Objective To investigate the microbial disinfection and sterilization effectiveness of an electron linear accelerator on the surface and interior of postal packages, and to design and conduct a penetrating radiation disinfection and sterilization experiment. Methods This experiment selected Bacillus pumilus E601 (ATCC 27142) as the indicator microbial strain for radiation. An experimental model of postal package was subjected to penetrating radiation with different dose gradients using high-energy electron beams generated by an S-band 10 MeV electron linear accelerator. The disinfection and sterilization effectiveness was assessed by culturing and counting B. pumilus after high-energy electron beam radiation treatment. A control group was established to analyze the influence of actual absorbed doses at different gradients on the disinfection and sterilization effectiveness of the electron linear accelerator. Results The actual absorbed doses of high-energy electron-beam radiation required to achieve 1-, 3-, and 6-log reductions of B. pumilus were 1.63, 5.07, and 10.22 kGy, respectively. Complete inactivation was achieved at an absorbed dose of 10.92 kGy, which met the processing requirements specified in the technical standard for ionizing-radiation disinfection. Conclusion The experimental data indicated that the actual absorbed dose for B. pumilus is linearly positively correlated with the log reduction of bacterial colonies killed by electron beam radiation. For disinfection and sterilization requirements in different scenarios, the required actual absorbed dose can be achieved by dynamically adjusting the operating speed of the under-beam transmission system.

Objective To understand the epidemiological characteristics of a clustered outbreak of severe fever with thrombocytopenia syndrome(SFTS)as well as the ecological tick monitoring results for Zibo City, and to provide a scientific basis for formulating prevention and control strategies. Methods A case definition was cited before epidemic investigations were performed. Epidemiological investigations were performed on the index cases and their close contacts. Blood samples were collected from cases and close contacts, and quantitative real-time RT-PCR was used to detect SFTS virus(SFTSV)nucleic acid sequences. A retrospective cohort study was conducted to analyze risk factors and develop prevention and control strategies. Results This clustered outbreak involved two index cases and six close contacts with no deaths. Case A exhibited symptom onset on July 26. SFTS was confirmed on August 2. Case B exhibited symptom onset on August 1, and SFTS was confirmed on August 3. Patient B reported a recent history of tick bites. In both index cases, the incubation period for SFTS was inferred to be 7-12 days. The time interval from symptom onset to clinical diagnosis in the two cases ranged from 2-8 days, with an average period of 5 days. SFTSV nucleic acid test result were positive for both patients, whereas all six close contacts tested negative. All captured ticks tested negative for SFTSV using quantitative real-time RT-PCR. The densities of parasitic and free-living ticks in the emergency monitoring area around the cases were 12.60 and 4.65 ticks/(flag·100 m). In 2024, the average parasitic tick index and free-living tick density index were 4.21 and 2.43 ticks/(flag ·100 m)in Yiyuan County, respectively. Conclusions No evidence of human-to-human transmission was found in the assessed SFTS clusters. The infections were likely acquired through tick bites during fieldwork, and the risk of a subsequent outbreak spreading was low.

ObjectiveTo investigate the possible mechanism of Shufeng Jiedu capsules （SFJD） in alleviating influenza A （H1N1） virus pneumonia and focus on its effect on Toll-like receptor （TLR） signaling pathway in respiratory epithelial cells. MethodsA mouse model of viral pneumonia was established via the A/PR/8/34 （PR8） strain of influenza A virus. Mice were randomly divided into a normal group， a PR8 infection （PR8） group， and an SFJD group （8.4 g·kg^-1）， with 10 mice in each group. The day of infection was designated as day 1. The SFJD group was administered intragastrically at a volume of 20 mL·kg^-1 daily， while the normal and PR8 groups were given an equal volume of deionized water. Micro-computed tomography （Micro-CT） was performed on day 5， and the mice were dissected to collect their lungs， after which the lung index was calculated to verify the therapeutic effect of SFJD. Single-cell sequencing was used to analyze the differentially expressed genes in respiratory epithelial cells. Multiplex fluorescence immunohistochemistry was employed to detect the expression of TLR， tumor necrosis factor receptor-associated factor 6 （TRAF6）， and myeloid differentiation factor 88 （MyD88） proteins in epithelial cell adhesion molecule （EpCAM）-positive cells， and the proportion of respiratory epithelial cells expressing TLR pathway proteins was calculated. Respiratory epithelial cells were then sorted by flow cytometry， and Western blot was used to detect the expression of TLR， MyD88， TRAF6， Toll-interleukin receptor domain-containing adaptor inducing interferon-β （TRIF）， inhibitor of κB kinase α （IKKα）， and nuclear factor-κB （NF-κB） in the sorted epithelial cells. Enzyme-linked immunosorbent assay （ELISA） was used to measure the levels of interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α） in lung tissue. ResultsAt the transcriptional level， SFJD reversed the expression of TLR signaling pathway genes in respiratory epithelial cells， downregulating multiple TLR signaling pathway-related genes （P<0.01）. At the protein level， SFJD significantly reduced the proportion of respiratory epithelial cells expressing TLR3 （P<0.05）， the expression levels of TLR2， TLR3， TLR4， TRIF， TRAF6， IKKα， and NF-κB in epithelial cells（P<0.05， P<0.01）， as well as the levels of pro-inflammatory cytokines IL-1β and TNF-α in lung tissue （P<0.01）. ConclusionSFJD may alleviate viral pneumonia by suppressing the expression of TLR in respiratory epithelial cells and their subsequent signaling cascades.

ObjectiveTo evaluate the pharmacological effects of verbenalin on both in vitro and in vivo infection models of human coronavirus 229E （HCoV-229E） and to preliminarily explore the antiviral mechanism of verbenalin through proteomic analysis. MethodsIn vitro， the cell counting kit-8 （CCK-8） for cell proliferation and viability assessment was used to establish a model of HCoV-229E-induced injury in human lung adenocarcinoma cells（A549）. A549 cells were divided into five groups： normal group， model group， and three verbenalin treatment groups （125， 62.5， and 31.25 μmol·L^-1）. The cell protective activity of verbenalin was evaluated through cell viability assay and immunofluorescence staining. In vivo， 30 BALB/c mice were randomly divided into normal group， model group， chloroquine group， and high-dose， low-dose verbenalin groups （40 and 20 mg·kg^-1）， with six mice per group. An HCoV-229E-induced mouse lung injury model was established to evaluate the therapeutic effects of verbenalin. Lung injury was assessed by detecting the lung index and lung inhibition rate. The severity of pulmonary inflammation cytokines was measured by enzyme-linked immunosorbent assay （ELISA）， while the lung morphology and structure were analyzed by micro-computed tomography （Micro-CT）. Hematoxylin and eosin （HE） staining was used to assess histopathological changes in lung tissue. Additionally， four-dimensional data-independent acquisition （4D-DIA） proteomics was employed to preliminarily explore the potential mechanisms of verbenalin in treating HCoV-229E-induced lung injury in mice， through differential protein expression screening， functional annotation， enrichment analysis， and protein-protein interaction network analysis. ResultsThe A549 cells were infected with HCoV-229E at the original viral titer for 36 hours to establish an in vitro infection model. The maximum non-toxic concentration of verbenalin was 125 μmol·L^-1， and the half-maximal cytotoxic concentration （CC₅₀） was 288.8 μmol·L^-1. Compared with the normal group， the model group showed a significant decrease in cell viability （P<0.01）， a significant increase in the proportion of dead cells （P<0.01）， mitochondrial damage， and a significant reduction in mitochondrial membrane potential （P<0.01）. After treatment with different concentrations of verbenalin （125， 62.5， and 31.25 μmol·L^-1）， cell viability was significantly increased （P<0.01）， and the proportion of dead cells was reduced （P<0.01）， with mitochondrial membrane potential restored （P<0.01）. In vivo experiments further confirmed the therapeutic effect of verbenalin on HCoV-229E-infected mice. Compared to the normal group， the model group showed a significant increase in the lung index （P<0.01）， severe lung tissue injury， lung volume enlargement， and a significant increase in the expression of inflammatory cytokines， including interleukin-6 （IL-6） and tumor necrosis factor-α （TNF-α） （P<0.01）. In contrast， in the verbenalin treatment groups， these pathological changes were significantly improved， with a reduction in the lung index （P<0.01）， alleviation of lung tissue injury， reduced lung volume enlargement， and a significant decrease in inflammatory cytokine expression （P<0.01）. Proteomics analysis revealed that， compared to the normal group， the model group showed enrichment in several antiviral immune-related signaling pathways， including the nuclear factor-κB （NF-κB） signaling pathway （P<0.05）. Compared to the model group， the verbenalin treatment group showed enrichment in several signaling pathways related to inflammatory response and autophagy （P<0.05）， suggesting that verbenalin may exert its antiviral and anti-inflammatory effects by regulating these pathways. ConclusionVerbenalin demonstrates significant therapeutic effects in both in vitro and in vivo HCoV-229E infection models， with its mechanism likely related to the NOD-like receptor protein 3 （NLRP3） inflammasome pathway and mitochondrial autophagy.

ObjectiveTo study the anti-inflammatory and immunomodulatory effects of Shufeng Jiedu capsules in a mouse model infected with human coronavirus 229E （HCoV-229E）. MethodsForty-eight BALB/c mice were randomly divided into a normal group， a model group， a chloroquine positive group （0.075 8 g·kg^-1）， and high-dose， medium-dose， and low-dose groups of Shufeng Jiedu capsules （1.872、0.936、0.468 g·kg^-1）， with eight mice in each group. The coronavirus infection model was established by intranasal infection with the HCoV-229E virus solution. On the fourth day after infection， the mice were killed by cervical dislocation. The pathological changes in the lung were evaluated by weighing the wet weight of the lung and calculating the lung index. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot （WB） techniques were used to detect the expression levels of key genes and proteins such as Toll-like receptor 4 （TLR4）， Toll/interleukin-1 receptor （TIR）-domain-containing adapter inducing interferon-β （TRIF）， tumor necrosis factor receptor-associated factor 6 （TRAF6）， TANK-binding kinase 1 （TBK1）， phospho-TANK-binding kinase 1 （p-TBK1）， interferon regulatory factor 3 （IRF3）， and phospho-interferon regulatory factor 3 （p-IRF3） in lung tissue. ResultsCompared with that in the normal group， the lung index of the mice in the model group was significantly increased （P<0.01）. There was a large amount of inflammatory exudation in the pulmonary interstitium， and the expression of TLR4， TRIF， TRAF6， TBK1， p-TBK1， IRF3， and p-IRF3 proteins was significantly increased （P<0.01）， indicating that HCoV-229E caused severe pulmonary inflammation. Compared with the model group， Shufeng Jiedu capsules at each dose significantly reduced the lung index of mice （P<0.01）， among which the lung index inhibition rate of the high-dose and medium-dose groups was 78.18% and 79.27%. At the same time， Real-time PCR and WB results showed that the medium-dose Shufeng Jiedu capsules significantly reduced the gene and protein expression levels of TLR4， TRIF， TRAF6， TBK1， p-TBK1， and p-IRF3 （P<0.05）. ConclusionShufeng Jiedu capsules can alleviate lung inflammation and tissue injury caused by coronavirus infection by inhibiting the excessive activation of the TLR4/TRIF/TBK1 signaling pathway.

Thirty SPF Kunming male mice aged 6-8 weeks were randomly divided into five groups:the control group,the model group,and the low,medium,and high dose groups of Dilong.Except for the control group,the other mice were continuously injected intraperitoneally with 80 mg/kg cyclophosphamide for 3 days to prepare an immunosuppressive model.After the model-ing was completed,the control group and the model group were given an equal amount of physio-logical saline by gavage,while the low,medium,and high dose Dilong groups were given 100,200,and 400 mg/kg of Dilong fermented material by gavage,respectively.The treatment lasted for 14 days,and thymus,spleen,blood,and intestinal contents were collected 2 hours after the last admin-istration.The results showed that cyclophosphamide caused a weight loss in mice during the exper-iment,reduced thymus index,white blood cells,lymphocytes,granulocytes,immunoglobulin levels in the blood,and disrupted gut microbiota.Dilong fermented material can effectively improve the decrease in body weight and thymus index of mice,increase the levels of immune cells and immu-noglobulin in the blood,improve the diversity and richness of intestinal microbiota,and increase the abundance of beneficial bacteria.Dilong fermented can effectively alleviate the immune suppres-sion and intestinal microbiota disorder caused by cyclophosphamide in mice.Considering all fac-tors,the optimal dosage is 200 mg/kg.

Five meroterpenoids, rhodonoids K-M (1-2), daurichromene E (3), and grifolins A-B (4-5), together with seven known compounds (6-12), were isolated from Rhododendron anthopogonoides. The chemical structures of these compounds were elucidated through comprehensive analysis of high-resolution electrospray ionization mass spectrometry (HR-ESI-MS), ultraviolet (UV), infrared spectroscopy (IR), and nuclear magnetic resonance (NMR) data. Their absolute configurations were determined by comparing experimental electronic circular dichroism (ECD) spectra with computed values. Notably, compounds 1 and 3 demonstrated significant inhibitory effects on lipopolysaccharide (LPS)-induced inflammation in RAW264.7 cells. These compounds markedly suppressed the mRNA expressions of inflammatory factors, including interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α) while also down-regulating the protein expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2).
Mice ; Rhododendron/chemistry* ; Animals ; Anti-Inflammatory Agents/isolation & purification* ; RAW 264.7 Cells ; Terpenes/isolation & purification* ; Molecular Structure ; Tumor Necrosis Factor-alpha/immunology* ; Cyclooxygenase 2/immunology* ; Nitric Oxide Synthase Type II/immunology* ; Macrophages/immunology* ; Interleukin-6/immunology* ; Lipopolysaccharides ; Interleukin-1beta/immunology*

Human cytomegalovirus (HCMV) poses a significant risk of neural damage during pregnancy. As the most prevalent intrauterine infectious agent in low- and middle-income countries, HCMV disrupts the development of neural stem cells, leading to fetal malformations and abnormal structural and physiological functions in the fetal brain. This review summarizes the current understanding of how HCMV infection dysregulates the Wnt signaling pathway to induce fetal malformations and discusses current management strategies.
Humans ; Cytomegalovirus Infections/virology* ; Wnt Signaling Pathway ; Pregnancy ; Female ; Cytomegalovirus/physiology* ; Pregnancy Complications, Infectious/virology* ; Congenital Abnormalities/virology* ; Animals

In order to investigate the effects of Fuzi Lizhong Oral liquid on immune function and in-testinal health of chicks,185 1-day-old healthy chicks were randomly divided into 4 groups.The blank control group(CG group)was given normal tap water;the high,medium and low dose groups(FZH group,FZM group and FZL group)were given tap water containing 5.00,2.50 and 1.25 g/L of Fuzi Lizhong Oral liquid,respectively.Starting from the first day of age,the drug was administered continuously for 5 d,and the blood was collected from the subwing vein on the sixth day of the test.The results showed that compared with CG group,thymus index in FZH group was significantly increased(P＜0.05).Compared with CG group,serum IgM,IgG and sIgA in FZH group were significantly increased(P＜0.05),and serum IgG and sIgA in FZM group were signifi-cantly increased(P＜0.05).Compared with CG group,the relative expression of Occludin and Claudin-1 mRNA in FZH group was significantly increased(P＜0.05),and the relative expression of ZO-1 mRNA in FZM and FZH groups was significantly increased(P＜0.05).Compared with CG group,Shannon index of FZH group was significantly increased(P＜0.05),Simpson index of FZH group was significantly decreased(P＜0.05),and many beneficial bacteria such as Strepto-coccus spinosus,Eubacillus spinosus and Lactobacillus spinosus played a synergistic role.The results showed that adding 5.00 g/L Fuzi Lizhong Oral liquid in drinking water could improve the immunity of chicks,maintain the intestinal barrier function of chicks,increase the intestinal flora richness and promote the intestinal health of chicks.