Nanodrug-Engineered Exosomes Achieve a Jointly Dual-Pathway Inhibition on Cuproptosis.

Cuproptosis, caused by an intracellular overload of copper (Cu) ions and overexpression of ferredoxin 1 (FDX1), is identified for its regulatory role in the skin wound healing process. This study verifies the presence of cuproptosis in skin wound beds and reactive oxygen species-induced cells model. To address the two pathways leading to cell cuproptosis, a nanodrug-engineered exosomes is proposed.

Laparoscopy-assisted versus open surgery for low rectal cancer (LASRE): 3-year survival outcomes of a multicentre, randomised, controlled, non-inferiority trial.

Background: Laparoscopic surgery is increasingly used for rectal cancer, but the long-term oncological outcomes for low rectal cancer have not been fully established. We aimed to evaluate the 3-year survival outcomes of laparoscopic surgery versus open surgery in the treatment of low rectal cancer.

Methods: This multicentre, randomised, controlled, non-inferiority trial was conducted at 22 tertiary hospitals in China.

Deformation Monitoring and Analysis of Baige Landslide (China) Based on the Fusion Monitoring of Multi-Orbit Time-Series InSAR Technology.

Due to the limitations inherent in SAR satellite imaging modes, utilizing time-series InSAR technology to process single-orbit satellite image data typically only yields one-dimensional deformation information along the LOS direction. This constraint impedes a comprehensive representation of the true surface deformation of landslides. Consequently, in this paper, after the SBAS-InSAR and PS-InSAR processing of the 30-view ascending and 30-view descending orbit images of the Sentinel-1A satellite, based on the imaging geometric relationship of the SAR satellite, we propose a novel computational method of fusing ascending and descending orbital LOS-direction time-series deformation to extract the landslide's downslope direction deformation of landslides.

Centromere Landscapes Resolved from Hundreds of Human Genomes.

High-fidelity (HiFi) sequencing has facilitated the assembly and analysis of the most repetitive region of the genome, the centromere. Nevertheless, our current understanding of human centromeres is based on a relatively small number of telomere-to-telomere assemblies, which have not yet captured its full diversity. In this study, we investigated the genomic diversity of human centromere higher order repeats (HORs) via both HiFi reads and haplotype-resolved assemblies from hundreds of samples drawn from ongoing pangenome-sequencing projects and reprocessed them via a novel HOR annotation pipeline, HiCAT-human.

The centromere landscapes of four karyotypically diverse Papaver species provide insights into chromosome evolution and speciation.

Understanding the roles played by centromeres in chromosome evolution and speciation is complicated by the fact that centromeres comprise large arrays of tandemly repeated satellite DNA, which hinders high-quality assembly. Here, we used long-read sequencing to generate nearly complete genome assemblies for four karyotypically diverse Papaver species, P. setigerum (2n = 44), P.

Graphene Quantum Dots Eradicate Resistant and Metastatic Cancer Cells by Enhanced Interfacial Inhibition.

Drug-resistant and metastatic cancer cells such as a small population of cancer stem cells (CSCs) play a crucial role in metastasis and relapse. Conventional small-molecule chemotherapeutics, however, are unable to eradicate drug-resistant CSCs owing to limited interface inhibitory effects. Herein, it is reported that enhanced interfacial inhibition leading to eradication of drug-resistant CSCs can be dramatically induced by self-insertion of bioactive graphene quantum dots (GQDs) into DNA major groove (MAG) sites in cancer cells.

Vertical migration behavior simulation and prediction of Pb and Cd in co-contaminated soil around Pb-Zn smelting slag site.

Heavy metal migration in soil poses a serious threat to the soil and groundwater. Understanding the migration pattern of heavy metals (HMs) under different factors could provide a more reasonable position for pollution evaluation and targetoriented treatment of soil heavy metal. In this study, the migration behavior of Pb and Cd in co-contaminated soil under different pH and ionic strength (NaCl concentration) was simulated using convective dispersion equation (CDE).

Sex-determining region Y gene promotes liver fibrosis and accounts for sexual dimorphism in its pathophysiology.

Background & Aims: Men are more prone to develop and die from liver fibrosis than women. In this study, we aim to investigate how sex-determining region Y gene (SRY) in hepatocytes promotes liver fibrosis.

Methods: Hepatocyte-specific Sry knock-in (KI), Sry knockout (KO), and Sry KI with platelet-derived growth factor receptor α (Pdgfrα) KO mice were generated.

Haplotype-resolved assemblies and variant benchmark of a Chinese Quartet.

Background: Recent state-of-the-art sequencing technologies enable the investigation of challenging regions in the human genome and expand the scope of variant benchmarking datasets. Herein, we sequence a Chinese Quartet, comprising two monozygotic twin daughters and their biological parents, using four short and long sequencing platforms (Illumina, BGI, PacBio, and Oxford Nanopore Technology).

Results: The long reads from the monozygotic twin daughters are phased into paternal and maternal haplotypes using the parent-child genetic map and for each haplotype.

Quartet DNA reference materials and datasets for comprehensively evaluating germline variant calling performance.

Background: Genomic DNA reference materials are widely recognized as essential for ensuring data quality in omics research. However, relying solely on reference datasets to evaluate the accuracy of variant calling results is incomplete, as they are limited to benchmark regions. Therefore, it is important to develop DNA reference materials that enable the assessment of variant detection performance across the entire genome.

Highly efficient production of ectoine via an optimized combination of precursor metabolic modules in Escherichia coli BL21.

Ectoine is an osmotic pressure protectant observed in various microorganisms and is widely used in cosmetics and pharmaceuticals. The market value of ectoine has increased considerably with social progress, resulting in high demand for ectoine production technology. Herein, a microbial cell factory in Escherichia coli that produces ectoine at high titers is described as developing efficient and environmentally friendly bio-based ectoine production technology.

HBXIP blocks myosin-IIA assembly by phosphorylating and interacting with NMHC-IIA in breast cancer metastasis.

Tumor metastasis depends on the dynamic balance of the actomyosin cytoskeleton. As a key component of actomyosin filaments, non-muscle myosin-IIA disassembly contributes to tumor cell spreading and migration. However, its regulatory mechanism in tumor migration and invasion is poorly understood.

Rapamycin improves Graves' orbitopathy by suppressing CD4+ cytotoxic T lymphocytes.

CD4+ cytotoxic T lymphocytes (CTLs) were recently implicated in immune-mediated inflammation and fibrosis progression of Graves' orbitopathy (GO). However, little is known about therapeutic targeting of CD4+ CTLs. Herein, we studied the effect of rapamycin, an approved mTOR complex 1 (mTORC1) inhibitor, in a GO mouse model, in vitro, and in patients with refractory GO.

Integrating cell interaction with transcription factors to obtain a robust gene panel for prognostic prediction and therapies in cholangiocarcinoma.

The efficacy of immunotherapy for cholangiocarcinoma (CCA) is blocked by a high degree of tumor heterogeneity. Cell communication contributes to heterogeneity in the tumor microenvironment. This study aimed to explore critical cell signaling and biomarkers induced cell communication during immune exhaustion in CCA.

Self-assembly of X-shaped antibody to combine the activity of IgG and IgA for enhanced tumor killing.

IgA can induce activation of neutrophils which are the most abundant cell type in blood, but the development of IgA as therapeutic has been confounded by its short half-life and a weak ability to recruit NK cells as effector cells. Therefore, we generated an X-shaped antibody (X-body) based on the principle of molecular self-assembly that combines the activities of both IgG and IgA, which can effectively recruit and activate NK cells, macrophages, and neutrophils to kill tumor cells. X-body was generated by using a self-assembly strategy.

Sorafenib triggers ferroptosis via inhibition of HBXIP/SCD axis in hepatocellular carcinoma.

Sorafenib, which inhibits multiple kinases, is an effective frontline therapy for hepatocellular carcinoma (HCC). Ferroptosis is a form of iron-dependent programmed cell death regulated by lipid peroxidation, which can be induced by sorafenib treatment. Oncoprotein hepatitis B X-interacting protein (HBXIP) participates in multiple biological pro-tumor processes, including growth, metastasis, drug resistance, and metabolic reprogramming.

Modular reconstruction and optimization of the trans-4-hydroxy-L-proline synthesis pathway in Escherichia coli.

Background: In recent years, there has been a growing demand for microbial production of trans-4-hydroxy-L-proline (t4Hyp), which is a value-added amino acid and has been widely used in the fields of medicine, food, and cosmetics. In this study, a multivariate modular metabolic engineering approach was used to remove the bottleneck in the synthesis pathway of t4Hyp.

Results: Escherichia coli t4Hyp synthesis was performed using two modules: a α-ketoglutarate (α-KG) synthesis module (K module) and L-proline synthesis with hydroxylation module (H module).