Machine Learning: A Potential Therapeutic Tool to Facilitate Neonatal Therapeutic Decision Making.

Bacterial infection is one of the major causes of neonatal morbidity and mortality worldwide. Finding rapid and reliable methods for early recognition and diagnosis of bacterial infections and early individualization of antibacterial drug administration are essential to eradicate these infections and prevent serious complications. However, this is often difficult to perform due to non-specific clinical presentations, low accuracy of current diagnostic methods, and limited knowledge of neonatal pharmacokinetics. Although neonatal medicine has been relatively late to embrace the benefits of machine learning (ML), there have been some initial applications of ML for the early prediction of neonatal sepsis and individualization of antibiotics. This article provides a brief introduction to ML and discusses the current state of the art in diagnosing and treating neonatal bacterial infections, gaps, potential uses of ML, and future directions to address the limitations of current studies. Neonatal bacterial infections involve a combination of physiologic development, disease expression, and treatment response outcomes. To address this complex relationship, future models could consider appropriate ML algorithms to capture time series features while integrating influences from the host, microbes, and drugs to optimize antimicrobial drug use in neonates. All models require prospective clinical trials to validate their clinical utility before clinical use.

Population pharmacokinetics of daptomycin in critically ill patients receiving extracorporeal membrane oxygenation.

BACKGROUND: Daptomycin is widely used in critically ill patients for Gram-positive bacterial infections. Extracorporeal membrane oxygenation (ECMO) is increasingly used in this population and can potentially alter the pharmacokinetic (PK) behaviour of antibiotics. However, the effect of ECMO has not been evaluated in daptomycin. Our study aims to explore the effect of ECMO on daptomycin in critically ill patients through population pharmacokinetic (PopPK) analysis and to determine optimal dosage regimens based on both efficacy and safety considerations. METHODS: A prospective, open-label PK study was carried out in critically ill patients with or without ECMO. The total concentration of daptomycin was determined by UPLC-MS/MS. NONMEM was used for PopPK analysis and Monte Carlo simulations. RESULTS: Two hundred and ninety-three plasma samples were collected from 36 critically ill patients, 24 of whom received ECMO support. A two-compartment model with first-order elimination can best describe the PK of daptomycin. Creatinine clearance (CLCR) significantly affects the clearance of daptomycin while ECMO has no significant effect on the PK parameters. Monte Carlo simulations showed that, when the MICs for bacteria are  ≥1 mg/L, the currently recommended dosage regimen is insufficient for critically ill patients with CLCR > 30 mL/min. Our simulations suggest 10 mg/kg for patients with CLCR between 30 and 90 mL/min, and 12 mg/kg for patients with CLCR higher than 90 mL/min. CONCLUSIONS: This is the first PopPK model of daptomycin in ECMO patients. Optimal dosage regimens considering efficacy, safety, and pathogens were provided for critical patients based on pharmacokinetic-pharmacodynamic analysis.

Physiological Functions of the Cello-Oligosaccharides Binding CebE in the Pathogenic Streptomyces sp. AMCC400023.

Potato common scab, an economically important disease worldwide, is caused by pathogenic Streptomyces strains mainly through the effects of thaxtomin. The cello-oligosaccharides binding protein CebE is proposed as a gateway to the pathogenic development of Streptomyces scabiei. In this study, two functional CebE encoding genes, GEO5601 and GEO7671, were identified in pathogenic Streptomyces sp. AMCC400023. With a higher binding affinity towards signal molecules, the deletion of GEO5601 severely impaired thaxtomin-producing capacity and reduced the strain's pathogenicity. Transcriptional analysis confirmed that CebE5601 is also responsible for the import and provision of carbon sources for cell growth. With lower binding affinity, the pathogenicity island (PAI)-localized CebE7671 may assume a new function of mediating the biological process of sporulation, given the significantly impaired formation of ΔGEO7671 spores. The mechanisms of action of CebE proteins unraveled in Streptomyces sp. AMCC400023 will help pave the way for more effective prevention of the potato common scab disease.

The impact of Lactococcus lactis KUST48 on the transcription profile of Aeromonas hydrophila-infected zebrafish spleen.

Aeromonas hydrophila, an aquatic pathogenic bacterium, has been found to infect many fish species and cause huge aquaculture losses. Antibiotics are the most common drugs used to treat these infections. However, antibiotic abuse can lead to the development of antibiotic resistance. Probiotics have the potential to replace antibiotics for preventing infections. Zebrafish (Danio rerio) is a model organism used to study the innate immune system and host-pathogen interactions. Currently, there is little information on how the fish immune system responds to A. hydrophila and probiotic treatment. To increase the understanding of the molecular mechanisms behind the zebrafish defense against A. hydrophila and provide evidence that antibiotics can be replaced by probiotics, a transcriptome analysis of the zebrafish spleen was conducted 48 hours after infection by A. hydrophila, as well as after treatment using Lactococcus lactis KUST48 4 hours after infection. A total of 36,499 genes were obtained. There were 3,337 genes found to have significant differential expression between treatment and control groups. According to further annotation and enrichment analysis, differentially expressed genes (DEGs) were involved in signal transduction, endocrine system cancer, and the immune system. Insulin resistance disappeared in the zebrafish after treatment. Quantitative real-time PCR was performed to confirm the significant regulation of immune defense DEGs, the results of which were consistent with the RNA-sequencing data. These results could serve as a basis for future studies on the immune response to A. hydrophila and provide suggestions for probiotic alternatives to antibiotics, which will be of great significance to aquaculture and environmental protection.IMPORTANCEIn recent years, the unreasonable use of antibiotics has led to the emergence of drug-resistant pathogenic bacteria, antibiotic residues, cross infection, toxic side effects, and so on, which has caused a serious threat to human food safety and life health. In recent years, many studies have demonstrated the potential of probiotics as a substitute for antibiotics, but there is still a lack of understanding of the molecular mechanisms underlying probiotic therapy. We conduct a research on the impact of Lactococcus lactis KUST48 on the transcription profile of Aeromonas hydrophila-infected zebrafish spleen. Mortality of zebrafish infected with A. hydrophila was significantly reduced after treatment with L. lactis KUST48. Our results can help to strengthen our understanding of the pathogenic mechanisms of zebrafish and provide a valuable reference for the molecular mechanisms of probiotic therapy.

A systematic review of risk prediction model of venous thromboembolism for patients with lung cancer.

BACKGROUND: Venous thromboembolism (VTE) increases the risk of death or adverse outcomes in patients with lung cancer. Therefore, early identification and treatment of high-risk groups of VTE have been the research focus. In this systematic review, the risk assessment tools of VTE in patients with lung cancer were systematically analyzed and evaluated to provide a reference for VTE management. METHODS: Relevant studies were retrieved from major English databases (The Cochrane Library, Embase, Web of Science, PubMed, Scopus, Medline) and Chinese databases (China National Knowledge Infrastructure [CNKI] and WanFang Data) until July 2023 and extracted by two researchers. This systematic review was registered at PROSPERO (no. CRD42023409748). RESULTS: Finally, two prospective cohort studies and four retrospective cohort studies were included from 2019. There was a high risk of bias in all included studies according to the Prediction Model Risk of Bias Assessment tool (PROBAST). In the included studies, Cox and logistic regression were used to construct models. The area under the receiver operating characteristic curve (AUC) of the model ranged from 0.670 to 0.904, and the number of predictors ranged from 4 to 11. The D-dimer index was included in five studies, but significant differences existed in optimal cutoff values from 0.0005 mg/L to 2.06 mg/L. Then, three studies validated the model externally, two studies only validated the model internally, and only one study validated the model using a combination of internal and external validation. CONCLUSION: VTE risk prediction models for patients with lung cancer have received attention for no more than 5 years. The included model shows a good predictive effect and may help identify the risk population of VTE at an early stage. In the future, it is necessary to improve data modeling and statistical analysis methods, develop predictive models with good performance and low risk of bias, and focus on external validation and recalibration of models.

Machine Learning: A New Approach for Dose Individualization.

The application of machine learning (ML) has shown promising results in precision medicine due to its exceptional performance in dealing with complex multidimensional data. However, using ML for individualized dosing of medicines is still in its early stage, meriting further exploration. A systematic review of study designs and modeling details of using ML for individualized dosing of different drugs was performed. We have summarized the status of the study populations, predictive targets, and data sources for ML modeling, the selection of ML algorithms and features, and the evaluation and validation of their predictive performance. We also used the Prediction model Risk of Bias Assessment Tool (PROBAST) to assess the risk of bias of included studies. Currently, ML can be used for both a priori and a posteriori dose selection and optimization, and it can also assist the implementation of therapeutic drug monitoring. However, studies are mainly focused on drugs with narrow therapeutic windows, predominantly immunosuppressants (N = 23, 35.9%) and anti-infectives (N = 21, 32.8%), and there is currently only very limited attention for special populations, such as children (N = 22, 34.4%). Most studies showed poor methodological quality and a high risk of bias. The lack of external validation and clinical utility evaluation currently limits the further clinical implementation of ML for dose individualization. We therefore have proposed several ways to improve the clinical relevance of the studies and facilitate the translation of ML models into clinical practice.

Exploring readiness for discharge, quality of discharge teaching, and fear of disease progression in lung cancer patients undergoing chemotherapy: A correlation analysis.

BACKGROUND: To explore the correlation between the current status of discharge preparation, quality of discharge teaching, and fear of disease progression among patients with lung cancer undergoing chemotherapy to provide a basis for improving patients' level of preparation. METHODS: In this cross-sectional study, convenience sampling was used to select 452 patients with lung cancer who received chemotherapy and were admitted to the Department of Medical Oncology of the Cancer Hospital, between February 2023 and April 2023. A general information questionnaire, discharge preparation scale, quality of discharge teaching scale, and fear of disease progression scale were used to conduct surveys 2 h before the patients were discharged. RESULTS: The score for discharge preparation among lung cancer patients with chemotherapy was 99.11 ± 14.79 and the item score was 8.26 ± 1.23. The score for quality of discharge teaching was 193.23 ± 37.69, and that for fear of disease progression was 25.47 ± 8.92. Multiple linear regression analysis showed that sex, marital status, treatment period, quality of discharge teaching, and fear of disease progression influenced discharge readiness among patients with lung cancer receiving chemotherapy. Pearson's correlation analysis showed that the total quality of the discharge guidance score was positively correlated with the discharge readiness score (r = 0.288, p < 0.001). In contrast, the total fear of disease progression score was negatively correlated with the discharge preparation score (r = -0.252, p < 0.001). CONCLUSION: Discharge readiness among patients with lung cancer receiving chemotherapy was relatively at the good level, and there was a significant correlation between readiness for discharge, discharge teaching and fear of disease progression in these patients. Therefore, it is necessary to provide effective discharge guidance and implement targeted intervention measures to further improve patient preparation, reduce the fear of disease progression, and promote patient ability of coping with the disease and overall satisfaction.

Changes in the Microbiome of Sugarcane (Saccharum spp. Hybrids.) Rhizosphere in Response to Manganese Toxicity.

Manganese toxicity has limited sugarcane (Saccharum spp. hybrid.) growth and production in acidic soils in south China. The rhizosphere plays an irreplaceable role in plant adaptation to soil abiotic stress, but the responses of the sugarcane rhizosphere to manganese toxicity are still unknown. We designed pot experiments in Mn-rich acidic soil, collected the sugarcane rhizosphere and bulk soil samples, and then investigated the changes in Mn-related soil parameters and microbiome. The results indicated that the water-soluble and exchangeable manganese concentrations in the sugarcane rhizosphere were significantly lower than that in the bulk soil, which was not associated with soil pH changes. In contrast, the number of bacteria and the activity of peroxidase, sucrase, urease, and laccase in the rhizosphere were significantly higher. The 16S rDNA sequencing results showed that the bacterial diversity and quantity along with the abundance of Proteobacteria in the rhizosphere were significantly higher than in the bulk soil, while the abundance of Acidobacteria was lower than in the bulk soil. The soil laccase activity and the number of bacteria decreased significantly with the increase in the manganese toxicity stress. Finally, the relative abundance of proteins associated with manganese transportation and oxidation was significantly higher in the rhizosphere soil. In summary, the Mn-induced response of the rhizosphere is an important mechanism in sugarcane adaptation to manganese toxicity in acidic soil.

Effects and mechanism of Rictor interference in podocyte injury induced by high glucose.

Rapamycin-insensitive companion of mTOR (Rictor) is a critical effector of mTOR protein complex 2 (mTORC2). The aim of the present study was to investigate the effect of Rictor in the mTORC2 signaling pathway in high glucose (HG)-induced diabetic podocyte injury by silencing the expression of Rictor. In the present study, mouse podocytes were treated with glucose (150 mM) and mannitol (200 mM), the Rictor gene was silenced using small interfering RNA (siRNA). Apoptosis was detected by flow cytometry, whereas podocyte cytoskeletal protein expression was detected by western blotting (WB) and immunofluorescence staining. The results demonstrated that, compared with that in the control group, the podocyte apoptotic rate was significantly increased in the mannitol group (negative group) and the groups that were treated with glucose (model groups). The podocyte apoptotic rate in the model + Rictor siRNA group was significantly decreased compared with that in the negative, model and the model glucose + siRNA negative control (NC) groups. WB indicated that the protein expression levels of podocalyxin and synaptopodin were reduced in the model and model + siRNA NC groups compared with those in the normal control and negative groups. Additionally, the protein expression levels of α-smooth muscle actin (α-SMA) and P-AKT/AKT were increased in the model and model + siRNA NC groups compared with the those in control and negative groups. Compared with those the model and model + siRNA NC groups, the protein expression levels of podocalyxin and synaptopodin were increased, whilst those of the α-SMA and P-AKT/AKT proteins were decreased, in the model + Rictor siRNA group. Results from immunofluorescence analysis were basically consistent with those of WB. Therefore, results of the present study suggest that silencing of the Rictor gene may reduce the damage to podocytes induced by HG, such that the Rictor/mTORC2 signaling pathway may be involved in the remodeling of podocyte actin cytoskeletal in diabetes.

Zhilong Huoxue Tongyu capsule ameliorates platelet aggregation and thrombus induced by aspirin in rats by regulating lipid metabolism and microRNA pathway.

INTRODUCTION: Zhilong Huoxue Tongyu capsule (ZLHX) is a traditional Chinese medicinal compound preparation, which exhibits obvious therapeutic effects on aspirin resistance (AR). However, the mechanism of ZLHX on AR is rarely reported. OBJECTIVES: This study aimed to explore the therapeutic effects of AR and the underlying mechanisms of ZLHX on AR rats. METHODS: An AR model was established through treatment with a high-fat, high-sugar, and high-salt diet for 12 weeks and oral administration of aspirin (27 mg/kg/day) and ibuprofen (36 mg/kg/day) in weeks 9-12. The rats were administrated with ZLHX (225, 450, and 900 mg/kg) from week 12 to week 16. Blood samples were collected after the experiment. Thromboelastography analysis was performed, and the levels of triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were determined. Furthermore, the levels of thromboxane B2 (TXB2) and 6-keto-prostaglandin F1α (6-keto-PGF1α) were determined with commercial ELISA kits. Finally, the gene expressions of microRNA-126-3p (miRNA-126-3p) and miRNA-34b-3p were detected through a real-time quantitative polymerase chain reaction. RESULTS: Results demonstrated that ZLHX significantly inhibited platelet aggregation in the AR rats. Moreover, ZLHX markedly decreased the levels of TC, TG, and LDL-C and increased the level of HDL-C. Meanwhile, ELISA results confirmed that ZLHX can elevate the expression levels of TXB2 and 6-keto-PGF1α. Further studies suggested that ZLHX significantly downregulated the expression levels of miRNA-126-3p and miRNA-34b-3p. CONCLUSION: This study revealed that the therapeutic effect of ZLHX might be related to the regulation of lipid metabolism and the miRNA pathway.

Spin State Disproportionation in Insulating Ferromagnetic LaCoO3 Epitaxial Thin Films.

The origin of insulating ferromagnetism in epitaxial LaCoO3 films under tensile strain remains elusive despite extensive research efforts are devoted. Surprisingly, the spin state of its Co ions, the main parameter of its ferromagnetism, is still to be determined. Here, the spin state in epitaxial LaCoO3 thin films is systematically investigated to clarify the mechanism of strain-induced ferromagnetism using element-specific X-ray absorption spectroscopy and dichroism. Combining with the configuration interaction cluster calculations, it is unambiguously demonstrated that Co3+ in LaCoO3 films under compressive strain (on LaAlO3 substrate) is practically a low-spin state, whereas Co3+ in LaCoO3 films under tensile strain (on SrTiO3 substrate) have mixed high-spin and low-spin states with a ratio close to 1:3. From the identification of this spin state ratio, it is inferred that the dark strips observed by high-resolution scanning transmission electron microscopy indicate the position of Co3+ high-spin state, i.e., an observation of a spin state disproportionation in tensile-strained LaCoO3 films. This consequently explains the nature of ferromagnetism in LaCoO3 films. The study highlights the importance of spin state degrees of freedom, along with thin-film strain engineering, in creating new physical properties that do not exist in bulk materials.

Identification of macrophage-related genes in sepsis-induced ARDS using bioinformatics and machine learning.

Sepsis-induced acute respiratory distress syndrome (ARDS) is one of the leading causes of death in critically ill patients, and macrophages play very important roles in the pathogenesis and treatment of sepsis-induced ARDS. The aim of this study was to screen macrophage-related biomarkers for the diagnosis and treatment of sepsis-induced ARDS by bioinformatics and machine learning algorithms. A dataset including gene expression profiles of sepsis-induced ARDS patients and healthy controls was downloaded from the gene expression omnibus database. The limma package was used to screen 325 differentially expressed genes, and enrichment analysis suggested enrichment mainly in immune-related pathways and reactive oxygen metabolism pathways. The level of immune cell infiltration was analysed using the ssGSEA method, and then 506 macrophage-related genes were screened using WGCNA; 48 showed differential expression. PPI analysis was also performed. SVM-RFE and random forest map analysis were used to screen 10 genes. Three key genes, SGK1, DYSF and MSRB1, were obtained after validation with external datasets. ROC curves suggested that all three genes had good diagnostic efficacy. The nomogram model consisting of the three genes also had good diagnostic efficacy. This study provides new targets for the early diagnosis of sepsis-induced ARDS.

Genistein protects benzotriazole ultraviolet stabilizer UV-234-induced hepatotoxicity by modulating ROS/Nrf2 and NF-κB signaling in yellow catfish (Pelteobagrus fulvidraco).

Benzotriazole ultraviolet stabilizers (BUVSs) are a group of anthropogenic chemicals widely used in commodities and industrial products, posing a potential threat to aquatic organisms. However, limited data are available on the toxicity effects of BUVSs in the liver, and no data are available on effective therapeutic strategies. In this study, we exployed aimed to explore the hepatotoxicity of 2-(benzotriazol-2-yl)-4,6-bis(2-phenylpropan-2-yl)phenol (UV-234) and reveal the preventive function of Genistein. At first, yellow catfish (Pelteobagrus fulvidraco) exposed to UV-234 (10 µg/L) showed up-regulated serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) and hepatic reactive oxygen species (ROS) overproduction, along with significantly reduced activities of antioxidants enzymes and nuclear factor erythroid-derived 2-related factor 2 (Nrf2) basal levels. In contrast, 100 mg/kg diet of Genistein improve the hepatic antioxidative capability of fish via activating Nrf2 pathway. Furthermore, we confirmed that UV-234 exposure could induce nuclear factor-κB (NF-κB)-driven inflammatory response, as evidenced by the hepatic inflammatory cells infiltration, lower levels of plasma complement C3 (C3) and complement C4 (C4) as well as higher mRNA levels of NF-κB and inflammatory cytokines. Conversely, feeding UV-234-exposed fish on Genistein-supplemented diets attenuated above adverse effects. Meanwhile, we confirmed that Genistein supplement protected liver apoptosis induced by UV-234 via suppressing up-regulated expression levels of pro-apoptotic genes (Bax, caspase3). In summary, our findings revealed that Genistein positively regulates the Nrf2-mediated antioxidant defenses and reduce NF-κB-driven inflammatory response, thus indirectly inhibiting hepatic damage induced by UV-234 in yellow catfish (Pelteobagrus fulvidraco).

Influence of hydrophilic polysaccharide fat replacers on the in vitro digestibility of protein in emulsion-type sausage.

Hydrophilic polysaccharides have been widely applied as fat replacers in meat products, but their effects on the digestibility of meat proteins has seldom been studied. Replacement of backfat in emulsion-type sausage with konjac gum (KG), sodium alginate (SA) and xanthan gum (XG) were found to reduce the released amino group (-NH2) during simulated gastric digestion and initial intestinal digestion. The suppressed gastric digestibility of protein was verified by the denser structures of protein gastric digests and reduced generation of peptides in gastric digestion when a polysaccharide was added. After the whole gastrointestinal digestion, high level of SA and XG resulted in larger digests and a more obvious SDS-PAGE band between 5 and 15 kDa, and KG and SA significantly reduced the total release of -NH2. Additional of KG, SA and XG were found to the increase the viscosity of the gastric digests mixture, which could account for the reduced hydrolysis efficiency of pepsin during the gastric digestion, as evidenced in the pepsin activity study (decreased by 12.2-39.1%). This work highlights the influence of polysaccharide fat replacer on the digestibility of meat protein by changing the matrix characteristics.

Comprehensive analysis of NAC transcription factors in Scutellaria baicalensis and their response to exogenous ABA and GA3.

The NAC is a plant-specific family of transcription factor that plays important roles in various biological processes. Scutellaria baicalensis Georgi, belongs to the Lamiaceae family and has been widely used as a traditional herb with a wide range of pharmacological activities, including antitumor, heat-clearing, and detoxifying functions. However, no study on the NAC family in S. baicalensis has been conducted to date. In the present study, we identified 56 SbNAC genes using genomic and transcriptome analyses. These 56 SbNACs were unevenly distributed across nine chromosomes and were phylogenetically divided into six clusters. Cis-element analysis identified plant growth and development-, phytohormone-, light-, and stress-responsive elements were present in SbNAC genes promoter regions. Protein-protein interaction analysis was performed using Arabidopsis homologous proteins. Potential transcription factors, including bHLH, ERF, MYB, WRKY, and bZIP, were identified and constructed a regulatory network with SbNAC genes. The expression of 12 flavonoid biosynthetic genes was significantly upregulated with abscisic acid (ABA) and gibberellin (GA3) treatments. Eight SbNAC genes (SbNAC9/32/33/40/42/43/48/50) also exhibited notable variation with two phytohormone treatments, among which SbNAC9 and SbNAC43 showed the most significant variation and deserved further study. Additionally, SbNAC44 displayed a positive correlation with C4H3, PAL5, OMT3, and OMT6, while SbNAC25 had negatively correlated with OMT2, CHI, F6H2, and FNSII-2. This study constitutes the first analysis of SbNAC genes and lays the basis foundation for further functional studies of SbNAC genes family members, while it may also facilitate the genetic improvement of plants and breeding of elite S. baicalensis varieties.

Lycopene abolishes typical polyhalogenated carbazoles (PHCZs)-induced hepatic injury in yellow catfish (Pelteobagrus fulvidraco): Involvement of ROS/PI3K-AKT/NF-κB signaling.

Aquatic ecosystems are being more contaminated with polyhalogenated carbazoles (PHCZs), which raising concerns about their impact on aquatic organisms. Lycopene (LYC) exhibits several beneficial properties for fish via enhance antioxidant defenses and improve immunity. In this study, we attempted to investigate the hepatotoxic effects of typical PHCZs 3, 6-dichlorocarbazole (3,6-DCCZ) and the protective mechanisms of LYC. In this study, we found that yellow catfish (Pelteobagrus fulvidraco) exposure to 3,6-DCCZ (1.2 mg/L) resulted in hepatic inflammatory infiltration and disordered hepatocyte arrangement. Besides, we observed that 3,6-DCCZ exposure resulted in hepatic reactive oxygen species (ROS) overproduction and excessive autophagosome accumulation, accompanied with inhibition of phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT) pathway. Subsequently, we confirmed that 3,6-DCCZ exposure triggered hepatic uncontrolled inflammatory response via activation of nuclear factor-κB (NF-κB) pathway, along with decreased plasma complement C3 (C3) and complement C4 (C4) levels. Meanwhile, yellow catfish exposed to 3,6-DCCZ exhibit an increased hepatic apoptosis phenomenon, as evidenced by the elevated number of positive TUNEL cells and upregulated expression of caspase3 and cytochrome C (CytC). In contrast, LYC treatment could alleviate the 3,6-DCCZ-induced pathological changes, hepatic ROS accumulation, autophagy, inflammatory response and apoptosis. To sum up, this study provided the demonstration that LYC exerts hepatoprotective effects to alleviate 3,6-DCCZ-induced liver damage by inihibiting ROS/PI3K-AKT/NF-κB signaling in yellow catfish.

Clinical factors of PICC-RVT in cancer patients: a meta-analysis.

PURPOSE: There is a lack of studies that systematically evaluate the clinical factors of PICC-RVT such as treatment, tumor stage, metastasis, and chemotherapy drugs in cancer patients. This study, therefore, aims to evaluate the clinical factors of catheter-related venous thrombosis in cancer patients with indwelling PICC to provide a basis for the clinical prevention and reduction of thrombosis. METHODS: Relevant studies were retrieved from major databases (PubMed, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), WanFang Data, and China Biology Medicine disc (CMB)) and searched from their earliest available dates until July 2022. If two or more studies had the same outcome, a meta-analysis using RevMan 5.4.1 was performed. This systematic review was registered at PROSPERO (number CRD42022358426). RESULTS: A total of 19 articles involving 19,824 patients were included for quantitative analysis. Meta-analysis of these studies indicated that a history of chemotherapy, tumor type, tumor stage, presence or absence of metastasis, and use of fluorouracil, etoposide, platinum drugs, and taxane were all risk factors for PICC catheter thrombosis in cancer patients. CONCLUSION: In clinical PICC catheter thrombosis prevention, patients with the above characteristics should be watched more closely than other patients, as they have a higher risk for PICC catheter thrombosis. Based on the present evidence at hand, radiotherapy cannot be considered to be related to the formation of PICC-RVT in cancer patients.

Transcriptomic and physiological analysis of the effect of octanoic acid on Meloidogyne incognita.

Root knot nematodes are the most devastating root pathogens, causing severe damage and serious economic losses to agriculture worldwide. Octanoic acid has been reported as one of the nematicides, and its mode of action is not fully understood. The main objective of this study was to elucidate the effect of octanoic acid on Meloidogyne incognita by transcriptomic analysis combined with physiological and biochemical assays. In the toxicity assays with octanoic acid, the threshold concentration with nematicidal activity and the maximum concentration to which nematodes could respond were 0.03 µL/mL and 0.08 µL/mL respectively. Microscopic observation combined with protein and carbohydrates assays confirmed that the structure of the second-stage juveniles (J2s) was severely disrupted after 72 h of immersion in octanoic acid. Transcriptome analysis has shown that octanoic acid can interfere with the nematode energy metabolism, lifespan and signaling. Although the effects are multifaceted, the findings strongly point to the cuticle, lysosomes, and extracellular regions and spaces as the primary targets for octanoic acid. In addition, nematodes can withstand the negative effects of low concentration of octanoic acid to some extent by up-regulating the defense enzyme system and heterologous metabolic pathways. These findings will help us to explore the nematicidal mechanism of octanoic acid and provide important target genes for the development of new nematicides in the future.

[Pathogenesis of glucocorticoid-induced osteoporosis based on label-free mass proteomics].

OBJECTIVE: To explore pathogenesis of glucocortocoid-induced osteoporosis(GIOP) based on label-free mass proteomics. METHODS: Twevle female Sprague-Dawley(SD) rats were randomly divided into two groups, named as sham group and GIOP group. After one-week adaptive feeding, the rats of GIOP group were administered with dexamethasone via intramuscular injection according to 2.5 mg/kg weighting, while the rats of sham group were administered with the same amount of saline, twice a week. The tibias of each group were collected after 8-week modeling and made pathological sections to confirm the success of modeling. Three samples of each group were picked up to perform label-free mass proteomics. After quality control, differentially expressed proteins were identified according to qualitative and quantitative analyses. Then gene ontology(GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis, cluster analysis as well as protein-protein interaction analysis were performed using bioinformatics analysis. RESULTS: Compared with sham group, the structure of bone trabecular in GIOP group showed abnormal arrangement, uneven distribution and obvious fragmentation, which could demonstrate successful modeling. A total of 47 differentially expressed proteins (DEPs) were identified including 20 up-regulated and 27 down-regulated proteins. The expression of protein nucleophosmin 1(NPM1), adipocyte plasma membrane associated protein (APMAP), cytochromec oxidase subunit 6A1 (COX6A1) and tartrate-resistant acid phosphatase (ACP5) showed a significant difference between two groups. KEGG results showed DEPs were enriched on metabolism-related pathways, immune-related pathways and AMP-activated kinase (AMPK) signaling pathway. CONCLUSION: Protein NPM1, APMAP, COX6A1 and ACP5 showed a close relationship with pathogenesis of GIOP, which could serve as potential biomarkers of GIOP. AMPK signaling pathway played an important role in the occurrence and development of GIOP, which could be regarded as potential signaling pathway to treatment GIOP.