Cytotoxicity of activator expression in CRISPR-based transcriptional activation systems.

CRISPR-based transcriptional activation (CRISPRa) has extensive research and clinical potential. Here, we show that commonly used CRISPRa systems can exhibit pronounced cytotoxicity. We demonstrate the toxicity of CRISPRa vectors expressing the activation domains (ADs) of the transcription factors p65 and HSF1, components of the synergistic activation mediator (SAM) CRISPRa system.

KSHV-encoded vIRF3 Cooperates with Cellular IRF4 to Drive Super-Enhancer Activity through Complex DNA Elements.

The Kaposi's sarcoma-associated herpesvirus (KSHV) oncoprotein vIRF3 is essential for the survival of primary effusion lymphoma (PEL) cells. vIRF3 cooperates with cellular IRF4 to activate super-enhancers (SEs) driving oncogenes including MYC and IRF4 itself. However, the vIRF3/IRF4-responsive DNA sequences underlying this cooperation are unknown.

Effects of different monochromatic light on anaerobic ammonia oxidation systems: performance, microbial characteristics and mechanism.

The weak resistance of anaerobic ammonia oxidizing bacteria (AnAOB) to harsh environment is the key problem facing the application of AnAOB process. In order to elucidate the mechanism of the effect of light on anammox systems, the nitrogen removal performance and microbial succession at different wavelengths were investigated. The results showed that the nitrogen removal performance of the UV light reactor significantly decreased, while that of the green light reactor increased.

Microbial Dynamics on Different Microplastics in Coastal Urban Aquatic Ecosystems: The Critical Roles of Extracellular Polymeric Substances.

Microplastics (MPs) serve as carriers for microbial community colonization, forming unique ecosystems known as plastispheres in urban aquatic ecosystems. However, interactions among microbes, extracellular polymeric substances (EPS), and MPs remain poorly understood. This study investigates microbial consortia and their EPS secretion behaviors across various plastispheres at two representative coastal urban water sites.

BAG2 Inhibits Cervical Cancer Progression by Modulating Type I Interferon Signaling through Stabilizing STING.

Cervical cancer possesses high morbidity and mortality rates, and a comprehensive understanding of its molecular underpinnings is essential for advancing clinical management strategies. The innate immune sensor STING, which activates type I interferon signaling, plays a pivotal role in enhancing anti-tumor activity. Despite increased attention to STING's involvement in cervical cancer, the regulatory mechanisms governing its protein homeostasis remain poorly understood.

SIX1 enhances aerobic glycolysis and progression in cervical cancer through ENO1.

Cervical cancer is a significant threat to women's health, and its incidence in China has been increasing in recent years. Treating advanced and recurrent cervical cancer has become increasingly challenging, highlighting the urgent need to identify new therapeutic targets for this disease. SIX1 is associated with cell proliferation, metastasis, and chemoresistance in various human malignancies.

PPP1R13L drives cervical cancer progression by suppressing p63-mediated PTEN transcription.

PPP1R13L is a conserved inhibitor of p53, selectively regulating a subset of p53 target genes. Previous studies have reported that PPP1R13L promotes cervical cancer progression, yet its precise mechanism remains unclear and warrants further investigation. In this study, we utilized public databases to reveal the correlation between PPP1R13L and tumor progression pathways.

Retargeting target-directed microRNA-decay sites to highly expressed viral or cellular miRNAs.

MicroRNAs (miRNAs) are pervasive regulators of gene expression, necessitating the development of tools to inhibit individual miRNAs for functional studies or therapeutic targeting. Specialized base-pairing configurations between a miRNA and an RNA target site can trigger the degradation of the targeting miRNA through target-directed miRNA decay (TDMD). Previous work has identified several natural sites that induce TDMD of specific miRNAs.

Cytotoxicity of Activator Expression in CRISPR-based Transcriptional Activation Systems.

CRISPR-based transcriptional activation (CRISPRa) has extensive research and clinical potential. Here, we show that commonly used CRISPRa systems can exhibit pronounced cytotoxicity. We demonstrate the toxicity of published and new CRISPRa vectors expressing the activation domains (ADs) of the transcription factors p65 and HSF1, components of the synergistic activation mediator (SAM) CRISPRa system.

Natural killer cell-related anti-tumour adoptive cell immunotherapy.

Chimeric antigen receptor- (CAR-)modified T cells have been successfully used to treat blood cancer. With the improved research on anti-tumour adoptive cell therapy, researchers have focused on immune cells other than T lymphocytes. Natural killer (NK) cells have received widespread attention as barriers to natural immunity.

Long non-coding RNA NEAT1 promotes aerobic glycolysis and progression of cervical cancer through WNT/β-catenin/PDK1 axis.

Background: Cervical cancer is one of the most common gynecological cancers. Accumulated evidence shows that long non-coding RNAs (lncRNAs) play essential roles in cervical cancer occurrence and progression, but their specific functions and mechanisms remain to be further explored.

Methods: The RT-qPCR assay was used to detect the expression of NEAT1 in cervical cancer tissues and cell lines.

Contrasting Responses and Phytoremediation Potential of Two Poplar Species to Combined Strontium and Diesel Oil Stress.

The soil pollution caused by diesel oil and heavy metals has become an increasingly serious environmental issue, with negative global-scale impacts. The remediation of contaminated soil requires special attention, in which phytoremediation has emerged as an ecofriendly solution. However, the response of plants to the combined stress of diesel oil and heavy metals remains largely unknown.

Design, synthesis and anticancer activity studies of 3-(coumarin-3-yl)-acrolein derivatives: Evidenced by integrating network pharmacology and assay.

Coumarin derivatives have diverse structures and show various significant biological activities. Aiming to develop more potent coumarin derivatives for cancer treatment, a series of coumarin acrolein hybrids were designed and synthesized by using molecular hybridization approach, and investigated for their antiproliferative activity against A549, KB, Hela and MCF-7 cancer cells as well as HUVEC and LO2 human normal cells. The results indicated that most of the synthesized compounds displayed remarkable inhibitory activity towards cancer cells but low cytotoxicity on normal cells.

Dissolved organic matter defines microbial communities during initial soil formation after deglaciation.

Ecosystem succession and pedogenesis reshuffle the composition and turnover of dissolved organic matter (DOM) and its interactions with soil microbiome. The changes of these connections are especially intensive during initial pedogenesis, e.g.

2-Deoxy-D-glucose simultaneously targets glycolysis and Wnt/β-catenin signaling to inhibit cervical cancer progression.

Cervical cancer is one of the most common female malignant tumors, with typical cancer metabolism characteristics of increased glycolysis flux and lactate accumulation. 2-Deoxy-D-glucose (2-DG) is a glycolysis inhibitor that acts on hexokinase, the first rate-limiting enzyme in the glycolysis pathway. In this research, we demonstrated that 2-DG effectively reduced glycolysis and impaired mitochondrial function in cervical cancer cell lines HeLa and SiHa.

CRISPR screens identify novel regulators of cFLIP dependency and ligand-independent, TRAIL-R1-mediated cell death.

Kaposi's sarcoma-associated herpesvirus (KSHV) causes primary effusion lymphoma (PEL). PEL cell lines require expression of the cellular FLICE inhibitory protein (cFLIP) for survival, although KSHV encodes a viral homolog of this protein (vFLIP). Cellular and viral FLIP proteins have several functions, including, most importantly, the inhibition of pro-apoptotic caspase 8 and modulation of NF-κB signaling.

[Spectral characteristics of dissolved organic matter and its environmental responses across successional stages in a glacier retreat area].

Dissolved organic matter (DOM), the most active type of soil organic matter, plays a key role in soil biogeochemical cycling. Therefore, exploring the source, composition, environmental response, and accumulation mechanism of DOM during vegetation succession has great significance for predicting soil carbon cycling. In this study, DOM was extracted from topsoil and subsoil at plots after 12, 30, 40, 50, 80, and 120 years of primary succession along the Hailuogou Glacier retreat area.

Umbilical Cord Blood-Derived Exosomes From Very Preterm Infants With Bronchopulmonary Dysplasia Impaired Endothelial Angiogenesis: Roles of Exosomal MicroRNAs.

Premature infants have a high risk of bronchopulmonary dysplasia (BPD), which is characterized by abnormal development of alveoli and pulmonary vessels. Exosomes and exosomal miRNAs (EXO-miRNAs) from bronchoalveolar lavage fluid are involved in the development of BPD and might serve as predictive biomarkers for BPD. However, the roles of exosomes and EXO-miRNAs from umbilical cord blood of BPD infants in regulating angiogenesis are yet to be elucidated.

White light, autofluorescence and narrow-band imaging bronchoscopy for diagnosing airway pre-cancerous and early cancer lesions: a systematic review and meta-analysis.

Background: We aimed to summarize the diagnostic accuracy of white light bronchoscopy (WLB) and advanced techniques for airway pre-cancerous lesions and early cancer, such as autofluorescence bronchoscopy (AFB), AFB combined with WLB (AFB + WLB) and narrow-band imaging (NBI) bronchoscopy.

Methods: We searched for eligible studies in seven electronic databases from their date of inception to Mar 20, 2015. In eligible studies, detected lesions should be confirmed by histopathology.