Since the outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, considerable attention has been paid on its epidemiology and clinical characteristics in children patients. However, it is also crucial for clinicians to summarize and investigate the co-infection of SARS-CoV-2 in children. We retrospectively reviewed the clinical manifestations, laboratory findings, and imaging characteristics of COVID-19 patients in co-infection group (CI, n = 27) and single infection group (SI, n = 54). Samples were tested for multiple pathogens. A high incidence (27/81, 33%) of co-infection in children with COVID-19 was revealed. The most frequent co-infected pathogen was mycoplasma pneumoniae (MP, 20/81, 25%), followed by virus (6/81, 7%), and bacteria (4/81, 5%). No significant difference in clinical characteristics, laboratory examinations, or hospital stay was observed between the patients with co-infections and those with monomicrobial, only lower in white blood cell counts (CI: 5.54 ± 0.36 vs SI: 7.38 ± 0.37, P = .002), neutrophil counts (CI: 2.20 ± 0.20 vs SI: 2.92 ± 0.23, P = .024) and lymphocyte counts (CI: 2.72 ± 0.024 vs SI: 3.87 ± 0.28, P = .006). Compared with the patients with monomicrobial, chest imaging of those with co-infections showed consolidation in more cases (CI: 29.6% vs SI: 11.1%, P = .038) and duration of positive in nucleic acid was shorter (CI: 6.69 ± 0.82 vs SI: 9.69 ± 0.74, P = .015). Co-infection was relatively common in children with COVID-19, almost 1/3 had co-infection, most commonly caused by MP. Co-infection did not cause a significant exacerbation in clinical manifestations.

Ulcerative colitis (UC) is a complex intestinal inflammation with an increasing risk of colitis-associated colorectal cancer (CAC). However, the pathogenesis is still unclear between active UC and inactive UC. Recently, it has been reported that pyroptosis-related genes (PRGs) are closely associated with inflammatory disease activity. Nevertheless, the specific roles of PRGs in the progression and treatment of UC and CAC remain unclear. In this study, we identified 30 differentially expressed PRGs based on the immune landscape of active and inactive UC samples. Meanwhile, weighted gene coexpression network analysis was applied to explore important genes associated with active UC. By intersecting with the differentially expressed PRGs, CASP5, GBP1, GZMB, IL1B, and IRF1 were selected as key PRGs to construct a pyroptosis-related signature (PR-signature). Then, logistic regression analysis was performed to validate the PR-signature and establish a pyroptosis-related score (PR-Score). We demonstrated that PR-Score had a powerful ability to distinguish active UC from inactive UC in multiple datasets. Besides, PR-Score was positively correlated with immune cell infiltration and inflammatory microenvironment in UC. Lower PR-Score was associated with a better response to anti-TNF therapy for patients with UC. Additionally, high-PR-Score was found to suppress CAC and improve the survival outcomes of patients with colorectal cancer. Finally, the levels of the PR-signature genes were validated both in vitro and in vivo. These findings can improve our understanding of PRGs in UC and provide new markers for predicting the occurrence of active UC or CAC and the treatment of UC.

Background: Napsin B Aspartic Peptidase, Pseudogene (NAPSB) was associated with CD4 + T cell infiltration in pancreatic ductal adenocarcinoma. However, the biological role of NAPSB in hepatocellular carcinoma (HCC) remains to be determined. Methods: The expression of NAPSB in HCC as well as its clinicopathological association were analyzed using data from several public datasets. qRT-PCR was used to verify the relative expression of NAPSB in patients with HCC using the Zhongnan cohort. Kaplan–Meier analyses, and univariate and multivariate Cox regression were conducted to determine the prognosis value of NAPSB on patients with HCC. Then enrichment analyses were performed to identify the possible biological functions of NAPSB. Subsequently, the immunological characteristics of NAPSB in the HCC tumor microenvironment (TME) were demonstrated comprehensively. The role of NAPSB in predicting hot tumors and its impact on immunotherapy and chemotherapy responses was also analyzed by bioinformatics methods. Results: NAPSB was downregulated in patients with HCC and high NAPSB expression showed an improved survival outcome. Enrichment analyses showed that NAPSB was related to immune activation. NAPSB was positively correlated with immunomodulators, tumor-infiltrating immune cells, T cell inflamed score and cancer-immunity cycle, and highly expressed in immuno-hot tumors. High expression of NAPSB was sensitive to immunotherapy and chemotherapy, possibly due to its association with pyroptosis, apoptosis and necrosis. Conclusions: NAPSB was correlated with an immuno-hot and inflamed TME, and tumor cell death. It can be utilized as a promising predictive marker for prognosis and therapy in HCC.

Background: The role of guanylate‐binding proteins (GBPs) in various cancers has been elucidated recently. However, our knowledge of the clinical relevance and biological characteristics of GBPs in hepatocellular carcinoma (HCC) remains limited.Methods: A total of 955 HCC patients were enrolled from five independent public HCC cohorts. The role of GBP molecules in HCC was preliminarily investigated, and a GBP family signature, termed GBPs‐score, was constructed by principal component analysis to combine the GBP molecule values. We revealed the effects of GBP genes and GBPs‐score in HCC via well‐established bioinformatics methods and validated GBP1‐5 experimentally in a tissue microarray (TMA) cohort.Results: GBPs molecules were closely associated with the prognosis of patients with HCC, and a high GBPs‐score highly inferred a favorable survival outcome. We also revealed high GBPs‐score was related to anti‐tumor immunity, the immune‐hot tumor microenvironment (TME), and immunotherapy response. Among the GBPs members, GBP1‐5 rather than GBP6/7 may be dominant in these fields. The TMA analysis based on immunohistochemistry showed positive correlations between GBP1‐5 and the immune‐hot TME with abundant infiltration of CD8⁺ T cells in HCC.Conclusions: Our integrative study revealed the genetic and immunologic characterizations of GBPs in HCC and highlighted their potential values as promising biomarkers for prognosis and immunotherapy.

Introduction: As the primary members of the deubiquitinase family, ubiquitin-specific proteases can regulate the efficacy of immunotherapy and mediate immune evasion. However, further research is needed to explore the influence of USP52 on the prognosis of colorectal cancer (CRC), the tumor immune microenvironment, and therapeutic response. Methods: The differential expression of USP52 between CRC and normal tissues was analyzed using multiple public databases. The relationship between USP52 with the prognosis and clinicopathological characteristics of CRC patients was evaluated, and a nomogram was constructed to predict patient survival based on USP52 expression. Subsequently, gene set variation analysis (GSVA) was used to explore the potential biological functions of USP52 in CRC. The impact of USP52 on the tumor microenvironment (TME) was estimated. Moreover, the effect of USP52 on the response to immunotherapy and chemotherapeutic drugs in CRC was investigated. Finally, the correlation between tumor mutation burden (TMB)/microsatellite instability (MSI) status and USP52 was explored. Results: The expression of USP52 was markedly upregulated in CRC, correlating with a poor prognosis in patients. GSVA uncovered a strong association between high USP52 and immune suppression. Furthermore, high USP52 was found to be correlated with a non-inflamed TME, resulting in reduced immune cell infiltration levels. Additionally, it was observed that patients with high USP52 exhibited low sensitivity to both immunotherapy and chemotherapeutic drugs. Lastly, high USP52 was negatively associated with high TMB and MSI. Conclusion: This study revealed the significance of USP52 in TME, efficacy of therapy, and clinical prognosis in CRC, offering novel insights for the therapeutic advancements in CRC.

The mechanisms underlying the limited response to immune checkpoint blockade (ICB) remain unclear. One explanation is that tumors escape cytotoxic T cell killing by disrupting interferon-gamma (IFN-γ) signaling. Here we show that guanylate-binding protein 2 (GBP2), an IFN-γ–inducible molecule, functions as a general amplifier of T cell–mediated cytotoxicity by promoting ferroptosis in melanoma. GBP2 enhances STAT1 activation and suppresses SLC7A11, thereby sensitizing tumor cells to ferroptotic death. Upon IFN-γ stimulation, GBP2 undergoes phase separation through an intrinsically disordered region, forming condensates that sequester SHP1 and sustain STAT1 activation. Disrupting GBP2 phase separation impairs ferroptosis, accelerates tumor growth, and weakens T cell–driven tumor control. GBP2 also increases HMGB1 release from ferroptotic cells, promoting cytotoxic T cell infiltration. These findings identify GBP2 as a key mediator linking IFN-γ signaling to ferroptosis and demonstrate that enhancing this pathway can improve tumor responsiveness to ICB immunotherapy.