CD70-targeted iPSC-derived CAR-NK cells display potent function against tumors and alloreactive T cells.

Clinical application of autologous chimeric antigen receptor (CAR)-T cells is complicated by limited targeting of cancer types, as well as the time-consuming and costly manufacturing process. We develop CD70-targeted, induced pluripotent stem cell-derived CAR-natural killer (NK) (70CAR-iNK) cells as an approach for universal immune cell therapy. Besides the CD70-targeted CAR molecule, 70CAR-iNK cells are modified with CD70 gene knockout, a high-affinity non-cleavable CD16 (hnCD16), and an interleukin (IL)-15 receptor α/IL-15 fusion protein (IL15RF).

[Advances in the application of comprehensive behavioral intervention in tic disorder].

Tic disorder is a neurodevelopmental disorder that occurs in children or adolescents, often attracting the attention of others due to involuntary, repetitive, and non-rhythmic tics, and drug therapy often causes negative emotions in children and their families due to its significant adverse reactions, poor compliance, and tendency of recurrence after drug withdrawal. In recent years, comprehensive behavioral intervention has shown great potential as a safe and effective treatment modality for tic disorders, with few adverse reactions. This article reviews the advances in the application of comprehensive behavioral intervention for tic disorder in China and abroad in the past 5 years, in order to provide a reference for clinical application.

The Neuroprotection of 1,2,4-Triazole Derivative by Inhibiting Inflammation and Protecting BBB Integrity in Acute Ischemic Stroke.

Background: The oxidative stress and neuroinflammation are important factors in acute ischemic stroke (AIS). Our former study showed the 1,2,4- triazole derivative (SYS18) had obviously neuroprotection by anti- oxidative stress on rat middle cerebral artery occlusion (MCAO) model.

Aim: In this study, we continue to investigate its neuroprotection by anti-inflammatory effects and protecting BBB integrity in AIS.

Prediction models for postoperative pulmonary complications in intensive care unit patients after noncardiac thoracic surgery.

Background: Postoperative pulmonary complication (PPC) is a leading cause of mortality and poor outcomes in postoperative patients. No studies have enrolled intensive care unit (ICU) patients after noncardiac thoracic surgery, and effective prediction models for PPC have not been developed. This study aimed to explore the incidence and risk factors and construct prediction models for PPC in these patients.

β-catenin mediates endodermal commitment of human ES cells via distinct transactivation functions.

Background: β-catenin, acting as the core effector of canonical Wnt signaling pathway, plays a pivotal role in controlling lineage commitment and the formation of definitive endoderm (DE) during early embryonic development. Despite extensive studies using various animal and cell models, the β-catenin-centered regulatory mechanisms underlying DE formation remain incompletely understood, partly due to the rapid and complex cell fate transitions during early differentiation.

Results: In this study, we generated new CTNNB1-/- human ES cells (hESCs) using CRISPR-based insertional gene disruption approach and systematically rescued the DE defect in these cells by introducing various truncated or mutant forms of β-catenin.

Testing multiplexed anti-ASFV CRISPR-Cas9 in reducing African swine fever virus.

Unlabelled: African swine fever (ASF) is a highly fatal viral disease that poses a significant threat to domestic pigs and wild boars globally. In our study, we aimed to explore the potential of a multiplexed CRISPR-Cas system in suppressing ASFV replication and infection. By engineering CRISPR-Cas systems to target nine specific loci within the ASFV genome, we observed a substantial reduction in viral replication .

Long-term effects of chronic exposure to electronic cigarette aerosol on the cardiovascular and pulmonary system in mice: A comparative study to cigarette smoke.

Electronic cigarettes (e-cigarettes) have rapidly gained popularity as alternatives to traditional combustible cigarettes. However, their long-term health impact remains uncertain. This study aimed to investigate the effects of chronic exposure to e-cigarette aerosol (ECA) in mice compared to conventional cigarette smoke (CS) exposure.

Role of steroid receptor-associated and regulated protein in tumor progression and progesterone receptor signaling in endometrial cancer.

Background: Steroid receptor-associated and regulated protein (SRARP) suppresses tumor progression and modulates steroid receptor signaling by interacting with estrogen receptors and androgen receptors in breast cancer. In endometrial cancer (EC), progesterone receptor (PR) signaling is crucial for responsiveness to progestin therapy. The aim of this study was to investigate the role of SRARP in tumor progression and PR signaling in EC.

A mechanism study of DUSP1 in inhibiting malignant progression of endometrial carcinoma by regulating ERK/AP-1 axis and dephosphorylation of EPHA2.

Endometrial carcinoma is one of the most common female malignancies worldwide. Based on our preliminary investigation, DUSP1 was identified as a potential biomarker for endometrial carcinoma prognosis, but its function and mechanism remained unclear. In this study, genes highly correlated with DUSP1 in endometrial cancer were found through correlation analysis, and the promoter sequence of DUSP1 was analyzed by PROMO program.

Pharmacokinetics and tissue distribution of bleomycin-induced idiopathic pulmonary fibrosis rats treated with cryptotanshinone.

Cryptotanshinone(CTS), a compound derived from the root of , has been linked to various of diseases, particularly pulmonary fibrosis. In the current study, we investigated the benefit of CTS on Sprague-Dawley (SD) rats induced by bleomycin (BLM) and established high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) methods to compare pharmacokinetics and tissue distribution in subsequent normal and modulated SD rats. The therapeutic effect of CTS on BLM-induced SD rats was evaluated using histopathology, lung function and hydroxyproline content measurement, revealing that CTS significantly improved SD rats induced by BLM.

Low-dose AAV-CRISPR-mediated liver-specific knock-in restored hemostasis in neonatal hemophilia B mice with subtle antibody response.

AAV-delivered CRISPR/Cas9 (AAV-CRISPR) has shown promising potentials in preclinical models to efficiently insert therapeutic gene sequences in somatic tissues. However, the AAV input doses required were prohibitively high and posed serious risk of toxicity. Here, we performed AAV-CRISPR mediated homology-independent knock-in at a new target site in mAlb 3'UTR and demonstrated that single dose of AAVs enabled long-term integration and expression of hF9 transgene in both adult and neonatal hemophilia B mice (mF9 -/-), yielding high levels of circulating human Factor IX (hFIX) and stable hemostasis restoration during entire 48-week observation period.

Trypsin inhibitor LH011 inhibited DSS-induced mice colitis alleviating inflammation and oxidative stress.

Ulcerative colitis (UC) is one type of inflammatory bowel disease, characterized by inflammation with infiltration and activation of macrophages in colonic tissue. LH011 is a trypsin inhibitor with potential anti-inflammatory effect. Here, we aim to assay the effects of LH011 on UC and further investigate the potential mechanisms and Dextran sulfate sodium (DSS, 3.

Evolving AAV-delivered therapeutics towards ultimate cures.

Gene therapy has entered a new era after decades-long efforts, where the recombinant adeno-associated virus (AAV) has stood out as the most potent vector for in vivo gene transfer and demonstrated excellent efficacy and safety profiles in numerous preclinical and clinical studies. Since the first AAV-derived therapeutics Glybera was approved by the European Medicines Agency (EMA) in 2012, there is an increasing number of AAV-based gene augmentation therapies that have been developed and tested for treating incurable genetic diseases. In the subsequent years, the United States Food and Drug Administration (FDA) approved two additional AAV gene therapy products, Luxturna and Zolgensma, to be launched into the market.

MicroRNA-92a -mediated endothelial to mesenchymal transition controls vein graft neointimal lesion formation.

Purpose: Long-term failure of vein grafts due to neointimal hyperplasia remains an important problem in coronary artery bypass graft surgery. Endothelial to mesenchymal transition (EndMT) contributes to vein graft vascular remodeling. However, there is little study on microRNA-mediated EndMT contributions to neointimal formation in vein graft.

Calcium and TRPV4 promote metastasis by regulating cytoskeleton through the RhoA/ROCK1 pathway in endometrial cancer.

Transient receptor potential vanilloid 4 (TRPV4) is a calcium-permeable cation channel that has been associated with several types of cancer. However, its biological significance, as well as its related mechanism in endometrial cancer (EC) still remains elusive. In this study, we examined the function of calcium in EC, with a specific focus on TRPV4 and its downstream pathway.

Gelsolin Promotes Cancer Progression by Regulating Epithelial-Mesenchymal Transition in Hepatocellular Carcinoma and Correlates with a Poor Prognosis.

Gelsolin (GSN), a cytoskeletal protein, is frequently overexpressed in different cancers and promotes cell motility. The biological function of GSN in hepatocellular carcinoma (HCC) and its mechanism remain unclear. The expression of GSN was assessed in a cohort of 188 HCC patients.

Deregulation of cell adhesion molecules is associated with progression and poor outcomes in endometrial cancer: Analysis of The Cancer Genome Atlas data.

Cell adhesion molecules (CAMs) determine the behavior of cancer cells during metastasis. Although some CAMs are dysregulated in certain types of cancer and are associated with cancer progression, to the best of our knowledge, a comprehensive study of CAMs has not been undertaken, particularly in endometrial cancer (EC). In the present study the expression of 225 CAMs in EC patients with various clinicopathological phenotypes were evaluated by statistical analysis using publicly available data from The Cancer Genome Atlas database.

Responses of AOA and AOB activity and DNA/cDNA community structure to allylthiourea exposure in the water level fluctuation zone soil.

Ammonia oxidation is mainly performed by ammonia-oxidizing archaea (AOA) and ammonia-oxidizing bacteria (AOB). Allylthiourea (ATU) has been found to specifically inhibit ammonia oxidation. However, the effect of ATU on AOA and AOB transcription has been infrequently studied.

The abundance and community structure of active ammonia-oxidizing archaea and ammonia-oxidizing bacteria shape their activities and contributions in coastal wetlands.

Aerobic ammonia oxidation, an important part of the global nitrogen cycle, is thought to be jointly driven by ammonia-oxidizing bacteria (AOB) and ammonia-oxidizing archaea (AOA) in coastal wetlands. However, the activities and contributions of AOA and AOB in coastal wetlands have remained largely unknown. Here, we investigated the oxidation capability of AOA and AOB in four types of typical coastal wetlands (paddy, estuary, shallow and reed wetland) in the Bohai region in China using DNA-based stable-isotope probing (DNA-SIP), quantitative PCR and high-throughput sequencing techniques.

The preventive effect of Chinese herbal preparation Xuebijing against hyperactive inflammation after hepato-pancreato-biliary surgery.

Background: Hepato-pancreato-biliary (HPB) surgery is a primary treatment for benign and malignant diseases of the liver, biliary tract, and pancreas. Hyperactive inflammation has been indicated as a critical risk factor of post-operation death after HPB surgery. Xuebijing is an anti-inflammatory intravenous herbal preparation made from traditional Chinese medicines.

Predicting prognosis of endometrioid endometrial adenocarcinoma on the basis of gene expression and clinical features using Random Forest.

Traditional clinical features are not sufficient to accurately judge the prognosis of endometrioid endometrial adenocarcinoma (EEA). Molecular biological characteristics and traditional clinical features are particularly important in the prognosis of EEA. The aim of the present study was to establish a predictive model that considers genes and clinical features for the prognosis of EEA.

Expression and clinical significance of KLK5-8 in endometrial cancer.

Kallikrein-related peptidase (KLK) family is one of the major serine proteases in tumor microenvironment, which plays a crucial role in cancer invasion and metastasis. A number of KLK family members have been found to be upregulated or downregulated in some cancers, and some KLKs may be potential biomarkers for cancers. However, little is known about the role of KLKs in endometrial carcinoma (EC).

Homology-independent multiallelic disruption via CRISPR/Cas9-based knock-in yields distinct functional outcomes in human cells.

Background: Cultured human cells are pivotal models to study human gene functions, but introducing complete loss of function in diploid or aneuploid cells has been a challenge. The recently developed CRISPR/Cas9-mediated homology-independent knock-in approach permits targeted insertion of large DNA at high efficiency, providing a tool for insertional disruption of a selected gene. Pioneer studies have showed promising results, but the current methodology is still suboptimal and functional outcomes have not been well examined.

New Turns for High Efficiency Knock-In of Large DNA in Human Pluripotent Stem Cells.

The groundbreaking CRISPR technology is revolutionizing biomedical research with its superior simplicity, high efficiency, and robust accuracy. Recent technological advances by a coupling CRISPR system with various DNA repair mechanisms have further opened up new opportunities to overcome existing challenges in knocking-in foreign DNA in human pluripotent stem cells, including embryonic stem cells (ESC) and induced pluripotent stem cells (iPSC). In this review, we summarized the very recent development of CRISPR-based knock-in strategies and discussed the results obtained as well as potential applications in human ESC and iPSC.