BRD9 inhibition overcomes oncolytic virus therapy resistance in glioblastoma.

Long-term survival of glioblastoma multiforme (GBM) remains challenging, spurring the development of novel therapies such as oncolytic virus therapy. While oncolytic virus shows promise in clinical trials, many patients do not respond to this therapy. Here, we perform a CRISPR screening and identify the non-canonical BRG1/BRM-associated factor (ncBAF) complex as a pivotal tumor-intrinsic factor for oncolytic virotherapy resistance.

A Constitutive Equation and Numerical Study on the Tensile Behavior of Reinforcing Steel Under Different Mass Loss Ratios.

This study investigates the mechanical degradation of HRB400 corroded reinforcing steel induced by corrosion and introduces a tailored constitutive model to capture the influence of mass loss ratios. A series of tensile tests were conducted following chloride-driven wet-dry cycles combined with a simulated marine corrosion environment, enabling the quantification of the relationship between mass loss ratios and mechanical performance. A degradation equation based on mass loss ratios was derived and benchmarked against both experimental data and the existing Hooputra's Ductile Damage (HDD) model.

Targeting overexpressed antigens in glioblastoma via CAR T cells with computationally designed high-affinity protein binders.

Chimeric antigen receptor (CAR) T cells targeting receptors on tumour cells have had limited success in patients with glioblastoma. Here we report the development and therapeutic performance of CAR constructs leveraging protein binders computationally designed de novo to have high affinity for the epidermal growth factor receptor (EGFR) or the tumour-associated antigen CD276, which are overexpressed in glioblastoma. With respect to T cells with a CAR using an antibody-derived single-chain variable fragment as antigen-binding domain, the designed binders on CAR T cells promoted the proliferation of the cells, the secretion of cytotoxic cytokines and their resistance to cell exhaustion, and improved antitumour performance in vitro and in vivo.

RBBP6 maintains glioblastoma stem cells through CPSF3-dependent alternative polyadenylation.

Glioblastoma is one of the most lethal malignant cancers, displaying striking intratumor heterogeneity, with glioblastoma stem cells (GSCs) contributing to tumorigenesis and therapeutic resistance. Pharmacologic modulators of ubiquitin ligases and deubiquitinases are under development for cancer and other diseases. Here, we performed parallel in vitro and in vivo CRISPR/Cas9 knockout screens targeting human ubiquitin E3 ligases and deubiquitinases, revealing the E3 ligase RBBP6 as an essential factor for GSC maintenance.

An Investigation on the Most Likely Failure Locations in the BEoL Stack of a 20 nm Chip Due to Chip Package Interaction with the Use of Novel Semi-Elliptical Cracks.

The era of 20 nm integrated circuits has arrived. There exist abundant heterogeneous micro/nano structures, with thicknesses ranging from hundreds of nanometers to sub-microns in the IC back end of the line stack, which put stringent demands on the reliability of the device. In this paper, the reliability issues of a 20 nm chip due to chip-package interaction during the reflow process is studied.

Analysis of the Overpressure Fields in a Shock Tube with Multi-Point Initiation.

Shock tubes can carry out dynamic mechanical impact tests on civil engineering structures. The current shock tubes mostly use an explosion with aggregate charge to obtain shock waves. Limited effort has been made to study the overpressure field in shock tubes with multi-point initiation.

Discussion on Static Resistance of Granite under Penetration.

A total of 9 tests were carried out with 30 mm and 78 mm caliber scaled projectiles penetrating into granite targets. The penetration depth, crater diameter, and mass loss rate were examined and discussed. The results indicate that the dimensionless penetration depth of large-caliber projectiles is 20% greater than small-caliber projectiles.

Single-cell multiomics analysis reveals regulatory programs in clear cell renal cell carcinoma.

The clear cell renal cell carcinoma (ccRCC) microenvironment consists of many different cell types and structural components that play critical roles in cancer progression and drug resistance, but the cellular architecture and underlying gene regulatory features of ccRCC have not been fully characterized. Here, we applied single-cell RNA sequencing (scRNA-seq) and single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq) to generate transcriptional and epigenomic landscapes of ccRCC. We identified tumor cell-specific regulatory programs mediated by four key transcription factors (TFs) (HOXC5, VENTX, ISL1, and OTP), and these TFs have prognostic significance in The Cancer Genome Atlas (TCGA) database.

Spindle pole body component 24 homolog potentiates tumor progression via regulation of SRY-box transcription factor 2 in clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is the most common pathological subtype of human kidney cancer with a high probability of metastasis. To understand the molecular processing essential for ccRCC tumorigenicity, we conducted an integrative in silico analysis of The Cancer Genome Atlas (TCGA) ccRCC dataset and clustered randomly interspersed short palindromic repeats (CRISPR) screening dataset of ccRCC cell lines from Depmap. We identified spindle pole body component 24 homolog (SPC24) as an essential gene for ccRCC cell lines with prognostic significance in the TCGA database.

Systematic Assessment of Transcriptomic Biomarkers for Immune Checkpoint Blockade Response in Cancer Immunotherapy.

Background: Immune checkpoint blockade (ICB) therapy has yielded successful clinical responses in treatment of a minority of patients in certain cancer types. Substantial efforts were made to establish biomarkers for predicting responsiveness to ICB. However, the systematic assessment of these ICB response biomarkers remains insufficient.

Identifying Cancer Driver lncRNAs Bridged by Functional Effectors through Integrating Multi-omics Data in Human Cancers.

The accumulation of somatic driver mutations in the human genome enables cells to gradually acquire a growth advantage and contributes to tumor development. Great efforts on protein-coding cancer drivers have yielded fruitful discoveries and clinical applications. However, investigations on cancer drivers in non-coding regions, especially long non-coding RNAs (lncRNAs), are extremely scarce due to the limitation of functional understanding.

CancerSEA: a cancer single-cell state atlas.

High functional heterogeneity of cancer cells poses a major challenge for cancer research. Single-cell sequencing technology provides an unprecedented opportunity to decipher diverse functional states of cancer cells at single-cell resolution, and cancer scRNA-seq datasets have been largely accumulated. This emphasizes the urgent need to build a dedicated resource to decode the functional states of cancer single cells.

TIP: A Web Server for Resolving Tumor Immunophenotype Profiling.

: Systematically tracking the tumor immunophenotype is required to understand the mechanisms of cancer immunity and improve clinical benefit of cancer immunotherapy. However, progress in current research is hindered by the lack of comprehensive immune activity resources and easy-to-use tools for biologists, clinicians, and researchers to conveniently evaluate immune activity during the "cancer-immunity cycle." We developed a user-friendly one-stop shop web tool called TIP to comprehensively resolve tumor immunophenotype.