Supplementary Fig. 1. Filter ICD related circRNAs.

Supplementary Fig. 8. cEMSY activates antiviral immune signaling.

Supplementary Fig. 6. In vitro and in vivo characterization of designed circRNA.

Aliphatic polycarbonates have attracted significant attention for their biodegradability and biocompatibility, yet there are also limitations impacting their applications, which usually need to be further optimized by post modification. Carbene polymerization of diazocompounds is an alternative method to undergo further modification for the aliphatic polycarbonates, due to its unique advantage of synthesizing highly functionalized polymers. In this work, the copolymerization of cyclic carbonates with diazoacetates was achieved through a post-addition strategy with the sequence of “cyclic monomer first added, followed by diazoacetate” catalyzed by Sn(Oct)2. Notably, the resulting nonconventional cyclic carbonate-diazoacetate copolymers exhibit novel fluorescence property despite lacking traditionally known conjugated fluorescent chromophores. In addition, its thermal stability can also be adjusted conveniently via multiple approaches by varying the monomers, or altering the feed ratio of the two kinds of monomers, or regulating the molecular weight of the copolymers.

Supplementary Fig. 7. In vitro-transcribed cEMSY combined with anti-PD-1 promotes antitumor cure.

Supplementary Fig. 2. Characteristics of cEMSY circRNA and expression profiles in LUAD.

Vascular invasion is associated with metastasis and poor prognosis in patients with lung adenocarcinoma (LUAD). Recent studies have highlighted the role of intercellular mitochondrial transfer, mediated by both contact-dependent and contact-independent mechanisms, in tumor progression. Here, we reveal an abnormal accumulation of mitochondria in vascular endothelial cells invaded by tumor cells. Further in vivo and in vitro experiments demonstrated that tumor cells can transfer mitochondria with highly expressed mitochondrial tRNA-derived small RNAs (tsRNAs), mt-5'tiRNA-34-GlnTTG, to endothelial cells. Mechanistic investigations indicated that mt-5'tiRNA-34-GlnTTG binds to FUBP3 and facilitates its translocation, ultimately enhancing ribosomal assembly efficiency and translation rates in endothelial cells. This molecular cascade leads to increased endothelial cell proliferation and migration, thereby promoting LUAD metastasis. Moreover, we demonstrated the potential clinical translational value of lipid nanoparticles(LNPs) encapsulating mt-5'tiRNA-34-GlnTTG inhibitors in animal experiments. Utilizing LNPs encapsulating mt-5'tiRNA-34-GlnTTG inhibitors effectively suppressed lung cancer metastasis in in vivo models. These findings reveal a novel mechanism of LUAD progression mediated by mitochondrial tsRNA transfer and highlight a promising therapeutic strategy for limiting metastatic spread.

Supplementary Fig. 3. cEMSY induces ICD in vitro.

Supplementary Fig. 10. cEMSY modulates immune responses through facilitating the translocation of TDP-43 into mitochondria.

5. cEMSY promotes ICD-driven anti-tumor immune surveillance.

The additive manufacturing process unique characteristics lead to the formation of structures with varying mechanical properties in different directions. However, current topology optimization methods often assume material isotropy, overlooking the anisotropy additive manufacturing materials. Hence, we propose a topology optimization method that accounts for additive manufacturing material anisotropy. We establish a local coordinate system to describe material anisotropy and integrate it into the SIMP variable density method, deriving the corresponding interpolation formula. The Kuhn-Tucker condition optimization criterion is applied to solve the problem, and an optimization program is developed. The method's feasibility and effectiveness are validated through numerical examples, and we extensively discuss the impact of material anisotropy and printing direction on topology optimization results. Research demonstrates that our proposed method is adept at solving both isotropic and anisotropic topology optimization problems. Moreover, the material degree of anisotropy and printing direction significantly influence topology optimization outcomes. Accounting for material anisotropy, the maximum principal stress difference in optimization results obtained under different printing directions can reach 52.26%.

Supplementary Fig. 4. cEMSY knockout abrogates the ability of cellular stressors to induce ICD.

Supplementary Fig. 11. cEMSY expression level affects patient prognosis in multiple clinical cancer cohorts.

Supplementary Fig. 9. mtDNA mediates the activation of ICD induced by cEMSY in vivo.

This study presents a systematic investigation of microstructure evolution and the mechanical response of a low-density steel during cold rolling with the thickness reduction of up to 90 %. With the strain increase, a three-stage deformation microstructural evolution from slip bands, to deformation twins, and eventually to shear bands has been observed based on detailed microstructure characterization. At the first stage (rolling reduction < 30 %), dislocation slip bands are the dominant deformation microstructure, due to the planar slip of dislocations. As strain increases, the band spacing is progressively refined with a saturation of similar to 50 nm. These slip bands gradually evolved into microbands as a result of strain localization and plastic instability. At the second deformation stage (30 %-50 % rolling reduction), deformation twinning is activated, which was seldom reported in low-density steel due to its high stacking fault energy. The deformation twins were found to be preferentially nucleated in the grains with orientations approaching (001) // rolling direction and (111) // rolling direction. At the last deformation stage (60 %-90 % rolling reduction), the deformation was mainly controlled by the formation of shear bands, generated in the areas with orientations close to (111) // normal direction. In the mechanical response aspect, the strength was progressively increased with increasing rolling reduction. The formation of deformation twins and shear bands could notably enhance the strength, exhibiting a distinct three-staged mechanical behavior during cold rolling. This research provided a thorough understanding of the distinct microstructure evolution and mechanical response of the low-density steel during cold rolling.

Increased blood pressure and triglyceride (TG) levels are linked to adverse pregnancy outcomes. Although the widespread acknowledgment that stage 2 hypertension serves as a significant predictor of preeclampsia, the prognostic significance of elevations in other blood pressure categories remains a subject of debate. Consequently, we intended to evaluate the joint influence of increased blood pressure and TG levels in the initial stages of pregnancy on preeclampsia risk and to identify a high-risk subgroup of individuals who require clinical attention. We conducted a retrospective cohort study including 78,016 individuals with singleton births at the Shanghai International Peace Maternity and Child Health Hospital (IPMCH) between January 2014 and December 2019. The study was approved by the IPMCH Institutional Review Board. Patients were classified into four groups on the basis of blood pressure readings taken during early stages of pregnancy: normotensive, elevated, stage 1 hypertension and stage 2 hypertension, stratified by TG levels (below or above the 90th percentile). Analysis using generalized additive models and logistic regression models was conducted to investigate the relationships among blood pressure, TG levels, and preeclampsia risk. Among the 78,016 patients, 2,204 (2.83

A metallized porphyrin-based COF shell was constructed on bimetal based NH 2 -Cu/Fe-MIL-101 nanoparticles, which demonstrates exceptional photo-Fenton catalytic efficiency and excellent stability.

Recurrent miscarriage is a chronic and heterogeneous pregnancy disorder lacking effective treatment. Alterations at the maternal-fetal interface are commonly observed in recurrent miscarriage, with the loss of certain cell subpopulations believed to be a key cause. Through single-cell sequencing of recurrent miscarriage patients and healthy donors, we aim to identify aberrancy of cellular features in recurrent miscarriage tissues, providing new insights into the research. Natural killer cells, the most abundant immune cells in the decidua, are traditionally classified into dNK1, dNK2, and dNK3. In this study, we identified a new subset, dNK1/2, absent in recurrent miscarriage tissues. This subset was named because it expresses biomarkers of both dNK1 and dNK2. With further analysis, we discovered that dNK1/2 cells play roles in immunoregulation and cytokine secretion. On the villous side of the interface, a notable decrease of extravillous trophoblast cells was identified in recurrent miscarriage tissues. We clustered extravillous trophoblasts into EVT1 (absent in recurrent miscarriage) and EVT2 (retained in recurrent miscarriage). Pseudotime analysis revealed distinct differentiation paths, identifying CCNB1, HMGB1, and NPM1 as EVT1 biomarkers. Additionally, we found that EVT1 is involved in the regulation of cell death, while EVT2 exhibited more angiogenic activity. Cell communication analysis revealed that interaction between EVT1 and dNK1/2 mediates chemotaxis and endothelial cell regulation, crucial for spiral artery remodeling. The loss of this interaction may impair decidualization, which is associated with recurrent miscarriage. In summary, we propose that the loss of dNK1/2 and EVT1 cells is a significant pathological feature of recurrent miscarriage. SUMMARY SENTENCE:The communication between EVT1 and dNK1/2 mediated the chemotaxis of EVT1 and facilitated regulation of endothelial cell death, initiating spiral artery remodeling. The loss of this specific cellular interaction may result in impaired decidualization, leading to recurrent miscarriage.