The epitranscriptional factor PCIF1 orchestrates CD8 T cell ferroptosis and activation to control antitumor immunity.

T cell-based immunotherapies have revolutionized cancer treatment, yet durable responses remain elusive. Here we show that PCIF1, an RNA N 2'-O-dimethyladenosine (mA) methyltransferase, negatively regulates CD8 T cell antitumor responses. Whole-body or T cell-specific Pcif1 knockout (KO) reduced tumor growth in mice.

USP8-governed GPX4 homeostasis orchestrates ferroptosis and cancer immunotherapy.

Ferroptosis is an iron-dependent type of regulated cell death resulting from extensive lipid peroxidation and plays a critical role in various physiological and pathological processes. However, the regulatory mechanisms for ferroptosis sensitivity remain incompletely understood. Here, we report that homozygous deletion of (ubiquitin-specific protease 8) in intestinal epithelial cells (IECs) leads to architectural changes in the colonic epithelium and shortens mouse lifespan accompanied by increased IEC death and signs of lipid peroxidation.

UFL1 ablation in T cells suppresses PD-1 UFMylation to enhance anti-tumor immunity.

UFMylation is an emerging ubiquitin-like post-translational modification that regulates various biological processes. Dysregulation of the UFMylation pathway leads to human diseases, including cancers. However, the physiological role of UFMylation in T cells remains unclear.

Cognitive Deficits and Alzheimer's Disease-Like Pathologies in the Aged Chinese Tree Shrew.

Alzheimer's disease (AD) is the most common chronic progressive neurodegenerative disease in the elderly. It has an increasing prevalence and a growing health burden. One of the limitations in studying AD is the lack of animal models that show features of Alzheimer's pathogenesis.

Targeting METTL3 reprograms the tumor microenvironment to improve cancer immunotherapy.

The tumor microenvironment (TME) is a heterogeneous ecosystem containing cancer cells, immune cells, stromal cells, cytokines, and chemokines which together govern tumor progression and response to immunotherapies. Methyltransferase-like 3 (METTL3), a core catalytic subunit for RNA N-methyladenosine (mA) modification, plays a crucial role in regulating various physiological and pathological processes. Whether and how METTL3 regulates the TME and anti-tumor immunity in non-small-cell lung cancer (NSCLC) remain poorly understood.

Coexistence of Multiple Functional Variants and Genes Underlies Genetic Risk Locus 11p11.2 of Alzheimer's Disease.

Background: Genome-wide association studies have identified dozens of genetic risk loci for Alzheimer's disease (AD), yet the underlying causal variants and biological mechanisms remain elusive, especially for loci with complex linkage disequilibrium and regulation.

Methods: To fully untangle the causal signal at a single locus, we performed a functional genomic study of 11p11.2 (the CELF1/SPI1 locus).

ERK and USP5 govern PD-1 homeostasis via deubiquitination to modulate tumor immunotherapy.

The programmed cell death protein 1 (PD-1) is an inhibitory receptor on T cells and plays an important role in promoting cancer immune evasion. While ubiquitin E3 ligases regulating PD-1 stability have been reported, deubiquitinases governing PD-1 homeostasis to modulate tumor immunotherapy remain unknown. Here, we identify the ubiquitin-specific protease 5 (USP5) as a bona fide deubiquitinase for PD-1.

Functional genomics identify causal variant underlying the protective CTSH locus for Alzheimer's disease.

Alzheimer's disease (AD) is the most prevalent age-related neurodegenerative disease, which has a high heritability of up to 79%. Exploring the genetic basis is essential for understanding the pathogenic mechanisms underlying AD development. Recent genome-wide association studies (GWASs) reported an AD-associated signal in the Cathepsin H (CTSH) gene in European populations.

Direct evidence of CRISPR-Cas9-mediated mitochondrial genome editing.

Pathogenic mitochondrial DNA (mtDNA) mutations can cause a variety of human diseases. The recent development of genome-editing technologies to manipulate mtDNA, such as mitochondria-targeted DNA nucleases and base editors, offer a promising way for curing mitochondrial diseases caused by mtDNA mutations. The CRISPR-Cas9 system is a widely used tool for genome editing; however, its application in mtDNA editing is still under debate.

Synthesis of Azepinoindoles via Pd-Catalyzed C(sp)-H Imidoylative Cyclization Reactions.

An efficient and convenient method for the construction of diverse free (N-H)-benzazepinoindoles by Pd-catalyzed C(sp)-H imidoylative cyclization of 3-(2-isocyanobenzyl)-1-indoles was developed. The reaction shows a wide substrate scope and can be scaled up, providing a practical route to valuable bioactive azepinoindoles.

USP8 inhibition reshapes an inflamed tumor microenvironment that potentiates the immunotherapy.

Anti-PD-1/PD-L1 immunotherapy has achieved impressive therapeutic outcomes in patients with multiple cancer types. However, the underlined molecular mechanism(s) for moderate response rate (15-25%) or resistance to PD-1/PD-L1 blockade remains not completely understood. Here, we report that inhibiting the deubiquitinase, USP8, significantly enhances the efficacy of anti-PD-1/PD-L1 immunotherapy through reshaping an inflamed tumor microenvironment (TME).

Positron Emission Tomography/Magnetic Resonance Imaging Radiomics in Predicting Lung Adenocarcinoma and Squamous Cell Carcinoma.

Objective: To investigate the diagnostic value of positron emission tomography (PET)/magnetic resonance imaging (MRI) radiomics in predicting the histological classification of lung adenocarcinoma and lung squamous cell carcinoma.

Methods: PET/MRI radiomics and clinical data were retrospectively collected from 61 patients with lung cancer. According to the pathological results of surgery or fiberscope, patients were divided into two groups, lung adenocarcinoma and squamous cell carcinoma group, which were set as positive for adenocarcinoma (40 cases) and negative for squamous cell carcinoma (21 cases).

Characterization, antioxidant, and anticancer activities of a neutral polysaccharide from Duchesnea indica (Andr.) Focke.

A neutral polysaccharide (DIP-1) from Duchesnea indica (Andr.) Focke was obtained by hot water extraction, ethanol precipitation and chromatographic separation (DEAE-52 cellulose anion-exchange column and Sephadex G-100 gel column). The physicochemical properties of DIP-1 were elucidated by gel permeation chromatography, monosaccharide composition, Fourier transform infrared spectrometry, UV-visible spectrophotometry, scanning electron microscope and Congo red test.

Synthesis and luminescence properties of brick-shaped lanthanum-organic frameworks with mesoporous and macroporous architectures.

Generally, metal-organic frameworks (MOFs) are made up from kinds of repeating microporous structure. Here, a series of Eu ions activated terephthalate-based lanthanum-organic frameworks (La-MOFs) was synthesized by a hydrothermal reaction. By controlling the reaction time, we obtained some unique brick-shaped La-MOFs in a micron scale size range, and these La-MOFs showed tunable mesoporous and macroporous architectures.