Quorum sensing positively regulates CPS-dependent Autographiviridae phage infection in Vibrio alginolyticus.

Quorum sensing (QS) orchestrates many bacterial behaviors, including virulence and biofilm formation, across bacterial populations. Nevertheless, the underlying mechanism by which QS regulates capsular polysaccharide (CPS)-dependent phage-bacterium interactions remains unclear. In this study, we report that QS upregulates the expression of CPS-dependent phage receptors, thus increasing phage adsorption and infection rates in Vibrio alginolyticus. We found that QS upregulated the expression of the ugd gene, leading to increased synthesis of Autographiviridae phage receptor CPS synthesis in V. alginolyticus. The signal molecule autoinducer-2 released by Vibrio from different sources can potentially enhance CPS-dependent phage infections. Therefore, our data suggest that inhibiting QS may reduce, rather than improve, the therapeutic efficacy of CPS-specific phages. IMPORTANCE: Phage resistance is a direct threat to phage therapy, and understanding phage-host interactions, especially how bacteria block phage infection, is essential for developing successful phage therapy. In the present study, we demonstrate for the first time that Vibrio alginolyticus uses quorum sensing (QS) to promote capsular polysaccharide (CPS)-specific phage infection by upregulating ugd expression, which is necessary for the synthesis of Autographiviridae phage receptor CPS. Although increased CPS-specific phage susceptibility is a novel trade-off mediated by QS, it results in the upregulation of virulence factors, promoting biofilm development and enhanced capsular polysaccharide production in V. alginolyticus. This suggests that inhibiting QS may improve the effectiveness of antibiotic treatment, but it may also reduce the efficacy of phage therapy.

Targeting tumorous Circ-E-Cadherinencoded C-E-Cad inhibits the recruitment and function of breast cancer-associated myeloid-derived suppressor cells.

We previously demonstrated that the C-E-cad protein encoded by circ-E-cadherin promotes the self-renewal of glioma stem cells. The expression pattern of C-E-cad in breast cancer and its potential function in the tumor microenvironment are unclear. The expression of circ-E-cadherin and C-E-cad was detected in breast cancer specimens. The influence of C-E-cad expression on MDSCs was assessed using FACS and in vivo tumorigenesis experiments. The synergistic effect of anti-C-E-cad and anti-PD-1 antibodies was validated in vivo. circ-E-cadherin and the encoded protein C-E-cad were found to be upregulated in breast cancer vs. normal samples. C-E-cad promotes the recruitment of MDSCs, especially PMN-MDSCs. C-E-cad activates EGFR signaling in tumor cells and promotes the transcription of CXCL8; moreover, C-E-cad binds to MDSCs and maintains glycolysis in PMN-MDSCs. Targeting C-E-cad enhanced anti-PD-1 efficiency. Our data suggested that C-E-cad is markedly overexpressed in breast cancer and promotes MDSC recruitment and survival. Targeting C-E-cad increases the efficacy of immune checkpoint inhibitor therapy.

A review of tire wear particles: Occurrence, adverse effects, and control strategies.

Tire wear particles (TWPs), common mixed particulate emerging contaminants in the environment, have global per capita emissions accounting for 0.23-1.9 kg/year, attracting global attention recently due to their wide detection, small size, mobility, and high toxicity. This review focuses on the occurrence characteristics of TWPs in multiple environmental media, adverse effects on organisms, potential toxicity mechanisms, and environmental risk prevention and control strategies of TWPs. The environmental fate of TWPs throughout the entire process is systematically investigated by the bibliometric analysis function of CiteSpace. This review supplements the gap in the joint toxicity and related toxicity mechanisms of TWPs with other environmental pollutants. Based on the risks review of TWPs and their additives, adverse impacts have been found in organisms from aquatic environments, soil, and humans, such as the growth inhibition effect on Chironomus dilutes. A multi-faceted and rationalized prevention and control treatment of "source-process-end" for the whole process can be achieved by regulating the use of studded tires, improving the tire additive formula, growing plants roadside, encouraging micro-degradation, and other methods, which are first reviewed. By addressing the current knowledge gaps and exploring prospects, this study contributes to developing strategies for reducing risks and assessing the fate of TWPs in multiple environmental media.

Psychometric testing of the Chinese version of the Perceived Maternal Parenting Self-Efficacy Scale among postpartum women.

BACKGROUND: Maternal parenting self-efficacy plays a critical role in facilitating positive parenting practices and successful adaption to motherhood. The Perceived Maternal Parenting Self-Efficacy Scale (PMPS-E), as a task-specific measure, confirms its psychometric properties in cultural contexts. Compared with other tools, the advantages of the PMPS-E are as follows: (i) specific context or time period during the lifespan of a child, (ii) explicitly assess parenting self-efficacy across a diverse enough range of parenting tasks or activities during the perinatal/postnatal period and (iii) having robust psychometric properties. The aim of this study was to translate and determine the psychometric properties of the PMPS-E among Chinese postpartum women (C-PMPS-E). METHOD: The cross-cultural adaptation process followed Beaton et al.'s intercultural debugging guidelines. A total of 471 women were included to establish the psychometric properties of the C-PMPS-E. Mothers were asked to complete the C-PMPS-E, Edinburgh Postnatal Depression Scale (EPDS), the Generalized Anxiety Disorder-7 (GAD-7) and several demographic questions. The psychometric testing of the C-PMPS-E was established through item analysis, construct validity and internal consistency reliability. RESULTS: Item analysis showed that the critical ratios of all items were greater than 3 between the low-score group and high-score group, and all item-total correlation coefficients were greater than 0.4. The fit indices showed that the original correlated four-factor model of C-PMPS-E was observed to be an excellent fit to the data. The PMPS-E was negatively correlated with the EPDS and GAD-7 demonstrating its discriminant validity. As expected, no significant correlation was found between PMPS-E total or subscale scores and mothers' age. In addition, statistically significant differences for parity were detected for C-PMPS-E total and subscale scores with multipara having higher scores. This was taken as further evidence of the scale known-groups discriminant validity. In terms of internal consistency, the Cronbach's alpha of the C-PMPS-E total scale was 0.950, and subscales ranged from 0.76 to 0.89. Furthermore, a ROC curve analysis was conducted to establish the ability of the C-PMPS-E to distinguish between symptoms of depression and symptoms of anxiety. A cut-off value of 55 was identified that resulted in good specificity and fair sensitivity. CONCLUSION: The C-PMPS-E is a reliable and valid tool to assess maternal parenting self-efficacy in a Chinese context.

Validation of the Chinese version of the autism spectrum knowledge scale general population version (ASKSG) with a parent sample.

BACKGROUND: The early detection and diagnosis of autism spectrum disorder (ASD) in children are a first step in determining follow-up assessments and personalized treatment plans. Parents play an extremely crucial role in children's development; therefore, it is essential to identify a valid and reliable instrument to evaluate the knowledge of parents about ASD. The aim of this study was to translate and determine the psychometric properties of the Autism Spectrum Knowledge Scale General Population Version (ASKSG) with a parent sample. DESIGN AND METHODS: A cross-sectional study was conducted with 858 parents of children aged 0-14 years in China. The demographic characteristics form and ASKSG were used for data collection. The psychometric properties of the ASKSG were evaluated by examining reliability, exploratory factor analysis (EFA), categorical confirmatory factor analysis (CCFA), unidimensionality, person and item reliability, item fit and item difficulty, and item-person mapping. RESULTS: The Cronbach's alpha coefficient of the ASKSG was 0.865. In terms of EFA, principal component analysis revealed a fixed number of five factors, explaining 41.642% of the total variance. For the CCFA, the structure of the thematically derived five-factor model was observed to be a marginal fit to the data. The eigenvalue was 31.00, with a variance of 62.7%. The person reliability was 0.85, and the person separation was 2.38. The item reliability was 1.00, and the item separation was 15.02. The infit and outfit statistical analysis fell within acceptable ranges from 0.75 to 1.35, and the item difficulty ranged from -2.43 to 2.44. An item-person map with excellent targeting would be symmetric along the vertical axis from more difficult endorsement at the top (question 1 and question 20) to easier endorsement at the bottom (question 1). Some items do appear to function differently across sexes, and they assess the latent trait unequally across both sexes. CONCLUSIONS: The Chinese version of the ASKSG is a reliable and valid tool for assessing knowledge of parents about ASD. PRACTICE IMPLICATIONS: Chinese ASKSG now offers medical professionals and teachers a robust means of assessing parental knowledge about ASD. Therefore, professionals may use the scale to help them screen or identify parents who are in need of additional support or advice.

First record of the genus Schizothorax in rivers of the Central Himalayas in China.

A total of 40 specimens of the genus Schizothorax (Cyprinidae: Schizothoracinae), including 10 matured males, 19 matured females and 11 juveniles, were captured from the Kirong Tsangpo River in China, which is located in the southern slope of the Central Himalayas. These specimens are identified as Schizothorax richardsonii (Grey, 1832) based on morphological characters and molecular analyses using mitochondrial Cyt b gene sequences. The Kirong population of S. richardsonii is relatively isolated from other populations in the Himalayas and has low genetic diversity. This is the first record of the genus Schizothorax fish in rivers of the Central Himalayas in China. As S. richardsonii is a vulnerable species on the IUCN Red List, a protection plan should be conducted to reduce the impact of anthropogenic disturbance by monitoring the natural population dynamics and assessing the ecological determinants of its distribution.

Omic horizon expression: a database of gene expression based on RNA sequencing data.

BACKGROUND: Gene expression profiles have important significance for gene expression characteristics and further functional studies. More attention has been given to the expression databases in humans and mice, but less attention has been given to rats, while rat models also play an irreplaceable role in biomedical experiments. RESULTS: To depict the rat gene expression profiles in mRNA expression levels, we analyzed over 2,700 RNA sequencing (RNA-Seq) samples from 48 tissues, 40 primary cell types and 25 cell lines; and then mapped them to the latest version of the rat genome reference, mRatBN7.2. Based on these datasets and reanalysis, we constructed a new database, the Omic Horizon Expression Database ( http://immudb.bjmu.edu.cn/expression.html ), which allows expressional profile query of over 25,000 rat genes based on non-redundant gene symbols. The database supports requests using gene symbols (or alias), Ensemble and Entrez gene IDs. Gene expression profiles can be queried in three categories: tissues, primary cells and cell lines. Application examples including expression profiling and comparison, as well as identification of novel rat genes, were illustrated to show the utility of the database. CONCLUSIONS: As an omic resource, the Omic Horizon Expression Database provides horizons of gene expression profiles across various tissues and cells, which greatly facilitates the identification of rat genes as well as functional clues.

Identification and validation of the reference genes in the echiuran worm Urechis unicinctus based on transcriptome data.

BACKGROUND: Real-time quantitative PCR (RT-qPCR) is a crucial and widely used method for gene expression analysis. Selecting suitable reference genes is extremely important for the accuracy of RT-qPCR results. Commonly used reference genes are not always stable in various organisms or under different environmental conditions. With the increasing application of high-throughput sequencing, transcriptome analysis has become an effective method for identifying novel stable reference genes. RESULTS: In this study, we identified candidate reference genes based on transcriptome data covering embryos and larvae of early development, normal adult tissues, and the hindgut under sulfide stress using the coefficient of variation (CV) method in the echiuran Urechis unicinctus, resulting in 6834 (15.82%), 7110 (16.85%) and 13880 (35.87%) candidate reference genes, respectively. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses revealed that the candidate reference genes were significantly enriched in cellular metabolic process, protein metabolic process and ribosome in early development and normal adult tissues as well as in cellular localization and endocytosis in the hindgut under sulfide stress. Subsequently, ten genes including five new candidate reference genes and five commonly used reference genes, were validated by RT-qPCR. The expression stability of the ten genes was analyzed using four methods (geNorm, NormFinder, BestKeeper, and ∆Ct). The comprehensive results indicated that the new candidate reference genes were more stable than most commonly used reference genes. The commonly used ACTB was the most unstable gene. The candidate reference genes STX12, EHMT1, and LYAG were the most stable genes in early development, normal adult tissues, and hindgut under sulfide stress, respectively. The log2(TPM) of the transcriptome data was significantly negatively correlated with the Ct values of RT-qPCR (Ct = - 0.5405 log2(TPM) + 34.51), which made it possible to estimate the Ct value before RT-qPCR using transcriptome data. CONCLUSION: Our study is the first to select reference genes for RT-qPCR from transcriptome data in Echiura and provides important information for future gene expression studies in U. unicinctus.

Feedforward loop between IMP1 and YAP/TAZ promotes tumorigenesis and malignant progression in glioblastoma.

YAP/TAZ have been identified as master regulators in malignant phenotypes of glioblastoma (GBM); however, YAP/TAZ transcriptional disruptor in GBM treatment remains ineffective. Whether post-transcriptional dysregulation of YAP/TAZ improves GBM outcome is currently unknown. Here, we report that insulin-like growth factor 2 (IGF2) mRNA-binding protein 1 (IGF2BP1 or IMP1) is upregulated in mesenchymal GBM compared with proneural GBM and correlates with worse patient outcome. Overexpression of IMP1 in proneural glioma stem-like cells (GSCs) promotes while IMP1 knockdown in mesenchymal GSCs attenuates tumorigenesis and mesenchymal signatures. IMP1 binds to and stabilizes m6A-YAP mRNA, leading to activation of YAP/TAZ signaling, depending on its m6A recognition and binding domain. On the other hand, TAZ functions as enhancer for IMP1 expression. Collectively, our data reveal a feedforward loop between IMP1 and YAP/TAZ maintaining GBM/GSC tumorigenesis and malignant progression and a promising molecular target in GBM.

Operative treatment of cystic prolactinomas: a retrospective study.

BACKGROUND: The optimal therapeutic approach for cystic prolactinomas remains unclear. This study aimed to evaluate the remission rates of prolactinoma patients after surgical treatment and the risk factors affecting postoperative remission in cystic prolactinoma patients. METHODS: The clinical data were retrospectively compiled from 141 patients with prolactinomas (including 41 cases of cystic prolactinomas, 21 cases of solid microprolactinomas and 79 cases of solid macroprolactinomas) who underwent transsphenoidal surgery (TSS) between April 2013 and October 2021 at the First Affiliated Hospital of Sun Yat-sen University. RESULTS: Early postoperative remission was achieved in 65.83% (n = 27/41) of cystic prolactinomas, 80.95% (n = 17/21) of solid microprolactinomas and 40.51% (n = 32/79) of solid macroprolactinomas. The mean length of follow up in all patients was 43.95 ± 2.33 months (range: 6-105 months). The follow-up remission rates were 58.54%, 71.43% and 44.30% in cystic, solid micro- and solid macroprolactinomas, respectively. For cystic prolactinomas, the early postoperative remission rates in the patients with preoperative dopamine agonists (DA) treatment were significantly higher than those without preoperative DA treatment (p = 0.033), but the difference in the follow-up remission rates between these two groups was not significant (p = 0.209). Multivariate stepwise logistic regression analysis indicated that tumor size and preoperative prolactin (PRL) levels < 200 ng/ml were independent predictors for early postoperative remission in cystic prolactinomas. CONCLUSION: For cystic prolactinomas, tumor size and preoperative PRL levels were independent predictors of early postoperative remission. Preoperative DA therapy combined with TSS may be more beneficial to cystic prolactinoma patients.

Cross-cultural adaptation and psychometric properties of the Chinese version of the Person-Centered Maternity Care Scale.

BACKGROUND: Increasing evidence show that women across the world face unacceptable mistreatment during childbirth. Person-centered maternity care is fundamental and essential to quality of healthcare services. The aim of this study was to translate and determine the psychometric properties of the Person-Centered Maternity Care (PCMC) Scale among Chinese postpartum women. METHODS: A cross-sectional study was conducted among 1235 post-partum women in China. The cross-cultural adaptation process followed the Beaton intercultural debugging guidelines. A total of 1235 women were included to establish the psychometric properties of the PCMC. A demographic characteristics form and the PCMC were used for data collection. The psychometric properties of the PCMC were evaluated by examining item analysis, exploratory factor analysis, known-groups discriminant validity, and internal consistency. RESULTS: The number of extracted common factors was limited to three (dignity & respect, communication & autonomy, supportive care), explaining a total variance of 40.8%. Regarding internal consistency, the Cronbach's alpha coefficient and split-half reliability of the full PCMC score were 0.989 and 0.852, respectively. CONCLUSIONS: The Chinese version of the PCMC is a reliable and valid tool to assess person-centered care during childbirth in China.

Application of a developed triple-classification machine learning model for carcinogenic prediction of hazardous organic chemicals to the US, EU, and WHO based on Chinese database.

Cancer, the second largest human disease, has become a major public health problem. The prediction of chemicals' carcinogenicity before their synthesis is crucial. In this paper, seven machine learning algorithms (i.e., Random Forest (RF), Logistic Regression (LR), Support Vector Machines (SVM), Complement Naive Bayes (CNB), K-Nearest Neighbor (KNN), XGBoost, and Multilayer Perceptron (MLP)) were used to construct the carcinogenicity triple classification prediction (TCP) model (i.e., 1A, 1B, Category 2). A total of 1444 descriptors of 118 hazardous organic chemicals were calculated by Discovery Studio 2020, Sybyl X-2.0 and PaDEL-Descriptor software. The constructed carcinogenicity TCP model was evaluated through five model evaluation indicators (i.e., Accuracy, Precision, Recall, F1 Score and AUC). The model evaluation results show that Accuracy, Precision, Recall, F1 Score and AUC evaluation indicators meet requirements (greater than 0.6). The accuracy of RF, LR, XGBoost, and MLP models for predicting carcinogenicity of Category 2 is 91.67%, 79.17%, 100%, and 100%, respectively. In addition, the constructed machine learning model in this study has potential for error correction. Taking XGBoost model as an example, the predicted carcinogenicity level of 1,2,3-Trichloropropane (96-18-4) is Category 2, but the actual carcinogenicity level is 1B. But the difference between Category 2 and 1B is only 0.004, indicating that the XGBoost is one optimum model of the seven constructed machine learning models. Besides, results showed that functional groups like chlorine and benzene ring might influence the prediction of carcinogenic classification. Therefore, considering functional group characteristics of chemicals before constructing the carcinogenicity prediction model of organic chemicals is recommended. The predicted carcinogenicity of the organic chemicals using the optimum machine leaning model (i.e., XGBoost) was also evaluated and verified by the toxicokinetics. The RF and XGBoost TCP models constructed in this paper can be used for carcinogenicity detection before synthesizing new organic substances. It also provides technical support for the subsequent management of organic chemicals.

Effects of Nutritionally Induced Obesity on Metabolic Pathways of Zebrafish.

Human obesity has become a global epidemic that can lead to many metabolic diseases, including insulin resistance, type 2 diabetes, dyslipidemia, hypertension and nonalcoholic fatty liver. The development of obesity is closely associated with excess food intake and energy imbalance, family history, lifestyle, psychology and other factors, but molecular mechanisms underlying the induction and development of obesity remain to be intensively studied under a variety of internal and external pathogenesis conditions. In this study, we generated two obesity models of zebrafish that were treated with a high-fat diet (HFD) or an overfeeding diet (DIO). Both HFD and DIO zebrafish exhibited higher levels of lipid accumulation, fat distribution, microvascular steatosis and ectopic accumulation of lipid droplets in liver and muscle than normal diet (NOD) fish. The comparison of transcriptome sequencing data for the livers of HFD, DIO and NOD groups identified common and specific genes and signaling pathways that are potentially associated with zebrafish obesity induced by HFD and/or DIO. These findings provide clues for further understanding the mechanisms of obesity development and preventing nutritionally induced obesity through targeting the common signaling pathways and biological processes.

Synthesis of Synthetic Musks: A Theoretical Study Based on the Relationships between Structure and Properties at Molecular Scale.

Synthetic musks (SMs), as an indispensable odor additive, are widely used in various personal care products. However, due to their physico-chemical properties, SMs were detected in various environmental media, even in samples from arctic regions, leading to severe threats to human health (e.g., abortion risk). Environmentally friendly and functionally improved SMs have been theoretically designed in previous studies. However, the synthesizability of these derivatives has barely been proven. Thus, this study developed a method to verify the synthesizability of previously designed SM derivatives using machine learning, 2D-QSAR, 3D-QSAR, and high-throughput density functional theory in order to screen for synthesizable, high-performance (odor sensitivity), and environmentally friendly SM derivatives. In this study, three SM derivatives (i.e., D52, D37, and D25) were screened and recommended due to their good performances (i.e., high synthesizability and odor sensitivity; low abortion risk; and bioaccumulation ability in skin keratin). In addition, the synthesizability mechanism of SM derivatives was also analyzed. Results revealed that high intramolecular hydrogen bond strength, electrostatic interaction, qH+ value, energy gap, and low EHOMO would lead to a higher synthesizability of SMs and their derivatives. This study broke the synthesizability bottleneck of theoretically designed environment-friendly SM derivatives and advanced the mechanism of screening functional derivatives.

Biodegradability analysis of Dioxins through in silico methods: Model construction and mechanism analysis.

The biodegradation treatment of dioxins has long been of interest due to its good ecological and economic effects. In this study, the biodegradability of polychlorinated dibenzo-p-dioxins (PCDDs) were investigated by constructing machine learning and multiple linear regression models. The maximum chlorine atomic charge (qHirshfeldCl+), which characterizes the biodegradation ability of PCDDs, was used as the response value. The random forest model was used to rank the importance on the 1471 descriptors of PCDDs, and the BCUTp-1 h, QXZ, JGI4, ATSC8c, VE3_Dt, topoShape, and maxwHBa were screened as the important descriptors by Pearson's correlation coefficient method. A quantitative structure-activity relationship (QSAR) model was constructed to predict the biodegradability of PCDDs. In addition, the extreme gradient boosting (XGBoost) and random forest model were also constructed and proved the good predictability of QSAR model. The biodegradability of polychlorinated dibenzofurans (PCDFs) can also be predicted by the constructed three models from a certain level after adjusting some model parameters, which further proved the versatility of the models. Besides, the sensitivity analysis of the QSAR model and a 3D-QSAR model was developed to investigate the biodegradability mechanisms of PCDDs. Results showed that the descriptors BCUTp-1 h, JGI4, and maxwHBa were the key descriptors in the biodegradability effect by the sensitivity analysis of the QSAR model. Coupled with the results of PCDDs biodegradability 3D-QSAR model, BCUTp-1 h, JGI4, and maxwHBa were confirmed as the main descriptors that affect the biodegradability of dioxins. This study provides a novel theoretical perspective for the research of the biodegradation of both PCDDs and PCDFs dioxins.

Environmental risk of tailings pond leachate pollution: Traceable strategy for leakage channel and influence range of leachate.

Identifying the leakage channel and the influencing range is essential for controlling the environmental risks of leachate from the tailings pond. The investigation of leachate pollution in tailings pond has the defect of focusing only on the scope of tailings pond in recent studies. This study innovatively built a comprehensive investigation and accurate verification system for leachate leakage of tailings pond integrated with the aeromagnetic survey, ground penetrating radar, hydrochemistry and isotope coupling methods. Geophysical exploration found that among the four fault zones, and the F1 was the channel for leachate to recharge the groundwater 2.53 km away from the tailings pond. The fissures inside the tailings pond were connected with the natural fissures outside, forming a leachate migration channel. The hydrochemistry and isotope characteristics showed that the groundwater far away from the tailings pond were polluted by arsenic containing leachate, which verified the geophysical exploration results. The significant correlation between arsenic and SO2-4 concentration indicated that arsenic in leachate originated from the oxidation release of sulfide minerals (i.e., arsenopyrite). This study sheds light on the comprehensive investigation of leachate leakage in the tailings pond. This development method also provides guidance for environmental risk identification of other contaminated sites.

An emerging role for cyclic dinucleotide phosphodiesterase and nanoRNase activities in Mycoplasma bovis: Securing survival in cell culture.

Mycoplasmas are host-restricted prokaryotes with a nearly minimal genome. To overcome their metabolic limitations, these wall-less bacteria establish intimate interactions with epithelial cells at mucosal surfaces. The alarming rate of antimicrobial resistance among pathogenic species is of particular concern in the medical and veterinary fields. Taking advantage of the reduced mycoplasma genome, random transposon mutagenesis was combined with high-throughput screening in order to identify key determinants of mycoplasma survival in the host-cell environment and potential targets for drug development. With the use of the ruminant pathogen Mycoplasma bovis as a model, three phosphodiesterases of the DHH superfamily were identified as essential for the proliferation of this species under cell culture conditions, while dispensable for axenic growth. Despite a similar domain architecture, recombinant Mbov_0327 and Mbov_0328 products displayed different substrate specificities. While rMbovP328 protein exhibited activity towards cyclic dinucleotides and nanoRNAs, rMbovP327 protein was only able to degrade nanoRNAs. The Mbov_0276 product was identified as a member of the membrane-associated GdpP family of phosphodiesterases that was found to participate in cyclic dinucleotide and nanoRNA degradation, an activity which might therefore be redundant in the genome-reduced M. bovis. Remarkably, all these enzymes were able to convert their substrates into mononucleotides, and medium supplementation with nucleoside monophosphates or nucleosides fully restored the capacity of a Mbov_0328/0327 knock-out mutant to grow under cell culture conditions. Since mycoplasmas are unable to synthesize DNA/RNA precursors de novo, cyclic dinucleotide and nanoRNA degradation are likely contributing to the survival of M. bovis by securing the recycling of purines and pyrimidines. These results point toward proteins of the DHH superfamily as promising targets for the development of new antimicrobials against multidrug-resistant pathogenic mycoplasma species.

Dermal exposure to synthetic musks: Human health risk assessment, mechanism, and control strategy.

Synthetic musks (SMs) have been widely used as odor additives in personal care products (PCPs). Dermal exposure to SMs is the main pathway of the accumulation of these chemicals in human kerateins and poses potential health risks. In this study, in silico methods were established to reduce the human health risk of SMs from dermal exposure by investigating the risk mechanisms, designing lower bioaccumulation ability SMs and suggesting proper PCP ingredients using molecular docking, molecular dynamics simulation, and quantitative structure-activity relationship (QSAR) models. The binding energy, a parameter reflecting the binding ability of SMs and human keratin protein (4ZRY), was used as the indicator to assess the human health risk of SMs. According to the mechanism analysis, total energy was found as the most influential molecular structural feature influencing the bioaccumulation ability of a SM, and as one of the main factors influencing the function (i.e., odor sensitivity) of an SM. The 3D-QSAR models were constructed to control the human health risk of SMs by designing lower-risk SMs derivatives. The phantolide (PHAN)- 58 was determined to be the optimum SM derivative with lower bioaccumulation ability (reduced 17.25%) and improved odor sensitivity (increased 7.91%). A further reduction of bioaccumulation ability of PHAN-58 was found when adding proper body wash ingredients (i.e., alkyl ethoxylate sulfate (AES), dimethyloldimethyl (DMDM), EDTA-Na4, ethylene glycol distearate (EGDS), hydroxyethyl cellulose (HEC), lemon yellow and octyl glucose), leading to a significant reduction of the bioaccumulation ability (42.27%) compared with that of PHAN. Results demonstrated that the proposed theoretical mechanism and control strategies could effectively reduce the human health risk of SMs from dermal exposure.

In-silico study of reducing human health risk of POP residues' direct (from tea) or indirect exposure (from tea garden soil): Improved rhizosphere microbial degradation, toxicity control, and mechanism analysis.

The accumulation of potentially harmful substances in tea garden soils and tea leaves, especially persistent organic pollutants (POPs), is a special concern for tea consumers worldwide. However, their potential health and ecological risks in tea gardens have rarely been investigated. This study proposed measures to improve the degradation ability of POPs by the tea rhizosphere and to reduce the human health risks caused by POPs after tea consumption. In this study, the binding energy values of six types of POPs and the degraded protein were used to reflect the degradation ability and calculated using molecular dynamic simulations. The main root secretions (i.e., catechin, glucose, arginine, and oxalic acid) were selected and applied with a combination of tea fertilizer and trace element combination (i.e., urea, straw, and copper element), leading to an improved degradation ability (49.59 %) of POPs. To investigate the mechanisms of the factors that affect the degradation ability, molecular docking, tensor singular value decomposition methods, multivariate correlation analysis and 2D-QSAR model were used. The results showed that the solvation energy and solvent accessible surface area are the main forces, and the molecular weight, boiling point, and topological radius of the POPs were the key molecular features affecting their degradation ability. Based on the three key characteristics, a diet avoidance scheme (i.e., avoiding lysine, maslinic acid, ethanol, perfluorocaproic acid, and cholesterol with tea), which can reduce the binding ability of POP residues to aromatic hydrocarbon receptors by 506.13 %. This work will provide theoretical strategies to improve the quality and safety of tea production and reduce the potential risks of harmful substance residues in tea garden soils and tea leaves.

Psychological Behavior, Work Stress, and Social Support of Frontline Nurses During the COVID-19 Pandemic.

Using a cluster sampling method, 248 nurses from frontline departments of three large general hospitals in Sichuan Province, China, were selected as participants in the current study. Risk perception and coping methods during the coronavirus disease 2019 (COVID-19) pandemic, negative emotions and psychological workload, and awareness of social support among nurses were studied. Negative emotions among nurses increased significantly, with fear being the most common (73.4%, n = 182). Psychological workload of nurses in close contact with patients with COVID-19 was higher than that of nurses in other positions (p < 0.05). Family was the major source of social support. Social support was negatively associated with depression (-0.206, p < 0.05), obsessive-compulsiveness/anxiety (-0.185, p < 0.05), and hypochondriasis (-0.234, p < 0.05). Psychological workload of nurses was positively correlated with depression (0.251, p < 0.05), neurasthenia (0.242, p < 0.05), and obsessive-compulsiveness/anxiety (0.231, p < 0.05). Nursing staff in frontline departments encountered psychological workload burdens to varying degrees during the COVID-19 pandemic. Thus, it is important to implement and strengthen psychological counseling for nurses in close contact positions, and to seek family and social support for nurses. [Journal of Psychosocial Nursing and Mental Health Services, 60(10), 21-27.].