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Insect meal inclusion in aquaculture feed has received increased interest as a sustainable alternative to fishmeal and recent evidence has shown additional effects on modulating the immune response. However, lack of effects of insect meal on fish immunity in a few studies have put these beneficial effects into question. The objective of this meta-analysis was to summarize the effects of fishmeal replacement with insect meal on the innate immune response of several fish species based on differential gene expression via qPCR. A systematic literature search was conducted using online databases including Web of Science and ScienceDirect that found 197 studies as of August 2023, however only 20 studies met the criteria of high-quality studies focused on the immune response of fish and were included in this meta-analysis. The most studied insect meal was from black soldier fly, followed by yellow mealworm, and the most commonly analyzed tissue was the liver, followed by the intestine. The effect of fishmeal replacement with insect meal on fish immune responses were examined using a mixed model, with study as the random effect. This meta-analysis found a non-linear (quadratic) relationship (P = 0.017) between immune gene expression fold change and the level of fishmeal replacement with insect meal. Based on the fitted quadratic curve, a 40 % replacement of fishmeal with insect meal resulted in the highest upregulated immune response in fish. Fish taxonomic family was also found to have an effect (P = 0.004) on immune gene expression, where the taxonomic family Moronidae was more affected, with an average fold change of 2.783 (± 0.325). Other variables examined, including the insect type, tissue analyzed, dietary crude protein level, did not affect the immune response (P > 0.05). This meta-analysis also found that dietary lipid had a significant correlation with immune gene expression, and should be taken into consideration in future studies and meta-analyses. These findings are impactful since they provide evidence for the optimal dietary replacement level of insect meals required to significantly affect the innate immune response across several fish species.

This research provides a rolling planning method for distribution networks, which takes into account shared energy storage capacity configuration and grid topology optimization due to the stochastic unpredictability of the planning scenarios and the interaction between multi-agents. First, the grid topology and the investment capacity of the shared energy storage are optimized by the gird company with the aim of minimizing the overall cost within the planning time scale, and a distribution network planning model that precisely satisfies the reliability requirements is built. Second, the operational utility model of prosumers is suggested based on the planning strategy of the grid company. The cooperation of grid company corporations with prosumers is established in the evolutionary game model. The differential evolution algorithm is used to realize the dynamic solution of the planning strategy by creating the replicator dynamic equation of the grid company. The IEEE-33 bus system is taken as an example for simulation analysis for demonstrating the usefulness of the suggested evolution game-based planning model, which can reduce network planning costs and system operational costs while optimizing prosumers’ load curves.

BackgroundAs the leading cause of chronic kidney disease, diabetic kidney disease (DKD) is an enormous burden for all healthcare systems around the world. However, its early diagnosis has no effective methods.MethodsFirst, gene expression data in GEO database were extracted, and the differential genes of diabetic tubulopathy were obtained. Immune-related genesets were generated by WGCNA and immune cell infiltration analyses. Then, differentially expressed immune-related cuproptosis genes (DEICGs) were derived by the intersection of differential genes and genes related to cuproptosis and immune. To investigate the functions of DEICGs, volcano plots and GO term enrichment analysis was performed. Machine learning and protein-protein interaction (PPI) network analysis helped to finally screen out hub genes. The diagnostic efficacy of them was evaluated by GSEA analysis, receiver operating characteristic (ROC) curve, single-cell RNA sequencing and the Nephroseq website. The expression of hub genes at the animal level by STZ -induced and db/db DKD mouse models was further verified.ResultsFinally, three hub genes, including FSTL1, CX3CR1 and AGR2 that were up-regulated in both the test set GSE30122 and the validation set GSE30529, were screened. The areas under the curve (AUCs) of ROC curves of hub genes were 0.911, 0.935 and 0.922, respectively, and 0.946 when taking as a whole. Correlation analysis showed that the expression level of three hub genes demonstrated their negative relationship with GFR, while those of FSTL1 displayed a positive correlation with the level of serum creatinine. GSEA was enriched in inflammatory and immune-related pathways. Single-nucleus RNA sequencing indicated the main distribution of FSTL1 in podocyte and mesangial cells, the high expression of CX3CR1 in leukocytes and the main localization of AGR2 in the loop of Henle. In mouse models, all three hub genes were increased in both STZ-induced and db/db DKD models.ConclusionMachine learning was combined with WGCNA, immune cell infiltration and PPI analyses to identify three hub genes associated with cuproptosis, immunity and diabetic nephropathy, which all have great potential as diagnostic markers for DKD and even predict disease progression.

BackgroundMechanical ventilation (MV) is vital for critically ill ICU patients but carries significant mortality risks. This study aims to develop a predictive model to estimate hospital mortality among MV patients, utilizing comprehensive health data to assist ICU physicians with early-stage alerts.MethodsWe developed a Machine Learning (ML) framework to predict hospital mortality in ICU patients receiving MV. Using the MIMIC-III database, we identified 25,202 eligible patients through ICD-9 codes. We employed backward elimination and the Lasso method, selecting 32 features based on clinical insights and literature. Data preprocessing included eliminating columns with over 90% missing data and using mean imputation for the remaining missing values. To address class imbalance, we used the Synthetic Minority Over-sampling Technique (SMOTE). We evaluated several ML models, including CatBoost, XGBoost, Decision Tree, Random Forest, Support Vector Machine (SVM), K-Nearest Neighbors (KNN), and Logistic Regression, using a 70/30 train-test split. The CatBoost model was chosen for its superior performance in terms of accuracy, precision, recall, F1-score, AUROC metrics, and calibration plots.ResultsThe study involved a cohort of 25,202 patients on MV. The CatBoost model attained an AUROC of 0.862, an increase from an initial AUROC of 0.821, which was the best reported in the literature. It also demonstrated an accuracy of 0.789, an F1-score of 0.747, and better calibration, outperforming other models. These improvements are due to systematic feature selection and the robust gradient boosting architecture of CatBoost.ConclusionThe preprocessing methodology significantly reduced the number of relevant features, simplifying computational processes, and identified critical features previously overlooked. Integrating these features and tuning the parameters, our model demonstrated strong generalization to unseen data. This highlights the potential of ML as a crucial tool in ICUs, enhancing resource allocation and providing more personalized interventions for MV patients.

Abstract Background Vibrio parahaemolyticus is a major foodborne pathogen that contaminates aquatic products and causes great economic losses to aquaculture. Because of the emergence of multidrug-resistant V. parahaemolyticus strains, bacteriophages are considered promising agents for their biocontrol as an alternative or supplement to antibiotics. In this study, a lytic vibriophage, vB_VpaM_R16F (R16F), infecting V. parahaemolyticus 1.1997T was isolated, characterized and evaluated for its biocontrol potential. Methods A vibriophage R16F was isolated from sewage from a seafood market with the double-layer agar method. R16F was studied by transmission electron microscopy, host range, sensitivity of phage particles to chloroform, one-step growth curve and lytic activity. The phage genome was sequenced and in-depth characterized, including phylogenetic and taxonomic analysis. Results R16F belongs to the myovirus morphotype and infects V. parahaemolyticus, but not nine other Vibrio spp. As characterized by determining its host range, one-step growth curve, and lytic activity, phage R16F was found to highly effective in lysing host cells with a short latent period (

In this paper, a new reliability assessing method for structures influenced by both aleatory and epistemic uncertainty simultaneously is developed. To handle hybrid types of uncertainties, chance theory is introduced to define a new hybrid reliability index. By mathematical derivation and theorems proofs, the new index is showed to be effective and compatible with hybrid types of uncertainties. Correspondingly, a generalized first-order second-moment (GFOSM) algorithm is established for practical reliability assessment of structures with hybrid uncertainties. Based on the first two moments of basic variables, the GFOSM method can perform fast and effective reliability assessment without large-scale integration operations and can be considered as an extension and expansion of the traditional FOSM method. Two numerical cases further illustrate the effectiveness and practicability of the proposed method from different perspectives.

Studies are lacking that investigate the dietary nutrient requirements of lake whitefish (Coregonus clupeaformis), a newly farmed fish species in Ontario, Canada. Dietary levels of protein and lipid must be optimized to ensure high growth performance for the commercial success of this species. Additionally, the inclusion of insect meal in the diet may improve growth and immune response. The objective of this study was to evaluate the effects of dietary protein:lipid ratios and insect meal as a feed additive on the growth performance and hepatic immune function of juvenile lake whitefish (301 ± 10 g). A 16-week (112 day) trial was performed with five diets including a commercial control diet (BCC), and four experimental diets with high or low levels of protein (54 and 48%, respectively) and lipid (18 and 12%, respectively). The high protein dietary groups contained 5% of full-fat black soldier fly larvae (Hermetia illucens). Fish weights, viscera, liver, and blood were collected for further analysis. Specific growth rate, thermal growth coefficient and weight gain were significantly higher in fish fed with the BCC and high protein high lipid (HPHL) diets. However, viscerosomatic index was found to be significantly higher in fish fed the BCC diet, thus HPHL is more optimal for non-visceral weight gain. Higher levels of plasma phosphorus, aspartate aminotransferase and potassium indicated poor growth and stress in fish fed low lipid diets. Relative expression of HSP70, involved in cellular repair, was significantly downregulated in fish fed high lipid diets, and no effects were found on the expression of innate immune and oxidative stress genes. Also, IL8 (CXCL8) and catalase were upregulated (non-significant) in fish fed the HPHL diet with the largest weight gain. No effects of insects were found on growth, plasma biochemistry or gene expression, which suggests 5% dietary inclusion was too low. Overall, we recommend a HPHL diet for the cultivation of lake whitefish based on improved growth performance, low viscera weight, improved plasma biochemistry and downregulation of cellular repair genes.

Abstract Molecular oxygen (O2) is essential for most biological reactions in mammalian cells. When the intracellular oxygen content decreases, it is called hypoxia. The process of hypoxia is linked to several biological processes, including pathogenic microbe infection, metabolic adaptation, cancer, acute and chronic diseases, and other stress responses. The mechanism underlying cells respond to oxygen changes to mediate subsequent signal response is the central question during hypoxia. Hypoxia-inducible factors (HIFs) sense hypoxia to regulate the expressions of a series of downstream genes expression, which participate in multiple processes including cell metabolism, cell growth/death, cell proliferation, glycolysis, immune response, microbe infection, tumorigenesis, and metastasis. Importantly, hypoxia signaling also interacts with other cellular pathways, such as phosphoinositide 3-kinase (PI3K)-mammalian target of rapamycin (mTOR) signaling, nuclear factor kappa-B (NF-κB) pathway, extracellular signal-regulated kinases (ERK) signaling, and endoplasmic reticulum (ER) stress. This paper systematically reviews the mechanisms of hypoxia signaling activation, the control of HIF signaling, and the function of HIF signaling in human health and diseases. In addition, the therapeutic targets involved in HIF signaling to balance health and diseases are summarized and highlighted, which would provide novel strategies for the design and development of therapeutic drugs.

BackgroundPancreatic cancer is an extremely malignant disease that poses a serious threat to the mental health of patients. Many cancer patients now use social media for online social support. However, the impact of social media on mental health is currently inconsistent in the academic community. Therefore, this study aimed to examine the mediating effects of online social support and psychological resilience in the relationship between social media use and mental health of pancreatic cancer patients.MethodsFour hundred and twenty-five valid questionnaires were collected through convenience sampling. All data were processed using SPSS 26.0 and AMOS 26.0. We examine the influence relationships among latent variables by constructing a structural equation model. Then SPSS Process Macro was used to test the chain mediating effect of the model.ResultsThe results showed that (1) anxiety situations occurred in 22.2% of participants (N = 94), while the incidence of depression was 20.2% (N = 86). (2) Social media use positively influenced online social support (β = 0.990, p

ObjectiveThe thalamus is an integrative hub of motor circuits in Parkinson’s disease (PD). This study aimed to investigate the alterations of structure and functional connectivity (FC) of the thalamic subregions in the tremor-dominant (TD) subtype and the postural instability and gait difficulty (PIGD) subtype in PD.MethodsA total of 59 drug-naïve patients (24 TD and 35 PIGD) and 37 healthy controls were recruited. The volumes of the thalamus and the thalamic subregions were calculated using FreeSurfer. Functional connectivity (FC) analysis of the resting-state functional MRI (rsfMRI) was conducted on the thalamic subregions. Finally, the altered structure and FC were used for correlation analysis with clinical motor scores and for further motor subtypes differentiation.ResultsThe volumes of the left posterior parietal thalamus (PPtha) in TD patients were significantly lower than those of PIGD patients. Compared with PIGD patients, TD patients exhibited higher FC between the thalamic subregions, the left middle temporal gyrus (MTG), the right dorsolateral superior frontal gyrus (SFGdl), the left middle occipital gyrus (MOG), and the right superior temporal gyrus (STG). Compared with HCs, TD patients showed higher FC between the thalamic subregions and the right SFGdl, as well as the left MOG. Compared with HCs, PIGD patients showed lower FC between the thalamic subregions and the left MTG. In addition, the altered FC was closely related to clinical symptoms and performed high-discriminative power in differentiating the motor subtypes.ConclusionIncreased FC between the thalamic subregions and the sensory cortices in TD patients may indicate a better compensatory capacity for impairment of sensory information integration than that in PIGD patients. The altered FC between the thalamus and the MTG was a potential biomarker for the distinction of the PD motor subtypes.

IntroductionActinobacillus pleuropneumoniae (A. pleuropneumoniae) is a member of Actinobacillus in family Pasteurellaceae. It is the causative agent of porcine pleuropneumonia, which has caused huge economic losses to pig industry over the world. Cysteine is a precursor of many important biomolecules and defense compounds in the cell. However, molecular mechanisms of cysteine transport in A. pleuropneumoniae are unclear.MethodsIn this study, gene-deleted mutants were generated and investigated, to reveal the roles of potential cysteine/cystine transport proteins FliY and YdjN of A. pleuropneumoniae.ResultsOur results indicated that the growth of A. pleuropneumoniae was not affected after fliY or ydjN single gene deletion, but absence of both FliY and YdjN decreased the growth ability significantly, when cultured in the chemically defined medium (CDM) supplemented with cysteine or cystine as the only sulfur source. A. pleuropneumoniae double deletion mutant ΔfliYΔydjN showed increased sensitivity to oxidative stress. Besides, trans-complementation of YdjN into ΔfliYΔydjN and wild type leads to increased biofilm formation in CDM. However, the virulence of ΔfliYΔydjN was not attenuated in mice or pigs.DiscussionThese findings suggest that A. pleuropneumoniae FliY and YdjN are involved in the cysteine/cystine acquisition, oxidative tolerance, and biofilm formation, but not contribute to the pathogenicity of A. pleuropneumoniae.

BackgroundThe HPV vaccination is a crucial line of defensing against cervical cancer. As a result of government support and positive publicity from the majority of media, a craze for HPV vaccination has occurred in China. Besides, the intentions to get the HPV vaccine among women of appropriate age is also influenced by families' and friends' attitudes and perceptions toward HPV vaccine. Therefore, the purpose of this study was to investigate how HPV related information exposure and injunctive norms affect young Chinese women's intentions to receive the HPV vaccine.MethodsA structural equation model was developed based on KAP theory, and 567 effective questionnaires were collected through an online survey. We used SPSS 26.0 for the reliability and validity analysis and the differential testing of demographic characteristics, and Amos 26.0 for the goodness-of-fit analysis and paths testing of the model.ResultsOur findings showed that (1) intention to receive HPV vaccine differed significantly in age (P = 0.046), educational background (P = 0.001), and occupation (P = 0.004). (2) Exposure to HPV related information positively affected knowledge about HPV (β = 0.316, P < 0.001) and intention to receive HPV vaccine (β = 0.141, P < 0.001). (3) Knowledge about HPV positively affected attitude toward HPV vaccine (β=0.341, P < 0.001), but negatively affected intention to receive HPV vaccine (β = −0.148, P < 0.05), and attitude toward HPV vaccine positively affected intention to receive HPV vaccine (β = 0.594, P < 0.001). (4) Injunctive norms positively affected attitude toward HPV vaccine (β = 0.362, P < 0.001) and intention to receive HPV vaccine (β = 0.420, P < 0.001).ConclusionsExposure to HPV related information influenced young Chinese women's intentions to receive the HPV vaccine and related knowledge, that is, the more frequently they were exposed to HPV related information, the stronger their intentions to receive the vaccine and the higher their HPV knowledge. Also, the perception and support of HPV vaccination by people around them will further influence their attitudes and intentions to receive the HPV vaccine.

BackgroundDepression, one of the most frequent non-motor symptoms in Parkinson’s disease (PD), was proposed to be related to neural network dysfunction in advanced PD patients. However, the underlying mechanisms in the early stage remain unclear. The study was aimed to explore the alterations of large-scale neural networks in de novo PD patients with depression.MethodsWe performed independent component analysis (ICA) on the data of resting-state functional magnetic resonance imaging from 21 de novo PD patients with depression (dPD), 34 de novo PD patients without depression (ndPD), and 43 healthy controls (HCs) to extract functional networks. Intranetwork and internetwork connectivity was calculated for comparison between groups, correlation analysis, and predicting the occurrence of depression in PD.ResultsWe observed an ordered decrease of connectivity among groups within the ventral attention network (VAN) (dPD < ndPD < HCs), mainly located in the left middle temporal cortex. Besides, dPD patients exhibited hypoconnectivity between the auditory network (AUD) and default mode network (DMN) or VAN compared to ndPD patients or healthy controls. Correlation analysis revealed that depression severity was negatively correlated with connectivity value within VAN and positively correlated with the connectivity value of AUD-VAN in dPD patients, respectively. Further analysis showed that the area under the curve (AUC) for dPD prediction was 0.863 when combining the intranetwork connectivity in VAN and internetwork connectivity in AUD-DMN and AUD-VAN.ConclusionOur results demonstrated that early dPD may be associated with abnormality of attention bias and especially auditory attention processing. Altered neural network connectivity is expected to be a potential neuroimaging biomarker to predict depression in PD.

The specific detection of oxytetracycline (OTC) residues is significant for food safety and environmental monitoring. However, rapid specific determination of OTC from various tetracyclines is still challenging due to their similar chemical structures. Here, nitrogen-doped carbon dots (NCDs) with excitation and pH-dependent optical properties and a high-fluorescence quantum yield were successfully synthesized, which were directly employed to fabricate a dual-response fluorescence probe by self-assembly with Eu3+ (NCDs/Eu3+) for the ratiometric determination of OTC. The addition of OTC into the probe greatly enhances the characteristic emission of Eu3+ due to the “antenna effect”, and the incorporation of NCDs into the probe further improves the Eu3+ fluorescence by remarkably weakening the quenching effect caused by H2O molecules and efficiently shortening the distance of energy transfer from OTC to Eu3+. Meanwhile, the fluorescence of NCDs apparently decreases due to aggregation-caused quenching. The results demonstrate that a ratiometric detection of OTC (0.1–25 µM) with a detection limit of 29 nM based on the double response signals is achieved. Additionally, visual semi-quantitative assay of OTC can be realized with the naked eye under a 365 nm UV lamp according to the fluorescence color change of the as-fabricated probe. This probe exhibits acceptable specificity and anti-interference for OTC assay, holding promise for the fast detection of OTC in real water and milk samples.

The qualitative and quantitative determination of marker protein is of great significance in the life sciences and in medicine. Here, we developed an electrochemical DNA biosensor for protein detection based on DNA self-assembly and the terminal protecting effects of small-molecule-linked DNA. This strategy is demonstrated using the small molecule biotin and its receptor protein streptavidin (SA). We immobilized DNA with a designed structure and sequence on the surface of the gold electrode, and we named it M1-Biotin DNA. M1-Biotin DNA selectively combines with SA to generate M1-Biotin-SA DNA and protects M1-Biotin DNA from digestion by EXO III; therefore, M1-Biotin DNA remains intact on the electrode surface. M1-Biotin-SA DNA was modified with methylene blue (MB); the MB reporter molecule is located near the surface of the gold electrode, which generates a substantial electrochemical signal during the detection of SA. Through this strategy, we can exploit the presence or absence of an electrochemical signal to provide qualitative target protein determination as well as the strength of the electrochemical signal to quantitatively analyze the target protein concentration. This strategy has been proven to be used for the quantitative analysis of the interaction between biotin and streptavidin (SA). Under optimal conditions, the detection limit of the proposed biosensor is as low as 18.8 pM, and the linear range is from 0.5 nM to 5 μM, showing high sensitivity. The detection ability of this DNA biosensor in complex serum samples has also been studied. At the same time, we detected the folate receptor (FR) to confirm that this strategy can be used to detect other proteins. Therefore, this electrochemical DNA biosensor provides a sensitive, low-cost, and fast target protein detection platform, which may provide a reliable and powerful tool for early disease diagnosis.

A microRNA (miRNA) detection platform composed of a rolling circle amplification (RCA) system and an allosteric deoxyribozyme system is proposed, which can detect miRNA-21 rapidly and efficiently. Padlock probe hybridization with the target miRNA is achieved through complementary base pairing and the padlock probe forms a closed circular template under the action of ligase; this circular template results in RCA. In the presence of DNA polymerase, RCA proceeds and a long chain with numerous repeating units is formed. In the presence of single-stranded DNA (H1 and H2), multi-component nucleic acid enzymes (MNAzymes) are formed that have the ability to cleave substrates. Finally, substrates containing fluorescent and quenching groups and magnesium ions are added to the system to activate the MNAzyme and the substrate cleavage reaction, thus achieving fluorescence intensity amplification. The RCA–MNAzyme system has dual signal amplification and presents a sensing platform that demonstrates broad prospects in the analysis and detection of nucleic acids.

Dopamine (DA) existed as small-molecules can serve as a versatile platform for secondary surface modified reactions in biomedical engineering and biosensors especially a surface plasmon resonance (SPR) sensor. For sensing modification purposes, the environment of DA polymerization may be varied. This study involved using DA for the modification of a gold film under different conditions. It was anticipated that the change of environmental conditions would have an influence on the immobilization reaction of DA onto the gold film, and hence the impact on the SPR phenomenon. These conditions included varying pH, using different kinds of buffers, varying DA concentrations in buffer solutions as well as the DA immobilization time which reflected the length of time that the gold film was being exposed to DA. It was found that both neutral and mildly alkaline conditions offered favorable immobilization environments with 2 mg/mL dopamine in pH 8.6 Tris buffer, producing the optimum reactive result on gold. It was observed that the SPR phenomenon became non-existence at pH 9.5 for 2-hour DA immobilization time. Under the optimum environmental condition, the critical DA immobilization time for the disappearance of SPR phenomenon was estimated to be 277 min (approx. 4.6 hours). The results from this work have produced a series of valuable data served as a good foundation for surface modification using DA.

The present study was undertaken to detect circulating IgG antibodies to peptide antigens derived from baculoviral IAP repeat‐containing protein 5 isoform 2 (BIRC5) and myc proto‐oncogene protein (MYC) in cervical cancer. A total of 107 female patients with cervical cancer of stages I and II, and 130 healthy female subjects were recruited for analysis of circulating IgG antibodies to BIRC5 and MYC. Student'st‐test showed significant differences in circulating levels of anti‐BIRC5 IgG (t= −4.27, df = 235,P< 0.0001) and anti‐MYC IgG (t= 3.51, df = 232,P= 0.0005) between the patient group and the control group. Receiver operating characteristic (ROC) analysis showed an area under the ROC curve (AUC) of 0.67 with sensitivity of 23.4% against specificity of 90% for the anti‐BIRC5 IgG assay and an AUC of 0.66 with sensitivity of 9.4% against specificity of 90.6% for the anti‐MYC IgG assay. Analysis of quality control samples gave an inter‐assay deviation of 8.9% in the anti‐BIRC5 IgG assay and 9.0% in the anti‐MYC IgG assay. This work suggests that anti‐BIRC5 IgG could serve as a biomarker for early diagnosis of cervical cancer although a panel of such tumor‐associated antigens is needed to develop a highly sensitive test.