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Lung cancer remains the leading cause of cancer-related mortality globally, with metastasis and recurrence as the primary determinants of poor prognosis. Despite advances in immunotherapy, intrinsic and acquired resistance to immune checkpoint inhibitors (ICIs) underscores the need to explore alternative immunomodulatory strategies. Emerging evidence highlights the critical yet dual roles of innate and adaptive immune cells within the tumor microenvironment (TME) in either restraining or facilitating metastatic dissemination. Adaptive immunity, dominated by T and B cells, orchestrates context-dependent antitumor responses or immunosuppression, while innate immune dysregulation fosters metastatic niches. We highlight translational opportunities, such as natural killer (NK) cell activation, macrophage reprogramming, and dendritic cell (DC)-based vaccines, alongside prognostic biomarkers like peripheral NK activity and tryptase + mast cell infiltration. This review summarizes the interplay of immune cell subsets, including T and B lymphocytes, macrophages, DCs, NK cells, and mast cells, in lung cancer progression. By synthesizing preclinical and clinical insights, this review identifies unresolved challenges and proposes targeting innate immunity as a promising avenue to augment current therapies and mitigate metastasis.

The generation of green hydrogen by water splitting is identified as a key strategic energy technology, and proton exchange membrane water electrolysis (PEMWE) is one of the desirable technologies for converting renewable energy sources into hydrogen. However, the harsh anode environment of PEMWE and the oxygen evolution reaction (OER) involving four‐electron transfer result in a large overpotential, which limits the overall efficiency of hydrogen production, and thus efficient electrocatalysts are needed to overcome the high overpotential and slow kinetic process. In recent years, noble metal‐based electrocatalysts (e.g., Ru/Ir‐based metal/oxide electrocatalysts) have received much attention due to their unique catalytic properties, and have already become the dominant electrocatalysts for the acidic OER process and are applied in commercial PEMWE devices. However, these noble metal‐based electrocatalysts still face the thorny problem of conflicting performance and cost. In this review, first, noble metal Ru/Ir‐based OER electrocatalysts are briefly classified according to their forms of existence, and the OER catalytic mechanisms are outlined. Then, the focus is on summarizing the improvement strategies of Ru/Ir‐based OER electrocatalysts with respect to their activity and stability over recent years. Finally, the challenges and development prospects of noble metal‐based OER electrocatalysts are discussed. In order to increase the efficiency of hydrogen production by water splitting, it is aimed to improve the anode oxygen evolution reaction (OER). The Ru/Ir‐based OER electrocatalysts are briefly categorized according to their existence forms and outline the OER catalytic mechanism. Importantly, strategies for the improvement of Ru/Ir‐based OER electrocatalysts in terms of activity and stability in recent years are summarized.

ObjectivesTo determine and validate alanine aminotransferase (ALT)-adapted dual cut-offs of liver stiffness measurements (LSMs) for assessing liver fibrosis with two-dimensional shear wave elastography (2D-SWE) in patients with chronic hepatitis B (CHB) infection.MethodsPatients with CHB infection who underwent liver biopsy to assess liver fibrosis were consecutively included. 2D-SWE confirmation thresholds with a positive likelihood ratio ≥10 and 2D-SWE exclusion thresholds with a negative likelihood ratio ≤0.1 were identified to rule in or rule out significant fibrosis and cirrhosis, respectively.ResultsThe first 515 patients (index cohort) and the next 421 patients (validation cohort) were included in the final analysis. The low and high cut-offs to rule out and rule in patients with significant fibrosis (≥ F2) were 5.4 kPa and 9.0 kPa, respectively, in patients with ALT levels ≤ 2 × the upper limit of normal (ULN) and 7.1 kPa and 11.2 kPa in patients with ALT levels > 2 × ULN. For cirrhosis (F4), the corresponding values were 8.1 kPa and 12.3 kPa in patients with ALT levels ≤ 2 × ULN and 11.9 kPa and 24.7 kPa in patients with ALT levels > 2 × ULN. The dual cut-off values showed an overall accuracy of more than 90% for diagnosis of the presence or absence of significant fibrosis and cirrhosis in the index and validation cohorts. There were no significant differences in the accuracy values between the cohorts (all p>0.05).ConclusionThe ALT-adapted dual cut-offs of LSMs showed high accuracy for diagnosis of the presence or absence of significant fibrosis and cirrhosis in patients with CHB infection.Key Points• The ALT-adapted dual cut-off values of LSMs showed high accuracy for diagnosis of the presence or absence of significant fibrosis and cirrhosis.• ALT levels did not influence the overall diagnostic accuracy for predicting significant fibrosis and cirrhosis.• The ALT-adapted dual cut-offs in patients with ALT levels > 2 × ULN were markedly higher than those in patients with ALT levels ≤ 2 × ULN.

Background Dermatofibrosarcoma protuberans (DFSP) is a rare, low- to intermediate-grade sarcoma, which represents a diagnostic imaging challenge. This study aimed to analyze the clinical and ultrasound features of primary and recurrent DFSP to improve the diagnosis. Methods Clinical, imaging, and pathological data from a total of 58 patients (23 patients with primary DFSP and 35 patients with recurrent DFSP) were retrospectively reviewed. Results There was no statistically significant difference in age, sex, tumor size, or echogenicity between the two groups. Most of the primary DFSP lesions involved the overlying dermis and hypodermis, while most of the recurrent DFSP lesions were fixated to more deeply seated structures at the original surgical incision. Red nodules on the skin were found more frequently in the primary group. There were statistically significant differences in the type of lesion and ultrasound tumor morphology ( p  < 0.050). The lesions in the primary group showed more tentacle-like projections or a “claw” sign, while the lesions in the recurrent group were more commonly oval, lobulated, and irregularly shaped. Hypervascularity was common in both groups. Conclusions For primary DFSP, a slow-growing, red nodule on the skin involving the overlying dermis and hypodermis, more frequently a hypoechoic mass with tentacle-like projections or a “claw” sign, was observed. For recurrent DFSP, palpable subcutaneous nodules or subcutaneous masses at the original surgical incision and oval, lobulated, and irregularly shaped lesions were more commonly observed. This may be useful for improving diagnostic accuracy.

Game theory studies the mathematical models for self-interested individuals. Nash equilibrium is arguably the most central solution in game theory. While finding the Nash equilibrium in general is known as polynomial parity arguments on directed graphs (PPAD)-complete, learning in games provides an alternative to approximate Nash equilibrium, which iteratively updates the player’s strategy through interactions with other players. Rules and models have been developed for learning in games, such as fictitious play and no-regret learning. Particularly, with recent advances in online learning and deep reinforcement learning, techniques from these fields greatly boost the breakthroughs in learning in games from theory to application. As a result, we have witnessed many superhuman game AI systems. The techniques used in these systems evolve from conventional search and learning to purely reinforcement learning (RL)-style learning methods, gradually getting rid of the domain knowledge. In this article, we systematically review the above techniques, discuss the trend of basic learning rules towards a unified framework, and recap applications in large games. Finally, we discuss some future directions and make the prospect of future game AI systems. We hope this article will give some insights into designing novel approaches.

Among malignant tumors, hepatocellular carcinoma (HCC) is both prevalent and highly lethal. Most patients with advanced-stage liver cancer have a poor prognosis. Death-associated protein 3 (DAP3) is reportedly related to tumors and may hold great promise for the future. DAP3 transcriptome data along with related clinical information were obtained from The Cancer Genome Atlas (TCGA), GEO, and ICGC databases. We assessed its prognostic value, clinical relevance, associated pathways, immune infiltration, gene mutations, and sensitivity to chemotherapeutics. A prognostic risk model was subsequently developed and evaluated using receiver operating characteristic (ROC) curves and Kaplan-Meier (KM) plots. Additionally, a nomogram was created and validated through calibration and decision curve analysis (DCA). Furthermore, quantitative real-time PCR (qRT-PCR), Western blot, and immunohistochemical (IHC) staining were performed to examine the expression of DAP3 in HCC. Finally, gene knockdown and overexpression experiments, along with cell counting kit-8 (CCK-8) assays, colony formation assays, and tests for cell apoptosis, migration, and invasion, were conducted to investigate the role of DAP3 in HCC. The study discovered that DAP3 expression was linked to HCC subtypes, and its high expression was linked to a poor prognosis. There were significant differences in immune infiltration level, mutation level, prognostic value and chemotherapeutic efficacy. Subsequently, we constructed a prognostic model and demonstrated that high risk score was significantly related to a poor survival rate. A predictive nomogram demonstrated that the nomogram model was effective prediction tool that can accurately predict the survival rate of patients with different clinical characteristics. Additionally, DAP3 expression significantly increased in both tissue samples and cell lines. Elevated levels of DAP3 were correlated with larger tumor size and higher alpha-fetoprotein (AFP) levels, and Cox analysis confirmed that DAP3 was a clinically independent prognostic marker. Finally, cell assays revealed that the knockdown of DAP3 significantly impeded cell proliferation and metabolic activity and induced apoptosis. Conversely, the overexpression of DAP3 had opposite effects on these cellular processes. Our study on DAP3 can provide a reference for HCC diagnosis, treatment and prognosis assessment.

Introduction: Although microwave ablation (MWA) is a promising technique for hepatocellular carcinoma (HCC) treatment, its 10-year efficacy is unknown. Objective: The objective of the study was to assess whether the advances in MWA for HCC translated into a real-world survival benefit. Methods: This retrospective study included 2,354 patients with Barcelona Clinic Liver Cancer (BCLC) stage 0 to B from 5 hospitals, with at least 2 years of follow-up for all the patients. Recurrence and survival were analyzed using the Kaplan-Meier method with time-period stratification. Results: A total of 5,326 HCCs (mean diameter, 2.9 cm ± 1.2) underwent 4,051 sessions of MWA with a median follow-up of 61.3 (0.6–169.5 range) months during 3 periods (2007–2010, 2011–2014, and 2015–2018). Technical success was achieved in 5,194 (97.5%) tumors with significant improvement over time, especially for >3.0-cm HCC (p < 0.001). Local tumor progression (LTP) showed no period-dependent advance, with >3.0-cm HCC and perivascular location being the risk factors for LTP. The median intrahepatic metastasis time was 27.6 (95% confidence interval [CI]: 25.2–28.8) months, with 5- and 10-year occurrence rates of 68.8% and 79.4%, respectively. The 5- and 10-year overall survivals were 63.9% and 41.1%, respectively, and BCLC stage 0, A, and all B patients showed an observable survival improvement over time (p < 0.001). The median disease-free survival time increased from 19.4 (95% CI: 16.5–22.6) months in 2007–2010 to 28.1 (95% CI: 25.9–32.3) months in 2015–2018. The improved survival for early recurrent (≤2 years) patients was period-dependent, as verified by Cox regression analyses. The major complications rate per procedure was 3.0% (122/4,051). Conclusions: These real-world data show that MWA provided an upward trend in survival for HCC patients with BCLC stage 0–B over a 12-year follow-up period. An encouraging clear survival benefit in early recurrent patients was also observed.

A series of novel harmine derivatives bearing a benzylindine substituent in position-1 of β-carboline ring were synthesized and evaluated as antitumor agents. The N2-benzylated β-carboline derivatives 3a–g represented the most interesting anticancer activities and compound 3c was found to be the most active agent to diverse cancer cell lines such as gastric carcinoma, melanoma and colorectal cancer. Notably, compound 3c showed low toxicity to normal cells. The treatment significantly induced cell apoptosis. Mechanistically, PI3K/AKT signaling pathway mediated compound 3c-induced apoptosis. Compound 3c inhibited phosphorylation of AKT and promoted the production of reactive oxygen species (ROS). The ROS scavenger, LNAC and GSH, could disturb the effect of compound 3c induced apoptosis and PI3K activity inhibitor LY294002 synergistically enhanced compound 3c efficacy. Moreover, the results from nude mice xenograft model showed that compound 3c treatment effectively inhibited tumor growth and decreased tumor weight. Collectively, our results demonstrated that compound 3c exerts apoptotic effect in cancer cells via suppression of phosphorylated AKT and evocation of ROS generation, which suggested that compound 3c might be served as a promising therapeutic agent for cancer treatment.

G protein-coupled receptors (GPCRs), the most extensive group of membrane receptors in humans, are crucial in controlling various physiological and pathological functions. Their involvement in tumorigenesis has garnered increasing attention in recent years. Gastric cancer (GC), which ranks among the most common cancers globally, is closely associated with dysregulated GPCR expression and aberrant signaling pathways. Accumulating evidence demonstrates that multiple GPCRs contribute to GC progression by modulating critical cellular processes—including proliferation, apoptosis, invasion, and metastasis, while establishing complex interplay networks within the tumor microenvironment (TME). However, a systematic understanding of the precise mechanistic actions of GPCRs in GC pathogenesis, along with their potential as diagnostic biomarkers and therapeutic targets, remains elusive. This review comprehensively delineates the expression profiles of GPCRs in GC, their signaling regulatory mechanisms, and dynamic crosstalk with the TME. We critically evaluate the translational value of GPCRs as diagnostic indicators and therapeutic targets, summarize current GPCR-targeted strategies, and propose future research directions to advance precision diagnosis and therapeutic management of GC.

Inflammasomes function as immune-signaling platforms that were assembled following detection of pathogens. NLRP1 and CARD8 are related inflammasomes that use their C-terminal (CT) fragments containing a caspase recruitment domain (CARD) and the UPA domain to initiate the inflammasome. At rest, dipeptidyl peptidases 8 and 9 (DPP8/9) inhibit inflammatory CT by interacting with the function-to-find domain (FIIND) of NLRP1/CARD8 and forming an inhibitory NLRP1/CARD8-DPP9 ternary complex consisting of DPP9, full-length NLRP1/CARD8, and NLRP1/CARD8 CT. However, the specific triggers of NLRP1 and CARD8 have not yet been fully identified. Here, we report that a tick-borne bunyavirus SFTSV infection activates the NLRP1 inflammasome in primary keratinocytes and the CARD8 inflammasome in macrophages in a similar manner by targeting the ternary inhibitory complex, respectively. Mechanistically, SFTSV NSs interact with NLRP1 and CARD8 via their FIIND domains, suggesting that DPP8/9 are likely to compete for binding; on the other hand, NSs promote the degradation of DPP8 and DPP9. Both contribute to more efficient destabilization of the DPP8/9 ternary complex and release the activated CT. Moreover, CARD8 deletion promotes SFTSV replication. In conclusion, we found a novel mechanism of viral protein activation of NLRP1 and CARD8 by disrupting the DPP9-binding checkpoint.