
本研究提出了一種創新的多組學量子機器學習框架(MQML-LungSC),用於整合數據、選擇獨特特徵、診斷分類以及識別與肺部亞型LUSC和LUAD相關的特徵。


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肺部亞型分類的多組學和量子機器學習整合

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SCARF1 形成雙聚體,其表皮生長因子(EGF)樣結構域呈現長彎曲構型。SCARF1 通過其中部位的正電荷殘基識別修飾的低密度脂蛋白。


SCARF1 (Scavenger receptor class F member 1, SREC-1 or SR-F1) is a type I transmembrane protein that recognizes multiple endogenous and exogenous ligands such as modified low-density lipoproteins (LDL) and is important for maintaining homeostasis and immunity. But the structural information and the mechanisms of ligand recognition of SCARF1 are largely unavailable. Here we solve the crystal structures of the N-terminal fragments of human SCARF1, which show that SCARF1 forms homodimers and its epidermal growth factor (EGF)-like domains adopt a long-curved conformation. Then we examine the interactions of SCARF1 with lipoproteins and are able to identify a region on SCARF1 for recognizing modified LDLs. The mutagenesis data show that the positively charged residues in the region are crucial for the interaction of SCARF1 with modified LDLs, which is confirmed by making chimeric molecules of SCARF1 and SCARF2. In addition, teichoic acids, a cell wall polymer expressed on the surface of gram-positive bacteria, are able to inhibit the interactions of modified LDLs with SCARF1, suggesting the ligand binding sites of SCARF1 might be shared for some of its scavenging targets. Overall, these results provide mechanistic insights into SCARF1 and its interactions with the ligands, which are important for understanding its physiological roles in homeostasis and the related diseases.

### Competing Interest Statement

The authors have declared no competing interest.

Structure of scavenger receptor SCARF1 and its interaction with lipoproteins

scarf1-的結構及其與脂蛋白的相互作用


SCARF1 的結構及其與脂蛋白的相互作用



整合蛋白質序列和表達水平數據可以提高對乳癌亞型的分子特徵的理解,並預測臨床結果。


整合蛋白質序列和表達水平以分析乳癌亞型的分子特徵


PA2gamma通過與C1QBP的相互作用並穩定C1QBP,增強線粒體氧化磷酸化功能,從而促進口腔鱗狀細胞癌的惡性進展。


Proteasome activator 28γ (PA28γ) plays a critical role in malignant progression of various tumors, however, its role and regulation are not well understood. Here, using oral squamous cell carcinoma (OSCC) as main research model, we discovered that PA28γ interacted with complement 1q binding protein (C1QBP), which is dependent on the N-terminus of C1QBP rather than the known functional domain (amino acids 168-213). Notably, we found that PA28γ can enhance C1QBP protein stability in OSCC. Functionally, PA28γ contributes to the malignant progression of OSCC by affecting mitochondrial morphology and oxidative phosphorylation (OXPHOS) through C1QBP in vitro and vivo. Mechanically, PA28γ upregulate the expression of optic atrophy 1 (OPA1), mitofusin 2 (MFN1), mitofusin 2 (MFN2) and the mitochondrial respiratory complex by C1QBP. Moreover, in a clinical cohort of OSCC patients, PA28γ was positively correlated with C1QBP expression and negatively correlated with prognosis. Therefore, C1QBP is also a potential target for the treatment and prognosis of cancer.

### Competing Interest Statement

The authors have declared no competing interest.

PA28γ promotes the malignant progression of tumor by elevating mitochondrial function via C1QBP

口腔鱗狀細胞癌惡性進展由pa2gamma通過提高線粒體功能和c1qbp而促進


口腔鱗狀細胞癌惡性進展由PA2gamma通過提高線粒體功能和C1QBP而促進



卵管在受孕和胚胎發育過程中會根據時間和空間動態調整其基因表達和蛋白質生產,以適應精子和胚胎的存在。


The oviduct is the site of fertilization and preimplantation embryo development in mammals. Evidence suggests that gametes alter oviductal gene expression. To delineate the adaptive interactions between the oviduct and gamete/embryo, we performed a multi-omics characterization of oviductal tissues utilizing bulk RNA-sequencing (RNA-seq), single-cell RNA-sequencing (scRNA-seq), and proteomics collected from distal and proximal at various stages after mating in mice. We observed robust region-specific transcriptional signatures. Specifically, the presence of sperm induces genes involved in pro-inflammatory responses in the proximal region at 0.5 days post-coitus (dpc). Genes involved in inflammatory responses were produced specifically by secretory epithelial cells in the oviduct. At 1.5 and 2.5 dpc, genes involved in pyruvate and glycolysis were enriched in the proximal region, potentially providing metabolic support for developing embryos. Abundant proteins in the oviductal fluid were differentially observed between naturally fertilized and superovulated samples. RNA-seq data were used to identify transcription factors predicted to influence protein abundance in the proteomic data via a novel machine learning model based on transformers of integrating transcriptomics and proteomics data. The transformers identified influential transcription factors and correlated predictive protein expressions in alignment with the in vivo -derived data. In conclusion, our multi-omics characterization and subsequent in vivo confirmation of proteins/RNAs indicate that the oviduct is adaptive and responsive to the presence of sperm and embryos in a spatiotemporal manner.

Significance Statement We conducted a detailed molecular study of how the oviduct changes its gene expression and protein production in response to sperm and embryos after mating in mice. We found that the oviduct has distinct molecular signatures in different regions - upper versus lower regions. Shortly after mating, inflammatory responses are turned on in the lower regions due to the presence of sperm. A bit later, metabolic genes ramp up in the lower regions, likely to provide nutrients for the developing embryos. Overall, this multi-omics study revealed the oviduct dynamically adapts its molecular makeup over time and space to accommodate and support sperm, eggs and embryos.

### Competing Interest Statement

The authors have declared no competing interest.

Multi-omics analyses and machine learning prediction of oviductal responses in the presence of gametes and embryos

自然受孕過程中卵管對配子和胚胎的多組學分析及機器學習預測


本研究系統性地探討了不同形狀的磁細菌磁小體在不同溫度下的磁性響應,揭示了磁小體中各向異性對其磁性行為的深遠影響。


探索磁細菌磁小體中各向異性的複雜相互作用


即使在開放基礎語言模型中,也可以通過逐步的學習過程提高長篇回答的事實性、語義相似性和詞彙組成。


改善生物醫學長篇問答的事實性


LYCHOS是一種新型的膜蛋白,融合了植物PIN運輸體和GPCR域,能夠感知膽固醇並調節mTORC1的活化。


Cryo-electron microscopy structures of the human lysosomal transmembrane protein LYCHOS show that it comprises a transporter-like domain fused to a G-protein-coupled receptor, and that the transporter domain is similar to the plant PIN family.

LYCHOS is a human hybrid of a plant-like PIN transporter and a GPCR - Nature

人類混合植物pin運輸體和gpcr的lychos


人類混合植物PIN運輸體和GPCR的LYCHOS



人類腸道內的梳狀細胞具有再生性幹細胞的特性,能夠在腸道受損後快速增殖並產生所有腸上皮細胞類型。


Four distinct tuft cell states are identified by combining analysis of primary human intestinal resection material and organoids, and studying tuft cell development shows that they represent a damage-induced reserve intestinal stem cell pool in humans.

Tuft cells act as regenerative stem cells in the human intestine - Nature

人類腸道內的梳狀細胞作為再生性幹細胞


TET2基因突變會導致全局性染色質開放和基因表達異常,從而促進白血病的發生和進展。這是通過TET2氧化RNA甲基化抑制MBD6介導的組蛋白去泛素化而實現的。


Chromatin-associated retrotransposon RNA 5-methylcytosine can be recognized by the methyl-CpG-binding-domain protein MBD6, which guides deubiquitination of nearby monoubiquitinated Lys119 of histone H2A to promote an open chromatin state in TET2-deficient cells.

RNA m5C oxidation by TET2 regulates chromatin state and leukaemogenesis - Nature

tet2基因突變導致白血病發生和進展的機制-透過氧化rna甲基化調控染色質狀態


TET2基因突變導致白血病發生和進展的機制:透過氧化RNA甲基化調控染色質狀態
