During tumor progression, the mechanical properties of the tumor microenvironment play a pivotal regulatory role. As core mechanical indicators, cellular stiffness and extracellular matrix stiffness profoundly influence tumor development through multiple pathways, including cytoskeletal remodeling, activation of signaling pathways, and metabolic regulation. Studies have demonstrated that the tissue stiffness of various solid tumors is significantly higher than that of corresponding normal tissues, while their cellular stiffness exhibits the opposite trend. This mechanical characteristic is also observed in oral squamous cell carcinoma and exerts crucial regulatory effects during tumor progression. This review systematically summarizes the molecular composition and regulatory mechanisms underlying the stiffness of tumor cells and extracellular matrix (ECM). Mainstream stiffness detection technologies such as atomic force microscopy, microfluidic deformation, and real-time deformability cytometry are outlined, with particular emphasis on their applications and limitations in oncology research. This review comprehensively analyzes how mechanical properties regulate key processes in tumor progression, including growth, proliferation, invasion, metastasis, angiogenesis, lymphangiogenesis, drug resistance, and immune escape. This review synthesizes biomechanics-based therapeutic strategies, including: ① targeting the regulation of tumor cell stiffness through cytoskeletal modulators and cholesterol-depleting agents to enhance immune responses; ② reducing ECM stiffness by matrix remodeling enzyme inhibitors, ECM component modulators, or receptor antagonists to improve drug delivery efficiency, and combining with immunotherapy or photothermal therapy for enhanced therapeutic effects; ③ enhancing the mechanical adaptability and anti-tumor activity of immune cells through pharmacological or genetic approaches. This review establishes a robust conceptual framework for developing novel anti-tumor therapeutic strategies and provides insights for future clinical management of oral squamous cell carcinoma.

The continuous emergence of SARS-CoV-2 variants as well as other potential future coronavirus has challenged the effectiveness of current COVID-19 vaccines. Therefore, there remains a need for alternative antivirals that target processes less susceptible to mutations, such as the formation of six-helix bundle (6-HB) during the viral fusion step of host cell entry. In this study, a novel high-throughput screening (HTS) assay employing a yeast-two-hybrid (Y2H) system was established to identify inhibitors of HR1/HR2 interaction. The compound IMB-9C, which achieved single-digit micromolar inhibition of SARS-CoV-2 and its Omicron variants with low cytotoxicity, was selected. IMB-9C effectively blocks the HR1/HR2 interaction in vitro and inhibits SARS-CoV-2-S-mediated cell-cell fusion. It binds to both HR1 and HR2 through non-covalent interaction and influences the secondary structure of HR1/HR2 complex. In addition, virtual docking and site-mutagenesis results suggest that amino acid residues A930, I931, K933, T941, and L945 are critical for IMB-9C binding to HR1. Collectively, in this study, we have developed a novel screening method for HR1/HR2 interaction inhibitors and identified IMB-9C as a potential antiviral small molecule against COVID-19 and its variants.

Objective:To investigate the differential impact of ultra-high-resolution photon-counting detector CT (UHR PCD-CT) and energy-integrating detector CT (EID-CT) on image quality and calcified plaque-induced luminal stenosis in coronary CT angiography (CCTA).Methods:This retrospective analysis was conducted on patients who underwent both EID-CT and UHR PCD-CT CCTA at the Geriatric Hospital of Nanjing Medical University between January 2021 and November 2024. A total of 141 patients were included in the study, within 46 patients having scans within a 12-month interval. Image quality of all coronary artery segments was subjectively evaluated. Patients with paired scans (interval≤12 months) were included for calcified plaque analysis. Subjective visualization of calcified plaques evaluated. The blooming artifact was calculated as an objective evaluation index for assessing the calcified plaques. Additionally, the degree of coronary artery lumen stenosis resulting from calcified plaques was assessed, along with the measurement of plaque volume and the Agatston score. Changes in lumen stenosis between the two scans were also evaluated. The Wilcoxon signed-rank test was used to compare the subjective scores of coronary artery image quality and calcified plaques between the two groups, and paired-sample t-tests were used to compare the blooming artifact and lumen stenosis degree. Results:The PCD-CT image quality score was significantly higher than that of EID-CT [PCD-CT : 5 (4,5), EID-CT: 4 (4,5); Z=-21.38, P<0.001]. Compared to EID-CT, PCD-CT reduced the blooming artifact (PCD-CT: 38.88%±9.09%, EID-CT: 50.11%±11.52%; t=-12.97, P<0.001), significantly improving the subjective score for visualization of calcified plaques [PCD-CT: 5 (4,5), EID-CT: 3 (2,3); Z=-9.68, P<0.001], and the measured lumen stenosis was notably lower in PCD-CT(PCD-CT:34.88%±18.20%, EID-CT:45.31%±23.42%; t=-9.93, P<0.001). Among 129 analyzed calcified plaques, luminal stenosis was reduced on PCD-CT in 110 plaques (85.3%) and increased in 19 (14.7%), including 4 plaques that had unclear boundaries with the adjacent lumen in EID-CT CCTA images, making the stenosis difficult to assess. Conclusion:Compared to EID-CT, UHR PCD-CT for CCTA significantly improves coronary artery image quality, provides clearer visualization of calcified plaques and adjacent lumen details, and it can reduce the overestimation of coronary artery caleified plaque stenosis.

Objective:To explore the correlation between serum hepcidin antimicrobial peptide (HAMP), secreted phosphoprotein 1 (SPP1), and regulator of G protein signaling 2 (RGS2) levels and the clinical pathological characteristics of gastric cancer patients, and their predictive value for postoperative recurrence or metastasis.Methods:A total of 92 gastric cancer patients treated at Handan First Hospital from March 2021 to March 2023 were selected as the gastric cancer group, and 92 healthy individuals who underwent physical examinations during the same period were selected as the control group. The serum levels of HAMP, SPP1 and RGS2 were compared between the two groups. According to the mean levels of HAMP, SPP1, and RGS2 in the serum of gastric cancer patients, they were divided into HAMP high level group and HAMP low level group, SPP1 high level group and SPP1 low level group, RGS2 high level group and RGS2 low level group. The clinicopathological characteristics of gastric cancer patients with different levels of HAMP, SPP1 and RGS2 were compared respectively. After a median follow-up of 18 months, gastric cancer patients were divided into a non-recurrence or metastasis group ( n=59) and a recurrence and metastasis group ( n=33) based on whether the tumor recurred or metastasized. The serum levels of HAMP, SPP1, and RGS2 were compared between the two groups of patients. The predictive value of HAMP, SPP1 and RGS2 for postoperative recurrence or metastasis in patients with gastric cancer was analyzed by using the receiver operator characteristic (ROC) curve. Results:Compared with the control group, the gastric cancer group had higher levels of serum HAMP [ (52.28±5.44) ng/ml vs. (31.22±4.18) ng/ml] and SPP1 [ (55.96±6.43) ng/ml vs. (36.99±5.25) ng/ml] ( t=29.44, P<0.001; t=21.92, P<0.001), and lower level of RGS2 [ (3.72±0.66) mg/L vs. (5.11±0.87) mg/L) ] ( t=12.21, P<0.001). There were statistically significant differences in maximum tumor diameter ( χ2=13.07, P<0.001; χ2=6.71, P=0.010; χ2=10.56, P=0.001), TNM staging ( χ2=7.42, P=0.006; χ2=6.36, P=0.012; χ2=5.39, P=0.020), lymph node metastasis ( χ2=23.41, P<0.001; χ2=6.52, P=0.011; χ2=13.11, P<0.001), and differentiation degree ( χ2=9.01, P=0.003; χ2=7.97, P=0.005; χ2=15.29, P<0.001) between the gastric cancer patients in the HAMP high level group ( n=44) and the HAMP low level group ( n=48), the SPP1 high level group ( n=43) and the SPP1 low level group ( n=49), and the RGS2 high level group ( n=50) and the RGS2 low level group ( n=42). Compared with the non-recurrence or metastatic group, the recurrence and metastatic group had higher levels of serum HAMP [ (59.26±5.66) ng/ml vs. (48.37±4.28) ng/ml] and SPP1 [ (62.85±6.36) ng/ml vs. (52.11±5.38) ng/ml] level ( t=10.40, P<0.001; t=8.60, P<0.001), and lower level of RGS2 [ (3.01±0.48) mg/L vs. (4.12±0.69) mg/L] ( t=8.19, P<0.001). ROC curve analysis showed that the area under the curve (AUC) values of serum HAMP, SPP1, and RGS2 levels alone for predicting postoperative recurrence or metastasis in gastric cancer patients were 0.777, 0.813, and 0.778, respectively. The AUC value of the combination of the three indicators for predicting postoperative recurrence or metastasis in gastric cancer patients was 0.871. The predictive efficacy of the combination of the three indicators for predicting postoperative recurrence or metastasis in gastric cancer patients was better than that alone ( Z=2.51, P=0.035; Z=2.61, P=0.032; Z=2.71, P=0.029) . Conclusions:The levels of HAMP and SPP1 in the serum of gastric cancer patients increase, while the level of RGS2 decreases, and the levels of the three are related to the maximum tumor diameter, TNM staging, lymph node metastasis and differentiation degree, and their combined detection has higher predictive value for postoperative recurrence or metastasis in gastric cancer patients.

Objective To explore the role of Schlafen4(SLFN4)in acute pneumonia induced by hypervirulent Klebsiella pneumoniae(hvKp)via intratracheal aerosolization.Methods Differential expression gene Slfn4 was identified after infection with hvKp based on RNA sequencing(RNA-seq)and single-cell RNA sequencing(scRNA-seq)data before Slfn4-/-mice were obtained via CRISPR/Cas gene editing technology.Slfn4-/-mice and wild mice were challenged via intratracheal aerosolization.Mortality and weight changes were recorded for 14 d,while pathological changes and expression levels of interleukin-6(IL-6),IL-17A,IL-1β,and tumor necrosis factor-α(TNF-α)were detected at 48 h post-infection.Results SLFN4 expression was significantly increased in wild mice after infection with hvKp.Survival was significantly increased,and weight loss was mitigated before gradual recovery in Slfn4-/-mice after infection.The knockout of SLFN4 attenuated alveolar wall thickening,diminished neutrophil infiltration,and suppressed pro-inflammatory cytokine production(IL-6,IL-17A,IL-1β,TNF-α)in the lung at 48 h post-infection.Conclusion The deletion of SLFN4 may suppress the expression of specific pro-inflammatory cytokines and attenuate neutrophil over-recruitment in the lung,thereby alleviating pneumonia in mice after hvKp infection.

Objective To explore the biological functions of pyroptosis-related genes in pneumonic plague using bioinformatics methods,and to evaluate their potential applicability as diagnostic markers.Methods The pneumonic plague-related dataset GSE220123 was retrieved from the Gene Expression Omnibus(GEO)database and screened for differentially expressed pyroptosis-related genes(DE-PRGs).The functions of DE-PRGs were studied via Gene Ontology(GO),Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses,and immune infiltration analysis.The hub genes were identified via protein-protein interaction(PPI)network analysis,and further screened for key genes with sustained high expression characteristics based on differential expression analysis.The relative expression levels of the key genes were verified using the reverse transcription real-time quantitative PCR(qPCR)method.Results A total of 17 DE-PRGs were screened,and PPI network analysis revealed 7 Hub genes.Among them,Casp4 continued to be up-regulated during the course of pneumonic plague.The results of reverse transcription qPCR were consistent with the those of bioinformatic analyses.Conclusion DE-PRGs play a crucial role in the immune response of pneumonic plague,especially Casp4,which has significant applications as a diagnostic biomarker and potential therapeutic target for pneumonic plague.

Objective To investigate the effects of long non coding RNA MAGI2 antisense chain RNA3(LncRNA MAGI2-AS3)on the migration,invasion,and epithelial mesenchymal transition(EMT)of gastric cancer(GCa)cells by regulating the miR-194-5 p/caveolin-1(CAV1)axis.Methods Fifty-two GCa patients who underwent surgical resection in our hospital from August 2022 to December 2023 were selected.Cancer and adjacent tissues were collected,and AGS,MKN45,HGC-27,and GES1 cells were cultured in vitro.The expression of MAGI2-AS3,miR-194-5p,and CAV1 in tissue samples and cell lines was analyzed.AGS cells were randomly separated into AGS group,sh-AGS group sh-MAGI2-AS3 group,miR-NC group,and in miR-194-5p group.The proliferation,apoptosis,migration,and invasion of cells in each group were compared.Immunoblotting was applied to analyze the expression of E-cadherin,CAV1,proliferating cell nuclear antigen(PCNA),N-cadherin,Bax,matrix metalloproteinase 2(MMP2),and vimentin of cells in each group.Dual luciferase assay was applied to analyze the relationship between MAGI2-AS3 and miR-194-5p,and between miR-194-5p and CAV1.Results The expression of MAGI2-AS3 mRNA,CAV1 mRNA,and positive expression rate of CAV1 protein in GCa tissue increased,while the expression of miR-194-5p mRNA decreased(P＜0.05).The expression of MAGI2-AS3 mRNA,CAV1 mRNA,and CAV1 protein in HGC-27,MKN45,and AGS cells was higher than that of GES1 cells,the expression of miR-194-5p mRNA was lower than that of GES1 cells(P＜0.05).Compared with the AGS and sh-AGS groups,the cell absorbance,number of clones,invasion and migration,expression of CAV1,PCNA,N-cadherin,MMP2,and vimentin in sh-MAGI2-AS3 group decreased,the apoptosis rate,expression of E-cadherin,and Bax increased(P＜0.05).Compared with the miR-NC group and sh-MAGI2-AS3 group,the cell absorbance,number of clones,invasion and migration,expression of CAV1,PCNA,N-cadherin,MMP2,and vimentin in in-miR-194-5p group increased,the apoptosis rate,expression of E-cadherin,and Bax reduced(P＜0.05).ENCORI database found that there were multiple binding sites between MAGI2-AS3 and miR-194-5p,and between miR-194-5p and CAV1.Compared with the WT-MAGI2-AS3+miR-NC group,the luciferase activity in the WT-MAGI2-AS3+miR-194-5p group decreased(P＜0.05),while compared with the WT-CAV1+miR-NC group,the luciferase activity in the WT-CAV1+miR-194-5p group decreased(P＜0.05).Conclusion LncRNA MAGI2-AS3 silencing can target miR-194-5p to downregulate CAV1,thereby inhibiting GCa cell migration,invasion,and EMT.

Objective To investigate the effects of long non coding RNA MAGI2 antisense chain RNA3(LncRNA MAGI2-AS3)on the migration,invasion,and epithelial mesenchymal transition(EMT)of gastric cancer(GCa)cells by regulating the miR-194-5 p/caveolin-1(CAV1)axis.Methods Fifty-two GCa patients who underwent surgical resection in our hospital from August 2022 to December 2023 were selected.Cancer and adjacent tissues were collected,and AGS,MKN45,HGC-27,and GES1 cells were cultured in vitro.The expression of MAGI2-AS3,miR-194-5p,and CAV1 in tissue samples and cell lines was analyzed.AGS cells were randomly separated into AGS group,sh-AGS group sh-MAGI2-AS3 group,miR-NC group,and in miR-194-5p group.The proliferation,apoptosis,migration,and invasion of cells in each group were compared.Immunoblotting was applied to analyze the expression of E-cadherin,CAV1,proliferating cell nuclear antigen(PCNA),N-cadherin,Bax,matrix metalloproteinase 2(MMP2),and vimentin of cells in each group.Dual luciferase assay was applied to analyze the relationship between MAGI2-AS3 and miR-194-5p,and between miR-194-5p and CAV1.Results The expression of MAGI2-AS3 mRNA,CAV1 mRNA,and positive expression rate of CAV1 protein in GCa tissue increased,while the expression of miR-194-5p mRNA decreased(P＜0.05).The expression of MAGI2-AS3 mRNA,CAV1 mRNA,and CAV1 protein in HGC-27,MKN45,and AGS cells was higher than that of GES1 cells,the expression of miR-194-5p mRNA was lower than that of GES1 cells(P＜0.05).Compared with the AGS and sh-AGS groups,the cell absorbance,number of clones,invasion and migration,expression of CAV1,PCNA,N-cadherin,MMP2,and vimentin in sh-MAGI2-AS3 group decreased,the apoptosis rate,expression of E-cadherin,and Bax increased(P＜0.05).Compared with the miR-NC group and sh-MAGI2-AS3 group,the cell absorbance,number of clones,invasion and migration,expression of CAV1,PCNA,N-cadherin,MMP2,and vimentin in in-miR-194-5p group increased,the apoptosis rate,expression of E-cadherin,and Bax reduced(P＜0.05).ENCORI database found that there were multiple binding sites between MAGI2-AS3 and miR-194-5p,and between miR-194-5p and CAV1.Compared with the WT-MAGI2-AS3+miR-NC group,the luciferase activity in the WT-MAGI2-AS3+miR-194-5p group decreased(P＜0.05),while compared with the WT-CAV1+miR-NC group,the luciferase activity in the WT-CAV1+miR-194-5p group decreased(P＜0.05).Conclusion LncRNA MAGI2-AS3 silencing can target miR-194-5p to downregulate CAV1,thereby inhibiting GCa cell migration,invasion,and EMT.

Objective To explore the influencing factors of reversible ischemic edema on cranial CT after mechanical thrombectomy for anterior circulation acute large vessel occlusive stroke(ALVOS).Methods A total of 142 patients with anterior circulation ALVOS who underwent mechanical thrombectomy in the First Hospital of Jiaxing from June 2022 to July 2024 were selected as research subjects.According to the results of the postoperative cranial CT scan after mechanical thrombectomy,they were divided into irreversible ischemic edema group(120 cases)and reversible ischemic edema group(22 cases).The baseline clinical data of the patients were collected.Multivariate Logistic regression analysis was used to identify the influencing factors for reversible ischemic edema on cranial CT after mechanical thrombectomy in patients with anterior circulation ALVOS.Receiver operating characteristic(ROC)curve was constructed to evaluate its predictive value for reversible ischemic edema.Results The results of multivariate Logistic regression analysis showed that age(OR=1.057,95％CI:1.018-1.102,P=0.005)and collateral circulation grade(OR=0.395,95％CI:0.186-0.769,P=0.010)were influencing factors for reversible ischemic edema on cranial CT after mechanical thrombectomy for anterior circulation ALVOS.ROC curve analysis results showed that age,collateral circulation grade and their combination had a certain predictive value for reversible ischemic edema on cranial CT after mechanical thrombectomy for anterior circulation ALVOS.The area under the curve(AUC)of age and collateral circulation grade was 0.664 and 0.715,respectively,and AUC of the combination was 0.785,the best cut-off value was 0.861,the sensitivity was 68.3％,and the specificity was 81.8％.Conclusion The low-density area in the ischemic region on cranial CT after mechanical thrombectomy for a small percentage of anterior circulation ALVOS may be reversible.Younger age and good collateral circulation compensation in patients undergoing mechanical thrombectomy are associated with reversible ischemic edema in postoperative cranial CT.

Objective To explore the influencing factors of reversible ischemic edema on cranial CT after mechanical thrombectomy for anterior circulation acute large vessel occlusive stroke(ALVOS).Methods A total of 142 patients with anterior circulation ALVOS who underwent mechanical thrombectomy in the First Hospital of Jiaxing from June 2022 to July 2024 were selected as research subjects.According to the results of the postoperative cranial CT scan after mechanical thrombectomy,they were divided into irreversible ischemic edema group(120 cases)and reversible ischemic edema group(22 cases).The baseline clinical data of the patients were collected.Multivariate Logistic regression analysis was used to identify the influencing factors for reversible ischemic edema on cranial CT after mechanical thrombectomy in patients with anterior circulation ALVOS.Receiver operating characteristic(ROC)curve was constructed to evaluate its predictive value for reversible ischemic edema.Results The results of multivariate Logistic regression analysis showed that age(OR=1.057,95％CI:1.018-1.102,P=0.005)and collateral circulation grade(OR=0.395,95％CI:0.186-0.769,P=0.010)were influencing factors for reversible ischemic edema on cranial CT after mechanical thrombectomy for anterior circulation ALVOS.ROC curve analysis results showed that age,collateral circulation grade and their combination had a certain predictive value for reversible ischemic edema on cranial CT after mechanical thrombectomy for anterior circulation ALVOS.The area under the curve(AUC)of age and collateral circulation grade was 0.664 and 0.715,respectively,and AUC of the combination was 0.785,the best cut-off value was 0.861,the sensitivity was 68.3％,and the specificity was 81.8％.Conclusion The low-density area in the ischemic region on cranial CT after mechanical thrombectomy for a small percentage of anterior circulation ALVOS may be reversible.Younger age and good collateral circulation compensation in patients undergoing mechanical thrombectomy are associated with reversible ischemic edema in postoperative cranial CT.