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Oncolytic viruses (OVs) show promise as a cancer treatment by selectively replicating in tumor cells and promoting antitumor immunity. However, the current immunogenicity induced by OVs for tumor treatment is relatively weak, necessitating a thorough investigation of the mechanisms underlying its induction of antitumor immunity. Here, we show that HSV-1-based OVs (oHSVs) trigger ZBP1-mediated PANoptosis (a unique innate immune inflammatory cell death modality), resulting in augmented antitumor immune effects. Mechanistically, oHSV enhances the expression of interferon-stimulated genes, leading to the accumulation of endogenous Z-RNA and subsequent activation of ZBP1. To further enhance the antitumor potential of oHSV, we conduct a screening and identify Fusobacterium nucleatum outer membrane vesicle ( Fn -OMV) that can increase the expression of PANoptosis execution proteins. The combination of Fn -OMV and oHSV demonstrates potent antitumor immunogenicity. Taken together, our study provides a deeper understanding of oHSV-induced antitumor immunity, and demonstrates a promising strategy that combines oHSV with Fn -OMV. The potential of oncolytic virus (OV) for cancer therapy is limited by the efficiency of immune response induced. Here the authors show that HSV-1-based OV is capable of triggering ZBP1-mediated PANoptosis resulting in effective tumor growth inhibition.

Tumor tertiary lymphoid structures (TLS), especially mature TLS (mTLS), have been associated with better prognosis and improved responses to immune checkpoint blockade (ICB), but the underlying mechanisms remain incompletely understood. Here, by performing single-cell RNA, antigen receptor sequencing and spatial transcriptomics on tumor tissue from head and neck squamous cell carcinoma (HNSCC) patients with different statuses of TLS, we observe that mTLS are enriched with stem-like T cells, and B cells at various maturation stages. Notably, progenitor exhausted CD4 + T cells, with features resembling follicular helper T cells, support these responses, by activating B cells to produce plasma cells in the germinal center, and interacting with DC-LAMP + dendritic cells to support CD8 + T cell activation. Conversely, non-mTLS tumors do not promote local anti-tumor immunity which is abundant of immunosuppressive cells or a lack of stem-like B and T cells. Furthermore, patients with mTLS manifest improved overall survival and response to ICB compared to those with non-mTLS. Overall, our study provides insights into mechanisms underlying mTLS-mediated intra-tumoral immunity events against cancer. The reason of mature tertiary lymphoid structures (mTLS) correlates with better prognosis and responses to immune checkpoint blockade (ICB) remains incompletely understood. By employing sequencing and spatial transcriptomics strategies, the authors show that mTLS are enriched with progenitor exhausted CD4 + T cells that promotes activation of T and B cells.

During low tides, intertidal algae experience prolonged high light stress. Efficient dissipation of excess light energy, measured as non-photochemical quenching (NPQ) of chlorophyll fluorescence, is therefore required to avoid photodamage. Light-harvesting regulation was studied in the intertidal macroalga Bryopsis corticulans, during high light and air exposure. Photosynthetic capacity and NPQ kinetics were assessed in different filament layers of the algal tufts and in intact chloroplasts to unravel the nature of NPQ in this siphonous green alga. We found that the morphology and pigment composition of the B. corticulans body provides functional segregation between surface sunlit filaments (protective state) and those that are underneath and undergo severe light attenuation (light-harvesting state). In the surface filaments, very high and sustained NPQ gradually formed. NPQ induction was triggered by the formation of transthylakoid proton gradient and independent of the xanthophyll cycle. PsbS and LHCSR proteins seem not to be active in the NPQ mechanism activated by this alga. Our results show that B. corticulans endures excess light energy pressure through a sustained protective NPQ, not related to photodamage, as revealed by the unusually quick restoration of photosystem II (PSII) function in the dark. This might suggest either the occurrence of transient PSII photoinactivation or a fast rate of PSII repair cycle.

The cellular uptake and tissue dispersion efficiency of nanomedicines are crucial for realizing their biological functionality. As a cutting-edge category of nanomedicine, covalent organic frameworks (COFs)-based photosensitizers, have been extensively employed in cancer phototherapy in recent years. However, the inherent aggregation tendency of COFs hinders their uptake by tumor cells and dispersion within tumor tissues, thereby limiting their therapeutic efficacy. In this study, we employed Fusobacterium nucleatum (F.n.), a prevalent intratumoral bacterium, to construct a bacterium membrane-wrapped COF, COF-306@FM, which is readily taken up by cancer cells and uniformly dispersed within tumor tissues. Meanwhile, the F.n. membrane can also serve as an immune adjuvant to warm up the “cold” tumor immune microenvironment by enhancing the CD8+ T and B cells infiltration, and inducing the formation of tumor-located tertiary lymphoid structures. Consequently, the response rate of αPD-L1 immunotherapy was drastically promoted to efficiently prevent tumor metastasis and recurrence, causing 84.6 % distant tumor inhibition and complete suppression of tumor metastasis. In summary, this innovative approach not only enhances the therapeutic potential of COFs but also opens up new avenues for integrating microbial and nanotechnological strategies in cancer treatment. [Display omitted] •The application of bacterial membrane addresses the aggregation tendency of COF and can serve as an immune adjuvant to improve antitumor immunity.•COF-306@FM successfully induced tertiary lymphoid structures in “cold” tumors, maximizing COF's immune activation effect.•The synergistic αPD-L1 immunotherapy and COF-306@FM contribute to an 84.6 % inhibition of distant tumors and prevent tumor recurrence and metastasis.•This innovative approach boosts the therapeutic potential of COFs and paves new way to integrate microbial and nanotech strategy in cancer treatment.

Background Tranexamic acid (TXA) has shown significant reductions in blood loss and transfusion rates in total knee arthroplasty (TKA). However, the optimal administration route continues to be debated. The aim of this trial was to compare the effectiveness of intravenous (IV) versus peri-articular injection (PAI) application of tranexamic acid in patients undergoing total knee arthroplasty. Methods We conducted a randomized controlled, double-blinded study. A total of 93 patients undergoing primary unilateral TKA were randomly distributed between 2 groups: the IV group (47 cases; 1 g TXA IV) and the PAI group (46 cases; 1 g TXA injected peri-articularly). The amount of total and hidden blood loss (HBL), drainage, transfusion rate, hemoglobin and hematocrit drift, and complications were recorded. Results Peri-articular injection of TXA reduced total blood loss ( P < 0.001) and HBL more than IV use of TXA ( P < 0.001). No patients in either group received a transfusion. No symptomatic deep venous thrombosis or other severe complications occurred. Conclusion Peri-articular injection of TXA significantly reduced total blood loss and hidden blood loss to a greater degree than IV injection in total knee arthroplasty without reduction of drainage volume. Trial registration Chinese Clinical Trial Registry, ChiCTR-INR-16010270 . Date of registration: December 27, 2016.

To compare the differences in floral composition and functions between the two types of microbiota, ileal contents and feces were collected from Sprague Dawley (SD) rats fed in a conventional or specific-pathogen free (SPF) environment and rats fed a high-fat diet (HFD), and the V3–V4 region of the 16S ribosomal ribonucleic acid (rRNA) gene in these rats was then amplified and sequenced. Compared with feces, about 60% of the bacterial genera in the ileum were exclusive, with low abundance (operational taxonomic units (OTUs) < 1000). Of bacteria shared between the ileum and feces, a few genera were highly abundant (dominant), whereas most had low abundance (less dominant). The dominant bacteria differed between the ileum and feces. Ileal bacteria showed greater β-diversity, and the distance between in-group samples was nearer than that between paired ileum–feces samples. Moreover, the ileum shared various biomarkers and functions with feces (p < 0.05). The HFD and SPF conditions had a profound influence on α-diversity and abundance but not on the exclusive/shared features or β-diversity of samples. The present findings suggested that, under conventional circumstances, fecal bacteria can represent approximately 40% of the low abundant ileal bacterial genera and that dominant fecal bacteria failed to represent the ileal dominant flora. Moreover, fecal flora diversity does not reflect β-diversity in the ileum.

C-X-C chemokine receptor type 4 and stromal cell–derived factor-1 were proven to play important roles in several types of cancer and in many biological processes connected with tumor growth, invasion, angiogenesis, and metastasis. However, the clinical significance of C-X-C chemokine receptor type 4 and stromal cell–derived factor-1 expression in colorectal cancer remains inaccurate. The purpose of this systematic meta-analysis is to investigate the role of C-X-C chemokine receptor type 4 and stromal cell–derived factor-1 as prognostic factors for survival and the association between C-X-C chemokine receptor type 4/ stromal cell–derived factor-1 and clinicopathology in colorectal cancer. Databases including PubMed, EMBASE, and Cochrane Library were searched for relevant literatures updated till January 2017. Review Manager 5.3 was used for data analysis. In our meta-analysis, C-X-C chemokine receptor type 4 expression is related to tumor–node–metastasis stage, tumor differentiation, liver metastasis, lymph node metastasis, distant metastasis, and diagnosis, and no correlation of C-X-C chemokine receptor type 4 expression with tumor size, gender, preoperative carcinoembryonic antigen, age, or vascular invasion has been observed. Stromal cell–derived factor-1 expression has no relationship with tumor–node–metastasis stage, lymph node metastasis, vascular invasion, age, gender, distant metastasis, or diagnosis. The expression of stromal cell–derived factor-1 has association with tumor differentiation. Moreover, the pooled hazard ratio for disease-free survival/overall survival showed that overexpression of C-X-C chemokine receptor type 4/stromal cell–derived factor-1 reduced disease-free survival/overall survival in colorectal cancer. Therefore, High expression of C-X-C chemokine receptor type 4/stromal cell–derived factor-1 which is essential in tumor progression can predict poor survival that may provide more advance prognostic clues to colorectal cancer patients.

While cancer immunotherapy has transformed clinical management for cancer patients, its low response rates remain a critical challenge to be addressed. Tumor immune evasion now extends beyond the tumor microenvironment (TME), as advanced tumors induce extramedullary hematopoiesis (EMH) in the spleen, leading to a substantial expansion of erythroid progenitor cells (EPCs) with potent immunosuppressive capacity. EPCs are typically transient populations in erythroid maturation and differentiation; however, under tumor burden, they undergo profound metabolic reprogramming that exacerbates their immunosuppressive effects. This review examines the role and mechanisms of tumor-hijacked metabolic reprogramming in EPCs and provides strategies for targeting this reprogramming to potentiate cancer immunotherapy. In particular, we synthesize the metabolic interplay between EPCs, tumor cells, and immune cells, integrating EPC metabolic reprogramming with established concepts of tumor cell metabolism and immunometabolism. Furthermore, this review outlines future directions for the field, including multi-modal approaches to decipher the mechanisms of EPC metabolic reprogramming, biomarker development, and metabolism-based targeted therapies, all aimed at improving survival and prognosis for cancer patients.

With the aim to provide an efficient platform for the elastic–plastic analysis of steel structures, reinforced concrete (RC) structures and steel–concrete composite structures, a program iFiberLUT based on the fiber model was developed within the framework of ABAQUS. This program contains an ABAQUS Fiber Generator which can automatically divide the beam and column cross sections into fiber sections, and a material library which includes several concrete and steel uniaxial material models. The range of applications of iFiberLUT is introduced and its feasibility is verified through previously reported test data of individual structural members as well as planar steel frames, RC frames and composite frames subjected to various loadings. The simulation results indicate that the developed program is able to achieve high calculation accuracy and favorable convergence within a wide range of applications.

The current criteria for defining the recurrence risks of stage II colorectal cancer (CRC) are not robust; therefore, we aimed to explore novel gene signatures to predict recurrence risks and to reveal the underlying mechanisms of stage II CRC. First, the gene expression profiles of 124 patients with stage II CRC from The Cancer Genome Atlas (TCGA) database were obtained to screen differentially expressed genes (DEGs). A total of 202 DEGs, including 128 upregulated and 74 downregulated, were identified in the recurrence group (n = 24) compared to the nonrecurrence group (n = 100). Furthermore, the top 5 DEGs (ZNF561, WFS1, SLC2A1, MFI2, and PTGR1) were identified by random forest variable hunting, and four (ZNF561, WFS1, SLC2A1, and PTGR1) were selected to create a four‐gene recurrent model (GRM), with an area under the curve (AUC) of 0.882 according to the receiver operating characteristic curve, and the robust diagnostic effectiveness of the GRM was further validated with another gene expression profiling dataset (GSE12032), with an AUC of 0.943. The diagnostic effectiveness of the GRM regarding recurrence was associated with poor disease‐free survival in all stages of CRC. In addition, gene ontology functional annotation and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses revealed 18 enriched functions and 6 enriched pathways. Four genes, ABCG2, CACNA1F, CYP19A1, and TF, were identified as hub genes by the protein‐protein interaction network, which further validated that these genes were correlated with a poor pathologic stage and overall survival in all stages of CRC. In conclusion, the GRM can effectively classify stage II CRC into groups of high and low risks of recurrence, thereby making up for the prognostic value of the traditional clinicopathological risk factors defined by the National Comprehensive Cancer Network guidelines. The hub genes may be useful therapeutic targets for recurrence. Thus, the GRM and hub genes could offer clinical value in directing individualized and precision therapeutic regimens for stage II CRC patients. This study finds indicators for predicting postoperative recurrence in patients with stage II colorectal cancer (CRC). Moreover, the gene recurrent model and hub genes potentially offer clinical values in directing individualized and precision therapeutic regimen be selection for stage II CRC.