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RNA is rarely used as a therapeutic target due to its flexible structure and instability. CRISPR‐Cas13a is a powerful tool for RNA knockdown, and the potential application of CRISPR‐Cas13a in cancer cells should be further studied. In this study, overexpression of LwCas13a by lentivirus in glioma cells reveals that crRNA‐EGFP induces a “collateral effect” after knocking down the target gene in EGFP‐expressing cells. EGFRvIII is a unique EGFR mutant subtype in glioma, and the CRISPR‐Cas13a system induces death in EGFRvIII‐overexpressing glioma cells. Bulk and single‐cell RNA sequencing analysis in U87‐Cas13a‐EGFRvIII cells confirm the collateral effect of the CRISPR‐Cas13a system. Furthermore, CRISPR‐Cas13a inhibits the formation of glioma intracranial tumors in mice. The results demonstrate the collateral effect of the CRISPR‐Cas13a system in cancer cells and the powerful tumor‐eliminating potential of this system. It is reported that a CRISPR/Cas13a system can exert a collateral effect after target recognition in glioma cells, indicating that the CRISPR/Cas13a system has great potential value for tumor elimination, especially for patients with specific oncogene mutations.

Background The biomass yield of Chlorella PY-ZU1 drastically increased when cultivated under high CO2 condition compared with that cultivated under air condition. However, less attention has been given to the microalgae photosynthetic mechanisms response to different CO2 concentrations. The genetic reasons for the higher growth rate, CO2 fixation rate, and photosynthetic efficiency of microalgal cells under higher CO2 concentration have not been clearly defined yet. Results In this study, the Illumina sequencing and de novo transcriptome assembly of Chlorella PY-ZU1 cells cultivated under 15% CO2 were performed and compared with those of cells grown under air. It was found that carbonic anhydrase (CAs, enzyme for interconversion of bicarbonate to CO2) dramatically decreased to near 0 in 15% CO2-grown cells, which indicated that CO2 molecules directly permeated into cells under high CO2 stress without CO2-concentrating mechanism. Extrapolating from the growth conditions and quantitative Real-Time PCR of CCM-related genes, the K m (CO2) (the minimum intracellular CO2 concentration that rubisco required) of Chlorella PY-ZU1 might be in the range of 80-192 μM. More adenosine triphosphates was saved for carbon fixation-related pathways. The transcript abundance of rubisco (the most important enzyme of CO2 fixation reaction) was 16.3 times higher in 15% CO2-grown cells than that under air. Besides, the transcript abundances of most key genes involved in carbon fixation pathways were also enhanced in 15% CO2-grown cells. Conclusions Carbon fixation and nitrogen metabolism are the two most important metabolisms in the photosynthetic cells. These genes related to the two most metabolisms with significantly differential expressions were beneficial for microalgal growth (2.85 g L−1) under 15% CO2 concentration. Considering the micro and macro growth phenomena of Chlorella PY-ZU1 under different concentrations of CO2 (0.04-60%), CO2 transport pathways responses to different CO2 (0.04-60%) concentrations was reconstructed.

IntroductionThe emergence of a novel coronavirus, SARS-CoV-2, has highlighted the need for rapid, accurate, and point-of-care diagnostic testing. As of now, there is not enough testing capacity in the world to meet the stated testing targets, which are expected to skyrocket globally for broader testing during reopeningAimThis review focuses on the development of lab-on-chip biosensing platforms for diagnosis of COVID-19 infection.ResultsWe discuss advantages of utilizing lab-on-chip technologies in response to the current global pandemic, including their potential for low-cost, rapid sample-to-answer processing times, and ease of integration into a range of healthcare settings. We then highlight the development of magnetic, colorimetric, plasmonic, electrical, and lateral flow-based lab-on-chip technologies for the detection of SARS-CoV-2, in addition to other viruses. We focus on rapid, point-of-care technologies that can be deployed at scale, as such devices could be promising alternatives to the current gold standard of reverse transcription-polymerase chain reaction (RT-PCR) diagnostic testing.ConclusionThis review is intended to provide an overview of the current state-of-the-field and serve as a resource for innovative development of new lab-on-chip assays for COVID-19 detection.

Checkpoint blockade therapies targeting programmed death ligand 1 (PD-L1) and its receptor programmed cell death 1 promote T cell-mediated immune surveillance against tumors and have been associated with significant clinical benefit in cancer patients. The long-stranded non-coding RNA HOTAIR is highly expressed and associated with metastasis in a variety of cancer types and promotes tumor metastasis at least in part through association with the PRC2 complex that induces redirection to hundreds of genes involved in tumor metastasis. Here, we report that HOTAIR is an activator lncRNA of the NF-κB pathway and demonstrate that its apparent upregulation promotes inflammatory signaling and immune escape in glioma cells. Bioinformatics analysis was used to elucidate the relationship between HOTAIR and NF-κB pathway in HOTAIR knockdown glioma cells. At the cytological level, protein hybridization and immunofluorescence were used to detect the response of proteins in the NF-κB signaling pathway to HOTAIR regulation. ChIP and ChIRP experiments identified HOTAIR target genes. Animal experiments verified alterations in inflammation and immune escape following HOTAIR knockdown and activity inhibition. HOTAIR activated the expression of proteins involved in NF-κB, TNFα, MAPK and other inflammatory signaling pathways. In addition, HOTAIR induced various proteins containing protein kinase structural domains and promoted the enrichment of proteins and complexes of important inflammatory signaling pathways, such as the TNFα/NF-κB signaling protein complex, the IκB kinase complex, and the IKKA-IKKB complex. In addition, HOTAIR aberrantly activated biological processes involved in glioma immune responses, T-cell co-stimulation and transcription initiation by RNA polymerase II. HOTAIR facilitated the induction of IκBα phosphorylation by suppressing the expression of the NF-κB upstream protein UBXN1, promoting NF-κB phosphorylation and nuclear translocation. , reduction of HOTAIR decreased PD-L1 protein expression, indicating that cells are more likely to be targeted by immune T cells. In conclusion, our results provide convincing evidence that lncRNA HOTAIR drives aberrant gene transcription and immune escape from tumor cells through the NF-κB pathway.

The heavy metal sources of large-scale raceway pond microalgae cultivation with flue gas were investigated to reduce heavy metal contents in microalgae during cultivation. The microalgae were cultivated with power plant flue gas (as C source) and circulating cooling seawater (added with N and P nutrients) for 6 days. The Pb, Cd, Hg, and As contents in microalgae were 0.91, 0.22, 0.08, and 0.28 ppm, respectively, which are nearly within the available national standard for food-grade microalgae. The heavy metal contents in microalgae with two membrane materials, namely, elastic polyethylene and random copolymer polypropylene, barely increased. The Hg, As, and Pb contents in microalgae cells cultivated with pure CO 2 were 16.67%, 69.23%, and 70.33% that of cells cultivated with CO 2 from flue gas. The Pb, As, and Hg contents in cells cultivated with fresh water were reduced by 38.46%, 15.38%, and 37.50%, respectively, compared with those cultivated with seawater. The heavy metal contents in microalgae were further reduced and controlled.

This study presents a dual-functional thin film, known as Ag nanoparticles decorated, ZnO nanorods coated silica nanofibers (AgNP-ZnONR-SNF), which demonstrates remarkable capabilities in both water purification and organic pollutants sensing. The 3D fibrous structure of ZnONR-SNF provides a large surface-area-to-volume ratio for piezo- and photo-catalytic degradation of organic pollutants under UV irradiation, achieving over 98% efficiency. Ag nanoparticles decorated on ZnONR-SNF form “hot-spot” that significantly enhance the surface-enhanced Raman spectroscopy (SERS) signal, resulting in an enhancement factor of 1056 and an experimental detection limit of 1 pg mL −1 . Furthermore, a machine learning algorithm is developed for the qualitative and quantitative detection of multiple contaminants, achieving high accuracy (92.3%) and specificity (89.3%) without the need for preliminary processing of Raman spectra. This work provides a promising nanoengineering solution for water purification and sensing with improved detection accuracy, purification efficiency, and cost-effectiveness.

Background Metabolism reprogramming plays a vital role in glioblastoma (GBM) progression and recurrence by producing enough energy for highly proliferating tumor cells. In addition, metabolic reprogramming is crucial for tumor growth and immune‐escape mechanisms. Epidermal growth factor receptor (EGFR) amplification and EGFR‐vIII mutation are often detected in GBM cells, contributing to the malignant behavior. This study aimed to investigate the functional role of the EGFR pathway on fatty acid metabolism remodeling and energy generation. Methods Clinical GBM specimens were selected for single‐cell RNA sequencing and untargeted metabolomics analysis. A metabolism‐associated RTK‐fatty acid‐gene signature was constructed and verified. MK‐2206 and MK‐803 were utilized to block the RTK pathway and mevalonate pathway induced abnormal metabolism. Energy metabolism in GBM with activated EGFR pathway was monitored. The antitumor effect of Osimertinib and Atorvastatin assisted by temozolomide (TMZ) was analyzed by an intracranial tumor model in vivo. Results GBM with high EGFR expression had characteristics of lipid remodeling and maintaining high cholesterol levels, supported by the single‐cell RNA sequencing and metabolomics of clinical GBM samples. Inhibition of the EGFR/AKT and mevalonate pathways could remodel energy metabolism by repressing the tricarboxylic acid cycle and modulating ATP production. Mechanistically, the EGFR/AKT pathway upregulated the expressions of acyl‐CoA synthetase short‐chain family member 3 (ACSS3), acyl‐CoA synthetase long‐chain family member 3 (ACSL3), and long‐chain fatty acid elongation‐related gene ELOVL fatty acid elongase 2 (ELOVL2) in an NF‐κB‐dependent manner. Moreover, inhibition of the mevalonate pathway reduced the EGFR level on the cell membranes, thereby affecting the signal transduction of the EGFR/AKT pathway. Therefore, targeting the EGFR/AKT and mevalonate pathways enhanced the antitumor effect of TMZ in GBM cells and animal models. Conclusions Our findings not only uncovered the mechanism of metabolic reprogramming in EGFR‐activated GBM but also provided a combinatorial therapeutic strategy for clinical GBM management.

Over 20% of cancer 'driver' genes encode chromatin regulators. Long noncoding RNAs (lincRNAs), which are dysregulated in various cancers, play a critical role in chromatin dynamics and gene regulation by interacting with key epigenetic regulators. It has been previously reported that the lincRNA HOTAIR mediates recruitment of polycomb repressive complex 2 (PRC2) leading to aberrant transcriptional silencing of tumor suppressor genes in glioma and breast cancer. Thus, lincRNA HOTAIR can serve as a promising therapeutic target. Herein, we identified a small-molecule compound AC1Q3QWB (AQB) as a selective and efficient disruptor of HOTAIR-EZH2 interaction, resulting in blocking of PRC2 recruitment and increasing tumor suppressors expression. Molecular docking and high-throughput screening were performed to identify the small compound, AQB. RIP and ChIRP assays were carried to assess the selective interference of AQB with the HOTAIR-EZH2 interaction. The effects of AQB on tumor malignancy were evaluated in a variety of cancer cell lines and orthotopic breast cancer models. The combination therapy of AQB and 3-Deazaneplanocin A (DZNep), an inhibitor of the histone methyltransferase EZH2 was used and in orthotopic breast cancer and glioblastoma patient-derived xenograft (PDX) models. Tumor cells highly expressing HOTAIR and EZH2 were sensitive to AQB. APC2, as one of the target genes, was significantly up-regulated by AQB and led to degradation of β-catenin resulting in suppression of Wnt/β-catenin signaling which may contribute to inhibition of tumor growth and metastasis and in orthotopic breast cancer models. Remarkably, AQB enhanced the toxicity of DZNep . In orthotopic breast cancer and glioblastoma patient-derived xenografts (PDX) models, the combination of low doses of AQB and DZNep realized much better killing than DZNep treatment alone. AQB is a HOTAIR-EZH2 inhibitor, which blocks PRC2 recruitment and has great potential as an effective agent for targeted cancer therapy.

Zinc oxide (ZnO) is a versatile semiconducting material with excellent piezoelectric properties, making it highly suitable for energy harvesting and sensing applications. The doping of ZnO with various elements has been recognized as an effective strategy to enhance its electrical and mechanical properties. This review article focuses on the advancements in piezoelectric energy harvesters and sensors utilizing doped ZnO. It delves into the role of various dopants in enhancing ZnO's piezoelectric properties, crucial for developing high‐performance piezoelectric nanogenerators and sensors. The article comprehensively examines material properties, synthesis methods, characterization techniques, and the implications of doping on ZnO's structural and functional aspects. It highlights significant research findings, identifies gaps in current knowledge, and suggests future research directions to further optimize doped ZnO materials for energy harvesting and sensing applications, reflecting on the growing interest and potential of doped ZnO in the field. This review provides a comprehensive overview of material properties, synthesis methods, and characterization techniques of doped ZnO, emphasizing the impact of doping on its structural and functional attributes. It highlights key findings, identifies knowledge gaps, and proposes future research directions to optimize doped ZnO for energy harvesting and sensing applications, showcasing its growing significance and potential in the field.

Amplification of epidermal growth factor receptor (EGFR) and active mutant EGFRvIII occurs frequently in glioblastoma (GBM) and contributes to chemo/radio‐resistance in various cancers, especially in GBM. Elucidating the underlying molecular mechanism of temozolomide (TMZ) resistance in GBM could benefit cancer patients. A genome‐wide screening under a clustered regularly interspaced short palindromic repeats (CRISPR)‐Cas9 library is conducted to identify the genes that confer resistance to TMZ in EGFRvIII‐expressing GBM cells. Deep sgRNA sequencing reveals 191 candidate genes that are responsible for TMZ resistance in EGFRvIII‐expressing GBM cells. Notably, E2F6 is proven to drive a TMZ resistance, and E2F6 expression is controlled by the EGFRvIII/AKT/NF‐κB pathway. Furthermore, E2F6 is shown as a promising therapeutic target for TMZ resistance in orthotopic GBM cell line xenografts and GBM patient‐derived xenografts models. After integrating clinical data with paired primary–recurrent RNA sequencing data from 134 GBM patients who received TMZ treatment after surgery, it has been revealed that the E2F6 expression level is a predictive marker for TMZ response. Therefore, the inhibition of E2F6 is a promising strategy to conquer TMZ resistance in GBM. A CRISPR‐Cas9 screening of temozolomide (TMZ) resistant glioblastoma cells is presented. NF‐κB is activated by TMZ treatment and EGFRvIII (epidermal growth factor receptor, EGFR) via PI3K/AKT, which leads to transcriptional induction of E2F6 expression. Cells with activated NF‐κB‐E2F6 survive under TMZ selection. TMZ withdrawal leads to cell proliferation and inhibition of NF‐κB/E2F6 prevents TMZ resistance.