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Abstract Angiogenesis is critical for colorectal cancer (CRC) progression, but its mechanisms remain unclear. Here, we reveal that ethylmalonic encephalopathy protein 1 (ETHE1), an essential enzyme in hydrogen sulfide catabolism, inhibits VEGF-A expression and tumor angiogenesis in vitro and in vivo. Moreover, we find that this biological function of ETHE1 depends on the STAT3/VEGF-A pathway. Further investigation demonstrates that ETHE1 promotes the interaction between T cell protein tyrosine phosphatase (TC45) and STAT3, resulting in decreased STAT3 phosphorylation and inhibition of the STAT3 signaling pathway. In clinical samples, we find that ETHE1 is downregulated in CRC and positively correlates with survival outcomes of CRC patients. Meanwhile, the negative correlation of ETHE1 and VEGF-A expression is verified in CRC specimens, and the patients with low ETHE1 and high VEGF-A expression exhibits poorer prognosis. Collectively, our study identifies ETHE1 as a novel regulator of tumor angiogenesis, implying its potential as a prognostic biomarker and promising antiangiogenic target for CRC patients.

Abstract Background With better patient selection and the increasing experience in patients undergoing hyperthermic intraperitoneal chemotherapy (HIPEC) combined surgery, the rate of severe postoperative complications and mortality decreased significantly. However, leukopenia and neutropenia were still a particular concern, and their relation to sarcopenia was not clarified. Methods Data of consecutive patients who underwent HIPEC for gastrointestinal cancer were collected and analyzed retrospectively between September 2020 and August 2022. Sarcopenia was assessed using psoas muscle index (PMI) at the L3 level on preoperative computed tomography (CT). Results Among 103 patients enrolled, 37 (35.9%) were classified as sarcopenic. Most leukopenia and neutropenia occurred during the hospital leaving period after HIPEC and surgery. Before the first time of postoperative chemotherapy, the blood tests revealed 11 (29.73%) and 6 (9.09%) patients were diagnosed with neutropenia in sarcopenia and no sarcopenia groups, respectively. Logistic regression analysis revealed sarcopenia was independently associated with the increased risk of neutropenia (OR 5.58, 95% CI 1.70–18.29, p = 0.005). An incremental albumin level was protective against the occurrence of leukopenia and neutropenia. Conclusions Sarcopenia and low albumin level were significantly associated with an increased rate of delayed neutropenia after HIPEC in that disease setting and could be the preoperative risk predictors.

Abstract Background Enterovirus (EV) infections are being increasingly seen in younger infants, often being more severe than in older children. The risk factors of EV infection in infants have been inadequately investigated till date. Methods We conducted a retrospective study on hospitalized children with laboratory-confirmed EV infection (50 infants aged 0–3 months and 65 older than 3 months) at a tertiary care center in China. Prevalence, clinical characteristics, and genetic features of the virus were analyzed, and independent predictors for severe infection were assessed. Results Clinical findings showed that severe infection was more common in infants aged 0–3 months than in older children (78.0% vs. 35.4%, p

Genogroup II genotype 4 (GII.4) norovirus causes acute gastroenteritis in children, and its infection is more severe than that of other genotypes. Early and precise detection and treatment are critical for controlling its spread and reducing the severity of infection. In this study, a rapid and efficient isothermal assay for the GII.4 norovirus detection (GII.4-CRISPR detection) was developed based on the CRISPR/Cas13a system. The assay can be applied without expensive instrumentation, and the results can be read via both fluorescence and lateral flow strip (LFS). The analytical sensitivity of this assay was 5 copies/reaction, and there was no cross-reaction with other genotypes of norovirus or other clinically common pathogens. There was a coincidence rate of 100% between our assay and commercial quantitative polymerase chain reaction. GII.4-CRISPR detection improves upon the shortcomings of some previously established molecular methods of detection, particularly with regard to accessibility. It provides an alternative tool for outbreak control and early diagnosis of GII.4 norovirus infection.

Abstract The aim of this study was to retrospectively compare hematological parameters among normal, α-, and β-thalassemia fetuses between 17 and 38 weeks of gestation. Pregnant women at risk of having fetuses with thalassemia major and underwent cordocentesis for prenatal diagnosis were recruited. Fetal cord blood samples were collected from 249 fetuses for hematological and DNA analysis. Fetuses were divided into subgroups according to thalassemia DNA genotypes. The average and gestational age of subjects were 27.95 ± 5.78 years and 27.78 ± 3.57 weeks, respectively. The distribution of α-thalassemia, β-thalassemia, and normal cases was 67.87%, 19.68%, and 12.45%, respectively. Significant differences in almost all the hematological parameters (HbF, HbA, Hb, HCT, MCV, MCH, MCHC, RDW, and NBRCs) were observed in three groups (P

Hand, foot, and mouth disease (HFMD) is a common infectious disease affecting mainly children under 5 years of age. Coxsackievirus A6 (CVA-6), a major causative pathogen of HFMD, has caused outbreaks in recent years. Currently, no effective vaccine or antiviral treatments are available. In this study, one-step reverse-transcription recombinase polymerase amplification (RT-RPA), combined with a disposable lateral flow strip (LFS) assay, was developed to detect CVA-6. This assay can be performed in less than 35 min at 37°C without expensive instruments, and the result can be observed directly with the naked eye. The sensitivity of the RT-RPA-LFS was 10 copies per reaction, which was comparable to that of the conventional real-time quantitative polymerase chain reaction (qPCR) assays. Moreover, the assay specificity was 100%. The clinical performance of the RT-RPA-LFS assay was evaluated using 142 clinical samples, and the coincidence rate between RT-RPA-LFS and qPCR was 100%. Therefore, our RT-RPA-LFS assay provides a simple and rapid approach for point-of-care CVA-6 diagnosis.

Abstract Background GALNTs (UDP-GalNAc; polypeptide N-acetylgalactosaminyltransferases) initiate mucin-type O-GalNAc glycosylation by adding N-GalNAc to protein serine/threonine residues. Abnormalities in O-GalNAc glycosylation are involved in various disorders such as Parkinson’s disease (PD), a neurodegenerative disorder. GALNT9 is potentially downregulated in PD patients. Methods To determine whether GALNT9 enrichment ameliorates cytotoxicity related to PD-like variations, a pcDNA3.1-GALNT9 plasmid was constructed and transfected into SH-SY5Y cells to establish a GALNT9-overexpressing cell model. Results Downregulation of GALNT9 and O-GalNAc glycosylation was confirmed in our animal and cellular models of PD-like variations. GALNT9 supplementation greatly attenuated cytotoxicity induced by MPP+ (1-Methyl-4-phenylpyridinium iodide) since it led to increased levels of tyrosine hydroxylase and dopamine, reduced rates of apoptosis, and significantly ameliorated MPP+-induced mitochondrial dysfunction by alleviating abnormal levels of mitochondrial membrane potential and reactive oxygen species. A long-lasting mPTP (mitochondrial permeability transition pores) opening and calcium efflux resulted in significantly lower activity in the cytochrome C-associated apoptotic pathway and mitophagy process, signifying that GALNT9 supplementation maintained neuronal cell health under MPP+ exposure. Additionally, it was found that glycans linked to proteins influenced the formation of protein aggregates containing α-synuclein, and GALNT9 supplement dramatically reduced such insoluble protein aggregations under MPP+ treatment. Glial GALNT9 predominantly appears under pathological conditions like PD-like variations. Conclusions GALNT9 enrichment improved cell survival, and glial GALNT9 potentially represents a pathogenic index for PD patients. This study provides insights into the development of therapeutic strategies for the treatment of PD.

Abstract Background Gastric cancer (GC) encompasses many different histological and molecular subtypes. It is a major driver of cancer mortality because of poor survival and limited treatment options. Personalised medicine in the form of patient-derived organoids (PDOs) represents a promising approach for improving therapeutic outcomes. The goal of this study was to overcome the limitations of current models by ameliorating organoid cultivation. Methods Organoids derived from cancer tissue were evaluated by haematoxylin and eosin staining, immunohistochemistry, mRNA, and whole-exome sequencing. Three representative chemotherapy drugs, 5-fluorouracil, docetaxel, and oxaliplatin, were compared for their efficacy against different subtypes of gastric organoids by ATP assay and apoptosis staining. In addition, drug sensitivity screening results from two publicly available databases, the Genomics of Drug Sensitivity in Cancer and Cancer Cell Line Encyclopaedia, were pooled and applied to organoid lines. Once key targeting genes were confirmed, chemotherapy was used in combination with poly (ADP ribose) polymerase (PARP)-targeted therapy. Results We successfully constructed GC PDOs surgically resected from GC patient tissue. PDOs closely reflected the histopathological and genomic features of the corresponding primary tumours. Whole-exosome sequencing and mRNA analysis revealed that changes to the original tumour genome were maintained during long-term culture. The drugs caused divergent responses in intestinal, poorly differentiated intestinal, and diffuse gastric cancer organoids, which were confirmed in organoid lines. Poorly differentiated intestinal GC patients benefited from a combination of 5-fluorouracil and veliparib. Conclusion The present study demonstrates that combining chemotherapy with PARP targeting may improve the treatment of chemotherapy-resistant tumours.

Abstract Background Trastuzumab and pertuzumab combination has been approved for the treatment of patients with HER2-positive metastatic breast cancer. However, trastuzumab and pertuzumab combination did not show improvement in overall survival in patients with HER2-positive metastatic gastric cancer. Methods We developed a new HER2-targeted monoclonal antibody, HLX22, targeting HER2 subdomain IV as trastuzumab but with non-overlapping epitopes. We examined the antitumor effects of this novel HER2-antibody in gastric cell lines and cell line-derived xenograft (CDX) and patient-derived xenograft (PDX) models. Results HLX22 in combination with HLX02 (trastuzumab biosimilar) induced enhancement of HER2/HER2 homodimers and HER2/EGFR heterodimers internalization, which ultimately led to the reduction in signal transductions involving STAT3, P70 S6, and AKT; gene expressions of FGF-FGFR-PI3K-MTOR, EGF-EGFR-RAS, TGF-β-SMAD, PLCG and cell cycle progression related pathways that favor tumor development, proliferation, progression, migration and survival in gastric cancer cell line NCI-N87 were also reduced. These differing but complementary actions contributed to the synergistic antitumor efficacy of the HLX22 and HLX02 combination in gastric cancer cell lines, CDX and PDX. In addition, HLX22 in combination with HLX02 demonstrated stronger antitumor efficacy than HLX02 and HLX11 (a potential pertuzumab biosimilar) combination treatment both in vitro and in vivo. Conclusions These results suggested that the application of non-competing antibodies HLX22 and HLX02 targeting HER2 subdomain IV together may be of substantial benefit to gastric cancer patients who currently respond suboptimal to trastuzumab therapy.

Abstract. Background:. Although significant advances have been made in the treatment of multiple myeloma (MM), leading to unprecedented response and survival rates among patients, the majority eventually relapse, and a cure remains elusive. This situation is closely related to an incomplete understanding of the immune microenvironment, especially monocytes/macrophages in patients with treatment-naïve MM. The aim of this study was to provide insight into the immune microenvironment, especially monocytes/macrophages, in patients with treatment-naïve MM. Methods:. This study used the single-cell RNA sequencing (scRNA-seq) data of both patients with MM and heathy donors to identify immune cells, including natural killer (NK) cells, T cells, dendritic cells (DCs), and monocytes/macrophages. Transcriptomic data and flow cytometry analysis of monocytes/macrophages were used to further examine the effect of monocytes/macrophages in treatment-naïve MM patients. Results:. A significant difference was observed between the bone marrow (BM) immune cells of the healthy controls and treatment-naïve MM patients through scRNA-seq. It is noteworthy that, through an scRNA-seq data analysis, this study found that interferon (IFN)-induced NK/T cells, terminally differentiated effector memory (TEMRA) cells, T-helper cells characterized by expression of IFN-stimulated genes (ISG+Th cells), IFN-responding exhausted T cells, mannose receptor C-type 1 (MRC1)+ DCs, IFN-responding DCs, MHCII+ DCs, and immunosuppressive monocytes/macrophages were enriched in patients with treatment-naïve MM. Significantly, transcriptomic data of monocytes/macrophages demonstrated that “don’t eat me”-related genes and IFN-induced genes increase in treatment-naïve MM patients. Furthermore, scRNA-seq, transcriptomic data, and flow cytometry also showed an increased proportion of CD16+ monocytes/macrophages and expression level of CD16. Cell–cell communication analysis indicated that monocytes/macrophages, whose related important signaling pathways include migration inhibitory factor (MIF) and interleukin 16 (IL-16) signaling pathway, are key players in treatment-naïve MM patients. Conclusions:. Our findings provide a comprehensive and in-depth molecular characterization of BM immune cell census in MM patients, especially for monocytes/macrophages. Targeting macrophages may be a novel treatment strategy for patients with MM.

In this study, SiO2 containing PAO6 microcapsules were endowed with surface active groups by polydopamine (PSPMS). Then the modified microcapsules were in situ grafted into phenolic resin (PF@PSPMS) to control the dispersion and bonding in high viscosity resin. Further, the tribological properties of the PF coating and the prepared liner were analyzed. The results show that the life of PF@PSPMS-coating is 73 times longer than that of PF-coating, the friction coefficient (COF) is reduced by 78%. Meanwhiles the COF of the corresponding liner is reduced from 0.11 to 0.06, and the wear amount is reduced from 64.07 μm to 23.07 μm. The wear mechanism shows that the breakage of PSPMS release lubricating oil at the friction interface, forming a coordinated solid-liquid lubrication effect with PTFE. At the same time, the presence of lubricating oil can remove the debris on the surface of the friction pair and improve the quality of the transfer film. In addition, the dispersion of silica fragments at the friction interface is conducive to improving the hardness and wear resistance. This work provides a new method for the dispersion of microcapsules in the liner and further explains the anti-friction and wear mechanism of silica microcapsules in the liner system, confirming the effectiveness of microcapsules in the liner system.

Objectives There is still controversy over the choice of treatment for end‐stage spinal metastases. With the continuous development of microwave technology in spinal tumors, related studies have reported that microwave combined with techniques such as pedicle screw fixation and percutaneous vertebroplasty can achieve the purpose of tumor ablation, relieving spinal cord compression, enhancing spinal stability, effectively relieving pain, and reducing recurrence rates. This study aimed to analyze the effectiveness of microwave ablation combined with decompression and pedicle screw fixation in the palliative management of spinal metastases with pathological fractures. Methods This retrospective study enrolled 82 patients with spinal metastases and pathological fractures treated between January 2016 and July 2020, with 44 patients undergoing pedicle screw fixation along with laminectomy (fixation group) and the remaining 38 receiving microwave ablation in addition to the treatment provided to group fixation (MWA group). Before surgery, all patients underwent pain assessment using the visual analogue scale (VAS) and evaluation of spinal cord injury using the Frankel classification. After surgery, the patients' prognoses were assessed using the Tomita score, modified Tokuhashi score system, and progression‐free survival. Additionally, we compared operative time and blood loss between the two groups. Survival analysis utilized the Kaplan–Meier method with a log‐rank test for group comparisons. Paired t‐tests and the Mann–Whitney U test were applied to metric and non‐normally distributed data, respectively. Neurological function improvement across groups was evaluated using the χ2 test. Results All patients were followed up for a median duration of 18 and 20 months in the fixation and MWA groups, respectively, with follow‐up periods ranging from 6 to 36 months. Statistically significant reductions in postoperative VAS scores were observed in all patients compared with their preoperative scores. The MWA group exhibited reduced blood loss (t = 2.74, p = 0.01), lower VAS scores at the 1‐ and 3‐month follow‐ups (t = 2.34, P = 0.02; t = 2.83, p = 0.006), and longer progression‐free survival than the fixation group (p = 0.03). Although the operation times in the MWA group were longer than those in the fixation group, this difference was not statistically significant (t = 6.06, p = 0.12). No statistically significant differences were found regarding improvements in spinal cord function between the two groups (p = 0.77). Conclusion Compared with decompression and pedicle screw fixation for treating spinal metastases with pathological fractures, microwave ablation combined with decompression and pedicle screw fixation showed better outcomes in terms of pain control, longer progression‐free survival, and lower blood loss without increasing operative time, which has favorable implications for clinical practice.

Pantothenate kinase-associated neurodegeneration (PKAN) is a rare autosomal recessive hereditary neurodegenerative disorder, usually caused by mutations in the pantothenate kinase 2 (PANK2) gene. We report a young female patient with atypical PKAN, harboring a novel heterozygous PANK2 mutation, diagnosed through clinical imaging and genetic analysis. The patient presented with dystonia and motor dysfunction after onset, but early brain MRI showed normal findings. Due to progressive symptom deterioration, her MRI was reevaluated and the characteristic “eye of the tiger” sign was identified. Further genetic testing revealed that she was a carrier of two heterozygous PANK2 mutations, one being a known pathogenic variant and the other unknown. Given the patient’s clinical presentation, progressive symptoms, and poor response to medication, we boldly attempted asymmetric bilateral deep brain stimulation (abDBS). Postoperative outcomes showed significant symptom improvement. This study suggests that early brain MRI in PKAN patients may not exhibit typical radiological features, leading to potential diagnostic omissions. Furthermore, it highlights the potential therapeutic effect of abDBS in atypical PKAN, particularly in patients with novel heterozygous PANK2 mutations. Asymmetric bilateral deep brain stimulation may represent a promising treatment approach.

Porcine reproductive and respiratory syndrome virus (PRRSV) is a major thread to the global swine industry, lack of effective control strategies. This study explores the regulatory role of a small non-coding RNA, miR-191-5p, in PRRSV infection. We observed that miR-191-5p significantly inhibits PRRSV in porcine alveolar macrophages (PAMs), contrasting with negligible effects in MARC-145 and HEK293-CD163 cells, suggesting a cell-specific antiviral effect. Further investigation unveiled that miR-191-5p directly targets the porcine epidermal growth factor receptor (EGFR), whose overexpression or EGF-induced activation suppresses type I interferon (IFN-I) signaling, promoting PRRSV replication. In contrast, siRNA-or miR-191-5p-induced EGFR downregulation or EGFR inhibitor boosts IFN-I signaling, reducing viral replication. Notably, this miRNA alleviates the suppressive effect of EGF on IFN-I signaling, underscoring its regulatory function. Further investigation revealed interconnections among miR-191-5p, EGFR and signal transducer and activator of transcription 3 (STAT3). Modulation of STAT3 activity influenced IFN-I signaling and PRRSV replication, with STAT3 knockdown countering EGFR activation-induced virus replication. Combination inhibition of STAT3 and miR-191-5p suggests that STAT3 acts downstream in EGFR’s antiviral response. Furthermore, miR-191-5p’s broad efficacy in restricting various PRRSV strains in PAMs was identified. Collectively, these findings elucidate a novel mechanism of miR-191-5p in activating host IFN-I signaling to inhibit PRRSV replication, highlighting its potential in therapeutic applications against PRRSV.

Rampant C-to-U RNA editing drives the mutation and evolution of SARS-CoV-2. While much attention has been paid to missense mutations, the C-to-U events leading to AUG and thus creating novel ORFs were uninvestigated. By utilizing the public time-course mutation data from the worldwide SARS-CoV-2 population, we systematically identified the “AUG-gain mutations” caused by C-to-U RNA editing. Synonymous mutations were of special focus. A total of 58 synonymous C-to-U sites are able to create out-of-frame AUG in coding sequence (CDS). These 58 synonymous sites showed significantly higher allele frequency (AF) and increasing rate (dAF/dt) than other C-to-U synonymous sites in the SARS-CoV-2 population, suggesting that these 58 AUG-gain events conferred additional benefits to the virus and are subjected to positive selection. The 58 predicted new ORFs created by AUG-gain events showed the following advantages compared to random expectation: they have longer lengths, higher codon adaptation index (CAI), higher Kozak scores, and higher tRNA adaptation index (tAI). The 58 putatively novel ORFs have high expressibility and are very likely to be functional, providing an explanation for the positive selection on the 58 AUG-gain mutations. Our study proposed a possible mechanism of the emergence of de novo genes in SARS-CoV-2. This idea should be helpful in studying the mutation and evolution of SARS-CoV-2.

Hardness and Young's modulus are critical indicators in the design of innovative Cu–Ni–Sn–Al alloys with desired elastic and strength properties. In this study, the composition-dependent hardness and Young's modulus in the fcc Cu–Ni–Sn–Al alloys were determined using high-throughput experiments, the CALPHAD (CALculation of PHAse Diagrams) approach, and machine learning (ML) model. By combining the diffusion-couples tool, nanoindentation, and electron probe microanalysis (EPMA) techniques, the 341 sets of composition-related hardness and Young's modulus in the fcc Cu–Ni–Sn–Al system, as well as its sub-binary and sub-ternary systems, were effectively determined. These measured data were subsequently utilized to establish the relationship of Young's modulus and hardness with respect to composition in the fcc Cu–Ni–Sn–Al system through the combined application of CALPHAD and back propagation (BP) artificial neural network machine learning models. A comparison between the two approaches revealed that the ML method achieves higher accuracy in ternary and quaternary alloys compared to the CALPHAD method. The impact of alloying elements on the values of hardness and Young's modulus was analyzed, demonstrating that the Ni content has the largest effect on hardness, while the Young's modulus increases with addition of Ni but decreases with the addition of Al and Sn. Finally, the effects of solute elements on the nanomechanical properties of aged Cu1-x(Ni3Sn)x and Cu–9Ni–6Sn-xAl alloys were examined.

Abstract The chemokine CXCL8, also known as the neutrophil chemotactic factor, plays a crucial role in mediating inflammatory responses and managing cellular immune reactions during viral infections. Porcine reproductive and respiratory syndrome virus (PRRSV) primarily infects pulmonary alveolar macrophages (PAMs), leading to acute pulmonary infections. In this study, we explored a novel long non-coding RNA (lncRNA), termed lnc-CAST, situated within the Cxcl8 gene locus. This lncRNA was found to be highly expressed in porcine macrophages. We observed that both lnc-CAST and CXCL8 were significantly upregulated in PAMs following PRRSV infection, and after treatments with lipopolysaccharide (LPS) or lipoteichoic acid (LTA). Furthermore, we noticed a concurrent upregulation of lnc-CAST and CXCL8 expression in lungs of PRRSV-infected pigs. We then determined that lnc-CAST positively influenced CXCL8 expression in PAMs. Overexpression of lnc-CAST led to an increase in CXCL8 production, which in turn enhanced the migration of epithelial cells and the recruitment of neutrophils. Conversely, inhibiting lnc-CAST expression resulted in reduced CXCL8 production in PAMs, leading to decreased migration levels of epithelial cells and neutrophils. From a mechanistic perspective, we found that lnc-CAST, localized in the nucleus, facilitated the enrichment of histone H3K27ac in CXCL8 promoter region, thereby stimulating CXCL8 transcription in a cis-regulatory manner. In conclusion, our study underscores the pivotal critical role of lnc-CAST in regulating CXCL8 production, offering valuable insights into chemokine regulation and lung damage during PRRSV infection.

Abstract Lithium-ion batteries (LIBs) are widely used in portable energy storage. The capacity of commercial graphite is difficult to improve due to the stoichiometry limit of LiC6 of graphite, thus new anodes need to be developed to meet the demand of high-energy–density LIB. The growing interest in graphitized carbon nitride (g-C3N4) stems from its structural resemblance to graphite and its capacity to offer abundant adsorption and intercalation sites. However, g-C3N4, as a semiconductor, has a low lithium transfer rate due to its poor conductivity and high diffusion resistance. Improving the electron transport rate of g-C3N4 and reducing the adsorption energy barrier of Li+ in g-C3N4 are the keys to improving the electrochemical performances of g-C3N4. In this study, lignin and melamine were homogeneously mixed using the spray drying method, followed by the preparation of covalently bonded C3N4/LC material through a one-step carbonization process. The uniform dispersion of g-C3N4 in amorphous carbon can improve the conductivity and reduce the diffusion energy barrier of Li+. As a result, the C3N4/LC-x anode has better electrochemical behavior, including higher reversible capacity, better rate performance, and cycle stability.

Water-lubricating bearings made of polymer-matrix composites have provided a new approach to prolong the service lifetime of key component in marine propulsion system. However, it was still crucial to find a convenient and effective material to manufacture the water-lubricating bearing with ultralow friction. Herein, a new kind of polyetheretherketone (PEEK) composite with ultralow coefficient of friction (COF), high mechanical strength and thermal stability has been developed. An 80.7% decrease in the COF of PEEK was achieved by incorporating the fillers. A possible mechanism between the heterogeneous nucleation and mobility hindrance of PEEK chain segment caused by different fillers was proposed. The ultralow COF endowed the water-lubricating bearing with low running noise and reduced energy consumption. The high mechanical strength and thermal stability caused the superior carrying capacity and reliability. Therefore, the prepared PEEK composites can be a possibility to realize the water-lubricating bearing with high durability and long service lifetime.

In order to obtain the preparation process and adsorption characteristics of insoluble dietary fiber from pomelo peel using composite enzyme method, the orthogonal test was used to optimize the extraction of insoluble dietary fiber from pomelo peel, and its characteristics were studied. The results showed that the optimal extraction conditions were as follows, material-liquid ratio of 1:40 g/mL, amylase addition amount of 0.6%, amylase hydrolysis time of 90 min, papain addition amount of 0.2% and papain hydrolysis time of 30 min. Under these conditions, the yield of pomelo peel IDF was 55.07%. The swelling capacity, water holding capacity, oil holding capacity and cation exchange capacity of pomelo peel IDF were 2.84±0.09 mL/g, 12.54±0.11 g/g, 1.54±0.02 g/g and 0.36±0.04 mmol/g, respectively. In addition, in vitro adsorption capability test indicated that the adsorption capacity of pomelo peel IDF for glucose, cholesterol and sodium cholate was 0.13±0.003 mmol/g, 12.27±0.020 mg/g and 53.25±0.100 mg/g, respectively. FT-IR results showed that pomelo peel IDF had characteristic absorption peaks of cellulose polysaccharides, which was consistent with the structure of dietary fiber. In summary, the extracted pomelo peel IDF exhibited good characteristics after optimizing the process. It can provide theoretical basis for the development and utilization of pomelo peel IDF.

Abstract. B-cell lymphoma is a group of hematological malignancies characterized by variable genetic and biological features and clinical behaviors. The tumor microenvironment (TME) is a complex network in tumors, which consists of surrounding blood vessels, extracellular matrix, immune and non-immune cells, and signaling molecules. Increasing evidence has shown that the TME, especially immune cells within, is a double-edged sword, acting either as a tumor killer or as a promoter of tumor progression. These pro-tumor activities are driven by subpopulations of immune cells that express typical markers but have unique transcriptional characteristics, making tumor-associated immune cells good targets for human anti-cancer therapy by ablating immunosuppressive cells or enhancing immune-activated cells. Thus, exploring the role of immune cells in the TME provides distinct insights for immunotherapy in B-cell lymphoma. In this review, we elucidated the interaction between immune cells and tumor cells and their function in the initiation, progression, and prognosis of B-cell lymphoma, from preclinical experiments to clinical trials. Furthermore, we outlined potential therapeutic approaches and discussed the potential clinical value and future perspectives of targeting immune cells in patients with B-cell lymphoma.

Objective To explore the application of machine learning in scientific and rational blood preparation and predictive analysis for surgical blood usage before liver transplantation surgery. Methods Clinical basic information including gender, age, clinical diagnosis and surgical methods of 356 liver transplantation patients were collected. The duration (Time) and preoperative laboratory test results of hemoglobin (Hb), hematocrit (Hct), platelet count (Plt), prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (Fib), total bilirubin (TBIL), albumin (ALB), creatinine (Crea) and total protein (TP), as well as the amount of intraoperative blood transfusion were collected. A machine learning model capable of predicting the risk of massive blood transfusion during liver transplantation surgery was established by Python, and was evaluated to select the optimal predictive model. Results Among the 7 machine learning models constructed, the logistic regression model performed the best (AUROC: 0.90, F1 score: 0.82), with an accuracy of 79.44% and precision of 79.69%, followed by the random forest classifier (AUROC: 0.87, F1 score: 0.83), with an accuracy of 79.44% and precision of 77.94%. Conclusion Establishing a machine learning prediction model by Python is of significant clinical importance for scientific blood preparation, predicting the risk of massive blood transfusion and ensuring the safety of blood use in liver transplantation surgery.

Abstract In this perspective, we present an overview of the research and advancement of lignocellulose-derived hard carbon anodes and their pivotal role in the commercialization of sodium-ion batteries. Hard carbon anodes, sourced from lignocellulosic biomasses, exhibit considerable promise due to their widespread availability, economical viability, and environmentally friendly attributes with zero carbon-dioxide emissions. Given the intricate compositions and composite nature of lignocellulosic materials, it becomes imperative to prioritize factors crucial for the fabrication of hard carbon anodes that exhibit enhanced sodium-ion storage capabilities. Thus, our study offers an extensive overview of the structure and performance nuances of hard carbon anodes derived from cellulose, hemicellulose, and lignin. Furthermore, it delves into the fundamental principles governing synthesis methodologies and confronts the challenges inherent in producing lignocellulose-derived hard carbon anodes tailored specifically for sodium-ion batteries. Graphical Abstract

Abstract Background The prognosis for hepatocellular carcinoma (HCC) remains suboptimal, characterized by high recurrence and metastasis rates. Although metalloimmunotherapy has shown potential in combating tumor proliferation, recurrence and metastasis, current apoptosis-based metalloimmunotherapy fails to elicit sufficient immune response for HCC. Results A smart responsive bimetallic nanovaccine was constructed to induce immunogenic cell death (ICD) through pyroptosis and enhance the efficacy of the cGAS-STING pathway. The nanovaccine was composed of manganese-doped mesoporous silica as a carrier, loaded with sorafenib (SOR) and modified with MIL-100 (Fe), where Fe3+, SOR, and Mn2+ were synchronized and released into the tumor with the help of the tumor microenvironment (TME). Afterward, Fe3+ worked synergistically with SOR-induced immunogenic pyroptosis (via both the classical and nonclassical signaling pathways), causing the outflow of abundant immunogenic factors, which contributes to dendritic cell (DC) maturation, and the exposure of double-stranded DNA (dsDNA). Subsequently, the exposed dsDNA and Mn2+ jointly activated the cGAS-STING pathway and induced the release of type I interferons, which further led to DC maturation. Moreover, Mn2+-related T1 magnetic resonance imaging (MRI) was used to visually evaluate the smart response functionality of the nanovaccine. Conclusion The utilization of metallic nanovaccines to induce pyroptosis-mediated immune activation provides a promising paradigm for HCC treatment.

Abstract Developing highly durable and active Pt-supported catalysts is currently the most prominent and practicable electrocatalyst design strategy for direct methanol fuel cells (DMFC) due to their high electrocatalytic stability and activity. Herein, we fabricated CeO2 nanorods with tiny Pt nanoparticles that possess good electrocatalytic behavior for methanol oxidation reaction (MOR). In addition, the presence of Ce3+ and small Pt nanoparticles (3.46 nm) enhanced strong metal interaction, facilitating the formation of oxygen vacancies on the CeO2 surface to boost the MOR performance. Hence, the Pt-CeO2 catalyst revealed high mass activity (1414.0 mA mg−1) and areal-specific activity (1.615 mA cm−2) towards MOR in an acidic electrolyte, which was three times that of the 20% Pt/C catalyst (545.4 mA mg−1 and 0.856 mA cm−2). Besides, the Pt-CeO2 catalyst exhibited excellent performance of MOR in an alkaline electrolyte and retained 90.44% of its initial mass activity after 5000 cycles due to the unique morphology and synergistic effects between Pt and CeO2. Pt-CeO2 is regarded as a promising MOR electrocatalyst for DMFC applications. Graphical Abstract

Directed evolution of viral vectors involves the generation of randomized libraries followed by artificial selection of improved variants. Directed evolution only yielded limited results in adenovirus (AdV) engineering until now, mainly due to insufficient complexities of randomized libraries. Meanwhile, clinical applications of AdVs as gene therapy or oncolytic vectors are still hampered by the predetermined tropism of natural types. To overcome this challenge, we hypothesized that randomized peptide insertions on the capsid surface can be incorporated into the AdV bioengineering toolbox for retargeting. Here we developed AdV-directed EVOlution protocols based on fiber knob peptide display. Human AdV-C5-derived libraries were constructed following three distinct protocols and selected on a panel of cancer cell lines, with the goal of identifying variants able to infect and lyse these tumor cells more efficiently. All protocols enabled the construction of high complexity libraries with up to 9.6 × 105 unique variants, an approximate 100-fold improvement compared with previously published AdV libraries. After selection, the most enriched variants, which were robustly selected in various cancer cell lines, did not display enhanced infectivity but rather more efficient replication and cell lysis. Selected inserts also conferred enhanced lysis ability to oncolytic AdVs restricted to telomerase-expressing cell lines.

ABSTRACTTo evaluate the performance of “Vaccination Rates Monitoring Report System” implemented by Shenzhen CDC, we conducted an analysis of the data quality and identify key areas for system improvement. Following evaluation guidelines provided by WHO and United States CDC, we established six evaluation attributes: representativeness, simplicity, acceptability, data reliability, stability and timeliness. In eastern, central and western regions of Shenzhen, we selected one district from each region, of which the local CDC and ten CHSCs under jurisdiction were chosen for evaluation. On-site inspections, questionnaires survey and interviews were utilized for data collection, while the Likert scale method was used for attributes rating evaluation. A total of 70 participants were surveyed, consisting of 60 CHSCs and 10 CDCs staff. The gender ratio was 1:2.5 (males to females), with the majority falling within the 25–34 age range (46%). Most participants held full-time positions (80%) and had more than 5 years of work experience (62%). The system achieved 100% coverage of all CHSCs and CDCs (100%). The cumulative percentage scores for the overall favorable options of simplicity, acceptability, data reliability, stability, and timeliness were 79%, 85%, 73%, 50%, and 71% respectively. The system operates normally with strong representativeness. Acceptability was rated as “good.” Simplicity, data reliability, and system timeliness were rated as “average,” while system stability was rated as “poor.” Based on these survey results, developers should urgently investigate reasons for poor stability, particularly addressing concerns from CHSCs users. Additionally, the issues and shortcomings identified in other attributes should also be gradually improved.

Summary: Background: Pancreatic ductal adenocarcinoma (PDAC) is a tumour entity with unmet medical need. To assess the therapeutic potential of oncolytic virotherapy (OVT) against PDAC, different oncolytic viruses (OVs) are currently investigated in clinical trials. However, systematic comparisons of these different OVs in terms of efficacy against PDAC and biomarkers predicting therapeutic response are lacking. Methods: We screened fourteen patient-derived PDAC cultures which reflect the intra- and intertumoural heterogeneity of PDAC for their sensitivity to five clinically relevant OVs, namely serotype 5 adenovirus Ad5-hTERT, herpes virus T-VEC, measles vaccine strain MV-NIS, reovirus jin-3, and protoparvovirus H-1PV. Live cell analysis, quantification of viral genome/gene expression, cell viability as well as cytotoxicity assays and titration of viral progeny were conducted. Transcriptome profiling was employed to identify potential predictive biomarkers for response to OV treatment. Findings: Patient-derived PDAC cultures showed individual response patterns to OV treatment. Twelve of fourteen cultures were responsive to at least one OV, with no single OV proving superior or inferior across all cultures. Known host factors for distinct viruses were retrieved as potential biomarkers. Compared to the classical molecular subtype, the quasi-mesenchymal or basal-like subtype of PDAC was found to be more sensitive to H-1PV, jin-3, and T-VEC. Generally, expression of viral entry receptors did not correlate with sensitivity to OV treatment, with one exception: Expression of Galectin-1 (LGALS1), a factor involved in H-1PV entry, positively correlated with H-1PV induced cell killing. Rather, cellular pathways controlling immunological, metabolic and proliferative signaling appeared to determine outcome. For instance, high baseline expression of interferon-stimulated genes (ISGs) correlated with relative resistance to oncolytic measles virus, whereas low cyclic GMP-AMP synthase (cGAS) expression was associated with exceptional response. Combination treatment of MV-NIS with a cGAS inhibitor improved tumour cell killing in several PDAC cultures and cells overexpressing cGAS were found to be less sensitive to MV oncolysis. Interpretation: Considering the heterogeneity of PDAC and the complexity of biological therapies such as OVs, no single biomarker can explain the spectrum of response patterns. For selection of a particular OV, PDAC molecular subtype, ISG expression as well as activation of distinct signaling and metabolic pathways should be considered. Combination therapies can overcome resistance in specific constellations. Overall, oncolytic virotherapy is a viable treatment option for PDAC, which warrants further development. This study highlights the need for personalised treatment in OVT. By providing all primary data, this study provides a rich source and guidance for ongoing developments. Funding: German National Science Foundation (Deutsche Forschungsgemeinschaft, DFG), German Cancer Aid (Deutsche Krebshilfe), German National Academic Scholarship Foundation (Studienstiftung des deutschen Volkes), Survival with Pancreatic Cancer Foundation.

In this paper, on the premise that the prior probability is unknown, a noise enhanced binary hypothesis-testing is investigated under the Minimax criterion for a general nonlinear system. Firstly, for lowering the decision risk, an additive noise is intentionally injected to the input and a decision is made under Minimax criterion based on the noise modified output. Then an optimization problem for minimizing the maximum of Bayesian conditional risk under an equality constraint is formulated via analyzing the relationship between the additive noise and the optimal noise modified Minimax decision rule. Furthermore, lemma and theorem are proposed to prove that the optimal noise is a constant vector, which simplifies the optimization problem greatly. An algorithm is also developed to search the optimal constant and the key parameter of detector, and further to determine the decision rule and the Bayes risk. Finally, simulation results about the original (in the absence of additive noise) and the noise-modified optimal decision solutions under Minimax criterion for a sine transform system are provided to illustrate the theoretical results.

Ischemic stroke, a devastating disease associated with high mortality and disability worldwide, has emerged as an urgent public health issue. A-kinase anchoring proteins (AKAPs) are a group of signal-organizing molecules that compartmentalize and anchor a wide range of receptors and effector proteins and have a major role in stabilizing mitochondrial function and promoting neurodevelopmental development in the central nervous system (CNS). Growing evidence suggests that dysregulation of AKAPs expression and activity is closely associated with oxidative stress, ion disorder, mitochondrial dysfunction, and blood-brain barrier (BBB) impairment in ischemic stroke. However, the underlying mechanisms remain inadequately understood. This review provides a comprehensive overview of the composition and structure of A-kinase anchoring protein (AKAP) family members, emphasizing their physiological functions in the CNS. We explored in depth the molecular and cellular mechanisms of AKAP complexes in the pathological progression and risk factors of ischemic stroke, including hypertension, hyperglycemia, lipid metabolism disorders, and atrial fibrillation. Herein, we highlight the potential of AKAP complexes as a pharmacological target against ischemic stroke in the hope of inspiring translational research and innovative clinical approaches.

Abstract Purpose This study was conducted to evaluate the prevalence and related factors of peripheral and posterior pole retinal changes in highly myopic Chinese children and adolescents. Methods A hospital-based cross-sectional study was designed. A total of 120 subjects with high myopia were recruited and underwent cycloplegic refraction, dilated fundus examination, and optical coherence tomography. A statistical analysis was performed to evaluate the factors associated with peripheral and posterior pole retinal changes. Results The mean spherical equivalent refraction of the subjects was − 8.74 ± 2.86 D, and the mean age was 11.45 ± 3.02 years. Snowflake retinal degeneration (27.5%), white without pressure (27.5%), snail-track degeneration (15%), and lattice degeneration (15%) were the most common peripheral retinal changes, while tessellated fundus (84.17%), optic nerve crescents (78.3%), and posterior staphyloma (11.7%) were the most common posterior changes. Subjects with peripheral changes were significantly older, with thinner choroids (OR = 1.194, 95% CI: 1.045–1.363, p = 0.009; OR = 0.993, 95% CI: 0.987–0.999, p = 0.022, respectively). Optic nerve crescents, tessellated fundus, and posterior scleral staphyloma were all associated with thin choroids (OR = 0.990, 95% CI: 0.983–0.997, p = 0.008; OR = 0.983, 95% CI: 0.974–0.991, p

Abstract Amorphous carbons are promising candidates as the anode materials for potassium-ion hybrid capacitors (PIHCs). The insufficient storage sites and inferior diffusion kinetics limit their potassium-ion storage capability. Edge nitrogen and morphology engineering are effective pathways to construct accessible active sites and enhanced diffusion kinetics. However, the organic integration of both pathways in amorphous carbon is still challenging. Herein, a “twice-cooking” strategy, including two-step carbonization processes at 700 °C, is designed to synthesize edge-nitrogen-rich lignin-derived carbon nanosheet framework (EN-LCNF). In the first-step carbonization process, the staged gas releases of CO and CO2 from CaC2O4 decomposition exfoliate the carbon matrix into a carbon nanosheet framework. In the second-step carbonization process, the generated CaO reacts with the cyanamide units of graphitic carbon nitride (g-C3N4) to form an edge-nitrogen-rich framework, which is then integrated into the meso-/macropores of carbon nanosheet framework through sp3-hybridized C–N bonds. EN-LCNF with a high edge-nitrogen level of 7.0 at.% delivers an excellent capacity of 310.3 mAh g−1 at 50 mA g−1, a robust rate capability of 126.4 mAh g−1 at 5000 mA g−1, and long cycle life. The as-assembled PIHCs based on EN-LCNF anode and commercial activated carbon cathode show a high energy density of 110.8 Wh kg−1 at a power density of 100 W kg−1 and excellent capacitance retention of 98.7% after 6000 cycles. This work provides a general strategy for the synthesis of edge-nitrogen-rich lignin-derived carbon materials for advanced potassium-ion storage. Graphical Abstract

Abstract Lithium‐ion batteries are widely used in portable electronics and electric vehicles due to their high energy density, stable cycle life, and low self‐discharge. However, irreversible lithium loss during the formation of the solid electrolyte interface greatly impairs energy density and cyclability. To compensate for the lithium loss, introducing an external lithium source, that is, a prelithiation agent, is an effective strategy to solve the above problems. Compared with other prelithiation strategies, cathode prelithiation is more cost‐effective with simpler operation. Among various cathode prelithiation agents, we first systematically summarize the recent progress of Li2S‐based prelithiation agents, and then propose some novel strategies to tackle the current challenges. This review provides a comprehensive understanding of Li2S‐based prelithiation agents and new research directions in the future.

In order to further improve the performance of polytetrafluoroethylene (PTFE) as lubricant additives, PTFE fiber bundles (PTFE-F) were prepared by wet spinning to enhance phenolic resin (PF), and PTFE powders (PTFE-P) were used as a contrast phase. PF-based composites were prepared by hot pressing sintering, and their tribological properties were tested by ball-on-disc friction tests. The results showed that the shore hardness and compressive strength of PF-15 wt% PTFE-F were severally 5.8 % and 58.6 % higher than that of PF-15 wt% PTFE-P. The COF of PF-15 wt% PTFE-F and PF-15 wt% PTFE-P were 0.102 and 0.088, while the wear rates were 2.53 × 10−7mm3/Nm and 1.59 × 10−4 mm3/Nm respectively, with a difference of 628 times. It has been demonstrated that the transfer film formed on the friction pair ball is multi-layer structure, which formed by the physical adhesion of PTFE and the tribochemical reaction between the PTFE and the steel ball. Therefore, the geometry effect idea can be used to fabricate a new kind of self-lubricating materials applied widely in the fields of navigation, aviation, and aerospace.

Abstract The breeding of crops with improved nitrogen use efficiency (NUE) is crucial for sustainable agriculture, but the involvement of epigenetic modifications remains unexplored. Here, we analyze the chromatin landscapes of two wheat cultivars (KN9204 and J411) that differ in NUE under varied nitrogen conditions. The expression of nitrogen metabolism genes is closely linked to variation in histone modification instead of differences in DNA sequence. Epigenetic modifications exhibit clear cultivar-specificity, which likely contributes to distinct agronomic traits. Additionally, low nitrogen (LN) induces H3K27ac and H3K27me3 to significantly enhance root growth in KN9204, while remarkably inducing NRT2 in J411. Evidence from histone deacetylase inhibitor treatment and transgenic plants with loss function of H3K27me3 methyltransferase shows that changes in epigenetic modifications could alter the strategy preference for root development or nitrogen uptake in response to LN. Here, we show the importance of epigenetic regulation in mediating cultivar-specific adaptation to LN in wheat.

The antitussive and expectorant effects of Ruanerli and its mechanism were investigated by methods of network pharmacology. The outcomes predicted were verified by molecular docking and animal experiments. The components and targets of Ruanerli were obtained by literature investigation and TCMSP database screen. Mapping with two groups of genes related to "cough" and "sputum" from GeneCards database, the target genes of antitussive and expectorant effects of Ruanerli were obtained. GO and KEGG enrichment analysis of the target genes was performed by Metascape platform. The PPI network among the target genes was constructed through STRING data platform. Cytoscape plugin CytoHubba was used to screen the Top10 genes related to antitussive and expectorant effects of Ruanerli, and KEGG pathway enrichment was performed on the Top10 genes through Metascape data platform to predict the possible signal pathways involved in antitussive and expectorant effects of Ruanerli. Autodock Vina was used for molecular docking between the predicted Top10 gene proteins and the Top 3 active ingredients of Ruanerli. Finally, the predicted results were verified by ammonia induced cough test and phenol red excretion test. According to the analysis of multiple databases, 51 chemical components and 282 corresponding targets have been reported, eighty of them were related to the antitussive and expectorant effects of Ruanerli. The Top10 genes selected by Degree value were mainly concentrated in infection and immune-related pathways. Molecular docking test showed that the Top10 genes had strong binding activity with the Top3 chemical components (Caffeic acid, Rutin and Valeraldehyde) in PPI network. Animal experiments showed that the cough induced by ammonia was significantly inhibited when treated with Ruanerli in mice. The levels of IL-6 and IL-13 in serum were reduced and the excretion of phenol red in mice trachea was increased. PCR and WB detection showed that the mRNA levels and protein expressions of inflammatory genes IL6, IL1B, VEGFA, PTGS2 and MAPK3 were decreased, suggesting that the antitussive and expectorant effects of Ruanerli might be related to decreasing the expression of inflammatory genes and the release of inflammatory factors.

Molybdenum nickel alloy has been proved to be an efficient noble-metal-free catalyst for hydrogen evolution reaction (HER) in alkaline medium, but its electrocatalytic activity and stability need to be further improved to meet industrial requirements. In this study, carboxymethylated enzymatic hydrolysis lignin (EHL) was used as a biomacromolecule frame to coordinate with transition metal ions and reduced by pyrolysis to obtain the MoNi4–NiO heterojunction (MoNi4–NiO/C). The oblate sphere structure of MoNi4–NiO/C exposed a large catalytic active surface to the electrolyte. As a result, the hydrogen evolution reaction of MoNi4–NiO/C displayed a low overpotentials of 41 mV to achieve 10 mA cm−2 and excellent stability of 100 h at 100 mA cm−2 in 1 mol L−1 KOH, which was superior to that of commercial Pt/C. Lignin assisted the formation of NiO to construct the MoNi4–NiO interface and MoNi4–NiO heterojunction structure, which reduced the energy barrier by forming a more favorable transition states and then promoted the formation of adsorbed hydrogen at the heterojunction interface through water dissociation in alkaline media, leading to the rapid reaction kinetics. This work provided an effective strategy for improving the electrocatalytic performance of noble-metal-free electrocatalysts encapsulated by lignin-derived carbon.

Sodium-ion battery (SIB) is an ideal candidate for large-scale energy storage due to high abundant sodium sources, relatively high energy density, and potentially low costs. Hard carbons, as one of the most promising anodes, could deliver high plateau capacities at low potentials, which boosts the energy densities of SIBs. Their slope capacities have been demonstrated from the defect adsorption of sodium ions, while the plateau capacity depends highly on intercalation and pore filling. Nevertheless, the specific structures of sodium ions stored in hard carbons have not been clarified, namely active sites of adsorption, intercalation, and pore-filling mechanisms. Therefore, delicate synthesis methods are required to prepare hard carbons with controllable specific structures, along with elucidating the precise active sites for enhancing the Na-ion storage performance. To offer databases for future designs, we summarized the synthesis strategies of hard carbon anodes for constructing active sites of plateau capacities. Synthesis methods were highlighted with corresponding influences on the meticulous structures of hard carbons and Na-ion storage behaviors. Last but not least, perspectives were proposed for developing hard carbon anodes from the points of research and practical applications.

Lactic acid bacteria (LAB) belong to a significant group of probiotic bacteria that provide hosts with considerable health benefits. Our previous study showed that pigs with abundant LAB had more robust immune responses in a vaccination experiment. In this study, 52 isolate strains were isolated from the pigs with superior immune responses. Out of these, 14 strains with higher antibacterial efficacy were chosen. We then assessed the probiotic features of the 14 LAB strains, including such as autoaggregation, coaggregation, acid resistance, bile salt resistance, and adhesion capability, as well as safety aspects such as antibiotic resistance, hemolytic activity, and the presence or absence of virulence factors. We also compared these properties with those of an opportunistic pathogen EB1 and two commercial probiotics (cLA and cLP). The results showed that most LAB isolates exhibited higher abilities of aggregation, acid and bile salt resistance, adhesion, and antibacterial activity than the two commercial probiotics. Out of the 14 strains, only LS1 and LS9 carried virulence genes and none had hemolytic activity. We selected three LAB strains (LA6, LR6 and LJ1) with superior probiotic properties and LS9 with a virulence gene for testing their safety in vivo. Strains EB1, cLA and cLP were also included as control bacteria. The results demonstrated that mice treated LAB did not exhibit any adverse effects on weight gain, organ index, blood immune cells, and ileum morphology, except for those treated with LS9 and EB1. Moreover, the antimicrobial effect of LR6 and LA6 strains was examined in vivo. The results indicated that these strains could mitigate the inflammatory response, reduce bacterial translocation, and alleviate liver, spleen, and ileum injury caused by Salmonella typhimurium infection. In addition, the LR6 treatment group showed better outcomes than the LA6 treatment group; treatment with LR6 substantially reduced the mortality rate in mice. The study results provide evidence of the probiotic properties of the LAB isolates, in particular LR6, and suggest that oral administration of LR6 could have valuable health-promoting benefits.