In ecotoxicological studies, some biological responses known as biomarkers can be used as powerful tools to evaluate the ecotoxicity. In this study, we investigated the disparity of responses shown by body-size spectra of periphytic ciliate communities when used as biomarkers to detect the toxicity of the broad-spectrum veternary antibiotic nitrofurazone. Briefly, in chronic exposure experiments ciliate communities were exposed to different concentrations (0, 1, 2, 4 and 8 mg ml-1) of nitrofurazone. Relative Abundance of ciliates in all body-size categories decreased significantly, whereas their frequency of occurrence and probability densities showed hormetic-like responses in a dose dependent manner. Additionally, body-size distinctness indices were influenced by toxic stress and significantly departed from an expectation at higher nitrofurazone concentrations. Taken together, our results demonstrated that body-size spectra and body-size distinctness offered clear evidence of nitrofurazone toxicity in periphytic ciliates. Body-size spectra can therefore be used as a pivotal biomarker to determine the ecotoxicity of nitrofurazone in aquatic environments.

Effects of nitrofurazone on ecosystem function in marine environments: A case study on microbial fauna.

To evaluate the effects of nitrofurazone on functional processes in marine ecosystems, periphytic protozoan communities were exposed to different concentrations of the antibiotic for a 10-day duration. Species trait distributions in the tested communities were observed during exposure to five concentrations of nitrofurazone. A fuzzy coding system with seven traits and seventeen categories was used to summarize the changes in functional patterns of the test organisms. Nitrofurazone had a significant influence on the function process of the periphytic ciliate communities. Bacterivores with flattened bodies were sensitive to the toxicant whereas sessile and cylindrical raptors showed a high tolerance to nitrofurazone, invariably dominating communities exposed to high concentrations. Bootstrapped-average analysis demonstrated a significant change in functional patterns at highest nitrofurazone concentrations (8 mg l-1). Based on these findings, it is suggested that nitrofurazone may negatively influence ecosystem function in marine environments.

Breast cancer combined with contralateral neck lymph node metastasis: a case report.

BACKGROUND: Contralateral neck lymph node metastasis is rare in primary breast cancer. Its clinical staging and treatment principles lack authoritative guidelines. A case of a 30-year-old breast cancer patient with contralateral neck lymph node metastasis is presented. The clinical treatment is discussed in combination with current research. CASE PRESENTATION: A 30-year-old woman presented with a right breast mass for 5 months and left neck lymph node enlargement for 5 days. Mammography showed a 33 mm*14.3 mm mass in the inner quadrant of the right breast. The ultrasound showed several hypoechoic nodules on the left side of the neck. Rapid intraoperative pathological examination diagnosed a right breast malignant tumor and poorly differentiated carcinoma of the left cervical lymph nodes. Then, right mastectomy was performed immediately. The patient was scheduled to undergo chemotherapy, molecular targeted therapy, radiotherapy and endocrine therapy after the operation. The long-term efficacy remains to be seen. CONCLUSION: The infrequent presentation of breast cancer with metastasis to the contralateral neck lymph node can be challenging for standard therapies.

Influence of tidal events on the body-size spectrum of periphytic ciliates for marine bioassessment using artificial substrata.

As an internal functional trait of a community, the body-size spectrum is a highly informative indicator for bioassessment of water/environmental quality in aquatic ecosystems. To determine the influence of tidal events on body-size spectra of protozoan periphytons, a 3-month baseline survey was conducted in Korean coastal waters using the polyurethane foam enveloped slide system (PFES) and conventional slide system (CS). The body-size spectrum of the protozoans showed a clear temporal pattern during the study period using both sampling systems. However, the temporal dynamics showed significantly different trajectories in the body-size spectrum between the two sampling methods during the study period. The bootstrapped average analysis revealed that the patterns of the body-size spectrum were significantly different between the PFES and CS systems, especially in terms of frequency of occurrence. These findings suggest that the tidal events may significantly influence body-size spectrum of periphytic ciliates for bioassessment in marine ecosystems.

An approach to evaluating the acute toxicity of nitrofurazone on community functioning using protozoan periphytons.

The acute toxicity of nitrofurazone on community functioning was studied using an acute toxicity test. Consequently, 14-day protozoan periphyton assemblages were used as test organism communities, under a range of nitrofurazone concentrations including 0 (control), 0.5, 3, 6, and 12 mg ml-1 within 0, 2, 4, 6, 8, 10, and 12 h time duration. Fuzzy coding system of functional traits classified the test protozoan periphyton community into six major traits and 15 categories. Briefly, community-weighted means (CWM) were used to identify the community functioning of test protozoan assemblage. Inferences demonstrate a drastic/significant variation in the functional patterns of the test organisms at a high concentration (12 mg ml-1) after an exposure time of 12 h, but the functional diversity indices leveled off at the exposure time of 10 h and then dropped sharply. These results suggested that nitrofurazone may significantly influence the community functioning in marine ecosystems.

Identification of N6-Methyladenosine-Related LncRNAs for Predicting Overall Survival and Clustering of a Potentially Novel Molecular Subtype of Breast Cancer.

We aimed to identify a signature comprising N6-methyladenosine (m6A)-related long non-coding RNAs (lncRNAs) and molecular subtypes associated with breast cancer (BRCA). We obtained data of BRCA samples from The Cancer Genome Atlas database. The m6A-related lncRNA prognostic signature (m6A-LPS) included 10 lncRNAs previously identified as prognostic m6A-related lncRNAs and was constructed using integrated bioinformatics analysis and validated. Accordingly, a risk score based on the m6A-LPS signature was established and shown to confirm differences in survival between high-risk and low-risk groups. Three distinct genotypes were identified, whose characteristics included features of the tumor immune microenvironment in each subtype. Our results indicated that patients in Cluster 2 might have a worse prognostic outcome than those in other clusters. The three genotypes and risk subgroups were enriched in different biological processes and pathways, respectively. We then constructed a competing endogenous RNA network based on the prognostic m6A-related lncRNAs. Finally, we validated the expression levels of target lncRNAs in 72 clinical samples. In summary, the m6A-LPS and the potentially novel genotype may provide a theoretical basis for further study of the molecular mechanism of BRCA and may provide novel insights into precision medicine.

Colonization dynamics of protozoan communities in marine bioassessment surveys using two modified sampling systems.

Colonization dynamics of protozoan communities were investigated at a depth of 1 m in the coastal waters of the Yellow Sea, northern China from May to June 2019, using modified glass slide (mGS) and modified polyurethane foam unit (mPFU) systems. The colonization process and growth curves of protozoa were well fitted to the MacArthur-Wilson and logistic models in both systems, respectively. However, they showed significant differences in both colonization dynamics and biodiversity/functional parameters between the mGS and mPFU systems. The H' (species diversity), the G (colonization rate), and Amax (maximum abundance) were higher, while the value of T90% (the time for reaching 90% equilibrium species number) was lower in the mGS system than those in the mPFU system. Multivariate analyses demonstrated that protozoa showed different models of colonization dynamics in both systems. The results suggest that the mGS system might be more effective than the mPFU system in marine bioassessment surveys.

Seasonal variability in biological trait pattern of biofilm-dwelling protozoa in colonization surveys for marine bioassessment.

Biological trait analysis (BTA) has been proved to be a powerful tool to evaluate marine water quality. The species trait distributions of biofilm-dwelling protozoa were studied in a coastal region of the Yellow Sea, northern China, during a four-season cycle. The BTA demonstrated that: (1) the protozoa showed a significant seasonal variability in biological trait pattern during the colonization process across four seasons; (2) the colonization dynamics in species trait distribution followed different temporal models; (3) the functional dynamics in spring and summer were significantly different from those in autumn and winter (P < 0.05); and (4) functional diversity showed lower values in spring and summer than in autumn and winter. These findings suggest that BTA is subject to a high seasonal variability during colonization surveys when protozoa are used as bioindicators of marine water quality.

Can tidal events influence monitoring surveys using periphytic ciliates based on biological trait analysis in marine ecosystems?

To identify the influence of tidal events on community functioning of periphytic ciliates for monitoring program and community research using biological trait analysis, a 3-month baseline survey was conducted in Korean coastal waters using the polyurethane foam enveloped slide system (PFES) and conventional slide system (CS). Although the periphytic ciliate communities had similar biological trait categories, they represented considerable differences in community functioning and functional diversity measures within the PFES and CS systems. Multivariate analyses revealed different ways of the temporal shift in community functioning of the ciliates in both systems. The dispersion analysis demonstrated that the CS system was sensitive to the strong disturbance of tidal current and circulation compared to the PFES system. These findings suggest that the strong tidal event may significantly influence the output of analysis on community functioning of periphytic ciliates for bioassessment in marine ecosystems.

Sorption of carbendazim on activated carbons derived from rape straw and its mechanism.

Due to the production and widespread application of pesticides, pesticide pollution poses a potential danger to human health and the ecosystem. Herein, activated carbons employing rape straw as a precursor were produced using H3PO4 as an activating agent at various temperatures (300-600 °C). The activated carbons differed with respect to the physicochemical properties, which were derived from elemental analysis, N2 sorption-desorption, FTIR, XPS, XRD, pHpzc, Boehm titration and blocking of the oxygen-containing groups. The oxygen-containing functional groups and the pore structure of the activated carbons obtained from the different preparation conditions were quite different. The as-prepared samples were applied as sorbents to remove carbendazim (CBD). The results indicated that the sorption of CBD was mainly dominated by partitioning at low concentrations of CBD. Meanwhile, electrostatic attractions played a more important role than hydrophobic interactions at a low initial pH; in contrast, as the initial pH increased, the hydrophobic interaction was the predominant sorption mechanism. Therefore, the results can be used to design some efficient and environmentally friendly adsorbents to reduce the risk of organic pollutants, especially organic pesticides, in aqueous solutions.

Real-time simultaneous detection of microbial contamination and determination of an ultra low-content active pharmaceutical ingredient in tazarotene gel by near-infrared spectroscopy.

This paper proposes and proves a real-time and non-destructive strategy for sensitive and simultaneous detection of microbial contamination and determination of an ultra low-content active pharmaceutical ingredient in tazarotene gel by near-infrared (NIR) spectroscopy. In this experiment, 88 samples of tazarotene gel (0.41-0.65 mg g-1 of tazarotene) were prepared using the standard addition method. Among them, 47 samples were inoculated with 50 µl of different concentrations of Escherichia coli (E. coli) DH5a in Luria-Bertani (LB) broth to give 1-4 log CFU g-1 of E. coli DH5a in the gel, 6 samples with 50 µl of LB broth, and 35 samples with nothing. Based on the gel NIR transflectance spectra, E. coli DH5a in the gel was detected by the counter propagation artificial neural network (CP-ANN) model with a classification accuracy of 100.0%, while tazarotene in the gel was simultaneously determined by the partial least squares regression (PLS) model with a root mean square error of cross-validation of 0.0232 mg g-1. Furthermore, 9 samples of real tazarotene gel were used to verify the practicality of the established NIR spectroscopy. The developed NIR strategy can be used to correctly and quickly release the pharmaceutical gels, required for sensitive and simultaneous control of microbial contamination and the active pharmaceutical ingredient (API) content, to the next stage.