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Abstract In the third-generation (3G) gravitational-wave (GW) detector era, multi-messenger GW observation for binary neutron star (BNS) merger events can exert great impacts on exploring cosmic expansion history. In this work, we comprehensively explore the potential of 3G GW standard siren observations in cosmological parameter estimations by considering 3G GW detectors and the future short $$\gamma $$ γ -ray burst (GRB) detector THESEUS-like telescope joint observations. Based on a 10-year observation of different detection strategies, we predict that the numbers of detectable GW-GRB events are 334–674 with the redshifts $$z

Abstract Objective This study was based on MRI features and number of tumor-infiltrating CD8 + T cells in post-operative pathology, in predicting meningioma recurrence risk. Methods Clinical, pathological, and imaging data of 102 patients with surgically and pathologically confirmed meningiomas were retrospectively analyzed. Patients were divided into recurrence and non-recurrence groups based on follow-up. Tumor-infiltrating CD8 + T cells in tissue samples were quantitatively assessed with immunohistochemical staining. Apparent diffusion coefficient (ADC) histogram parameters from preoperative MRI were quantified in MaZda. Considering the high correlation between ADC histogram parameters, we only chose ADC histogram parameter that had the best predictive efficacy for COX regression analysis further. A visual nomogram was then constructed and the recurrence probability at 1- and 2-years was determined. Finally, subgroup analysis was performed with the nomogram. Results The risk factors for meningioma recurrence were ADCp1 (hazard ratio [HR] = 0.961, 95% confidence interval [95% CI]: 0.937 ~ 0.986, p = 0.002) and CD8 + T cells (HR = 0.026, 95%CI: 0.001 ~ 0.609, p = 0.023). The resultant nomogram had AUC values of 0.779 and 0.784 for 1- and 2-years predicted recurrence rates, respectively. The survival analysis revealed that patients with low CD8 + T cells counts or ADCp1 had higher recurrence rates than those with high CD8 + T cells counts or ADCp1. Subgroup analysis revealed that the AUC of nomogram for predicting 1-year and 2-year recurrence of WHO grade 1 and WHO grade 2 meningiomas was 0.872 (0.652) and 0.828 (0.751), respectively. Conclusions Preoperative ADC histogram parameters and tumor-infiltrating CD8 + T cells may be potential biomarkers in predicting meningioma recurrence risk. Clinical relevance statement The findings will improve prognostic accuracy for patients with meningioma and potentially allow for targeted treatment of individuals who have the recurrent form.

Abstract Background After spinal cord injury (SCI), a large number of survivors suffer from severe motor dysfunction (MD). Although the injury site is in the spinal cord, excitability significantly decreases in the primary motor cortex (M1), especially in the lower extremity (LE) area. Unfortunately, M1 LE area-targeted repetitive transcranial magnetic stimulation (rTMS) has not achieved significant motor improvement in individuals with SCI. A recent study reported that the M1 hand area in individuals with SCl contains a compositional code (the movement-coding component of neural activity) that links matching movements from the upper extremities (UE) and the LE. However, the correlation between bilateral M1 hand area excitability and overall functional recovery is unknown. Objective To clarify the changes in the excitability of the bilateral M1 hand area after SCI and its correlation with motor recovery, we aim to specify the therapeutic parameters of rTMS for SCI motor rehabilitation. Methods This study is a 12-month prospective cohort study. The neurophysiological and overall functional status of the participants will be assessed. The primary outcomes included single-pulse and paired-pulse TMS. The second outcome included functional near-infrared spectroscopy (fNIRS) measurements. Overall functional status included total motor score, modified Ashworth scale score, ASIA Impairment Scale grade, spinal cord independence measure and modified Barthel index. The data will be recorded for individuals with SCI at disease durations of 1 month, 2 months, 4 months, 6 months and 12 months. The matched healthy controls will be measured during the same period of time after recruitment. Discussion The present study is the first to analyze the role of bilateral M1 hand area excitability changes in the evaluation and prediction of overall functional recovery (including motor function and activities of daily living) after SCI, which will further expand the traditional theory of the predominant role of M1, optimize the current rTMS treatment, and explore the brain-computer interface design for individuals with SCI. Trial registration number ChiCTR2300068831.

Abstract. Normal pregnancy is a contradictory and complicated physiological process. Although the fetus carries the human leukocyte antigen (HLA) inherited from the paternal line, it does not cause maternal immune rejection. As the only exception to immunological principles, maternal–fetal immune tolerance has been a reproductive immunology focus. In early pregnancy, fetal extravillous trophoblast cells (EVTs) invade decidual tissues and come into direct contact with maternal decidual immune cells (DICs) and decidual stromal cells (DSCs) to establish a sophisticated maternal–fetal crosstalk. This study reviews previous research results and focuses on the establishment and maintenance mechanism of maternal–fetal tolerance based on maternal–fetal crosstalk. Insights into maternal–fetal tolerance will not only improve understanding of normal pregnancy but will also contribute to novel therapeutic strategies for recurrent spontaneous abortion, pre-eclampsia, and premature birth.

Abstract Background Osteosarcoma (OS) is the most common bone malignant tumor in children, and its prognosis is often poor. Anoikis is a unique mode of cell death.However, the effects of Anoikis in OS remain unexplored. Method Differential analysis of Anoikis-related genes was performed based on the metastatic and non-metastatic groups. Then LASSO logistic regression and SVM-RFE algorithms were applied to screen out the characteristic genes. Later, Univariate and multivariate Cox regression was conducted to identify prognostic genes and further develop the Anoikis-based risk score. In addition, correlation analysis was performed to analyze the relationship between tumor microenvironment, drug sensitivity, and prognostic models. Results We established novel Anoikis-related subgroups and developed a prognostic model based on three Anoikis-related genes (MAPK1, MYC, and EDIL3). The survival and ROC analysis results showed that the prognostic model was reliable. Besides, the results of single-cell sequencing analysis suggested that the three prognostic genes were closely related to immune cell infiltration. Subsequently, aberrant expression of two prognostic genes was identified in osteosarcoma cells. Nilotinib can promote the apoptosis of osteosarcoma cells and down-regulate the expression of MAPK1. Conclusions We developed a novel Anoikis-related risk score model, which can assist clinicians in evaluating the prognosis of osteosarcoma patients in clinical practice. Analysis of the tumor immune microenvironment and chemotherapeutic drug sensitivity can provide necessary insights into subsequent mechanisms. MAPK1 may be a valuable therapeutic target for neoadjuvant chemotherapy in osteosarcoma.

Much effort has been devoted to improving treatment efficiency for osteosarcoma (OS). However, most current approaches result in poor therapeutic responses, thus indicating the need for the development of other therapeutic options. This study developed a multifunctional nanoparticle, PDA-MOF-E-M, an aggregation of OS targeting, programmed death targeting, and near-infrared (NIR)-aided targeting. At the same time, a multifunctional nanoparticle that utilises Fe-MOFs to create a cellular iron-rich environment and erastin as a ferroptosis inducer while ensuring targeted delivery to OS cells through cell membrane encapsulation is presented. The combination of PDA-MOF-E-M and PTT increased intracellular ROS and LPO levels and induced ferroptosis-related protein expression. A PDA-based PTT combined with erastin showed significant synergistic therapeutic improvement in the anti-tumour efficiency of the nanoparticle in vitro and vivo. The multifunctional nanoparticle efficiently prevents the osteoclasia progression of OS xenograft bone tumors in vivo. Finally, this study provides guidance and a point of reference for clinical approaches to treating OS.

Abstract In order to propose a reliable method for assessing the safety condition for single-tower steel box girder Suspension bridges over the sea, a condition monitoring system is established by installing sensors on the bridge structure. The system is capable of gathering monitoring data that influence the safety status of the bridge. These include cable tension, load on the main tower and pylon, bearing displacement, wind direction, wind speed, and ambient temperature and humidity. Furthermore, an improved Analytic Hierarchy Process (AHP) algorithm is developed by integrating a hybrid triangular fuzzy number logic structure. This improvement, coupled with comprehensive fuzzy evaluation methods, improves the consistency, weight determination, and security evaluation capabilities of the AHP algorithm. Finally, taking the No.2 Channel Bridge as an example and based on the data collected by the health monitoring system, the application of the safety assessment method proposed in this paper provides favorable results in evaluating the overall safety status of the bridge in practical engineering applications. This provides a basis for management decisions by bridge maintenance departments. This project confirms that the research results can provide a reliable method for assessing the security status of relevant areas.

Abstract Background Invasive fungal infection (IFI) has become an increasing problem in NICU neonates, and end-organ damage (EOD) from IFI is one of the leading causes of morbidity and mortality in neonates. This study was conducted to summarize clinical data on epidemiology, risk factors, causative pathogens, and clinical outcomes of IFI-associated EOD among neonates in a center in China for the sake of providing references for prevention and treatment of fungal infections in neonates in future. Methods The clinical data of IFI neonates who received treatment in a tertiary NICU of China from January 2009 to December 2022 were retrospectively analyzed, including causative pathogens and the incidence of EOD. The neonates were divided into EOD group and non-EOD (NEOD) group. The general characteristics, risk factors and clinical outcomes of the two groups were compared. Results Included in this study were 223 IFI neonates (137 male and 86 female) with a median gestational age (GA) of 30.71 (29,35) weeks and a median birth weight (BW) of 1470 (1120,2150) g. Of them, 79.4% were preterm infants and 50.2% were born at a GA of ≥ 28,

Abstract Background Circulating tumor cells (CTCs) hold immense promise in guiding treatment strategies for advanced gastric cancer (GC). However, their clinical impact has been limited due to challenges in identifying epithelial-mesenchymal transition (EMT)-CTCs using conventional methods. Methods To bridge this knowledge gap, we established a detection platform for CTCs based on the distinctive biomarker cell surface vimentin (CSV). A prospective study involving 127 GC patients was conducted, comparing CTCs enumeration using both EpCAM and CSV. This approach enabled the detection of both regular and EMT-CTCs, providing a comprehensive analysis. Spiking assays and WES were employed to verify the reliability of this marker and technique. To explore the potential inducer of CSV+CTCs formation, a combination of Tandem Mass Tag (TMT) quantitative proteomics, m6A RNA immunoprecipitation–qPCR (MeRIP–qPCR), single-base elongation- and ligation-based qPCR amplification method (SELECT) and RNA sequencing (RNA-seq) were utilized to screen and confirm the potential target gene. Both in vitro and in vivo experiments were performed to explore the molecular mechanism of CSV expression regulation and its role in GC metastasis. Results Our findings revealed the potential of CSV in predicting therapeutic responses and long-term prognosis for advanced GC patients. Additionally, compared to the conventional EpCAM-based CTCs detection method, the CSV-specific positive selection CTCs assay was significantly better for evaluating the therapeutic response and prognosis in advanced GC patients and successfully predicted disease progression 14.25 months earlier than radiology evaluation. Apart from its excellent role as a detection marker, CSV emerges as a promising therapeutic target for attenuating GC metastasis. It was found that fat mass and obesity associated protein (FTO) could act as a potential catalyst for CSV+CTCs formation, and its impact on the insulin-like growth factor-I receptor (IGF-IR) mRNA decay through m6A modification. The activation of IGF-I/IGF-IR signaling enhanced the translocation of vimentin from the cytoplasm to the cell surface through phosphorylation of vimentin at serine 39 (S39). In a GC mouse model, the simultaneous inhibition of CSV and blockade of the IGF-IR pathway yielded promising outcomes. Conclusion In summary, leveraging CSV as a universal CTCs marker represents a significant breakthrough in advancing personalized medicine for patients with advanced GC. This research not only paves the way for tailored therapeutic strategies but also underscores the pivotal role of CSV in enhancing GC management, opening new frontiers for precision medicine.

Abstract Background The prognostic nutritional index (PNI), integrating nutrition and inflammation markers, has been increasingly recognized as a prognostic predictor in diverse patient cohorts. Recently, its effectiveness as a predictive marker for acute kidney injury (AKI) in various clinical settings has gained attention. This study aims to assess the predictive accuracy of the PNI for AKI in critically ill populations through systematic review and meta-analysis. Methods A systematic review was conducted using the databases MEDLINE, EMBASE, PubMed, and China National Knowledge Infrastructure up to August 2023. The included trials reported the PNI assessment in adult population with critical illness and its predictive capacity for AKI. Data on study characteristics, subgroup covariates, and diagnostic performance of PNI, including sensitivity, specificity, and event rates, were extracted. A diagnostic test accuracy meta-analysis was performed. Subgroup analyses and meta-regression were utilized to investigate the sources of heterogeneity. The GRADE framework evaluated the confidence in the meta-analysis’s evidence. Results The analysis encompassed 16 studies with 17 separate cohorts, totaling 21,239 patients. The pooled sensitivity and specificity of PNI for AKI prediction were 0.67 (95% CI 0.58–0.74) and 0.74 (95% CI 0.67–0.80), respectively. The pooled positive likelihood ratio was 2.49 (95% CI 1.99–3.11; low certainty), and the negative likelihood ratio was 0.46 (95% CI 0.37–0.56; low certainty). The pooled diagnostic odds ratio was 5.54 (95% CI 3.80–8.07), with an area under curve of summary receiver operating characteristics of 0.76. Subgroup analysis showed that PNI’s sensitivity was higher in medical populations than in surgical populations (0.72 vs. 0.55; p

Abstract A bridge disease identification approach based on an enhanced YOLO v3 algorithm is suggested to increase the accuracy of apparent disease detection of concrete bridges under complex backgrounds. First, the YOLO v3 network structure is enhanced to better accommodate the dense distribution and large variation of disease scale characteristics, and the detection layer incorporates the squeeze and excitation (SE) networks attention mechanism module and spatial pyramid pooling module to strengthen the semantic feature extraction ability. Secondly, CIoU with better localization ability is selected as the loss function for training. Finally, the K-means algorithm is used for anchor frame clustering on the bridge surface disease defects dataset. 1363 datasets containing exposed reinforcement, spalling, and water erosion damage of bridges are produced, and network training is done after manual labelling and data improvement in order to test the efficacy of the algorithm described in this paper. According to the trial results, the YOLO v3 model has enhanced more than the original model in terms of precision rate, recall rate, Average Precision (AP), and other indicators. Its overall mean Average Precision (mAP) value has also grown by 5.5%. With the RTX2080Ti graphics card, the detection frame rate increases to 84 Frames Per Second, enabling more precise and real-time bridge illness detection.

Abstract Objective This study aimed to assess the functions of cell division cycle protein 45 (CDC45) in Non-small cell lung cancer (NSCLC) cancer and its effects on stemness and metastasis. Methods Firstly, differentially expressed genes related to lung cancer metastasis and stemness were screened by differential analysis and lasso regression. Then, in vitro, experiments such as colony formation assay, scratch assay, and transwell assay were conducted to evaluate the impact of CDC45 knockdown on the proliferation and migration abilities of lung cancer cells. Western blotting was used to measure the expression levels of related proteins and investigate the regulation of CDC45 on the cell cycle. Finally, in vivo model with subcutaneous injection of lung cancer cells was performed to verify the effect of CDC45 on tumor growth. Results This study identified CDC45 as a key gene potentially influencing tumor stemness and lymph node metastasis. Knockdown of CDC45 not only suppressed the proliferation and migration abilities of lung cancer cells but also caused cell cycle arrest at the G2/M phase. Further analysis revealed a negative correlation between CDC45 and cell cycle-related proteins, stemness-related markers, and tumor mutations. Mouse experiments confirmed that CDC45 knockdown inhibited tumor growth. Conclusion As a novel regulator of stemness, CDC45 plays a role in regulating lung cancer cell proliferation, migration, and cell cycle. Therefore, CDC45 may serve as a potential target for lung cancer treatment and provide a reference for further mechanistic research and therapeutic development.

Abstract Background Cancer-associated fibroblasts (CAFs) play a crucial role in the tumor microenvironment of lung adenocarcinoma (LUAD) and are often associated with poorer clinical outcomes. This study aimed to screen for CAF-specific genes that could serve as promising therapeutic targets for LUAD. Methods We established a single-cell transcriptional profile of LUAD, focusing on genetic changes in fibroblasts. Next, we identified key genes associated with fibroblasts through weighted gene co-expression network analysis (WGCNA) and univariate Cox analysis. Then, we evaluated the relationship between glutathione peroxidase 8 (GPX8) and clinical features in multiple independent LUAD cohorts. Furthermore, we analyzed immune infiltration to shed light on the relationship between GPX8 immune microenvironment remodeling. For clinical treatment, we used the tumor immune dysfunction and exclusion (TIDE) algorithm to assess the immunotherapy prediction efficiency of GPX8. After that, we screened potential therapeutic drugs for LUAD by the connectivity map (cMAP). Finally, we conducted a cell trajectory analysis of GPX8+ CAFs to show their unique function. Results Fibroblasts were found to be enriched in tumor tissues. Then we identified GPX8 as a key gene associated with CAFs through comprehensive bioinformatics analysis. Further analysis across multiple LUAD cohorts demonstrated the relationship between GPX8 and poor prognosis. Additionally, we found that GPX8 played a role in inducing the formation of an immunosuppressive microenvironment. The TIDE method indicated that patients with low GPX8 expression were more likely to be responsive to immunotherapy. Using the cMAP, we identified beta-CCP as a potential drug-related to GPX8. Finally, cell trajectory analysis provided insights into the dynamic process of GPX8+ CAFs formation. Conclusions This study elucidates the association between GPX8+ CAFs and poor prognosis, as well as the induction of immunosuppressive formation in LUAD. These findings suggest that targeting GPX8+ CAFs could potentially serve as a therapeutic strategy for the treatment of LUAD.

IntroductionScreening excellent bacterial strains for fermentation is the key to improving the nutritional value and bioavailability of soybean meal (SBM). This study investigated the application of Bacillus subtilis-fermented soybean meal (FSBM) on the feed of Pacific white shrimp (Litopenaeus vannamei).MethodsFSBM was used to replace 0%, 25%, 50%, 75%, and 100% fish meal, and the feeding trial was lasted for 8 weeks (initial weight: 0.9 g). Results and discussionThe amino acid profile in the whole shrimp body was tested. FSBM substitution only significantly reduced the content lysine in whole shrimp body, but increased the content of arginine. Fatty acid data showed that the content of n-6 PUFAs in whole shrimp was significantly increased by FSBM substitution. In muscle, FSBM substitution significantly reduced the content of MUFAs, but increased the content of PUFAs including C18:3n-3, C18:2n-6 and C20:4n-6. No hepatopancreas structure modifications appeared in the 25% group compared with the control group. Subsequently, we investigated the response patterns of different organs to FSBM substitution from antioxidant, endoplasmic reticulum stress and immunity. A high proportion of FSBM significantly reduced the content of GSH in hemolymph and hepatopancreas, while increased the mRNA expression of cat. FSBM substitution did not affect the activities of antioxidant enzymes in the intestine. However, the mRNA expression level of hsp70 in the intestine was significantly reduced by FSBM. In terms of immunity, the mRNA expression levels of lgbp and penaeidin in the hepatopancreas showed a significant linear increase trend. In muscle, high proportion of FSBM significantly increased the mRNA expression of imd. FSBM substitution did not significantly affect the expression of immune genes in the intestine. In terms of endoplasmic reticulum stress, FSBM substitution significantly increased the mRNA expression of eif2α in the hepatopancreas. In muscle, FSBM substitution inhibited the mRNA expression of bip. In the intestine, FSBM replacing 75% of fish meal significantly increased the mRNA expression of bip and ire1. In summary, this study indicated that when the fish meal content account for 40% in diets (dry weight), the screened Bacillus subtilis-FSBM can replace 25% of fish meal protein without reducing the antioxidant and immune abilities of shrimp.

The grey wolf optimizer is a widely used parametric optimization algorithm. It is affected by the structure and rank of grey wolves and is prone to falling into the local optimum. In this study, we propose a grey wolf optimizer for fusion cell-like P systems. Cell-like P systems can parallelize computation and communicate from cell membrane to cell membrane, which can help the grey wolf optimizer jump out of the local optimum. Design new convergence factors and use different convergence factors in other cell membranes to balance the overall exploration and utilization capabilities of the algorithm. At the same time, dynamic weights are introduced to accelerate the convergence speed of the algorithm. Experiments are performed on 24 test functions to verify their global optimization performance. Meanwhile, a support vector machine model optimized by the grey wolf optimizer for fusion cell-like P systems has been developed and tested on six benchmark datasets. Finally, the optimizing ability of grey wolf optimizer for fusion cell-like P systems on constrained optimization problems is verified on three real engineering design problems. Compared with other algorithms, grey wolf optimizer for fusion cell-like P systems obtains higher accuracy and faster convergence speed on the test function, and at the same time, it can find a better parameter set stably for the optimization of support vector machine parameters, in addition to being more competitive on constrained engineering design problems. The results show that grey wolf optimizer for fusion cell-like P systems improves the searching ability of the population, has a better ability to jump out of the local optimum, has a faster convergence speed, and has better stability.

IntroductionAdoption of allogeneic T cells directly supplements the number of T cells and rapidly induces T-cell immunity, which has good efficacy for treating some tumors and immunodeficiency diseases. However, poor adoptive T-cell engraftment and graft-versus-host disease (GVHD) limit the application of these methods. Alloreactive T-cell clones were eliminated from the donor T-cell repertoire, and the remaining T-cell clones were prepared as Tscm for T-cell adoptive treatment to reconstruct recipient T-cell immunity without GVHD.MethodsThe subjects in this study included three different strains of mice. Lymphocytes from mice (C57BL/6) were used as the donor T-cell repertoire, from which the Tscm allo-reactive T cell clone was depleted (ATD-Tscm). This was confirmed by showing that the Tscm was not responsive to the alloantigen of the recipient (BALB/c). To prepare ATD-Tscm cells, we used recipient lymphocytes as a simulator, and coculture of mouse and recipient lymphocytes was carried out for 7 days. Sorting of non-proliferative cells ensured that the prepared Tscm cells were nonresponsive. The sorted lymphocytes underwent further expansion by treatment with TWS119 and cytokines for an additional 10 days, after which the number of ATD-Tscm cells increased. The prepared Tscm cells were transferred into recipient mice to observe immune reconstitution and GVHD incidence.ResultsOur protocol began with the use of 1×107 donor lymphocytes and resulted in 1 ×107 ATD-Tscm cells after 17 days of preparation. The prepared ATD-Tscm cells exhibited a nonresponse upon restimulation of the recipient lymphocytes. Importantly, the prepared ATD-Tscm cells were able to bind long and reconstitute other T-cell subsets in vivo, effectively recognizing and answering the “foreign” antigen without causing GVHD after they were transferred into the recipients.DiscussionOur strategy was succeeded to prepare ATD-Tscm cells from the donor T-cell repertoire. The prepared ATD-Tscm cells were able to reconstitute the immune system and prevent GVHD after transferred to the recipients. This study provides a good reference for generating ATD-Tscm for T-cell adoptive immunotherapy.

Abstract The trade winds cause strong upwelling in the eastern equatorial Pacific, and create the eastern Pacific Cold Tongue (EPCT) that has far‐reaching impacts on global climate. However, large discrepancies persist in quantifying 20th‐century EPCT sea surface temperature (SST) changes across different instrumental data sets. Here we synthesize four coral Sr/Ca‐SST records from the tropical central‐eastern Pacific to develop a Cold Tongue Index (CTI) reconstruction for 1887–1997. The coral CTI record shows a rapid 20th century warming of the EPCT, suggesting an underestimation of warming trends in instrumental CTI records. The decadal to multidecadal changes in reconstructed EPCT SST show an association with the Walker Circulation. Our reconstruction indicates that recent EPCT cooling during the global warming hiatus is not unusual in the context of the 20th century. Our results provide new evidence for 20th century EPCT SST changes and an observational constraint for predicting future tropical climate changes.

High-velocity, large-coupling acoustic mode is the eternal pursuit of microacoustic research. Surface mode on piezoelectric films supported by an acoustic Bragg reflector (ABR) stack is one possible solution for realizing such a goal. However, some acoustic modes exhibit lower couplings in experiments than theoretically predicted, especially when metal layers are used as high-impedance layers in the ABR. The mechanism of this performance deterioration is still unclear. In this work, the electric field distribution in a piezoelectric plate mounted to an ABR stack is analyzed by considering the inductive current effect in conductive ABR layers. The field distribution required by one mode is found to be distorted by the effect, which results in a reduction in the excitation efficiency for the mode. We propose the use of another acoustic mode with a concentrated electric field in the top layers. As analyzed in comparison, the impact of the inductive effect on the mode is negligible. On an optimized crystal cut of lithium niobate, the selected mode exhibits 22.64% coupling and an acoustic velocity of 6006 m/s.

The SARS-CoV-2, responsible for the COVID-19 pandemic, poses a significant threat to global healthcare. Peptide and peptide-based inhibitors, known for their safety, efficacy, and selectivity, have recently emerged as promising candidates for treating late-developing viral infections. In this study, three peptides were selected to target different stages of viral invasion, specifically ACE2 and S protein binding, as well as membrane fusion. The objective was to assess their ability to impede the entry of the SARS-CoV-2 Spike pseudotyped virus. Our findings revealed that a combination of these three peptides demonstrated enhanced antiviral effects. This outcome substantiates the feasibility of developing effective peptide combinations to combat diseases related to SARS-CoV-2. Moreover, the three-peptide combinations, designed to target multiple aspects of SARS-CoV-2 viral entry, exhibited heightened viral inhibition and broad-spectrum antiviral properties.

This study examined the effects of feeding largemouth bass (Micropterus salmoides) with diets containing different doses of astaxanthin (0, 50, 100, 150, and 200 mg/kg) for 8 weeks. The results showed that the values of weight gain significantly increased from 620.32 ± 50.38% to 826.14 ± 33.49% as dietary astaxanthin levels increased from 0 mg/kg to 100 mg/kg. When the astaxanthin level exceeded 150mg/kg, the weight gain rate showed a downward trend, but there was no significant difference among of the 100, 150 and 200 mg/kg groups. The feed conversion ratio (FCR) and protein efficiency ratio (PER) were also improved by adding astaxanthin to diets (P < 0.05). Meanwhile, adding astaxanthin to the feed increased the length and thickness of intestinal villus and muscle layer thickness (P < 0.05). The astaxanthin supplementation increased the expression of the NF-E2-related factor (Nrf2) gene and reduced malondialdehyde (MDA) content and the expression of apoptosis genes Caspase-9 and Caspase-3 (P < 0.05), indicating that it has a good antioxidant ability. Furthermore, adding astaxanthin increased the content of non-specific immune markers and decreased the expression levels of the inflammatory factors interleukin-15 (IL-15) and tumor necrosis factor-α (TNF-α). Moreover, fish fed diets with astaxanthin exhibited lower blood cortisol levels (P < 0.05). The proportions of C20:4n6 (ARA) and C20:5n3 (EPA) in the liver decreased with increasing dietary astaxanthin levels. Based on WGR and SGR values, the optimal addition level of astaxanthin in largemouth bass feed is 134.8 mg/kg ~ 135.75 mg/kg. In summary, the appropriate dietary astaxanthin enhanced the antioxidant capacity and immune response of largemouth bass and had a positive effect on its intestinal health.