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In edge computing scenarios for remote sensing image interpretation, two fundamental challenges constrain the effectiveness of federated fine-tuning: the limited computational capacity of edge devices restricts the multi-scale feature learning capability of lightweight deployed models, while the highly heterogeneous and imbalanced data distributions (Non-IID settings) across clients render conventional parameter aggregation strategies ineffective. To address these challenges jointly, this paper proposes Fed-RSAdapter, a federated fine-tuning framework for remote sensing imagery based on multi-scale adapter modules. On the edge side, a multi-scale adapter architecture with cross-layer dense connections and feature map concatenation alignment is introduced. By inserting lightweight adapter modules in parallel within a frozen backbone, the proposed design captures multi-scale spatial characteristics inherent in high-resolution remote sensing imagery while confining trainable parameters to less than 5% of the full model, thereby satisfying strict on-device computational and communication constraints. On the server side, a parameter similarity-aware aggregation strategy is designed to handle client heterogeneity. Client adapter parameters are normalized and mapped into a similarity matrix via Gaussian kernel distance, enabling the server to perform personalized weighted aggregation that balances global generalization with client-specific adaptation. Extensive experiments on scene classification, object detection, and semantic segmentation benchmarks demonstrate that Fed-RSAdapter achieves an average improvement of 3.75% in overall accuracy for scene classification, 0.74% in mAP for object detection, and 0.25% in overall accuracy for semantic segmentation over federated baselines, while reducing the volume of transmitted parameters to approximately 4.93% of that required by conventional full-parameter federated learning. These results demonstrate the communication-efficient fine-tuning capability of the proposed framework under federated remote sensing settings. We further clarify that actual deployment on embedded edge hardware is not directly evaluated in this work and is therefore treated as an important direction for future validation rather than an experimentally proven conclusion.

Background A large number of Fusobacterium nucleatum (Fn) are present in colorectal cancer (CRC) tissues of patients who relapse after chemotherapy, and Fn has been reported to promote oxaliplatin and 5-FU chemoresistance in CRC. Pathogens such as bacteria and parasites stimulate exosome production in tumor cells, and the regulatory mechanism of exosomal circRNA in the transmission of oxaliplatin and 5-FU chemotherapy resistance in Fn-infected CRC remains unclear. Methods Hsa_circ_0004085 was screened by second-generation sequencing of CRC tissues. The correlation between hsa_circ_0004085 and patient clinical response to oxaliplatin/5-FU was analyzed. Exosome tracing experiments and live imaging systems were used to test the effect of Fn infection in CRC on the distribution of hsa_circ_0004085. Colony formation, ER tracking analysis and immunofluorescence were carried out to verify the regulatory effect of exosomes produced by Fn-infected CRC cells on chemotherapeutic resistance and ER stress. RNA pulldown, LC–MS/MS analysis and RIP were used to explore the regulatory mechanism of downstream target genes by hsa_circ_0004085. Results First, we screened out hsa_circ_0004085 with abnormally high expression in CRC clinical samples infected with Fn and found that patients with high expression of hsa_circ_0004085 in plasma had a poor clinical response to oxaliplatin/5-FU. Subsequently, the circular structure of hsa_circ_0004085 was identified. Fn infection promoted hsa_circ_0004085 formation by hnRNP L and packaged hsa_circ_0004085 into exosomes by hnRNP A1. Exosomes produced by Fn-infected CRC cells transferred hsa_circ_0004085 between cells and delivered oxaliplatin/5-FU resistance to recipient cells by relieving ER stress. Hsa_circ_0004085 enhanced the stability of GRP78 mRNA by binding to RRBP1 and promoted the nuclear translocation of ATF6p50 to relieve ER stress. Conclusions Plasma levels of hsa_circ_0004085 are increased in colon cancer patients with intracellular Fn and are associated with a poor response to oxaliplatin/5-FU. Fn infection promoted hsa_circ_0004085 formation by hnRNP L and packaged hsa_circ_0004085 into exosomes by hnRNP A1. Exosomes secreted by Fn-infected CRC cells deliver hsa_circ_0004085 between cells. Hsa_circ_0004085 relieves ER stress in recipient cells by regulating GRP78 and ATF6p50, thereby delivering resistance to oxaliplatin and 5-FU. Graphical Abstract

Human epidermal growth factor receptor 2 (HER2) is a protein that is overexpressed in some types of cancer, including breast and urothelial cancer. Here we found that HER2 was present in a portion of colon cancer patients, raising the possibility of using anti-HER2 therapy. RC48, a novel antibody-drug conjugate (ADC) comprising cytotoxic monomethyl auristatin E (MMAE) and an anti-HER2 antibody tethered via a linker, showed a comparable therapeutic effect in both HER2 low expressed (IHC2+/FISH- or IHC+) and high expressed urothelial cancer patients. In vitro studies using colon cancer cell lines showed that RC48 effectively impeded the proliferation of HER2-positive cells, indicating its potential as a treatment for HER2-positive colon cancer. Mechanism study showed that RC48 not only induces cell cycle arrest but also disrupts HER2-mediated restain of cGAS-STING signaling, potentially activating an immune response against the cancer cells. The administration of RC48 significantly reduced the growth of HER2-positive colon cancer and made HER2-positive colon cancer cells more susceptible to immunotherapy. The results of our study will contribute to determining the feasibility of RC48 as a therapeutic option for HER2-positive colon cancer.

Pancreatic cancer is one of the most malignant tumors due to its highly aggressive nature, but pancreatic metastases to the colorectum are extremely rare. A 43-year-old male patient complained of increased stool frequency. Colonoscopy revealed a prominence lesion in the rectum and computed tomography (CT) scan confirmed a rectal mass. CT scan also showed retroperitoneal masses in the pancreatic tail involving the spleen and adjacent blood vessels. The patient was initially misdiagnosed as having rectal cancer with pancreatic metastasis. After immunohistochemical staining results became available, the diagnosis was changed to pancreatic ductal adenocarcinoma with rectal metastasis. Elevated CA19-9 also supported the diagnosis. In conclusion, we describe a case of synchronous colonic metastasis from pancreatic cancer. Although rare, the suspicion of pancreatic metastases to the rectum should be excluded when a patient has both rectal and pancreatic masses.

The efficacy and safety of induction-immunotherapy followed by surgery for unresectable Stage III non-small cell lung cancer (NSCLC) remain challenging. In this open-label, single-center, phase II clinical umbrella trial (ChiCTR2000035367), 100 unresectable Stage III NSCLC patients are enrolled. Patients with PD-L1 expression ≥ 50% but contraindications to anti-angiogenic therapy receive immuno-monotherapy. Patients with PD-L1 expression ≥ 1% and no contraindications to anti-angiogenic therapy receive immunotherapy plus anti-angiogenesis therapy. Patients with PD-L1 expression between 1% and 49%, contraindications to anti-angiogenic therapy, or negative/unknown PD-L1 expression receive chemoimmunotherapy. The primary endpoint is the major pathological response (MPR) rate. Among 47 surgically-treated patients, the MPR rate is 61.7% (95% confidence interval [CI]: 46.4%-75.5%), achieving the prespecified endpoint. For secondary endpoints, the objective response rate for all patients is 54.0% (95% CI: 43.7-64.0). The median event-free survival is 29.9 months (95% CI: 17.0-42.7). Most common adverse event is anemia (49.0%). Exploratory transcriptomic analyses reveal Bone Marrow Stromal Cell Antigen 1 (BST1) as a promising biomarker for response to chemoimmunotherapy. Generally, for unresectable stage III NSCLC patients, anti-PD1 based induction-therapy according to PD-L1 expression and contraindication to antiangiogenic therapy followed by surgery is a feasible option. Induction-immunotherapy before surgery has been suggested for patients with unresectable stage III non-small cell lung cancer (NSCLC). Here, the authors report a phase 2 umbrella clinical trial where patients with unresectable stage III NSCLC receive anti-PD1-based induction-therapy based on PD-L1 expression and contraindications to antiangiogenic therapy.

Aumolertinib, a third-generation epidermal growth factor receptor tyrosine kinase inhibitor ( EGFR -TKI), is widely utilized for advanced EGFR -mutant non-small cell lung cancer patients (NSCLCm). This single-arm, phase II trial (NCT04685070) assessed the feasibility of neoadjuvant Aumolertinib for unresectable stage III NSCLCm. Fifty-six patients were enrolled, with 51 participants receiving neoadjuvant Aumolertinib (110 mg/day, orally) and forming the intention-to-treat population. The primary endpoint was objective response rate (ORR). Secondary endpoints included major pathological response (MPR) rate, pathological complete response (pCR) rate, complete (R0) resection rate, event-free survival (EFS), overall survival (OS), and treatment-related adverse events (TRAEs). The ORR was 70.6% (95% confidence interval: 58%-84%), meeting the pre-specified primary endpoint. Additionally, twenty-three (45.1%) participants converted into resectable disease and underwent surgery. Among them, R0 resection, MPR and pCR rates were 100%, 21.7%, and 13.0%, respectively. The median EFS and OS were not reached. While, the 1- and 2-year EFS rates were 88.2% and 58.8%, respectively. Fatigue (49.0%), alanine aminotransferase concentration elevation (39.2%), and rash (35.3%) were the most common treatment-related adverse events (TRAEs). Grade 3/4 TRAEs occurred in 5 patients (9.8%), and no grade 5 TRAE was recorded. RNA-sequencing based analysis revealed increased infiltration of CD8 + T-cells in post-treatment tumors compared to baseline, particularly in responsive and Ex19-Del mutation tumors. Collectively, neoadjuvant Aumolertinib showed promising efficacy and a surgical conversion rate with a tolerable safety profile for unresecable NSCLCm in stage III, potentially involved in the remodeling of tumor microenvironment. Aumolertinib is a third generation EGFR tyrosine kinase inhibitors, approved for use in patients with advanced EGFR-mutant non-small cell lung cancer (NSCLC). Here, the authors report a phase 2 clinical trial investigating neoadjuvant aumolertinib in patients with unresectable stage III EGFR-mutant NSCLC.

A large number of Fusobacterium nucleatum (Fn) are present in colorectal cancer (CRC) tissues of patients who relapse after chemotherapy, and Fn has been reported to promote oxaliplatin and 5-FU chemoresistance in CRC. Pathogens such as bacteria and parasites stimulate exosome production in tumor cells, and the regulatory mechanism of exosomal circRNA in the transmission of oxaliplatin and 5-FU chemotherapy resistance in Fn-infected CRC remains unclear. Hsa_(c)irc₀004085 was screened by second-generation sequencing of CRC tissues. The correlation between hsa_(c)irc₀004085 and patient clinical response to oxaliplatin/5-FU was analyzed. Exosome tracing experiments and live imaging systems were used to test the effect of Fn infection in CRC on the distribution of hsa_(c)irc₀004085. Colony formation, ER tracking analysis and immunofluorescence were carried out to verify the regulatory effect of exosomes produced by Fn-infected CRC cells on chemotherapeutic resistance and ER stress. RNA pulldown, LC-MS/MS analysis and RIP were used to explore the regulatory mechanism of downstream target genes by hsa_(c)irc₀004085. First, we screened out hsa_(c)irc₀004085 with abnormally high expression in CRC clinical samples infected with Fn and found that patients with high expression of hsa_(c)irc₀004085 in plasma had a poor clinical response to oxaliplatin/5-FU. Subsequently, the circular structure of hsa_(c)irc₀004085 was identified. Fn infection promoted hsa_(c)irc₀004085 formation by hnRNP L and packaged hsa_(c)irc₀004085 into exosomes by hnRNP A1. Exosomes produced by Fn-infected CRC cells transferred hsa_(c)irc₀004085 between cells and delivered oxaliplatin/5-FU resistance to recipient cells by relieving ER stress. Hsa_(c)irc₀004085 enhanced the stability of GRP78 mRNA by binding to RRBP1 and promoted the nuclear translocation of ATF6p50 to relieve ER stress. Plasma levels of hsa_(c)irc₀004085 are increased in colon cancer patients with intracellular Fn and are associated with a poor response to oxaliplatin/5-FU. Fn infection promoted hsa_(c)irc₀004085 formation by hnRNP L and packaged hsa_(c)irc₀004085 into exosomes by hnRNP A1. Exosomes secreted by Fn-infected CRC cells deliver hsa_(c)irc₀004085 between cells. Hsa_(c)irc₀004085 relieves ER stress in recipient cells by regulating GRP78 and ATF6p50, thereby delivering resistance to oxaliplatin and 5-FU.

Background Body temperature (BT) is routinely measured and can be controlled in critical care settings. BT can impact patient outcome, but the relationship between BT and mortality has not been well-established. Methods A retrospective cohort study was conducted based on the MIMIC-IV ( N  = 43,537) and eICU ( N  = 75,184) datasets. The primary outcome and exposure variables were hospital mortality and first 48-h median BT, respectively. Generalized additive models were used to model the associations between exposures and outcomes, while adjusting for patient age, sex, APS-III, SOFA, and Charlson comorbidity scores, temperature gap, as well as ventilation, vasopressor, steroids, and dialysis usage. We conducted subgroup analysis according to ICU setting, diagnoses, and demographics. Results Optimal BT was 37 °C for the general ICU and subgroup populations. A 10% increase in the proportion of time that BT was within the 36–38 °C range was associated with reduced hospital mortality risk in both MIMIC-IV (OR 0.91; 95% CI 0.90–0.93) and eICU (OR 0.86; 95% CI 0.85–0.87). On the other hand, a 10% increase in the proportion of time when BT < 36 °C was associated with increased mortality risk in both MIMIC-IV (OR 1.08; 95% CI 1.06–1.10) and eICU (OR 1.18; 95% CI 1.16–1.19). Similarly, a 10% increase in the proportion of time when BT > 38 °C was associated with increased mortality risk in both MIMIC-IV (OR 1.09; 95% CI 1.07–1.12) and eICU (OR 1.09; 95% CI 1.08–1.11). All patient subgroups tested consistently showed an optimal temperature within the 36–38 °C range. Conclusions A BT of 37 °C is associated with the lowest mortality risk among ICU patients. Further studies to explore the causal relationship between the optimal BT and mortality should be conducted and may help with establishing guidelines for active BT management in critical care settings.

Immunochemotherapy has shown promising outcomes in treating small-cell lung cancer. To explore whether surgery after immunochemotherapy benefits patients with stage I‒III small-cell lung cancer, we conducted a phase II trial (NCT04539977). Eligible patients received four cycles of anti-PD-L1 antibody (TQB2450) therapy and chemotherapy, followed by surgery or radiotherapy and one-year maintenance immunotherapy (TQB2450). Forty patients were enrolled between December 2020 and January 2023. Thirty-eight (95.0%) patients had stage III disease. We found that the objective response rate, as the primary endpoint of this study, was 92.5% (95% CI: 83.9%‒100%) in the intention-to-treat population. At a median follow-up of 25.8 months, the median event-free survival (EFS) was 16.2 months. The median overall survival (OS) was not reached. The major pathological response and pathological complete response rate of operative patients ( n  = 21) were 61.9% and 42.9%, respectively. The 24-month EFS and 24-month OS of operative patients were 61.9% and 85.7%, respectively. All patients with N1 disease ( n  = 9) underwent surgery, with the 24-month EFS of 66.7% and 24-month OS of 88.9%. The most common TQB2450-specific adverse event was rash of grade 1‒2 (12.5%). We further explored the biomarker of immunochemotherapy and molecular changes during immunochemotherapy through bulk-RNA sequencing and whole-exome sequencing. We demonstrated that PRSS8 was a potential biomarker for poor effectiveness of immunochemotherapy. In conclusion, surgery after neoadjuvant immunochemotherapy is feasible for treating patients with stage I‒III small-cell lung cancer.

In the context of inverse reinforcement learning (IRL) with a single expert, adversarial inverse reinforcement learning (AIRL) serves as a foundational approach to providing comprehensive and transferable task descriptions. However, AIRL faces practical performance challenges, primarily stemming from the framework's overly idealized decomposability condition, the unclear proof regarding the potential equilibrium in reward recovery, or questionable robustness in high-dimensional environments. This paper revisits AIRL in high-dimensional scenarios where the state space tends to infinity. Specifically, we first establish a necessary and sufficient condition for reward transferability by examining the rank of the matrix derived from subtracting the identity matrix from the transition matrix. Furthermore, leveraging random matrix theory, we analyze the spectral distribution of this matrix, demonstrating that our rank criterion holds with high probability even when the transition matrices are unobservable. This suggests that the limitations on transfer are not inherent to the AIRL framework itself, but are instead related to the training variance of the reinforcement learning algorithms employed within it. Based on this insight, we propose a hybrid framework that integrates on-policy proximal policy optimization in the source environment with off-policy soft actor-critic in the target environment, leading to significant improvements in reward transfer effectiveness.