Rapidly Manufactured CAR-T with Conserved Cell Stemness and Distinctive Cytokine-Secreting Profile Shows Improved Anti-Tumor Efficacy.

The emergence of chimeric antigen receptor T-cell (CAR-T) immunotherapy holds great promise in treating hematologic malignancies. While advancements in CAR design have enhanced therapeutic efficacy, the time-consuming manufacturing process has not been improved in the commercial production of CAR-T cells. In this study, we developed a "DASH CAR-T" process to manufacture CAR-T cells in 72 h and found the excelling anti-tumor efficacy of DASH CAR-T cells over conventionally manufactured CAR-T cells.

BRISC-Mediated PPM1B-K63 Deubiquitination and Subsequent TGF-β Pathway Activation Promote High-Fat/High-Sucrose Diet-Induced Arterial Stiffness.

Background: Metabolic syndrome heightens cardiovascular disease risk primarily through increased arterial stiffness. We previously demonstrated the involvement of YAP (Yes-associated protein) in high-fat/high-sucrose diet (HFHSD)-induced arterial stiffness via modulation of PPM1B (protein phosphatase Mg/Mn-dependent 1B)-lysine63 (K63) deubiquitination. In this study, we aimed to elucidate the role and mechanisms underlying PPM1B deubiquitination in HFHSD-induced arterial stiffness.

A Systematic Method to Detect Next-Generation Sequencing-Based Microsatellite Instability in Plasma Cell-Free DNA: plasmaMSI.

Microsatellite instability (MSI) detection using tumor tissue is a well-established prognostic and predictive biomarker for certain types of cancers. However, tumor tissue samples are less convenient to obtain than blood plasma samples. The main challenge facing next-generation sequencing-based MSI detection in blood plasma samples is the ultralow signal/noise ratio in plasma cell-free DNA (cfDNA).

Effects of surfactin stress on gene expression and pathological changes in Spodoptera litura.

Spodoptera litura (S. litura) is a polyphagous pest of the family Lepidoptera, which causes damage and yields losses to many crops. The long-term use of chemical pesticides for control not only seriously threatens environmental health, but also causes S.

FMNL3 Promotes Migration and Invasion of Breast Cancer Cells via Inhibiting Rad23B-Induced Ubiquitination of Twist1.

Breast cancer is a heterogeneous malignant tumor, and its high metastasis rate depends on the abnormal activation of cell dynamics. Formin-like protein 3 (FMNL3) plays an important role in the formation of various cytoskeletons that participate in cell movement. The objective of this study was to explore the function of FMNL3 in breast cancer progression and endeavor to reveal the molecular mechanism of this phenomenon.

Cardiac intravoxel incoherent motion diffusion-weighted imaging to assess myocardial microcirculation dysfunction in hypertension.

Background: Myocardial microcirculation dysfunction is the most potent predictor of adverse cardiovascular events in hypertension. The current study aimed to apply intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) to assess hypertension-related microcirculation dysfunction.

Methods: In this prospective study, 102 participants were recruited from our hospital and underwent cardiac magnetic resonance (CMR) examination on a 3T scanning system.

Sustained amphiregulin expression in intermediate alveolar stem cells drives progressive fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal fibrotic disease. Recent studies have highlighted the persistence of an intermediate state of alveolar stem cells in IPF lungs. In this study, we discovered a close correlation between the distribution pattern of intermediate alveolar stem cells and the progression of fibrotic changes.

Effect of Stroke Etiology on Endovascular Treatment for Acute Basilar-Artery Occlusion: A Post Hoc Analysis of the ATTENTION Randomized Trial.

Background: Stroke etiology could influence the outcomes in patients with basilar-artery occlusion (BAO). This study aimed to evaluate the differences in efficacy and safety of best medical treatment (BMT) plus endovascular treatment (EVT) versus BMT alone in acute BAO across different stroke etiologies.

Methods: The study was a post hoc analysis of the ATTENTION trial (Trial of Endovascular Treatment of Acute Basilar-Artery Occlusion), which was a multicenter, randomized trial at 36 centers in China from February 2021 to September 2022.

Heterologous survey of 130 DNA transposons in human cells highlights their functional divergence and expands the genome engineering toolbox.

Experimental studies on DNA transposable elements (TEs) have been limited in scale, leading to a lack of understanding of the factors influencing transposition activity, evolutionary dynamics, and application potential as genome engineering tools. We predicted 130 active DNA TEs from 102 metazoan genomes and evaluated their activity in human cells. We identified 40 active (integration-competent) TEs, surpassing the cumulative number (20) of TEs found previously.

Microwave Ablation versus Surgical Resection for US-detected Multifocal T1N0M0 Papillary Thyroid Carcinoma: A 10-Center Study.

Background Microwave ablation (MWA) is currently under preliminary investigation for the treatment of multifocal papillary thyroid carcinoma (PTC) and has shown promising treatment efficacy. Compared with surgical resection (SR), MWA is minimally invasive and could preserve thyroid function. However, a comparative analysis between MWA and SR is warranted to draw definitive conclusions.

NMR and MS reveal characteristic metabolome atlas and optimize esophageal squamous cell carcinoma early detection.

Metabolic changes precede malignant histology. However, it remains unclear whether detectable characteristic metabolome exists in esophageal squamous cell carcinoma (ESCC) tissues and biofluids for early diagnosis. Here, we conduct NMR- and MS-based metabolomics on 1,153 matched ESCC tissues, normal mucosae, pre- and one-week post-operative sera and urines from 560 participants across three hospitals, with machine learning and WGCNA.

Mask-Pyramid Network: A Novel Panoptic Segmentation Method.

In this paper, we introduce a novel panoptic segmentation method called the Mask-Pyramid Network. Existing Mask RCNN-based methods first generate a large number of box proposals and then filter them at each feature level, which requires a lot of computational resources, while most of the box proposals are suppressed and discarded in the Non-Maximum Suppression process. Additionally, for panoptic segmentation, it is a problem to properly fuse the semantic segmentation results with the Mask RCNN-produced instance segmentation results.

Visualizing the Habenula Using 3T High-Resolution MP2RAGE and QSM: A Preliminary Study.

Background And Purpose: The habenula is a key node in the regulation of emotion-related behavior. Accurate visualization of the habenula and its reliable quantitative analysis is vital for the assessment of psychiatric disorders. To obtain high-contrast habenula images and allow them to be compatible with clinical applications, this preliminary study compared 3T MP2RAGE and quantitative susceptibility mapping with MPRAGE by evaluating the habenula segmentation performance.

Monocytes Release Pro-Cathepsin D to Drive Blood-to-Brain Transcytosis in Diabetes.

Background: Microvascular complications are the major outcome of type 2 diabetes progression, and the underlying mechanism remains to be determined.

Methods: High-throughput RNA sequencing was performed using human monocyte samples from controls and diabetes. The transgenic mice expressing human CTSD (cathepsin D) in the monocytes was constructed using CD68 promoter.

Engineered poly(A)-surrogates for translational regulation and therapeutic biocomputation in mammalian cells.

Here, we present a gene regulation strategy enabling programmable control over eukaryotic translational initiation. By excising the natural poly-adenylation (poly-A) signal of target genes and replacing it with a synthetic control region harboring RNA-binding protein (RBP)-specific aptamers, cap-dependent translation is rendered exclusively dependent on synthetic translation initiation factors (STIFs) containing different RBPs engineered to conditionally associate with different eIF4F-binding proteins (eIFBPs). This modular design framework facilitates the engineering of various gene switches and intracellular sensors responding to many user-defined trigger signals of interest, demonstrating tightly controlled, rapid and reversible regulation of transgene expression in mammalian cells as well as compatibility with various clinically applicable delivery routes of in vivo gene therapy.

Safety, immunogenicity, and efficacy of a modified COVID-19 mRNA vaccine, SW-BIC-213, in healthy people aged 18 years and above: a phase 3 double-blinded, randomized, parallel controlled clinical trial in Lao PDR (Laos).

Background: The mRNA vaccine has demonstrated significant effectiveness in protecting against SARS-CoV-2 during the pandemic, including against severe forms of the disease caused by emerging variants. In this study, we examined safety, immunogenicity, and relative efficacy of a heterologous booster of the lipopolyplex (LPP)-based mRNA vaccine (SW-BIC-213) versus a homologous booster of an inactivated vaccine (BBIBP) in Laos.

Methods: In this phase 3 clinical trial, which was randomized, parallel controlled and double-blinded, healthy adults aged 18 years and above were recruited from the Southern Savannakhet Provincial Hospital and Champhone District Hospital.

Pharmaceutical targeting of OTUB2 sensitizes tumors to cytotoxic T cells via degradation of PD-L1.

PD-1 is a co-inhibitory receptor expressed by CD8 T cells which limits their cytotoxicity. PD-L1 expression on cancer cells contributes to immune evasion by cancers, thus, understanding the mechanisms that regulate PD-L1 protein levels in cancers is important. Here we identify tumor-cell-expressed otubain-2 (OTUB2) as a negative regulator of antitumor immunity, acting through the PD-1/PD-L1 axis in various human cancers.