Cyclic catalysis of intratumor Fe3+/2+ initiated by a hollow mesoporous iron sesquioxide nanoparticle for ferroptosis therapy of large tumors.

Numerous nanoparticles have been utilized to deliver Fe2+ for tumor ferroptosis therapy, which can be readily converted to Fe3+via Fenton reactions to generate hydroxyl radical (•OH). However, the ferroptosis therapeutic efficacy of large tumors is limited due to the slow conversion of Fe3+ to Fe2+via Fenton reactions. Herein, a strategy of intratumor Fe3+/2+ cyclic catalysis is proposed for ferroptosis therapy of large tumors, which was realized based on our newly developed hollow mesoporous iron sesquioxide nanoparticle (HMISN). Cisplatin (CDDP) and Gd-poly(acrylic acid) macrochelates (GP) were loaded into the hollow core of HMISN, whose surface was modified by laccase (LAC). Fe3+, CDDP, GP, and LAC can be gradually released from CDDP@GP@HMISN@LAC in the acidic tumor microenvironment. The intratumor O2 can be catalyzed into superoxide anion (O2•-) by LAC, and the intratumor NADPH oxidases can be activated by CDDP to generate O2•-. The O2•- can react with Fe3+ to generate Fe2+, and raise H2O2 level via the superoxide dismutase. The generated Fe2+ and H2O2 can be fast converted into Fe3+ and •OH via Fenton reactions. The cyclic catalysis of intratumor Fe3+/2+ initiated by CDDP@GP@HMISN@LAC can be used for ferroptosis therapy of large tumors.

Study on psychological resilience and associated influencing factors in lung cancer patients with bone metastases.

BACKGROUND: Evaluating the psychological resilience of lung cancer (LC) patients helps understand their mental state and guides future treatment. However, there is limited research on the psychological resilience of LC patients with bone metastases. AIM: To explore the psychological resilience of LC patients with bone metastases and identify factors that may influence psychological resilience. METHODS: LC patients with bone metastases who met the inclusion criteria were screened from those admitted to the Third Affiliated Hospital of Wenzhou Medical University. The psychological scores of the enrolled patients were collected. They were then grouped based on the mean psychological score: Those with scores lower than the mean value were placed in the low-score group and those with scores equal to or greater than the mean value was placed in the high-score group. The baseline data (age, gender, education level, marital status, residence, monthly income, and religious beliefs), along with self-efficacy and medical coping mode scores, were compared. RESULTS: This study included 142 LC patients with bone metastases admitted to our hospital from June 2022 to December 2023, with an average psychological resilience score of 63.24 ± 9.96 points. After grouping, the low-score group consisted of 69 patients, including 42 males and 27 females, with an average age of 67.38 ± 9.55 years. The high-score group consisted of 73 patients, including 49 males and 24 females, with a mean age of 61.97 ± 5.00 years. χ 2 analysis revealed significant differences between the two groups in education level (χ 2 = 6.604, P = 0.037), residence (χ 2 = 12.950, P = 0.002), monthly income (χ 2 = 9.375, P = 0.009), and medical coping modes (χ 2 = 19.150, P = 0.000). Independent sample t-test showed that the high-score group had significantly higher self-efficacy scores (t = 3.383, P = 0.001) and lower age than the low-score group (t = 4.256, P < 0.001). Furthermore, multivariate logistic regression hazard analysis confirmed that self-efficacy is an independent protective factor for psychological resilience [odds ratio (OR) = 0.926, P = 0.035, 95% confidence interval (CI): 0.862-0.995], while age (OR = 1.099, P = 0.003, 95%CI: 1.034-1.169) and medical coping modes (avoidance vs confrontation: OR = 3.767, P = 0.012, 95%CI: 1.342-10.570; resignation vs confrontation: OR = 5.687, P = 0.001, 95%CI: 1.974-16.385) were identified as independent risk factors. A predictive model based on self-efficacy, age, and medical coping modes was developed. The receiver operating characteristic analysis showed an area under the curve value of 0.778 (95%CI: 0.701-0.856, P < 0.001), indicating that the model has good predictive performance. CONCLUSION: LC patients with bone metastases are less psychologically resilient than the general population. Factors such as self-efficacy, age, and medical coping modes influence their psychological resilience. Patients with low self-efficacy, old age, and avoidance/resignation coping modes should be closely observed.

[Oscillation-static cycle cultivation enhances the synthesis of triterpenes and mycelium activity in Ganoderma lucidum].

Ganoderma lucidum is a precious fungus with both edible and medicinal values and has a long history of medical use. Triterpenes as the main active components endow G. lucidum with anti-tumor, antioxidant, and other pharmacological activities. The present study endeavors to establish a proficient liquid-state fermentation technology for the enhanced production of triterpenes. In view of the limitations inherent in conventional submerged fermentation and oscillation-static two-stage cultivation, this study established an oscillation-static cycle cultivation process and optimized the cultivation conditions by building an artificial neural network model based on genetic algorithms. The cultivation conditions for the high-yield production of triterpenes were optimized as follows: 2.8 days of oscillation, 7.3 days of static cultivation, 0.2 day of oscillation, and 0.3 day of static cultivation. Under these conditions, the content of triterpenes reached 20.82 mg/g. The yield of triterpenes reached 129.09 mg/L, showing a remarkable increase of 324.78% compared with that of the Z10J0 method. Moreover, the established method shortened the cultivation cycle by 10.6 days. The mycelia cultivated under this regimen exhibited commendable anti-tumor and antioxidant activities. This study not only presents an economical liquid-state fermentation approach but also streamlines the fermentation flow, reduces fermentation duration, and effectively ameliorates drawbacks associated with conventional cultivation methods. In addition, this study gives valuable insights into the scaled application of liquid-state fermentation in the high-yield production of triterpenes, which showcases broad prospects.

Exploring the transcriptomic landscape of moyamoya disease and systemic lupus erythematosus: insights into crosstalk genes and immune relationships.

Background: Systemic Lupus Erythematosus (SLE) is acknowledged for its significant influence on systemic health. This study sought to explore potential crosstalk genes, pathways, and immune cells in the relationship between SLE and moyamoya disease (MMD). Methods: We obtained data on SLE and MMD from the Gene Expression Omnibus (GEO) database. Differential expression analysis and weighted gene co-expression network analysis (WGCNA) were conducted to identify common genes. Subsequently, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on these shared genes. Hub genes were further selected through the least absolute shrinkage and selection operator (LASSO) regression, and a receiver operating characteristic (ROC) curve was generated based on the results of this selection. Finally, single-sample Gene Set Enrichment Analysis (ssGSEA) was utilized to assess the infiltration levels of 28 immune cells in the expression profile and their association with the identified hub genes. Results: By intersecting the important module genes from WGCNA with the DEGs, the study highlighted CAMP, CFD, MYO1F, CTSS, DEFA3, NLRP12, MAN2B1, NMI, QPCT, KCNJ2, JAML, MPZL3, NDC80, FRAT2, THEMIS2, CCL4, FCER1A, EVI2B, CD74, HLA-DRB5, TOR4A, GAPT, CXCR1, LAG3, CD68, NCKAP1L, TMEM33, and S100P as key crosstalk genes linking SLE and MMD. GO analysis indicated that these shared genes were predominantly enriched in immune system process and immune response. LASSO analysis identified MPZL3 as the optimal shared diagnostic biomarkers for both SLE and MMD. Additionally, the analysis of immune cell infiltration revealed the significant involvement of activation of T and monocytes cells in the pathogenesis of SLE and MMD. Conclusion: This study is pioneering in its use of bioinformatics tools to explore the close genetic relationship between MMD and SLE. The genes CAMP, CFD, MYO1F, CTSS, DEFA3, NLRP12, MAN2B1, NMI, QPCT, KCNJ2, JAML, MPZL3, NDC80, FRAT2, THEMIS2, CCL4, FCER1A, EVI2B, CD74, HLA-DRB5, TOR4A, GAPT, CXCR1, LAG3, CD68, NCKAP1L, TMEM33, and S100P have been identified as key crosstalk genes that connect MMD and SLE. Activation of T and monocytes cells-mediated immune responses are proposed to play a significant role in the association between MMD and SLE.

Comprehensive Serum Proteomic and Metabolomic Profiles of Pediatric Patients with Moyamoya Disease Reveal Core Pathways.

Background: Moyamoya disease (MMD) signifies a cerebrovascular disorder with obscure origin and a more rapid and severe progression in children than adults. This investigation aims to uncover age-associated distinctions through proteomic and metabolomic profiling to gain insights into the underlying mechanisms of MMD. Methods: Twelve MMD patients-six children and six adults-along with six healthy controls (HC), participated, each providing a 10 mL blood sample. Serum proteomic and metabolomic analyses were conducted using ultra-performance liquid chromatography and high-resolution mass spectrometry, complemented by bioinformatics to identify differential biomolecules and their interactions. Pathway implications were ascertained using GO and KEGG enrichment analysis. Results: Notable proteomic and metabolomic discrepancies were observed between pediatric and adult MMD subjects. A total of 235 and 216 proteins varied in adult and pediatric cases compared to HCs, with 73 proteins shared. In addition, 129 and 74 anionic, plus 96 and 104 cationic metabolites, were differentially expressed in the pediatric and adult groups, respectively, with 34 anionic and 28 cationic metabolites in common. Age-specific biomolecules further characterized these distinctions. Enrichment analysis pinpointed immunity and inflammation pathways, with vitamin digestion and absorption highlighted as pivotal in pediatric MMD. Conclusion: This study unveils distinct metabolic and proteomic patterns within pediatric and adult MMD patients. The critical role of the vitamin digestion and absorption pathway in the pathogenesis of pediatric MMD offers novel insight into disease mechanisms.

Study on the elimination characteristics of smoke particles with different materials using electric agglomeration technology.

Fire smoke, consisting of solid particles and liquid droplets, poses risks of asphyxiation, poisoning, making it a significant contributor to fire-related fatalities and environmental pollution. The exploration of effective smoke control methods represents a vital approach to reducing the threat of fire smoke to public health and safety. This study aims to determine the characteristics of elimination for the fire smoke generated from burning four typical materials, thereby validating the universality of electric agglomeration smoke elimination technology. The results indicate that the elimination efficiency of electric agglomeration varies with the material type of the smoke. The rate of change in smoke transmittance from fast to slow is: polyvinyl chloride (PVC), polystyrene (PS), wood, and styrene butadiene rubber (SBR), respectively. With an external potential of 4 kV, PVC smoke reaches the safe threshold after 12.1 s, while SBR smoke achieves it in just 4.9 s. Analysis of the microscopic morphology of agglomerates with scanning electron microscopy (SEM) reveals that particle size distribution is an important factor affecting electric agglomeration elimination. This is because larger initial particles carry a greater charge, enabling the formation of larger agglomerates for more efficient removal. This study provides theoretical guidance for the practical application of electric agglomeration in eliminating smoke particles.

[Effect of Modified Xiaoyao Powder on intestinal barrier and intestinal flora in mice with metabolic associated fatty liver disease based on "gut-liver axis"].

This study explores the effects and mechanisms of Modified Xiaoyao Powder on the intestinal barrier and intestinal flora in mice with metabolic associated fatty liver disease(MAFLD) based on the " gut-liver axis". Sixty male C57BL/6 mice were randomly divided into the normal group, model group, bifidobacterium tetrad tablet group(SQ), and Modified Xiaoyao Powder groups with low,medium and high doses(XL, XM, XH), with 10 mice in each group. All the mice were administrated with a high-fat diet to build the MAFLD model except the normal group and then treated with related drugs for 12 weeks. Body mass, liver wet weight, and liver index were detected. Serum aspartate aminotransferase(AST), alanine aminotransferase(ALT), total cholesterol(TC), triacylglycerol(TG), low density lipoprotein cholesterol(LDL-C), high density lipoprotein cholesterol(HDL-C), and lipopolysaccharide(LPS)levels were detected using the biochemical kits. The contents of tumor necrosis factor-α(TNF-α) and interleukin(IL-6) in the liver were tested simultaneously. The morphological changes of the liver and intestine were observed using hematoxylin-eosin(HE) staining and oil red O staining. The goblet cells in the ileum were detected by periodic acid Schiff and alcian blue stain(AB-PAS) staining.The expression of zonula occludens-1(ZO-1), recombinant occludin(occludin), and recombinant claudin 1(claudin-1) in ileum and colon were detected by immunohistochemistry and Western blot. The changes of intestinal flora in mice were analyzed by 16S rRNA gene sequencing. The results showed that compared with the normal group, body weight, liver wet weight and liver index in the model group increased. The contents of TC, TG, ALT, AST, LDL-C, and LPS in the serum of the model group increased, while HDL-C decreased. Meanwhile, the contents of TNF-α and IL-6 in liver tissue increased and liver lipid accumulation increased, indicating successful model induction. Compared with the model group, body weight, liver wet weight, and liver index were decreased in XM,XH groups and SQ group. Serum levels of TC, TG, LDL-C, ALT and AST in XM group and SQ group were significantly decreased,and HDL-C levels were increased. The levels of IL-6, TNF-α in liver tissue and serum LPS in the XL, XM groups and SQ group were significantly decreased. The protein expression of claudin-1, occludin and ZO-1 in XL, XM groups and SQ group were increased. The analysis of intestinal flora showed that compared with the model group, Modified Xiaoyao Powder with a medium dose could significantly improve the richness and diversity of intestinal flora in mice. At the phylum level, the Firmicutes/Bacteroidetes(F/B) ratio decreased; at the genus level, Lactobacillus, Brautella, Bacteroides, and Ackermannia increased, while Prevotella, Desulfovibrio and Turicibacter decreased. The main differential species were Odorbacteraceaeae and Peptostreptococcaceae. In conclusion, Modified Xiaoyao Powder could inhibit inflammation, regulate intestinal flora homeostasis, and promote the repair of the intestinal mucosal barrier in mice with MAFLD.

Bilateral superselective adrenal artery embolization for bilateral primary aldosteronism: a novel approach in an efficacy and safety proof-of-principle trial.

Superselective adrenal artery embolization (SAAE) offers a novel approach for treating primary aldosteronism (PA). In this study, we aimed to assess the efficacy and safety of SAAE for the treatment of PA based on the lateralization results obtained from adrenal vein sampling (AVS).In this prospective study, we enrolled 40 patients with PA who underwent SAAE. The patients were categorized into two groups, unilateral PA and bilateral PA, based on AVS results. Clinical parameters and biochemical markers were assessed at 3 and 12 months postoperatively. The primary outcomes were changes in blood pressure and defined daily dose (DDD) of antihypertensive medications compared to baseline. Thirty-eight patients achieved technical success, with favorable clinical and biochemical efficacy rates. At three months postoperatively, the clinical efficacy rates were 79.2% and 78.6% for the UPA and BPA groups, respectively. At 12 months, the rates were 83.3% and 71.4%, respectively. Both groups exhibited a significant decrease in average blood pressure at 3 and 12 months compared with baseline (P < 0.001), and there was also a notable reduction in DDD (P < 0.05). At three months, the biochemical efficacy rates were 61.9% and 58.3% in the UPA and BPA groups, respectively. Due to loss to follow-up, biochemical indicators were not assessed at 12 months postoperatively. No severe adverse reactions occurred during or after SAAE. Patients with both UPA and BPA can benefit from SAAE. The superiority of bilateral adrenal artery embolization in the treatment of BPA over unilateral adrenal artery embolization requires further investigation.

iDHS-RGME: Identification of DNase I hypersensitive sites by integrating information on nucleotide composition and physicochemical properties.

As pivotal markers of chromatin accessibility, DNase I hypersensitive sites (DHSs) intimately link to fundamental biological processes encompassing gene expression regulation and disease pathogenesis. Developing efficient and precise algorithms for DHSs identification holds paramount importance for unraveling genome functionality and elucidating disease mechanisms. This study innovatively presents iDHS-RGME, an Extremely Randomized Trees (Extra-Trees)-based algorithm that integrates unique feature extraction techniques for enhanced DHSs prediction. Specifically, iDHS-RGME utilizes two feature extraction approaches: Reverse Complementary Kmer (RCKmer) and Geary Spatial Autocorrelation (GSA), which comprehensively capture sequence attributes from diverse angles, bolstering information richness and accuracy. To address data imbalance, Borderline-SMOTE is employed, followed by Maximum Information Coefficient (MIC) for meticulous feature selection. Comparative evaluations underscored the superiority of the Extra-Trees classifier, which was subsequently adopted for model prediction. Through rigorous five-fold cross-validation, iDHS-RGME achieved remarkable accuracies of 94.71 % and 95.07 % on two independent datasets, outperforming previous models in terms of both precision and effectiveness.

Pt-Ru atomic alloys confined in mesoporous carbon hollow spheres for accelerating methanol oxidation.

Active and durable electrocatalysts are essential for commercializing direct methanol fuel cells. However, Pt-based catalysts, extensively utilized in the methanol oxidation reaction (MOR), are suffered from resource scarcity and CO poisoning, which degrade MOR activity severely. Herein, Pt1Rux bimetallic catalysts were synthesized by confining Pt1Rux alloys within the shells of mesoporous carbon hollow spheres (MCHS) via a vacuum-assisted impregnation method (Pt1Rux@MCHS). The confinement effect induced by mesoporous carbon hollow spheres resulted in a robust structure of Pt1Ru3@MCHS with an ultrafine dispersion of alloy nanoparticles. The experimental and theoretical results confirmed that the boosting electrocatalytic activity and stability of the MOR over Pt1Ru3@MCHS were contributed to the regulated electronic structure as well as the superior CO tolerance of atomic Pt site caused by the electronic interaction between single Pt atoms and Ru nanoparticles. This strategy is versatile for the rational design of Pt-based bimetallic catalysts and has a positive impact on MOR performance.

MHIPM: Accurate Prediction of Microbe-Host Interactions Using Multiview Features from a Heterogeneous Microbial Network.

Current studies have demonstrated that microbe-host interactions (MHIs) play important roles in human public health. Therefore, identifying the interactions between microbes and hosts is beneficial to understanding the role of the microbiome and their underlying mechanisms. However, traditional wet-lab experimental approaches are insufficient for large-scale exploration of candidate microbes, as they are costly, laborious, and time-consuming. Thus, it is critical to prioritize microbe-interacting hosts by computational approaches for further biological experimental validation. In this work, we proposed a novel deep learning-based method called MHIPM, to predict MHIs by utilizing multisource biological information. Specifically, we first constructed a heterogeneous microbial network that consisted of human proteins, viruses, bacteriophages (phages), and pathogenic bacteria. Next, we used one of the largest protein language models, ESM-2, and a document embedding model, doc2vec, combined with a self-attention mechanism to extract the interview features from protein sequences. Then, an inductive learning-based model, GraphSAGE, was used to capture the intraview features from the heterogeneous network. Experimental results on three prediction tasks indicated that the MHIPM model consistently achieved better performance than seven baseline algorithms and its four variants. In addition, case studies and molecular docking experiments for two human proteins further confirmed the effectiveness of our model. In conclusion, MHIPM is an efficient and robust method in predicting MHIs and provides plausible candidate microbes for biological experiments. MHIPM is available at https://github.com/JIENWU/MHIPM.

The Overflow Effects of Movement Behaviour Change Interventions for Children and Adolescents: A Systematic Review and Meta-Analysis of Randomised Controlled Trials.

BACKGROUND: Considering the finite time within a 24-h day, the distribution of time spent on movement behaviours has been found to be associated with health outcomes. OBJECTIVES: This systematic review and meta-analysis aimed to summarise and evaluate the overflow effects of interventions targeting a single behaviour (physical activity, sedentary behaviour/screen time, or sleep) on other non-targeted behaviours among children and adolescents. METHODS: Six databases (MEDLINE [Ovid], PsycINFO [ProQuest], EMBASE [Ovid], PubMed, Web of Science and SPORTDiscus [EBSCO]) were searched for relevant studies published before 13 May, 2024. Randomised controlled trials and clustered randomised controlled trials that targeted a single behaviour and also assessed the effects on non-targeted behaviours, comprised of healthy children under the age of 18 years, were included. Movement behaviours can be measured either objectively or subjectively. The revised Cochrane risk-of-bias tool for randomised trials was adopted to evaluate the risk of bias. RESULTS: A total of 102 studies with 45,998 participants from 21 countries were identified, and 60 of them with 26,183 participants were incorporated into the meta-analysis. The meta-analysis demonstrated that physical activity interventions led to a reduction in the proportion of each day spent in sedentary behaviour (mean difference = - 0.95% of wear time, 95% confidence interval - 1.44, - 0.45, I2 = 39%). Sedentary behaviour interventions resulted in increased standing time (mean difference = 3.87%, 95% confidence interval 1.99, 5.75, I2 = 0%). Interventions targeting screen time did not yield changes in physical activity or sleep. The findings on the effectiveness of sleep interventions on non-targeted behaviours and of physical activity interventions on sleep were inconclusive. CONCLUSIONS: Overall, the findings suggested that interventions aimed at increasing physical activity or reducing sedentary behaviour had overflow effects on non-targeted behaviours, but the effect sizes were small. Additional evidence is needed to reach definitive conclusions regarding the impact of behaviour change interventions on sleep and of the overflow effects of sleep interventions.

Biodegradation of low-density polyethylene by mixed fungi composed of Alternaria sp. and Trametes sp. isolated from landfill sites.

With the development of industry and modern manufacturing, nondegradable low-density polyethylene (LDPE) has been widely used, posing a rising environmental hazard to natural ecosystems and public health. In this study, we isolated a series of LDPE-degrading fungi from landfill sites and carried out LDPE degradation experiments by combining highly efficient degrading fungi in pairs. The results showed that the mixed microorganisms composed of Alternaria sp. CPEF-1 and Trametes sp. PE2F-4 (H-3 group) had a greater degradation effect on heat-treated LDPE (T-LDPE). After 30 days of inoculation with combination strain H-3, the weight loss rate of the T-LDPE film was approximately 154% higher than that of the untreated LDPE (U-LDPE) film, and the weight loss rate reached 0.66 ± 0.06%. Environmental scanning electron microscopy (ESEM) and Fourier transform infrared spectroscopy (FTIR) were used to further investigate the biodegradation impacts of T-LDPE, including the changes on the surface and depolymerization of the LDPE films during the fungal degradation process. Our findings revealed that the combined fungal treatment is more effective at degrading T-LDPE than the single strain treatment, and it is expected that properly altering the composition of the microbial community can help lessen the detrimental impact of plastics on the environment.

Effectiveness of a parent-focused intervention targeting 24-hour movement behaviours in preschool-aged children: a randomised controlled trial.

BACKGROUND: Interventions focusing on individual behaviours (physical activity, sedentary behaviour, sleep) of preschool-aged children have been widely studied. However, there is a lack of understanding about integrated interventions that target all three 24-hour movement behaviours. This is the first study to assess the effectiveness of an intervention aimed at improving all three 24-hour movement behaviours among preschoolers in Hong Kong. METHODS: A 12-week randomised controlled trial with a 12-week follow-up was conducted. Parent-child pairs were randomised to integrated approach (targeting all three behaviours), dyadic approach (targeting physical activity and sedentary behaviour including screen time), or wait-list control group. Utilising the Internet-based delivery, this intervention consisted of education materials, workshops, and interactive questionnaires and reminders. Two intervention groups employed the same strategies, with the only difference being that the integrated approach targeted sleep in addition to physical activity and sedentary behaviour. The outcomes were preschoolers' overall 24-hour movement behaviours which were assessed by the Activity Sleep Index (ASI), movement behaviour composition, and absolute duration of movement behaviours. Generalised estimating equations were conducted to evaluate the intervention. RESULTS: A total of 147 preschoolers (4.8 ± 0.9 years old, 56.5% boys) and their parents were included. Preschoolers in all groups had a lower ASI at follow-up compared with baseline. Preschoolers in the integrated approach had a smaller decline in ASI at follow-up, compared to that in the control group (3.41; 95% confidence interval [CI] = 0.07, 6.76). Preschoolers in both intervention groups had a smaller reduction of the composition of time spent in physical activity at follow-up, and a decreased screen time at postintervention and follow-up. No significant differences were found for the sleep subcomponent. Furthermore, preschoolers in the dyadic approach had a smaller increase in the sedentary behaviour subcomponent (vs. CONTROL: - 0.21; 95% CI = - 0.37, - 0.05) at follow-up. CONCLUSIONS: Both intervention groups showed a decrease in screen time at postintervention, but there were no significant changes in other behaviours. The favourable changes observed at follow-up demonstrated the effectiveness of both intervention approaches on alleviating the decline in the composition of time spent in physical activity and reducing screen time and revealed the possible effectiveness of the integrated approach in promoting overall movement behaviours among preschoolers. TRIAL REGISTRATION: The study is prospectively registered at the Chinese Clinical Trial Registry (ChiCTR2200055958).

Holistic understanding of trimethoprim resistance in Streptococcus pneumoniae using an integrative approach of genome-wide association study, resistance reconstruction, and machine learning.

Antimicrobial resistance (AMR) is a public health threat worldwide. Next-generation sequencing (NGS) has opened unprecedented opportunities to accelerate AMR mechanism discovery and diagnostics. Here, we present an integrative approach to investigate trimethoprim (TMP) resistance in the key pathogen Streptococcus pneumoniae. We explored a collection of 662 S. pneumoniae genomes by conducting a genome-wide association study (GWAS), followed by functional validation using resistance reconstruction experiments, combined with machine learning (ML) approaches to predict TMP minimum inhibitory concentration (MIC). Our study showed that multiple additive mutations in the folA and sulA loci are responsible for TMP non-susceptibility in S. pneumoniae and can be used as key features to build ML models for digital MIC prediction, reaching an average accuracy within ±1 twofold dilution factor of 86.3%. Our roadmap of in silico analysis-wet-lab validation-diagnostic tool building could be adapted to explore AMR in other combinations of bacteria-antibiotic. IMPORTANCE: In the age of next-generation sequencing (NGS), while data-driven methods such as genome-wide association study (GWAS) and machine learning (ML) excel at finding patterns, functional validation can be challenging due to the high numbers of candidate variants. We designed an integrative approach combining a GWAS on S. pneumoniae clinical isolates, followed by whole-genome transformation coupled with NGS to functionally characterize a large set of GWAS candidates. Our study validated several phenotypic folA mutations beyond the standard Ile100Leu mutation, and showed that the overexpression of the sulA locus produces trimethoprim (TMP) resistance in Streptococcus pneumoniae. These validated loci, when used to build ML models, were found to be the best inputs for predicting TMP minimal inhibitory concentrations. Integrative approaches can bridge the genotype-phenotype gap by biological insights that can be incorporated in ML models for accurate prediction of drug susceptibility.

A study on the effect of fluorescently stained micro(nano)plastics on the full life history of Skeletonema costatum.

As a new type of environmental pollutant, micro(nano)plastics have become a research hotspot in recent years, and their effects on the full life history of marine microalgae have not been studied. To investigate the effects of micro(nano)plastics on the growth, photosynthesis, physiological morphology and interaction of microalgae during the full life cycle, we selected fluorescently stained polystyrene (PS) plastic microbeads as the target pollutant. By sampling and testing the growth rate, photosynthesis and physiological morphology parameters of algal species, the influence of different concentrations of PS (10, 50 and 100 mg/L) and different particle sizes (0.1, 0.5 and 1 µm) on the full life history of Skeletonema costatum (S. costatum) was investigated. The results showed that after adding PS (particle sizes of 0.5 and 1 µm), the response of S. costatum showed a dual character, while adding the same kind of microplastics (MPs) with a particle size of 0.1 µm inhibited S. costatum throughout the full life cycle. Compared with previous studies, short-term experimental data may overestimate the true ecological risks of MPs. In addition, 0.1 µm fluorescent-stained MPs obviously accumulated around the microalgae, indicating that MPs mainly adhered to the surface of algal cells and may enter the food chain by direct or indirect ways, which can cause negative effects on the aquatic ecosystem. This study supports a more accurate assessment of the true risk of MPs to marine aquatic ecosystems.

Uncovering the symptom relationship among sleep quality, anxiety, and depression in Chinese patients with breast cancer: multidimensional data validation using PSQI versus actigraphy.

PURPOSE: The interplay between sleep quality, anxiety, and depression among breast cancer patients remains poorly understood. This study aimed to investigate and compare the symptoms relationships among these three factors in Chinese breast cancer patients, utilizing two sleep assessments. METHODS: Our study encompassed 288 participants diagnosed with breast cancer, from whom we collected demographic information through questionnaires. Sleep quality symptoms were assessed using the Pittsburgh Sleep Quality Index (PSQI) and wrist actigraphy, while anxiety and depression symptoms were measured using the Hospital Anxiety and Depression Scale (HADS). Network analyses were conducted using R to calculate the centrality (strength) and further identify central symptoms and bridge symptoms in two networks that differed by sleep assessments. Central symptoms are closely related to other symptoms, whereas bridge symptoms indicate that symptoms may increase spread risk between different conditions. RESULTS: In the network using PSQI data, "I have lost interest in my appearance" had the highest strength centrality (rs = 2.417), followed by "sleep duration" (rs = 1.068) and "sleep efficiency" (rs = 0.955). In the network using wrist actigraphy data, "wake after sleep onset" had the highest strength value (rs = 2.437), followed by "sleep efficiency" (rs = 2.397) and "sleep latency" (rs = 1.506). Two bridge symptoms were identified: "I feel cheerful" and "I look forward with enjoyment to things" in both networks. CONCLUSIONS: Depressive symptoms played a leading role in the sleep-anxiety-depression network, underscoring the need for targeted intervention tailored to survivors' specific needs. IMPLICATIONS FOR CANCER SURVIVORS: Health workers can give priority to symptom-specific screening and therapies, incorporating psychological support into standard cancer care.

Preparation of PBAT microplastics and their potential toxicity to zebrafish embryos and juveniles.

The extensive use of traditional non-biodegradable plastics results in the generation of microplastics (MPs), forming a new pollutant that can pose significant environmental risks. Biodegradable plastics (BP) possess degradation properties and can partially replace conventional plastics, thereby reducing pollution. However, further investigation is needed into the toxicity of biodegradable microplastics (BMPs) on aquatic organisms. This study explores the toxic effects of PBAT microplastics (PBAT-BMPs) and microplastics produced from degradable PBAT/TPS (thermoplastic starch) composite film (PBAT/TPS-BMPs) on zebrafish embryos. Our findings indicate that the presence of microplastics on the embryo's surface increases with higher BMPs concentration. Nonetheless, PBAT-BMPs tend to aggregate and are blocked by the embryonic membrane, thus diminishing their toxic effects on the embryo. Acute toxicity experiments revealed that 30 mg/L of PBAT-BMPs significantly reduced the survival rate of zebrafish embryos, whereas PBAT/TPS-BMPs had a lesser effect on survival. Both types of BMPs influenced the hatching rate of the embryos, leading to prolonged incubation periods. Additionally, both types of BMPs impacted the locomotor behavior of zebrafish larvae, causing an increase in larval locomotor speed. However, these BMPs had little impact on larval body development and heartbeat behavior. Fluorescent microplastic tracer experiments demonstrated that PBAT-BMPs persisted in juvenile fish for at least 144 h and were difficult to metabolize and excrete. Our study aims to gain a better understanding of the potential effects of BMPs on aquatic ecosystems and biological health, as well as to propose effective strategies for reducing environmental pollution and protecting organisms.

Adaptation of Fusarium Head Blight Pathogens to Changes in Agricultural Practices and Human Migration.

Fusarium head blight (FHB) is one of the most destructive wheat diseases worldwide. To understand the impact of human migration and changes in agricultural practices on crop pathogens, here population genomic analysis with 245 representative strains from a collection of 4,427 field isolates of Fusarium asiaticum, the causal agent of FHB in Southern China is conducted. Three populations with distinct evolution trajectories are identifies over the last 10,000 years that can be correlated with historically documented changes in agricultural practices due to human migration caused by the Southern Expeditions during the Jin Dynasty. The gradual decrease of 3ADON-producing isolates from north to south along with the population structure and spore dispersal patterns shows the long-distance (>250 km) dispersal of F. asiaticum. These insights into population dynamics and evolutionary history of FHB pathogens are corroborated by a genome-wide analysis with strains originating from Japan, South America, and the USA, confirming the adaptation of FHB pathogens to cropping systems and human migration.