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Abstract: Over the past decade, the field of holography has gained significant ground due to advances in computational imaging. However, the utilization of computational tools is hampered by the mismatch between experimental setups and the conceptual model. Differentiable holography (), a novel framework for automatically self‐calibrating experimental imperfections in inverse holographic imaging, is presented here. The technique is demonstrated on auto‐focused complex field imaging from a single intensity‐only inline hologram.

Abstract Background T cells play a pivotal role in chemotherapy-triggered anti-tumor effects. Emerging evidence underscores the link between impaired anti-tumor immune responses and resistance to paclitaxel therapy in triple-negative breast cancer (TNBC). Tumor-related endothelial cells (ECs) have potential immunoregulatory activity. However, how ECs regulate T cell activity during TNBC chemotherapy remains poorly understood. Methods Single-cell analysis of ECs in patients with TNBC receiving paclitaxel therapy was performed using an accessible single-cell RNA sequencing (scRNA-seq) dataset to identify key EC subtypes and their immune characteristics. An integrated analysis of a tumor-bearing mouse model, immunofluorescence, and a spatial transcriptome dataset revealed the spatial relationship between ECs, especially Tumor necrosis factor receptor (TNFR) 2+ ECs, and CD8+ T cells. RNA sequencing, CD8+ T cell proliferation assays, flow cytometry, and bioinformatic analyses were performed to explore the immunosuppressive function of TNFR2 in ECs. The downstream metabolic mechanism of TNFR2 was further investigated using RNA sequencing, cellular glycolysis assays, and western blotting. Results In this study, we identified an immunoregulatory EC subtype, characterized by enhanced TNFR2 expression in non-responders. By a mouse model of TNBC, we revealed a dynamic reduction in the proportion of the CD8+ T cell-contacting tumor vessels that could co-localize spatially with CD8+ T cells during chemotherapy and an increased expression of TNFR2 by ECs. TNFR2 suppresses glycolytic activity in ECs by activating NF-κB signaling in vitro. Tuning endothelial glycolysis enhances programmed death-ligand (PD-L) 1-dependent inhibitory capacity, thereby inducing CD8+ T cell suppression. In addition, TNFR2+ ECs showed a greater spatial affinity for exhausted CD8+ T cells than for non-exhausted CD8+ T cells. TNFR2 blockade restores impaired anti-tumor immunity in vivo, leading to the loss of PD-L1 expression by ECs and enhancement of CD8+ T cell infiltration into the tumors. Conclusions These findings reveal the suppression of CD8+ T cells by ECs in chemoresistance and indicate the critical role of TNFR2 in driving the immunosuppressive capacity of ECs via tuning glycolysis. Targeting endothelial TNFR2 may serve as a potent strategy for treating TNBC with paclitaxel.

Abstract Activating interferon responses with STING agonists (STINGa) is a current cancer immunotherapy strategy, and therapeutic modalities that enable tumor-targeted delivery via systemic administration could be beneficial. Here we demonstrate that tumor cell-directed STING agonist antibody-drug-conjugates (STINGa ADCs) activate STING in tumor cells and myeloid cells and induce anti-tumor innate immune responses in in vitro, in vivo (in female mice), and ex vivo tumor models. We show that the tumor cell-directed STINGa ADCs are internalized into myeloid cells by Fcγ-receptor-I in a tumor antigen-dependent manner. Systemic administration of STINGa ADCs in mice leads to STING activation in tumors, with increased anti-tumor activity and reduced serum cytokine elevations compared to a free STING agonist. Furthermore, STINGa ADCs induce type III interferons, which contribute to the anti-tumor activity by upregulating type I interferon and other key chemokines/cytokines. These findings reveal an important role for type III interferons in the anti-tumor activity elicited by STING agonism and provide rationale for the clinical development of tumor cell-directed STINGa ADCs.

Abstract During the ageing process, TNF‐α can promote the expansion of myeloid‐derived suppressor cells (MDSCs). However, it remains unclear which receptor(s) of TNF‐α are involved in and how they modulate this process. Here, we report that TNFR2 hyperexpression induced by either TNF‐α or IL‐6, two proinflammatory factors of senescence‐associated secretory phenotype (SASP), causes cellular apolarity and differentiation inhibition in aged MDSCs. Ex vivo overexpression of TNFR2 in young MDSCs inhibited their polarity and differentiation, whereas in vivo depletion of Tnfr2 in aged MDSCs promotes their differentiation. Consequently, the age‐dependent increase of TNFR2 versus unaltered TNFR1 expression in aged MDSCs significantly shifts the balance of TNF‐α signaling toward the TNFR2–JNK axis, which accounts for JNK‐induced impairment of cell polarity and differentiation failure of aged MDSCs. Consistently, inhibiting JNK attenuates apolarity and partially restores the differentiation capacity of aged MDSCs, suggesting that upregulated TNFR2/JNK signaling is a key factor limiting MDSC differentiation during organismal ageing. Therefore, abnormal hyperexpression of TNFR2 represents a general mechanism by which extrinsic SASP signals disrupt intrinsic cell polarity behavior, thereby arresting mature differentiation of MDSCs with ageing, suggesting that TNFR2 could be a potential therapeutic target for intervention of ageing through rejuvenation of aged MDSCs.

Abstract Increasing the application of nitrogen fertilizer is the main approach to increase rice production, but it also brings problems of environmental pollution and increases agricultural production costs. Cultivating high‐yielding and high nitrogen use efficiency (NUE) rice varieties is an important approach to solving this problem. The rice varieties carrying dep1 (dense and erect panicle 1) have both high grain yield and high NUE. However, their plant traits have not been fully explored. In this study, two rice near‐isogenic lines carrying dep1 (NIL‐DEP1 and NIL‐dep1) were grown in paddy fields under 0, 120 and 270 kg N ha−1. We analyzed agronomic traits of panicle type, plant type, leaves and roots, and physiological traits of vascular bundles, photosynthetic rate and carbon and nitrogen transport. The results showed that the NIL‐dep1 exhibited higher grain yield and NUE than NIL‐DEP1, mainly due to the higher spikelet number per panicle, grain filling percentage and dry matter production. Compared with NIL‐DEP1, NIL‐dep1 had improved flag leaf morpho–physiological traits, including erect flag leaves, greater leaf thickness and specific leaf weight, higher root dry weight, root length, root volume and root surface area, and a better canopy structure, as reflected by a lower light interception percent and canopy extinction coefficient, leading to better photosynthetic performance and dry matter production. In addition, NIL‐dep1 exhibited better vascular bundle traits of peduncle and enhanced dry matter, stem carbon and nitrogen translocation during grain filling. In conclusion, NIL‐dep1 had high grain yield and NUE by improved agronomic and physiological traits and increasing carbon and nitrogen translocation during grain filling. These traits mentioned above could be used to select and breed high grain yield with high NUE rice varieties.

Rapid diagnosis and real-time monitoring are of great important in the fight against cancer. However, most available diagnostic technologies are time-consuming and labor-intensive and are commonly invasive. Here, we describe CytoExam, an automatic liquid biopsy instrument designed based on inertial microfluidics and impedance cytometry, which uses a deep learning algorithm for the analysis of circulating tumor cells (CTCs). In silico and in vitro experiments demonstrated that CytoExam could achieve label-free detection of CTCs in the peripheral blood of cancer patients within 15 min. The clinical applicability of CytoExam was also verified using peripheral blood samples from 10 healthy donors and >50 patients with breast, colorectal, or lung cancer. Significant differences in the number of collected cells and predicted CTCs were observed between the 2 groups, with variations in the dielectric properties of the collected cells from cancer patients also being observed. The ultra-fast and minimally invasive features of CytoExam may pave the way for new paths for cancer diagnosis and scientific research.

The performance and operational stability of non-clogging pumps can be affected by cavitation. To accurately identify the cavitation state of the non-clogging pump and provide technical references for monitoring its operation, a study was conducted on the optimization of Elman neural networks for cavitation monitoring and identification using the Improved Lévy Flight Bat Algorithm (ILBA) on the basis of the traditional Bat Algorithm (BA). The ILBA employs multiple bats to interact and search for targets and utilizes the local search strategy of Lévy flight, effectively avoiding local minima by taking advantage of the non-uniform random walk characteristics of large jumps. The ILBA algorithm demonstrates superior performance compared to other traditional algorithms through simulation testing and comparative calculations with eight benchmark test functions. On this basis, the optimization of the weights and thresholds of the Elman neural network was carried out by the improved bat algorithm. This leads to an enhancement in the accuracy of the neural network for identifying and classifying cavitation data, and the establishment of the ILBA-Elman cavitation diagnosis model was achieved. Collect pressure pulsation signals at the tongue of the non-clogging pump volute through cavitation tests. Through the cavitation feature extraction method based on Variational Mode Decomposition (VMD) and Multi-scale Dispersion Entropy (MDE), the interference signal can be effectively suppressed and the complexity of the time series can be measured from multiple angles, thereby creating a cavitation feature data set. The improved cavitation diagnosis model (ILBA-Elman) can realize the effective identification of the cavitation characteristics of non-clogging pumps through a variety of algorithm comparison experiments.

Abstract Cancer-associated fibroblasts (CAFs), the principal constituent of the heterogenous tumor microenvironment, have been shown to promote tumor progression; however, the underlying mechanism is still less clear. Here, we find that transgelin (TAGLN) protein levels increased in primary CAFs isolated from human lung cancer, compared with those in paired normal fibroblasts. Tumor microarrays (TMAs) revealed that increased stromal TAGLN levels correlates with more lymphatic metastasis of tumor cells. In a subcutaneous tumor transplantation model, overexpression of Tagln in fibroblasts also increased tumor cell spread in mice. Further experiments show that Tagln overexpression promoted fibroblast activation and mobility in vitro. And TAGLN facilitates p-p65 entry into the nucleus, thereby activating the NF-κB signaling pathway in fibroblasts. Activated fibroblasts promote lung cancer progression via enhancing the release of pro-inflammatory cytokines, especially interleukine-6 (IL-6). Our study revealed that the high levels of stromal TAGLN is a predictive risk factor for patients with lung cancer. Targeting stromal TAGLN may present an alternative therapeutic strategy against lung cancer progression.