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Relapsed or refractory acute myeloid leukemia (R/R AML) characterized by aberrant myeloid cell production in the bone marrow (BM) was challenged by a lack of potent therapeutics.Human iPSC-derived nature killer cells (iNKs), as a potent cellular therapy for R/R AML, show limited BM infiltration due to low expression of the BM homing chemokine receptor (C-X-C chemokine receptor type 4, CXCR4).While engineering iPSC with high CXCR4 expression hampers its differentiation to hematopoietic stem cells, this limitation can be circumvented by regulatable CXCR4 expression at the iNK stage through genetic engineering.CXCR4-iNKs exhibit improved cytotoxicity against BM-resident tumors, and this efficacy could be further augmented by the incorporation of chimeric antigen receptor targeting AML antigens. iPSC-derived natural killer cells (iNKs) have emerged as a promising cellular therapy, especially for the refractory or relapsed acute myeloid leukemia (R/R AML) patients, but limited research focused on the chemotaxis of iNKs. Here we demonstrate that C-X-C chemokine receptor type 4 (CXCR4) is significantly reduced in iNKs, resulting in impaired bone marrow (BM) infiltration, which cannot be rescued by constitutively expressed CXCR4 in iPSC due to CXCR4-induced differentiation failure. To address this, we developed a strategy to allow specific expression of CXCR4 during the iNK maturation stage without compromising the final iNK yield and function. The engineered iNKs exhibited enhanced BM infiltration, resulting in improved therapeutic effects in AML murine models. This, brought attention to iNK chemotaxis, provided a meaningful strategy by incorporating well-designed gene editing with stem cells for cell product development, and obtained improved effective NK cells for AML therapy. [Display omitted] iPSCs provide an ideal resource for generating immune cells, with well-established methodologies enabling the derivation of diverse cell types, including natural killer (NK) cells (iNKs). These iNKs have exhibited cytotoxicity against a range of cancers, including both hematologic and solid malignancies, thereby presenting a promising approach for cell-based therapies. In this study, we integrated iNK differentiation with CRISPR-based gene editing to develop cell products with enhanced antitumor functionality. This technology has currently achieved Technology Readiness Level (TRL) 5, indicating it is feasible to advance to clinical trials. Specifically, the expression of CXCR4 was challenged by its effect on hematopoietic stem cell (HSC) differentiation, which resulted in limited infiltration of final iNKs into bone marrow. Through precise genetic engineering techniques, we established a regulatable gene expression system to mitigate potential adverse effects during the differentiation process. This study underscores the importance of in vivo distribution and chemotaxis profiling in the development of cell-based product, highlighting the need for the optimization of manufacturing processes. In this study, He et al. developed an optimized method that combines iPSC differentiation, chemotaxis regulation, and genetic engineering to produce a potential iPSC-derived nature killer cells product with enhanced therapeutic efficacy against bone marrow-resident tumors, such as acute myeloid leukemia and multiple myeloma.

TP391.4; 光场成像存在空间和角度分辨率折衷问题,导致从光场中提取角点及直线特征的精度不高,影响光场相机标定精度,为此提出了一种基于离心圆共自配极三角形的光场相机标定方法.分析了离心圆极点-极线关系,推导了离心圆共自配极三角形的性质.根据光场相机多投影中心模型对平面及二次曲面的映射,设计了一种离心圆标定板,重建了共自配极三角形并计算平面单应,实现了基于离心圆共自配极三角形的光场相机标定的线性初始化和非线性优化方法.仿真和真实数据上的实验结果表明该方法可精确标定光场相机,且稳定便捷.

为摸清粮食主产区耕地非粮化的总体状况，揭示非粮化的空间分异特征及其成因，以徐州市为研究区域，运用空间自相关分析法、冗余分析法与案例分析法，研究粮食主产区非粮化空间分异特征、主导因素及其作用机制。研究表明：徐州市法定耕地内（LF，10.25%）、永久基本农田范围内（BF，7.30%）、两区划定范围内（FF，2.67%）非粮化率呈依次递减态势，城区非粮化率高于远郊；非粮化面积超过500 hm2的乡镇为6个，分布于远郊南部和西北角，但非粮化率则从中心向远郊递减扩散。非粮化率在FF范围内存在2个高-高集聚区，不同于LF和BF，城区周边明显高于其他区域；RDA分析显示社会经济变量解释了91.85%的非粮化面积特征向量的变化，主要驱动因子包含常住人口、农业人口、农业收入、土地流转率、农业机械总动力，其中非农业收入和农业机械劳动力分别是城区与远郊的关键驱动因子。研究表明，粮食主产区非粮化率总体不高，以菜地占用为主，但不同范围、不同区位非粮化率差异明显，必须高度重视并谨慎对待社会经济因素驱动作用。

线粒体DNA（mtDNA）的异质性（heteroplasmy）是多种不同序列的mtDNA拷贝共存于一个个体的现象，对线粒体、细胞和组织的机能产生明显的影响。粪便是野生动物研究中最易得的材料，含有动物肠上皮脱落的细胞及其DNA，其中的mtDNA异质性可以反映个体在各种因素影响下肠上皮细胞DNA的稳定性，为揭示个体的适合度、生态对策等提供新的线索。梅花鹿（Cervus nippon）是森林生态系统中的关键物种，其肠上皮中mtDNA异质性的特点尚未见报道。本研究用27只6～96月龄的圈养梅花鹿粪便样本，采用PCR扩增子高通量测序技术，对mtDNA D-loop区的异质性进行定量分析。结果显示：D-loop区广泛分布着异质性位点，但相对集中于第175～368位碱基的高变区（HyperHPR），而第597～687位碱基区间则较少发生，为保守区（HypoHPR）。HyperHPR异质性突变的多样性（HDα）极显著高于HypoHPR（P < 0.001）。转换（TS）是主要碱基替换类型，其发生频率远高于颠换（TV）。HyperHPR中TS/TV平均为0.11，而HypoHPR平均为0.19，说明异质性突变在HypoHPR受到更强的选择性清除。无论是在D-loop区、HyperHPR与HypoHPR，雌雄个体之间异质性突变指标均无显著差异（D-loop区，