BACKGROUND:Patellar tendonitis can present as tendon degeneration that fails to heal due to tissue overload and incomplete recovery.Patellar tendonitis is a predisposition to high jumping and its pathogenesis has not been clearly defined.OBJECTIVE:To explore the stress-strain relationship of patellar tendon in the take-off technique of high jump through the finite element model with accurate human anatomical structure,so as to provide ideas for the prevention and rehabilitation of patellar tendinitis.METHODS:Based on the CT and MRI imaging data of the lower extremity(including the knee and ankle)of one subject(22 years old,183 cm height,70 kg body mass),a three-dimensional finite element model of the lower extremity was reconstructed using medical imaging software,reverse engineering software and modeling software.The plantar pressure of the take-off leg was collected in eight subjects by gait testing system,and the technical action of high jump take-off was collected by motion capture system.The captured data were imported into human sports biomechanics software for analysis,and kinematic and kinetic data were obtained as the boundary conditions of finite element model for finite element simulation analysis.RESULTS AND CONCLUSION:The force borne by the patellar tendon reached 3.29 times of its own body mass when the subjects took off.In the take-off stage,the peak values of normal equivalent stress,strain and shear stress of the patellar tendon were 127.76 MPa,0.81 and 37.69 MPa,respectively,which were in the nonlinear region of the stress-strain curve,and the peak values were distributed in the proximal and posterior parts of patellar tendon.To conclude,the high patellar tendon force,strain and shear stress caused by the load of 3.29 times its own body mass during take-off are related to the induction of patellar tendinitis.

ObjectiveTo evaluate the antitumor activity of Periplaneta americana extract（PAE） against human-derived lung adenocarcinoma organoids（LUAD-PDOs） and to elucidate its potential mechanism based on transcriptomics. MethodsFresh tumor and adjacent normal tissues from patients with LUAD were collected to construct LUAD-PDOs and normal lung organoid（Nor-PDOs） models using 3D organoid culture technology. The effective intervention concentration of PAE was determined using the cell counting kit-8（CCK-8） assay. Experimental groups included the model group（LUAD-PDOs）， normal group， model administration group（LUAD-PDOs+PAE）， and normal administration group（Nor-PDOs+PAE）. Hematoxylin-eosin（HE） staining was used to observe the pathological structures of PDOs， immunohistochemistry（IHC） was performed to detect the expressions of the proliferation marker Ki-67 and lung adenocarcinoma differentiation markers cytokeratin-7（CK-7） and Napsin A， TUNEL staining was applied to detect cell apoptosis. RNA sequencing（RNA-Seq） was conducted to identify differentially expressed genes（DEGs）， followed by Gene Ontology（GO）， Kyoto Encyclopedia of Genes and Genomes（KEGG）， and Gene Set Enrichment Analysis（GSEA）， alongside protein-protein interaction（PPI） network analysis to screen core mechanisms. Finally， key targets were validated by integrating external database analysis with immunofluorescence（IF）. ResultsNor-PDOs and LUAD-PDOs that highly recapitulated the pathological characteristics of the primary tissues were successfully established. The CCK-8 assay determined that the effective intervention concentration of PAE was 16 g·L^-1. Morphological observation showed that Nor-PDOs exhibited lumen-forming structures， whereas LUAD-PDOs displayed dense， solid structures. CCK-8 and TUNEL assays revealed that， compared with the model group， PAE intervention inhibited the proliferation of LUAD-PDOs and promoted apoptosis in LUAD cells， while showing no significant effect on the viability of Nor-PDOs. Transcriptomic analysis identified 719 DEGs that were significantly reversed after PAE intervention（347 up-regulated and 372 down-regulated）（P<0.05）. GO enrichment analysis indicated that DEGs in the model administration group were significantly enriched in biological processes related to cell cycle regulation compared to the model group. KEGG pathway analysis revealed that PAE affected pathways related to proliferation and metabolism， including pathways in cancer and the p53 signaling pathway. GSEA further confirmed that PAE significantly enhanced the activity of the p53 signaling pathway（P<0.05）. PPI network analysis indicated that breast cancer type 1 susceptibility protein（BRCA1） and checkpoint kinase 1（CHEK1） were the core down-regulated targets in the p53 pathway. IF verified the high expression of BRCA1 and CHEK1 in LUAD-PDOs and their significant downregulation after PAE intervention（P<0.05）. Furthermore， survival analysis based on The Cancer Genome Atlas（TCGA） database indicated that low expression of BRCA1 and CHEK1 was significantly associated with prolonged overall survival in patients with LUAD（P<0.05）. ConclusionPAE effectively inhibits proliferation of LUAD-PDOs and promotes their apoptosis， its anti-tumor mechanism is potentially associated with the activation of the p53 signaling pathway， with BRCA1 and CHEK1 genes likely serving as key downstream targets for the effects of PAE.

ObjectiveThe malaria parasites remodel the host erythrocyte structure by exporting parasite proteins that interact with the membrane skeleton proteins of red blood cells (RBCs), facilitating their intracellular survival and pathogenicity. Skeleton-binding protein 1 (SBP1) is a conserved exported protein across Plasmodium species. In Plasmodium falciparum, SBP1 has been reported to interact with erythrocyte membrane skeleton proteins 4.1R and spectrin, while its contribution to erythrocyte remodeling and parasite virulence in Plasmodium berghei (Pb) remains unclear. This study aims to determine whether PbSBP1 associates with the host cytoskeletal protein 4.1R and to investigate its role in the remodeling of host RBCs and the pathogenicity of Plasmodium berghei. MethodsIn Plasmodium berghei, the relationship between PbSBP1 and the erythrocyte cytoskeletal protein 4.1R was examined using co-immunoprecipitation. A Pbsbp1 gene knockout mutant of Plasmodium berghei (Pbsbp1∆) was generated based on the principle of double crossover homologous recombination. The deformability of erythrocytes infected with Pbsbp1∆ parasites was assessed using microfluidic methods. Microchannels with an array of cylindrical pillars were used to detect modifications in infected RBC deformability. The infected RBCs were squashed between the rows and recovered between the columns and the transit velocity (μm/s) of infected RBCs travelling through the microchannel was recorded. The component of the erythrocyte membrane skeleton junctional complex, tropomodulin (TMOD), was fluorescently labeled, and the cytoskeletal network of infected erythrocytes was imaged using super-resolution stochastic optical reconstruction microscopy (STORM) to analyze ultrastructural changes in the cytoskeleton of wild-type (WT) and Pbsbp1∆-infected erythrocytes. Actin-based junctional complexes were displayed as individual clusters by the labeled TMOD in the STORM images, and the cluster densities and distances between adjacent clusters of infected RBCs were calculated. Additionally, rodent malaria models (BALB/c mice) and experimental cerebral malaria models (C57BL/6 mice) were employed to monitor the growth of Pbsbp1∆ and WT parasites during the intraerythrocytic stage and their capacity to induce cerebral malaria in mice. ResultsPbSBP1 may participate in the remodeling of infected erythrocytes through direct or indirect interaction with the erythrocyte cytoskeletal protein 4.1R. Microfluidic assays revealed that the deformability of erythrocytes infected with Pbsbp1∆ parasites was significantly enhanced compared to those infected with WT parasites. STORM imaging further demonstrated that the ultrastructure of the erythrocyte cytoskeleton in Pbsbp1∆-infected cells was altered relative to that in WT-infected erythrocytes. The distances between nearest neighbors of clusters had a tendency to increase while the cluster densities were decreased in Pbsbp1∆-infected RBCs compared to WT-infected RBCs. Subsequent phenotypic analysis indicated that the growth rate of Pbsbp1∆ parasites during the intraerythrocytic stage was significantly slower than that of WT parasites, and their ability to induce cerebral malaria in mice was also attenuated. These findings suggest that PbSBP1 is involved in the remodeling of the erythrocyte membrane skeleton, likely through its direct or indirect interaction with protein 4.1R, thereby regulating the deformability of infected erythrocytes and influencing the pathogenicity of the blood-stage parasites. ConclusionThis study establishes a role for PbSBP1 in host erythrocyte remodeling and parasite virulence, providing new research strategies for the prevention and treatment of malaria.

Olfactory receptors (ORs) form the largest superfamily of G protein-coupled receptors (GPCRs). Traditionally recognized for their role in the nasal olfactory epithelium, where they mediate the sense of smell, accumulating evidence has firmly established their ectopic expression in non-olfactory tissues, including the intestine, lungs, and kidneys. The intestine, as the primary site for nutrient digestion and absorption, harbors a highly complex chemical environment. To adapt to this environment, the gut employs a sophisticated network of “chemosensors” to monitor luminal contents and maintain homeostasis. Among these sensors, intestinal ORs have emerged as crucial functional components, serving as a molecular bridge that connects environmental chemical signals—such as food-derived odorants—to specific physiological responses. This discovery has significantly deepened our understanding of how dietary flavors and compounds influence intestinal physiology at the molecular level. This review systematically summarizes the expression profiles, ligand classification, and biological functions of ORs within the gastrointestinal tract. Studies indicate that intestinal ORs exhibit distinct spatial distribution patterns across different gut segments and display cell-type specificity, particularly within enterocytes and enteroendocrine cells. These receptors function as versatile sensors capable of recognizing a wide variety of ligands, including exogenous dietary components, gut microbiota metabolites such as short-chain fatty acids, and endogenous small molecules like azelaic acid. Upon activation by specific ligands, intestinal ORs trigger intracellular signaling cascades, primarily involving the AC-cAMP-PKA pathway or calcium influx channels. A major focus of this review is to elucidate the molecular mechanisms by which these receptors regulate the secretion of gut hormones. Activation of specific ORs in enteroendocrine cells has been shown to stimulate the release of hormones such as glucagon-like peptide-1 (GLP-1), peptide YY (PYY), and serotonin (5-HT), thereby modulating systemic energy metabolism, glucose homeostasis, and gastrointestinal motility. Furthermore, the review addresses the critical roles of ORs in immune regulation and pathology. Evidence suggests that specific ORs contribute to the maintenance of intestinal immune homeostasis and may offer protection against inflammation. Beyond their involvement in inflammatory responses, ORs such as Olfr78 have been shown to regulate the differentiation and function of intestinal endocrine cells. Similarly, Olfr544 has been demonstrated to alleviate intestinal inflammation by remodeling the gut microbiome and metabolome. These findings collectively suggest that specific ORs hold promise as therapeutic targets for mitigating intestinal inflammation and maintaining gut homeostasis. Additionally, the review explores the emerging role of ORs in cancer. Although OR expression is often downregulated in tumor tissues compared to normal mucosa, activation of specific ORs by certain ligands can inhibit tumor cell proliferation and migration and induce apoptosis via pathways such as MEK/ERK and p38 MAPK. Conversely, other receptors, such as OR7C1, may serve as biomarkers for cancer-initiating cells. In conclusion, intestinal ORs represent a vital component of the gut’s sensory network. The review also discusses the translational potential of these findings. By elucidating the precise pairing relationships between dietary components and specific ORs, novel therapeutic strategies could be developed. Intestinal ORs may thus emerge as promising targets for nutritional and pharmacological interventions in metabolic diseases, inflammatory bowel diseases, and malignancies.

BACKGROUND:Patellar tendonitis can present as tendon degeneration that fails to heal due to tissue overload and incomplete recovery.Patellar tendonitis is a predisposition to high jumping and its pathogenesis has not been clearly defined.OBJECTIVE:To explore the stress-strain relationship of patellar tendon in the take-off technique of high jump through the finite element model with accurate human anatomical structure,so as to provide ideas for the prevention and rehabilitation of patellar tendinitis.METHODS:Based on the CT and MRI imaging data of the lower extremity(including the knee and ankle)of one subject(22 years old,183 cm height,70 kg body mass),a three-dimensional finite element model of the lower extremity was reconstructed using medical imaging software,reverse engineering software and modeling software.The plantar pressure of the take-off leg was collected in eight subjects by gait testing system,and the technical action of high jump take-off was collected by motion capture system.The captured data were imported into human sports biomechanics software for analysis,and kinematic and kinetic data were obtained as the boundary conditions of finite element model for finite element simulation analysis.RESULTS AND CONCLUSION:The force borne by the patellar tendon reached 3.29 times of its own body mass when the subjects took off.In the take-off stage,the peak values of normal equivalent stress,strain and shear stress of the patellar tendon were 127.76 MPa,0.81 and 37.69 MPa,respectively,which were in the nonlinear region of the stress-strain curve,and the peak values were distributed in the proximal and posterior parts of patellar tendon.To conclude,the high patellar tendon force,strain and shear stress caused by the load of 3.29 times its own body mass during take-off are related to the induction of patellar tendinitis.

Foodborne illnesses caused by Salmonella pose significant threats to worldwide public health safety.In this study,a rapid method for screening viable Salmonella in oyster sauce and milk was developed by utilizing an electronic microbial growth analyzer(EMGA).Target food samples were diluted 10-fold with RVS broth and loaded into test tubes.Test tubes were positioned in the EMGA to determine the bacterial growth curves and the time required to reach the maximum growth rate(Tmgr).Using Salmonella typhimurium(S.typhimurium)asan model species,there was linear relationship between the logarithmic value of viable bacterial concentration(lgC)and Tmgr over the range of 5×101-5×106 CFU/mL,with a detection limit of 10 CFU/mL.For oyster sauce,the regression equation was Tmgr(min)=-80.775lg[C/(CFU/mL)]+754.96(R2=0.9907),and the recovery rates of S.typhimurium ranged from 95.2%to 119.8%,with relative standard deviations(RSD)ranging from 3.5%to 16.3%.For milk,the regression equation was Tmgr(min)=-71.922 lg[C/(CFU/mL)]+618.65(R2=0.9985),with recovery rates ranging from 98.4%to 110.6%and RSD ranging from 6.4%to 12.8%.The EMGA method required only one portable instrument,and involving only three manual steps,i.e.,dilution,transfer,and insertion.When S.typhimurium contamination reached 106 CFU/mL,the total time consumption,from the unwrapping of samples to the readout of bacterial concentration,was no more than 7 h.When applied to detection of actual oyster sauce and milk samples,the new method demonstrated strong consistency with plate counting results in positive detection rates.This method was superior to the plate counting method,which was generally considered as a gold standard,in terms of accuracy,precision,simplicity and efficiency,representing a promising alternative for the on-site screening and quantification of viable Salmonella in oyster sauce and milk products.

Aim To study the protective effect of the silibinin derivative Sil-1 on acute myocardial ischemia in SD rats and its mechanism of action.Methods Af-ter 18 hours of oxygen-glucose deprivation and treat-ment of H9c2 cells,the protective effect of Sil-1 on rat cardiomyocytes was examined.SD rats were treated 30 minutes before surgery,followed by 24 h ligation of the left anterior descending coronary artery.The cardiopro-tective effects of Sil-1 and its mechanisms for improving myocardial ischemic injury were investigated using pro-teomics technology.Results In vitro,compared with the control group,the activity of H9c2 cells in the mod-el group showed reduced cell viability,increased dead cells,elevated ROS and higher levels of LDH and in-flammatory cytokines TNF-α,IL-1β and IL-6 in the culture medium.Sil-1 could improve the above condi-tions to different degrees.In vivo,compared with the control group,rats in the model group showed signifi-cantly higher T waves on electrocardiogram,significant ischemic areas in the heart section,disorganized ar-rangement of cardiomyocytes,increased inflammatory factor infiltration and elevated CK,CK-MB,LDH and inflammatory factors TNF-α,IL-6 and IL-1β.Besides,NF-κB phosphorylation levels in myocardial tissue in-creased.Sil-1 improved the above conditions to varying degrees.The results of proteomics showed that 90 pro-teins were found between the control vs model group and the Sil-1 vs model group,and KEGG enrichment a-nalysis showed that MAPK,chemokines,VEGF and other signaling pathways were abundant.Western blot results showed that Sil-1 blocked the phosphorylation of ERK,JNK and p38 MAPK.Conclusions Sil-1 inhib-its the MAPK pathway by blocking the phosphorylation of JNK,ERK,and p38 MAPK,and achieves a protec-tive effect on rats with acute myocardial infarction.

Objective To investigate the effect of epifriedelanol(Epi)on gene expression of P-glycoprotein(P-gp)in human colorectal adenocarcinoma cell line LS174T and its mechanism.Methods LS174T cells were divided into control group and experimental-L,-M,-H groups.Experimental-L,-M,-H groups were treated with 5,10,20 μmol·L-1 Epi,respectively.Control group was treated with 0.1％dimethyl sulfoxide.Polymerase chain reaction was used to detect the mRNA expression level of P-gp.Theeffect of Epi on multidrug resistance protein 1(MDR1/P-gp)luciferase activity was investigated by pregnane X receptor(PXR)-MDR1/P-gp dual luciferase reporter gene assay.In addition,Western Blot was used to detect the protein expression level of P-gp and the nuclear factor-κB(NF-κB)pathway related proteins.Results The relative expression levels of P-gp mRNA in experimental-M,-H groups and control group were 52.24±5.19,23.00±3.52 and 100.00±9.00;the relative expression levels of P-gp protein were 86.37±9.96,74.85±15.92 and 100.00±12.91;the relative activities P-gp luciferase were 230.19±41.32,203.10±52.84 and 279.67±19.20;the relative expression levels of p65(RelA/p65)in nucleus were 132.36±23.93,145.96±25.15 and 100.00±10.88;the relative expression levels of phosphorylation NF-κB inhibits protein kinase α/β(p-IKKα/β)in cytoplasm were 184.00±54.82,290.10±49.59 and 100.00±15.34;the relative expression levels of phosphorylated NF-κB inhibitory protein α(p-IκBα)in cytoplasm were 125.73±18.77,133.69±20.25 and 100.00±8.12;the relative expression levels of IκBα in cytoplasm were 78.36±14.83,70.44±14.57 and 100.00±22.82,respectively.The above indexes of experimental-M and experimental-H groups were compared with control group,and the differences were statistically significant(P＜0.05,P＜0.01,P＜0.001).Conclusion Epi can down-regulate the gene expression of P-gp in human colorectal adenocarcinoma cell line LS174T,and the mechanism may be related to activation of NF-κB and suppression of PXR.

Objective To explore the solution of local water-fat separation swap artifacts(WFS-SA)on nasopharyngeal T1WI-itera-tive decomposition of water and fat with echo asymmetry and least-squares estimation(T1WI-IDEAL)enhanced examination images.Methods Thirty-seven patients with obvious WFS-SA on nasopharyngeal enhanced examination using the A group T1WI-IDEAL param-eters were collected.Scans with modified parameters B,C,and D groups were subsequently performed based on the A group parame-ters.Subjective ratings of image quality were conducted on the four image groups,and the image signal-to-noise ratio(SNR)of the posterior wall of the nasopharynx and medulla oblongata was quantified.The total number of artifact slices(TAS),total artifact area(TAA),and maximum single-slice artifact area(SSAAmax)of the WFS-SA in the four image groups were recorded.The consistency of image quality ratings between the two technologists was analyzed via the intraclass correlation coefficient(ICC),and one-way analysis of variance or rank-sum test was used to compare the SNR,TAS,TAA,and SSAAmax among the four image groups.Results The subjective rating for modified B,C,and D groups of T1WI-IDEAL images by two technologists was deemed satisfactory(ICC=0.721-0.928,P<0.001).Significant variations in image quality ratings were observed among the three groups(H=45.131,P<0.001),with ratings for C and D groups surpass-ing those for B group(P<0.001).The TAS,TAA,and SSAAmax exhibited a decreasing pattern on T1WI-IDEAL images across A,B,C,and D groups,with statistically significant variances observed among all groups(P<0.001).Moreover,the SNR of the medulla oblongata layer in D group displayed a notably higher value compared to A,B groups,with statistically significant distinctions(P<0.001).Conclusion By combining the reduction of the echo train length(ETL)to 2 with the implementation of a double shimming,the occurrence of WFS-SA on nasopharyngeal T1WI-IDEAL enhanced examination images can be minimized and the overall image quality can be enhanced.