Relationship between family function and anxiety among nurses during the COVID-19 pandemic: a mediating role of expressive suppression.

BACKGROUND: The aims of the present study were to investigate the incidence of nurses who suffered anxiety during the COVID-19 pandemic and to explore how expressive suppression influences the relationship between family function and anxiety. METHODS: This study used cross-sectional research and simple random sampling. A total of 300 questionnaires were distributed and 254 questionnaires were qualified after invalid questionnaires were proposed, thus a total of 254 female nurses from a tertiary hospital were included in this study. The measurement included General demographic questionnaires, the Self-Scale Anxiety, Scale (SAS), Emotion Regulation Strategies Questionnaire (ERQ), and Family Function Assessment (FAD). T-test, nonparametric Wilcoxon or Kruskal-Wallis test, χ2 test, Pearson or Spearman correlation analysis, multiple stepwise regression and bootstrap methods was performed to analyze the data. RESULTS: In this study, 22.4% of the nurses exhibited anxiety symptoms, with 17.7% eliciting mild anxiety symptoms, 4.3% showing moderate anxiety symptoms and 0.4% with severe anxiety symptoms. Family function and expressive suppression were positively associated with anxiety severity. And family function influenced anxiety among nurses via direct and indirect (Expressive suppression -mediated) pathways. CONCLUSIONS: Expressive suppression partially mediated the influence of family function on anxiety symptom. To this end, nurse administrators should establish a robust mental health support system encompassing psychological counseling and emotional support groups. Furthermore, nurse administrators should consistently inquire about nurses' family situations, encourage nurses to articulate their emotions and needs candidly, both within the domestic sphere and the workplace, while refraining from excessive self-repression.

Perineural Invasion in Cervical Cancer: A Hidden Trail for Metastasis.

Perineural invasion (PNI), the neoplastic invasion of nerves, is an often overlooked pathological phenomenon in cervical cancer that is associated with poor clinical outcomes. The occurrence of PNI in cervical cancer patients has limited the promotion of Type C1 surgery. Preoperative prediction of the PNI can help identify suitable patients for Type C1 surgery. However, there is a lack of appropriate preoperative diagnostic methods for PNI, and its pathogenesis remains largely unknown. Here, we dissect the neural innervation of the cervix, analyze the molecular mechanisms underlying the occurrence of PNI, and explore suitable preoperative diagnostic methods for PNI to advance the identification and treatment of this ominous cancer phenotype.

RNA-Seq analysis of the fruiting bodies and mycelia of angel-wing mushroom Pleurocybella porrigens that cause acute encephalopathy.

OBJECTIVE: In 2004, after consuming angel-wing mushrooms, Pleurocybella porrigens, 59 incidents of food poisoning were reported in Japan. Consequently, 17 individuals died of acute encephalopathy. In 2023, we proved that a lectin, pleurocybelline, and pleurocybellaziridine from this mushroom caused damage to the brains of mice. Although we reported genomic and transcriptomic data of P. porrigens in 2013, the assembly quality of the transcriptomic data was inadequate for accurate functional annotation. Thus, we obtained detailed transcriptomic data on the fruiting bodies and mycelia of this mushroom using Illumina NovaSeq 6000. RESULTS: De novo assembly data indicated that the N50 lengths for the fruiting bodies and mycelia were improved compared with those previously reported. The differential expression analysis between the fruiting bodies and the mycelia revealed that 1,937 and 1,555 genes were significantly up-regulated in the fruiting bodies and the mycelia, respectively. The biological functions of P. porrigens transcripts, including PA biosynthetic pathways, were investigated using BLAST search, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes pathway analysis. The obtained results revealed L-valine, a predicted precursor of PA, is biosynthesized in the fruiting bodies and mycelia. Furthermore, real-time RT-PCR was performed to evaluate the accuracy of the results of differential expression analysis.

Ion-Exchanging Lead-Free Perovskite with Tunable Emission Wavelengths for Chemical and Fluorescent Double-Modal Anticounterfeiting Application.

Novel and covert fluorescence is quite desirable for fluorescent anticounterfeiting application. Here, Cs2InCl5·H2O/Sb and Cs2NaInCl6/Sb with high photoluminescence quantum yields (PLQYs) of 99.61 and 99.9%, respectively, were achieved. Considering the excellent optical performances together with the high similarity of the two crystal structures, we tried to realize the crystal structure transition from Cs2InCl5·H2O/Sb to Cs2NaInCl6/Sb by an ion-exchange method. It was well done by just adding the NaCl precursor with different concentrations in the Cs2InCl5·H2O/Sb product. Interestingly, a gradual color change from yellow to orange, warm white, white, cool white, and blue was achieved in the process of crystal structure transition. The energy-transfer dynamic models of Cs2InCl5·H2O/Sb, the white product, and Cs2NaInCl6/Sb were identified. The chemical reaction and UV fluorescence properties made it possible for application in chemical and fluorescent double-modal anticounterfeiting and highly decreased the possibility of being cracked and copied. Especially, when salt for daily cooking was used to replace NaCl, a similar phenomenon happened as that of the 99.9% NaCl precursor, which made it easy to be applicated. The combination of chemical and optical verifications provides two levels of security and unbreakable encryption. The results demonstrate that the transition from Cs2InCl5·H2O/Sb to Cs2NaInCl6/Sb is highly promising in fluorescent anticounterfeiting application.

Integrated bioinformatics investigation of adenylyl cyclase family co-expression network in bladder cancer followed by preliminary validation of member 2 (ADCY2) in tumorigenesis and prognosis.

Background: The adenylyl cyclase (ADCY) gene family encodes enzymes responsible for the synthesis of cyclic adenosine monophosphate (cAMP) from adenosine triphosphate (ATP), which comprises nine transmembrane isoforms (ADCYs 1-9). Although ADCYs correlate with intracellular signalling and tumorigenesis in different malignancies, their roles in bladder cancer remain unclear. Methods: Utilizing the bladder urothelial carcinoma (BLCA) dataset from The Cancer Genome Atlas (TCGA), we employed the R package 'limma' to identify differential genes. Subsequent correlation analysis with corresponding clinical data was conducted. Prognostic significance of ADCY family genes was assessed through survival analysis. Univariate and multivariate Cox regression determined ADCY2 as a potential independent risk factor for BLCA. Validation was performed using immunohistochemistry results from independent cohorts. Additionally, we delved into the mechanism of genetic variations, methylation modifications, and signalling pathways of ADCY family genes. Evaluation of their role in the immune microenvironment was achieved through R packages single-sample gene set enrichment analysis (ssGSEA), CIBERPORT, and ESTIMATE. Results: Cases of bladder cancer were retrieved from TCGA, and the transcriptionally differentially expressed members of ADCY were identified (members 2, 4, and 5). Genomic alteration, epigenomic modification, clinicopathological characteristics and clinical survival were systematically investigated. A co-expression network was established based on the intersection of correlated genes, which was centred around ADCY2, ADCY4, and ADCY5. Enrichment analysis revealed that correlated genes were involved in epithelial-mesenchymal transition (EMT). The ADCY2 was selected as the most representative biomarker for prognosis in bladder cancer. Bladder tumour with higher ADCY2 expression had higher prognostic risk and worse survival outcomes. Moreover, ADCY2 was correlated with classic immune checkpoints, and a better responsiveness to immunotherapy was exhibited in high-expression subsets. To ameliorate universality of the conclusion, our study also included several real-world cohorts into the preliminary validation, using datasets from the Gene Expression Omnibus (GEO; GSE13507), tissue microarray (TMA) with 80 bladder cancer inclusion and clinical trial IMvigor210, which were associated with immunotherapy sensitivity, prognosis, and common biomarker presentation. Conclusions: Our study reveals that ADCY family has prognostic value in patients with bladder cancer; the ADCY2 is a prominent prognostic biomarker. The bioinformatics analyses and validation provide direction for further functional and mechanistic studies on the screened members of ADCY family.

Comprehensive analysis of macrophage-related genes in prostate cancer by integrated analysis of single-cell and bulk RNA sequencing.

Macrophages, as essential components of the tumor immune microenvironment (TIME), could promote growth and invasion in many cancers. However, the role of macrophages in tumor microenvironment (TME) and immunotherapy in PCa is largely unexplored at present. Here, we investigated the roles of macrophage-related genes in molecular stratification, prognosis, TME, and immunotherapeutic response in PCa. Public databases provided single-cell RNA sequencing (scRNA-seq) and bulk RNAseq data. Using the Seurat R package, scRNA-seq data was processed and macrophage clusters were identified automatically and manually. Using the CellChat R package, intercellular communication analysis revealed that tumor-associated macrophages (TAMs) interact with other cells in the PCa TME primarily through MIF - (CD74+CXCR4) and MIF - (CD74+CD44) ligand-receptor pairs. We constructed coexpression networks of macrophages using the WGCNA to identify macrophage-related genes. Using the R package ConsensusClusterPlus, unsupervised hierarchical clustering analysis identified two distinct macrophage-associated subtypes, which have significantly different pathway activation status, TIME, and immunotherapeutic efficacy. Next, an 8-gene macrophage-related risk signature (MRS) was established through the LASSO Cox regression analysis with 10-fold cross-validation, and the performance of the MRS was validated in eight external PCa cohorts. The high-risk group had more active immune-related functions, more infiltrating immune cells, higher HLA and immune checkpoint gene expression, higher immune scores, and lower TIDE scores. Finally, the NCF4 gene has been identified as the hub gene in MRS using the "mgeneSim" function.

SM-CycleGAN: crop image data enhancement method based on self-attention mechanism CycleGAN.

Crop disease detection and crop baking stage judgement require large image data to improve accuracy. However, the existing crop disease image datasets have high asymmetry, and the poor baking environment leads to image acquisition difficulties and colour distortion. Therefore, we explore the potential of the self-attention mechanism on crop image datasets and propose an innovative crop image data-enhancement method for recurrent generative adversarial networks (GANs) fused with the self-attention mechanism to significantly enhance the perception and information capture capabilities of recurrent GANs. By introducing the self-attention mechanism module, the cycle-consistent GAN (CycleGAN) is more adept at capturing the internal correlations and dependencies of image data, thus more effectively capturing the critical information among image data. Furthermore, we propose a new enhanced loss function for crop image data to optimise the model performance and meet specific task requirements. We further investigate crop image data enhancement in different contexts to validate the performance and stability of the model. The experimental results show that, the peak signal-to-noise ratio of the SM-CycleGAN for tobacco images and tea leaf disease images are improved by 2.13% and 3.55%, and the structural similarity index measure is improved by 1.16% and 2.48% compared to CycleGAN, respectively.

COVID-19 acts like a stress test, uncovering the vulnerable part of the human body: a retrospective study of 1640 cases in China.

BACKGROUND: Since the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection exhibits multi-organ damage with diverse complications, the correlation between age, gender, medical history and clinical manifestations of novel coronavirus disease 2019 (COVID-19) patients was investigated. METHODS: 1640 patients who were infected with SARS-CoV-2 and hospitalized at the First Affiliated Hospital of Ningbo University from 22 December 2022 to 1 March 2023 were categorized and analysed. Normal distribution test and variance homogeneity test were performed. Based on the test results, one-way analysis of variance, Pearson's chi-squared test and logistic regression analysis were conducted in the study. RESULTS: According to the ANOVA, there was a significant difference in the age distribution (P = .001) between different clinical presentations, while gender did not (P = .06). And regression analysis showed that age, hypertension, atherosclerosis and cancer were significant hazard factors for the development of predominant clinical manifestations in patients hospitalized with novel COVID-19. Additionally, infection with SARS-CoV-2 has the potential to exacerbate the burden on specific diseased or related organs. CONCLUSION: The elderly who are infected with SARS-CoV-2 ought to be treated with emphasis not only on antiviral therapy but also on individualized treatment that takes their medical history and comorbidities into account.

Lipid metabolism: the potential targets for toxoplasmosis treatment.

Toxoplasmosis is a zoonosis caused by Toxoplasma gondii (T. gondii). The current treatment for toxoplasmosis remains constrained due to the absence of pharmaceutical interventions. Thus, the pursuit of more efficient targets is of great importance. Lipid metabolism in T. gondii, including fatty acid metabolism, phospholipid metabolism, and neutral lipid metabolism, assumes a crucial function in T. gondii because those pathways are largely involved in the formation of the membranous structure and cellular processes such as division, invasion, egress, replication, and apoptosis. The inhibitors of T. gondii's lipid metabolism can directly lead to the disturbance of various lipid component levels and serious destruction of membrane structure, ultimately leading to the death of the parasites. In this review, the specific lipid metabolism pathways, correlative enzymes, and inhibitors of lipid metabolism of T. gondii are elaborated in detail to generate novel ideas for the development of anti-T. gondii drugs that target the parasites' lipid metabolism.

Biochar's role in improving pakchoi quality and microbial community structure in rhizosphere soil.

Background: Biochar amendments enhance crop productivity and improve agricultural quality. To date, studies on the correlation between different amounts of biochar in pakchoi (Brassica campestris L.) quality and rhizosphere soil microorganisms are limited, especially in weakly alkaline soils. The experiment was set up to explore the effect of different concentrations of biochar on vegetable quality and the correlation between the index of quality and soil bacterial community structure changes. Methods: The soil was treated in the following ways via pot culture: the blank control (CK) without biochar added and with biochar at different concentrations of 1% (T1), 3% (T2), 5% (T3), and 7% (T4). Here, we investigatedthe synergistic effect of biochar on the growth and quality of pakchoi, soil enzymatic activities, and soil nutrients. Microbial communities from pakchoi rhizosphere soil were analyzed by Illumina MiSeq. Results: The results revealed that adding 3% biochar significantly increased plant height, root length, and dry weight of pakchoi and increased the contents of soluble sugars, soluble proteins, Vitamin C (VC), cellulose, and reduced nitrate content in pakchoi leaves. Meanwhile, soil enzyme activities and available nutrient content in rhizosphere soil increased. This study demonstrated that the the microbial community structure of bacteria in pakchoi rhizosphere soil was changed by applying more than 3% biochar. Among the relatively abundant dominant phyla, Gemmatimonadetes, Anaerolineae, Deltaproteobacteria and Verrucomicrobiae were reduced, and Alphaproteobacteria, Gammaproteobacteria, Bacteroidia, and Acidimicrobiia relative abundance increased. Furthermore, adding 3% biochar reduced the relative abundance of Gemmatimonas and increased the relative abundances of Ilumatobacter, Luteolibacter, Lysobacter, Arthrobacter, and Mesorhizobium. The nitrate content was positively correlated with the abundance of Gemmatimonadetes, and the nitrate content was significantly negatively correlated with the relative abundance of Ilumatobacter. Carbohydrate transport and metabolism in the rhizosphere soil of pakchoi decreased, and lipid transport and metabolism increased after biochar application. Conclusion: Overall, our results indicated that applying biochar improved soil physicochemical states and plant nutrient absorption, and affected the abundance of dominant bacterial groups (e.g., Gemmatimonadetes and Ilumatobacter), these were the main factors to increase pakchoi growth and promote quality of pakchoi. Therefore, considering the growth, quality of pakchoi, and soil environment, the effect of using 3% biochar is better.

Effect of the mitochondrial uncoupling agent BAM15 against the Toxoplasma gondii RH strain and Prugniaud strain.

BACKGROUND: Toxoplasmosis is a zoonotic disease caused by the infection of the protozoa Toxoplasma gondii (T. gondii), and safe and effective therapeutic drugs are lacking. Mitochondria, is an important organelle that maintains T. gondii survival, however, drugs targeting mitochondria are lacking. METHODS: The cytotoxicity of BAM15 was detected by CCK-8 and the in vitro effects of BAM15 was detected by qPCR, plaque assay and flow cytometry. Furthermore, the ultrastructural changes of T. gondii after BAM15 treatment were observed by transmission electron microscopy, and further the mitochondrial membrane potential (ΔΨm), ATP level and reactive oxygen species (ROS) of T. gondii after BAM15 treatment were detected. The pharmacokinetic experiments and in vivo infection assays were performed in mice to determine the in vivo effect of BAM15. RESULTS: BAM15 had excellent anti-T. gondii activity in vitro and in vivo with an EC50 value of 1.25 µM, while the IC50 of BAM15 in Vero cells was 27.07 µM. Notably, BAM15 significantly inhibited proliferation activity of T. gondii RH strain and Prugniaud strain (PRU), caused T. gondii death. Furthermore, BAM15 treatment induced T. gondii mitochondrial vacuolation and autolysis by TEM. Moreover, the decrease in ΔΨm and ATP level, as well as the increase in ROS production further confirmed the changes CONCLUSIONS: Our study identifies a useful T. gondii mitochondrial inhibitor, which may also serve as a leading molecule to develop therapeutic mitochondrial inhibitors in toxoplasmosis.'

Monoterpenoid indole alkaloids from Alstonia scholaris and their Toxoplasma gondii inhibitory activity.

Nine previously unreported various types of monoterpenoid indole alkaloids, together with seven known analogues were isolated from the stem barks of Alstonia scholaris through a silica gel free methodology. The structures of 1-9 were elucidated by spectroscopic data analysis, electronic circular dichroism calculations, and single-crystal X-ray diffraction. Compound 1 is a modified echitamine-type alkaloid with a novel 6/5/5/7/6/6 hetero hexacyclic bridged ring system, and 8 and 9 exist as a zwitterion and trifluoroacetate salt, respectively. The anti-Toxoplasma activity of all isolates on infected Vero cells were evaluated, which revealed that compound 14 at 0.24 µM displayed potent activity. This study expanded the structural diversity of alkaloids of A. scholaris, and presented their potential application in anti-Toxoplasma drug development.

How education level affects postoperative rehabilitation and follow-up: a single-center experience.

BACKGROUND: Radical prostatectomy remains the fundamental treatment for prostate cancer, and improving patients' compliance with postoperative follow-ups is essential for improving patients' quality of life. This study investigates the effect of education levels on patients' recovery and follow-up after radical prostatectomy. METHODS: Data from 1,112 patients undergoing radical prostatectomy between 2011 and 2020 were collected using medical records, and "pc-follow" systems were used to collect patients' baseline information, education level, pathological information, number of outpatient visits, the time interval between each visit, and PSA test data. RESULTS: Regarding postoperative outpatient data, there was no difference in the number of outpatient visits among the different education level groups in Shanghai (P = 0.063). A significant difference was found in the interval between outpatient visits among the groups (P < 0.001). Furthermore, significant differences were detected in the number and duration of outpatient clinic visits among the education level groups in all patients (P = 0.016, P = 0.0027). By contrast, no significant difference was found in the recovery time of urinary continence between all patients and those in Shanghai, grouped according to education level (P = 0.082, P = 0.68). For all patients and patients in the Shanghai area, the number of PSA follow-ups increased gradually with an increasing level of education (P < 0.001, P = 0.0029). CONCLUSIONS: Education level affected the number of postoperative clinic visits, compliance, and the number of PSA tests. However, no significant effect on the recovery of urinary continence was found. Further, clinicians must increase their focus on patients with low education levels to achieve equitable access to health services for all patients.

Identification of novel molecular subtypes and a signature to predict prognosis and therapeutic response based on cuproptosis-related genes in prostate cancer.

Background: Prostate cancer (PCa) is the most common malignant tumor of the male urinary system. Cuproptosis, as a novel regulated cell death, remains unclear in PCa. This study aimed to investigate the role of cuproptosis-related genes (CRGs) in molecular stratification, prognostic prediction, and clinical decision-making in PCa. Methods: Cuproptosis-related molecular subtypes were identified by consensus clustering analysis. A prognostic signature was constructed with LASSO cox regression analyses with 10-fold cross-validation. It was further validated in the internal validation cohort and eight external validation cohorts. The tumor microenvironment between the two risk groups was compared using the ssGSEA and ESTIMATE algorithms. Finally, qRT-PCR was used to explore the expression and regulation of these model genes at the cellular level. Furthermore, 4D Label-Free LC-MS/MS and RNAseq were used to investigate the changes in CRGs at protein and RNA levels after the knockdown of the key model gene B4GALNT4. Results: Two cuproptosis-related molecular subtypes with significant differences in prognoses, clinical features, and the immune microenvironment were identified. Immunosuppressive microenvironments were associated with poor prognosis. A prognostic signature comprised of five genes (B4GALNT4, FAM83D, COL1A, CHRM3, and MYBPC1) was constructed. The performance and generalizability of the signature were validated in eight completely independent datasets from multiple centers. Patients in the high-risk group had a poorer prognosis, more immune cell infiltration, more active immune-related functions, higher expression of human leukocyte antigen and immune checkpoint molecules, and higher immune scores. In addition, anti-PDL-1 immunotherapy prediction, somatic mutation, chemotherapy response prediction, and potential drug prediction were also analyzed based on the risk signature. The validation of five model genes' expression and regulation in qPCR was consistent with the results of bioinformatics analysis. Transcriptomics and proteomics analyses revealed that the key model gene B4GALNT4 might regulate CRGs through protein modification after transcription. Conclusion: The cuproptosis-related molecular subtypes and the prognostic signature identified in this study could be used to predict the prognosis and contribute to the clinical decision-making of PCa. Furthermore, we identified a potential cuproptosis-related oncogene B4GALNT4 in PCa, which could be used as a target to treat PCa in combination with cuproptosis.

Heterologous expression of the lectin CmRlec from Cordyceps militaris (Cordycipitaceae, Ascomycota) in Escherichia coli.

Ascomycete lectins may play an important role in their life cycle. In this report, we mined a ricin B-type lectin, named CmRlec, from the Cordyceps militaris genome by homology search. Furthermore, we succeeded in the soluble expression of CmRlec using ß-glucuronidase as a solubilization tag and demonstrated that this lectin is a novel chitin-recognizing lectin.

Smoke exposure levels prediction following laboratory combustion of Pinus koraiensis plantation surface fuel.

High concentrations of harmful gases released from forest fire will pose a short-term hazard to fire-fighters' cardiopulmonary function, even threaten their lives. In this study, laboratory experiments were conducted to examine the relationship between harmful gases concentrations and burning environment and fuel characteristics. In the experiments, fuel beds were created with controlled moisture contents and fuel loads; a wind tunnel device was used to conduct 144 trials, each with a specific wind speed. The easily predicted fire behavioral characteristics and the harmful gases concentrations such as CO, CO2, NOx, SO2 which were released during fuel combustion were measured and analyzed. The results showed that the influences of wind speed, fuel moisture content, and fuel load on the flame length are in accordance with the fundamental theory of forest combustion. The contributions by controled variables to the influence on the short-term exposure concentration of CO and CO2 can be ranked as fuel load > wind speed > fuel moisture. The R2 of the established linear model that was used to predict Mixed Exposure Ratio was 0.98. Our results can help protect the health and lives of forest fire-fighters and can be used by forest fire smoke management to guide fire suppression.

Chlorine Dioxide Reprograms Rhizosphere Microbial Communities to Enrich Interactions with Tobacco (Nicotiana tabacum).

For decades chlorine dioxide has been used in water disinfection with excellent results. As the scope of application expands, chlorine dioxide has the potential for soil disinfection. We used amplicon sequencing and gas chromatography-mass spectrometry to compare the changes of four mixed rhizosphere microbial community samples and 12 tobacco leaf volatile samples four months after the flood irrigation with chlorine dioxide in different concentrations (0, 2, 4, 8 mg/l). Phenotypic data of 60 tobacco plants were also collected. The effects of chlorine dioxide on rhizosphere microorganisms were positively correlated with dose gradients. Bacteria responded more strongly in both community structure and metabolic pathways than fungi. Five new bacterial phyla (Firmicutes, Bacteroidota, Myxococcota, Patescibacteria, Verrucomicroboata) appeared in chlorine dioxide treatment groups, while the fungal community only appeared as one new fungal phylum (Basidomycota). Alterations in 271 predicted metabolic bacterial pathways were found. However, in the fungal community were only 10 alternations. The correlations between leaf volatile compounds and rhizosphere microorganisms under the influence of chlorine dioxide treatment could be observed based on network results. However, natural connectivity had already been declining rapidly when less than 20% of the network's nodes were removed. Therefore, the microbe-metabolite network is not stable. It might be why chlorine dioxide treatments did not significantly affect tobacco quality (p = 0.754) and phenotype (p = 0.867). As a comprehensive investigation of chlorine dioxide in agriculture, this study proves the effectiveness and safety of chlorine dioxide soil disinfection and widens the application range of chlorine dioxide.

Effect of the pseudomonas metabolites HQNO on the Toxoplasma gondii RH strain in vitro and in vivo.

Toxoplasmosis is a widespread disease in humans and animals. Currently, toxoplasmosis chemotherapy options are limited due to severe side effects. There is an urgent need to develop new drugs with better efficacy and few side effects. HQNO, a cytochrome bc1 and type II NADH inhibitor in eukaryotes and bacteria, possesses extensive bioactivity. In this study, the cytotoxicity of HQNO was evaluated in Vero cells. The in vitro effects of HQNO were determined by plaque assay and qPCR assay. To determine the in vivo effect of HQNO, pharmacokinetic experiments and in vivo infection assays were performed in mice. The changes in tachyzoites after HQNO exposure were examined by transmission electron microscopy (TEM), MitoTracker Red CMXRos staining, ROS detection and ATP detection. HQNO inhibited T. gondii invasion and proliferation with an EC50 of 0.995 µM. Pharmacokinetic experiments showed that the Cmax of HQNO (20 mg/kg·bw) was 3560 ± 1601 ng/mL (13.73 µM) in healthy BALB/c mouse plasma with no toxicity in vivo. Moreover, HQNO induced a significant decrease in the parasite burden load of T. gondii in mouse peritoneum. TEM revealed alterations in the mitochondria of T. gondii. Further assays verified that HQNO also decreased the mitochondrial membrane potential (ΔΨm) and ATP levels and enhanced the level of reactive oxygen species (ROS) in T. gondii. Hence, HQNO exerted anti-T. gondii activity, which may be related to the damage to the mitochondrial electron transport chain (ETC).

Corrigendum: Acute and subacute toxicity assessment of oxyclozanide in Wistar rats.

[This corrects the article DOI: 10.3389/fvets.2019.00294.].

A prognostic cuproptosis-related lncRNA predictive signature for bladder cancer patients.

Cuproptosis is a novel form of cell death in tumours. However, the clinical impact and mechanism of cuproptosis in bladder cancer (BC) remain unclear. This study aimed to explore the functions of long noncoding RNAs (lncRNAs) related to cuproptosis in BC and develop a prognostic predictive model. RNA sequencing and clinicopathological data were derived from The Cancer Genome Atlas and randomly divided into training and validation groups. Cuproptosis-related lncRNAs were identified by Cox regression analysis and least absolute shrinkage and selection operator, and the patients were divided into high- and low-risk groups according to the median value of the signature-based risk score. We established a signature of 17 cuproptosis-associated lncRNAs in the training set. In both sets, patients with higher signature-based risk scores had a notably higher probability of death (P ≤ 0.001) and a shorter survival duration. Cox regression analyses confirmed the risk score as an independent predictor of BC prognosis in the entire set. The area under the curve (AUC) values for 1-, 3-, and 5-year survival were 0.767, 0.734, and 0.764, respectively, confirming that the signature could determine the prognosis of BC. A signature-based nomogram was developed, and its prediction accuracy was validated using calibration curves. Several drugs, including Gemcitabine, Oxaliplatin, Mitoxantrone, Camptothecin, Cytarabine and Irinotecan may benefit low-risk BC patients more. Finally, in vitro experiments confirmed that the cuproptosis-related lncRNAs are highly expressed in bladder cancer cells after cuproptosis induced by exogenous copper ions. In conclusion, a cuproptosis-related lncRNA signature independently predicted prognosis in BC, indicating a possible mechanism and clinical treatment approach.