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Noninvasive imaging-based assessment of tumor-associated neutrophils for prognosis and immunotherapy response in gastric cancer: a multicenter study 基于无创影像学评估肿瘤相关中性粒细胞对胃癌预后和免疫治疗反应的影响:一项多中心研究
IF 10.7 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2026-02-01 DOI: 10.1016/j.jare.2026.01.082
Wenbo Zheng, Zepang Sun, Wei Wang, James Edward Han, Md Tauhidul Islam, Wencheng Li, Qingyu Yuan, Chuanli Chen, Sujuan Xi, Zihan Li, Xiaoyan Wang, Lin Wu, Wenjun Xiong, Tao Chen, Guoxin Li, Zhenhui Li, Jiang Yu, Yuming Jiang

Introduction

Tumor-associated neutrophils (TAN) critically promote gastric cancer progression. However, current assessment relies on invasive biopsies that preclude serial monitoring. Noninvasive tools to quantify TAN infiltration are urgently required.

Objectives

To develop and validate a noninvasive, CT-based ensemble machine learning radiomic biomarker for mapping TAN infiltration in gastric cancer, and to assess its utility for prognosis stratification and the prediction of response to anti-PD-1 immunotherapy.

Methods

In this multicenter study of 2,170 gastric cancer patients across eight cohorts, we developed EnmlbaRB, an ensemble machine-learning-based CT radiomic biomarker. Portal venous-phase scans were processed to extract features, with mRMR-Boruta algorithms identifying 11 radiomic signatures (six peritumoral and five intratumoral signatures). These were integrated via a five-tier heterogeneous stacking architecture supervised by the immunohistochemistry-derived CD66b + TAN status (high/medium/low). The validation spanned six independent cohorts, including 177 anti-PD-1-treated patients.

Results

External validation demonstrated robust performance: EnmlbaRB predicted TAN status with an AUC of 0.71 (95%CI: 0.65–0.78) and 80.74% specificity. Critically, TAN-Low patients exhibited significantly superior 5-year overall survival compared to TAN-High across all cohorts (e.g., SYSUCC cohort: 64.12% vs. 46.78%, p < 0.05). In the anti-PD-1 cohorts, the TAN-Low subgroups achieved 1.9-fold higher disease control rates (83.9% vs 44.1%; p < 0.001) and significantly prolonged median progression-free survival (>41.9 vs 6.2 months; HR = 0.162, p < 0.001), establishing clear clinical utility for immunotherapy stratification.

Conclusions

This study is the first clinically validated noninvasive solution for mapping the TAN infiltration status in gastric cancer. EnmlbaRB effectively stratified the patients based on survival outcomes and immunotherapy responsiveness. This paradigm empowers clinicians to personalize therapeutic sequencing based on evolving TAN biology, thereby addressing the critical need for adaptive treatment strategies for advanced gastric cancer management.
肿瘤相关中性粒细胞(TAN)对胃癌的进展有重要的促进作用。然而,目前的评估依赖于侵入性活检,排除了串行监测。目前迫切需要量化TAN浸润的无创工具。目的开发和验证一种无创的、基于ct的集成机器学习放射组学生物标志物,用于胃癌中TAN的浸润,并评估其在预后分层和预测抗pd -1免疫治疗反应中的应用。在这项跨8个队列的2170名胃癌患者的多中心研究中,我们开发了EnmlbaRB,一种基于机器学习的集成CT放射组学生物标志物。门静脉期扫描被处理以提取特征,mRMR-Boruta算法识别11个放射特征(6个肿瘤周围和5个肿瘤内特征)。这些通过免疫组织化学衍生的CD66b + TAN状态(高/中/低)监督的五层异质堆叠架构进行整合。验证跨越6个独立队列,包括177名抗pd -1治疗的患者。结果外部验证表明,EnmlbaRB预测TAN状态的AUC为0.71 (95%CI: 0.65-0.78),特异性为80.74%。关键的是,在所有队列中,TAN-Low患者的5年总生存率明显优于TAN-High患者(例如,SYSUCC队列:64.12%对46.78%,p <; 0.05)。在抗pd -1队列中,TAN-Low亚组的疾病控制率提高了1.9倍(83.9% vs 44.1%; p <; 0.001),并显著延长了中位无进展生存期(>41.9 vs 6.2个月;HR = 0.162,p <; 0.001),为免疫治疗分层建立了明确的临床应用。结论本研究是第一个经临床验证的用于胃癌中TAN浸润状态的无创检测方法。EnmlbaRB基于生存结果和免疫治疗反应性有效地对患者进行分层。这种模式使临床医生能够基于不断发展的TAN生物学来个性化治疗测序,从而解决了晚期胃癌管理中适应性治疗策略的关键需求。
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引用次数: 0
HB023: A glutamine antagonist prodrug boosting antitumor lmmunity via PD-L1 suppression and mitochondrial membrane remodeling HB023:一种谷氨酰胺拮抗剂,通过抑制PD-L1和线粒体膜重塑增强抗肿瘤免疫
IF 10.7 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2026-02-01 DOI: 10.1016/j.jare.2026.01.077
Junyan Zhuang, Ye Chen, Yi Zhang, Yongrui Hai, Renming Fan, Jiarui Dou, Xintong Lu, Wenhui Wang, Bingjie Zhang, Zhuang Hou, Lei Liang, Yang Liu, Gaofei Wei

Introduction

Glutamine is a key nutrient that supports tumor cell metabolism, biosynthesis, and proliferation. It also shapes the tumor microenvironment and modulates cell death pathways. Glutamine antagonists have emerged as effective therapeutic agents by both disrupting tumor energy metabolism and enhancing antitumor immune responses. However, recent evidence reveals a paradoxical effect: glutamine deprivation can induce PD-L1 expression on tumor cells, facilitating immune escape and reducing the efficacy of immunotherapies.

Objectives

This study aims to overcome the immune evasion triggered by glutamine deprivation by developing a dual-functional therapeutic strategy that enhances metabolic stress while simultaneously inhibiting PD-L1 expression. The ultimate goal is to strengthen antitumor immunity and improve therapeutic outcomes.

Methods

We designed and synthesized a novel prodrug, HB023, by covalently linking a glutamine metabolism inhibitor with JQ1, a well-characterized PD-L1 inhibitor. We evaluated the effects of HB023 on tumor cell pyroptosis, energy metabolism, PD-L1 expression, T cell-mediated cytotoxicity, and macrophage polarization using a combination of in vitro cell-based assays and in vivo tumor models.

Results

HB023 significantly enhanced glutamine starvation in tumor cells, leading to increased pyroptosis and restricted energy supply. It effectively downregulated PD-L1 expression, which restored T cell cytotoxic activity. Additionally, HB023 induced mitochondrial membrane remodeling in macrophages, promoting M1 polarization and thereby enhancing innate immune responses. These mechanisms cooperatively activated both adaptive and innate antitumor immunity, thereby conferring HB023 with superior antitumor efficacy compared with JQ1, JHU083, or their combination.

Conclusion

HB023 successfully addresses the challenge of glutamine deprivation-induced immune escape by integrating metabolic inhibition with immune checkpoint blockade. This dual-modulatory approach reprograms the tumor immune microenvironment and improves immunotherapeutic efficacy, representing a promising strategy for advancing cancer treatment.
谷氨酰胺是支持肿瘤细胞代谢、生物合成和增殖的关键营养素。它还塑造肿瘤微环境并调节细胞死亡途径。谷氨酰胺拮抗剂通过破坏肿瘤能量代谢和增强抗肿瘤免疫反应而成为有效的治疗药物。然而,最近的证据揭示了一个矛盾的效应:谷氨酰胺剥夺可以诱导肿瘤细胞上的PD-L1表达,促进免疫逃逸,降低免疫治疗的效果。本研究旨在通过开发一种增强代谢应激同时抑制PD-L1表达的双功能治疗策略来克服由谷氨酰胺剥夺引发的免疫逃避。最终目的是增强抗肿瘤免疫,改善治疗效果。方法通过谷氨酰胺代谢抑制剂与PD-L1抑制剂JQ1的共价连接,设计并合成了一种新的前药HB023。我们利用体外细胞实验和体内肿瘤模型,评估了HB023对肿瘤细胞焦亡、能量代谢、PD-L1表达、T细胞介导的细胞毒性和巨噬细胞极化的影响。结果shb023显著增强肿瘤细胞的谷氨酰胺饥饿,导致细胞焦亡增加,能量供应受限。它能有效下调PD-L1的表达,从而恢复T细胞的细胞毒活性。此外,HB023诱导巨噬细胞线粒体膜重塑,促进M1极化,从而增强先天免疫应答。这些机制协同激活了适应性和先天抗肿瘤免疫,从而使HB023比JQ1、JHU083或它们的组合具有更好的抗肿瘤功效。结论hb023通过结合代谢抑制和免疫检查点阻断,成功解决了谷氨酰胺剥夺诱导的免疫逃逸的挑战。这种双调节方法重编程了肿瘤免疫微环境,提高了免疫治疗效果,代表了一种有前途的癌症治疗策略。
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引用次数: 0
Non-invasive and painless mid-infrared modulation increases collagen in human and mouse skin 非侵入性和无痛中红外调制增加胶原蛋白在人类和老鼠的皮肤
IF 10.7 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2026-01-30 DOI: 10.1016/j.jare.2026.01.069
Zeyu Wang, Jiahui Zhu, Yuting Wang, Tianxing Hu, Shuai Chen, Senlin Xu, Yaoying Li, Xiang Liao, Shanshan Liang, Yang Li, Xuanyue Wang, Sunny C. Li, Yan Yang, Hongbo Jia, Xiaowei Chen, Xing Fan, Lan Ge, Jianxiong Zhang
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引用次数: 0
Chromosome-level genome of wild-simulated Panax ginseng identifies SNP markers for germplasm and medicinal quality evaluation 模拟野生人参染色体水平基因组鉴定种质和药用质量评价SNP标记
IF 10.7 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2026-01-30 DOI: 10.1016/j.jare.2026.01.062
Xuejiao Liao, Yidan Xi, Baosheng Liao, Shuiming Xiao, Shuai Guo, Haoyu Hu, Zhihai Huang, Deqiang Dou, Shilin Chen, Jiang Xu
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引用次数: 0
Simultaneous engineering of the surface (oxygen/amorphous carbon) and interface (amorphous carbon/ZnO) of ZnO using a one-spoon amorphous carbon deposition technique 采用一勺非晶碳沉积技术对ZnO的表面(氧/非晶碳)和界面(非晶碳/ZnO)进行同步工程处理
IF 10.7 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2026-01-30 DOI: 10.1016/j.jare.2026.01.057
Jimyeong Park, Minseo Kim, Changhyun Jin, Kyu Hyoung Lee, Myung Sik Choi
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引用次数: 0
Unmasking human T cell receptor germline diversity: 335 novel alleles identified in 47 Pangenome reference individuals using the gAIRR Suite 揭示人类T细胞受体种系多样性:使用gAIRR套件在47个泛基因组参考个体中鉴定出335个新的等位基因
IF 10.7 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2026-01-30 DOI: 10.1016/j.jare.2026.01.053
Yu-Hsuan Yang, Chi-Yuan Yao, Mao-Jan Lin, Kuan-Ta Huang, Yu-Hui Lin, Yi-Hui Huang, I-Hsuan Chiu, Sheng-Kai Lai, Chih-Yeh Chen, Ya-Chien Yang, Chia-Lang Hsu, Jacob Shujui Hsu, Chien-Yu Chen, Pei-Lung Chen
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引用次数: 0
Asprosin-driven metabolic-epigenetic rewiring attenuates mesenchymal stem cell senescence with therapeutic benefits for infarcted hearts 阿斯桃素驱动的代谢-表观遗传重布线减轻间充质干细胞衰老,对梗死心脏有治疗益处
IF 10.7 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2026-01-30 DOI: 10.1016/j.jare.2026.01.073
Zhengbin Zhang, Ziqian Wang, Liwen Zhu, Tong Chen, Rundu Chen, Zhengfeng Wu, Jie Chen, Honghong Zhang, Mingyi Wang, Jie Liu, Ning Hua, Shunying Hu, Yundai Chen
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引用次数: 0
Skin regeneration axis under metal-based nanozymes: from chronic wound healing to structural and functional restoration 金属基纳米酶的皮肤再生轴:从慢性伤口愈合到结构和功能修复
IF 10.7 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2026-01-30 DOI: 10.1016/j.jare.2026.01.068
Ze-Ming Zhuang, Kai Guo, Zhang-Rui Wu, Yi Wang, Xin-Cao Zhong, Chun-Ye Chen, Zi-Xuan Feng, Yan-Ze Yu, Hai-Qi Zhang, Min-Hong Tan, Tao Zhang, Xiao-Ying Lin, Yong Wang, Wei-Qiang Tan
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引用次数: 0
Cellular and molecular mechanisms of nasolacrimal duct obstruction: New insights into CD4+ T cell-MIF-fibroblast pathways 鼻泪管阻塞的细胞和分子机制:对CD4+ T细胞- mif -成纤维细胞通路的新认识
IF 10.7 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2026-01-28 DOI: 10.1016/j.jare.2026.01.060
Xinyue Yu, Shanshan Liu, Youao Zhang, Rongxin Chen, Chaojuan Wen, Jingya Zhu, Xielan Kuang, Kerui Wang, Hao Huang, Yan Mao, Ping Xu, Jianhua Yan, Qingjiong Zhang, Xuanwei Liang, Huangxuan Shen
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引用次数: 0
An injectable microsphere-reinforced system for sustained delivery of Adipo-MBV in adipose tissue engineering 脂肪组织工程中用于持续递送Adipo-MBV的可注射微球增强系统
IF 10.7 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2026-01-27 DOI: 10.1016/j.jare.2026.01.058
Mmi Xu, Jianwei Chen, Yi Sun, Han Yang, Hongli Ji, Tao Xu, Feng Lu, Yunfan He
Tissue engineering has become prominence in soft-tissue reconstruction. Adipogenesis and angiogenesis are important in the formation of engineering adipose tissue. Although acellular adipose matrix (AAM) possesses potential in adipogenic induction, obvious limitations remain in the realization of the authentic physiological regeneration. Matrix-bound nanovesicles (MBVs), located on the extracellular matrix (ECM) scaffold, provide cues for the adipogenesis property of AAM. The bioactive components within ECM are influenced by the isolation procedures.
组织工程已成为软组织重建的重点。脂肪生成和血管生成是工程脂肪组织形成的重要过程。虽然脱细胞脂肪基质(AAM)具有诱导脂肪生成的潜力,但在实现真正的生理再生方面仍存在明显的局限性。位于细胞外基质(ECM)支架上的基质结合纳米囊泡(mbv)为AAM的脂肪形成特性提供了线索。ECM中的生物活性成分受分离过程的影响。
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引用次数: 0
期刊
Journal of Advanced Research
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