iCRISEE: an integrative analysis of CRISPR screen by reducing false positive hits.

Clustered regularly interspaced short palindromic repeats associated protein 9 (CRISPR/Cas9) technology has become a popular tool for the study of genome function, and the use of this technology can achieve large-scale screening studies of specific phenotypes. Several analysis tools for CRISPR/Cas9 screening data have been developed, while high false positive rate remains a great challenge. To this end, we developed iCRISEE, an integrative analysis of CRISPR ScrEEn by reducing false positive hits. iCRISEE can dramatically reduce false positive hits and it is robust to different single guide RNA (sgRNA) library by introducing precise data filter and normalization, model selection and valid sgRNA number correction in data preprocessing, sgRNA ranking and gene ranking. Furthermore, a powerful web server has been presented to automatically complete the whole CRISPR/Cas9 screening analysis, where we integrated the main hypothesis in multiple algorithms as a full workflow, including quality control, sgRNA extracting, sgRNA alignment, sgRNA ranking, gene ranking and pathway enrichment. In addition, output of iCRISEE, including result mapping, sample clustering, sgRNA ranking and gene ranking, can be easily visualized and downloaded for publication. Taking together, iCRISEE presents to be the state-of-the-art and user-friendly tool for CRISPR screening data analysis. iCRISEE is available at https://www.icrisee.com.

MOF derived core-shell CuO/C with temperature-controlled oxygen-vacancy for real time analysis of glucose.

Introducing oxygen-vacancy into the surface of the non-enzymatic sensor is supposed to be an effective way to improve inherently low catalytic activity and specificity of non-enzymatic sensors. In this work, CuO/C was synthesized at different temperatures using metal-organic frameworks as sacrificial templates to receive additional content of oxygen-vacancy. The product with the highest oxygen vacancy was found at 400 °C (named CuO/C-400 °C), which increased catalytically active sites and enhanced the charge-transfer efficiency. The sensing performance was afterward explored by amperometry under an optimal applied potential at 0.5 V (vs. SCE), presenting a broad detection range from 5.0 µM to 25.325 mM (R2 = 0.9998) with a sensitivity of 244.71 µA mM- 1 cm- 2, and a detection limit of 1 µM. Furthermore, the reliability and selectivity of CuO/C-400 °C sensors were extensively explored in the presence of artificial serum/saliva samples with gradient glucose concentrations. The human blood samples were also detected with high recoveries compared with the clinical Hexokinase method. Hence, the prepared CuO/C-400 °C sensor with a broad detection range and high selectivity can be applied for the diabetes diagnosis ex vivo without further dilution for real-time analysis in practical applications.

Ultrasensitive Detection of Amyloid-ß Using Cellular Prion Protein on the Highly Conductive Au Nanoparticles-Poly(3,4-ethylene dioxythiophene)-Poly(thiophene-3-acetic acid) Composite Electrode.

A highly sensitive electrochemical impedance sensor for amyloid beta oligomer (AßO) was fabricated using a cellular prion protein (PrPC) bioreceptor linked with poly(thiophene-3-acetic acid) transducer. An additional thin layer of poly(3,4-ethylene dioxythiophene) embedded with gold nanoparticles was employed to provide high electrical conductivity and a large surface area. The sensing performace was investigated in terms of sensitivity and detection range. The fabricated sensor exhibited extremely low detection limit at a subfemtomolar level with a wide detection range from 10-8 to 104 nM and its utility was established in mice infected with Alzheimer's disease (AD). The developed AßO sensor could be utilized for early diagnosis of AD.

Application of Polypyrrole-Based Electrochemical Biosensor for the Early Diagnosis of Colorectal Cancer.

Although colorectal cancer (CRC) is easy to treat surgically and can be combined with postoperative chemotherapy, its five-year survival rate is still not optimistic. Therefore, developing sensitive, efficient, and compliant detection technology is essential to diagnose CRC at an early stage, providing more opportunities for effective treatment and intervention. Currently, the widely used clinical CRC detection methods include endoscopy, stool examination, imaging modalities, and tumor biomarker detection; among them, blood biomarkers, a noninvasive strategy for CRC screening, have shown significant potential for early diagnosis, prediction, prognosis, and staging of cancer. As shown by recent studies, electrochemical biosensors have attracted extensive attention for the detection of blood biomarkers because of their advantages of being cost-effective and having sound sensitivity, good versatility, high selectivity, and a fast response. Among these, nano-conductive polymer materials, especially the conductive polymer polypyrrole (PPy), have been broadly applied to improve sensing performance due to their excellent electrical properties and the flexibility of their surface properties, as well as their easy preparation and functionalization and good biocompatibility. This review mainly discusses the characteristics of PPy-based biosensors, their synthetic methods, and their application for the detection of CRC biomarkers. Finally, the opportunities and challenges related to the use of PPy-based sensors for diagnosing CRC are also discussed.

Recent advances in sensor-integrated brain-on-a-chip devices for real-time brain monitoring.

Brain science has remained in the global spotlight as an important field of scientific and technological discovery. Numerous in vitro and in vivo animal studies have been performed to understand the pathological processes involved in brain diseases and develop strategies for their diagnosis and treatment. However, owing to species differences between animals and humans, several drugs have shown high rates of treatment failure in clinical settings, hindering the development of diagnostic and treatment modalities for brain diseases. In this scenario, microfluidic brain-on-a-chip (BOC) devices, which allow the direct use of human tissues for experiments, have emerged as novel tools for effectively avoiding species differences and performing screening for new drugs. Although microfluidic BOC technology has achieved significant progress in recent years, monitoring slight changes in neurochemicals, neurotransmitters, and environmental states in the brain has remained challenging owing to the brain's complex environment. Hence, the integration of BOC with new sensors that have high sensitivity and high selectivity is urgently required for the real-time dynamic monitoring of BOC parameters. As sensor-based technologies for BOC have not been summarized, here, we review the principle, fabrication process, and application-based classification of sensor-integrated BOC, and then summarize the opportunities and challenges for their development. Generally, sensor-integrated BOC enables real-time monitoring and dynamic analysis, accurately measuring minute changes in the brain and thus enabling the realization of in vivo brain analysis and drug development.

Ten-Gram-Scale Mechanochemical Synthesis of Ternary Lanthanum Coordination Polymers for Antibacterial and Antitumor Activities.

As rare-earth coordination polymers (CPs) have appreciable antimicrobial properties, ternary lanthanum CPs have been widely synthesized and investigated in recent years. Here, we report convenient, solvent-free reactions between the lanthanum salt and two ligands at mild temperatures that form ternary lanthanum nanoscale CPs with 10-gram-scale. The structural features and morphologies were characterized using a scanning electron microscope (SEM), Fourier transform infrared spectrometer (FT-IR), ultraviolet-visible (UV-Vis), X-ray diffractometer (XRD), X-ray Photoelectron Spectroscopy (XPS), Brunauer-Emmett-Teller (BET), elemental analysis, inductively coupled plasma mass spectrometry (ICP-MS), electrospray ionization mass spectrometry (ESI-MS), nuclear magnetic resonance (NMR), dynamic light scattering (DLS) and analyzer, and thermogravimetric and differential thermal analyzer (TG-DTA). Furthermore, the in vitro antibacterial activities of these ternary hybrids were studied using the zone of inhibition (ZOI) method, minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and transmission electron microscope (TEM) and were found to have excellent antibacterial properties. The in vitro antitumor activities were performed in determining the absorbance values by CCK-8 (Cell Counting Kit-8) assay. This facile synthetic method would potentially enable the mass production of ternary lanthanum CPs at room temperature, which can be promising candidates as antibacterial compounds and antitumor agents.

Porous Carbon Boosted Non-Enzymatic Glutamate Detection with Ultra-High Sensitivity in Broad Range Using Cu Ions.

A non-enzymatic electrochemical sensor, based on the electrode of a chitosan-derived carbon foam, has been successfully developed for the detection of glutamate. Attributed to the chelation of Cu ions and glutamate molecules, the glutamate could be detected in an amperometric way by means of the redox reactions of chelation compounds, which outperform the traditional enzymatic sensors. Moreover, due to the large electroactive surface area and effective electron transportation of the porous carbon foam, a remarkable electrochemical sensitivity up to 1.9 × 104 µA/mM∙cm2 and a broad-spectrum detection range from nM to mM scale have been achieved, which is two-orders of magnitude higher and one magnitude broader than the best reported values thus far. Furthermore, our reported glutamate detection system also demonstrates a desirable anti-interference ability as well as a durable stability. The experimental revelations show that the Cu ions chelation-assisted electrochemical sensor with carbon foam electrode has significant potential for an easy fabricating, enzyme-free, broad-spectrum, sensitive, anti-interfering, and stable glutamate-sensing platform.

Regulation of Ferroptosis Pathway by Ubiquitination.

Ferroptosis is an iron-dependent form of programmed cell death, which plays crucial roles in tumorigenesis, ischemia-reperfusion injury and various human degenerative diseases. Ferroptosis is characterized by aberrant iron and lipid metabolisms. Mechanistically, excess of catalytic iron is capable of triggering lipid peroxidation followed by Fenton reaction to induce ferroptosis. The induction of ferroptosis can be inhibited by sufficient glutathione (GSH) synthesis via system Xc- transporter-mediated cystine uptake. Therefore, induction of ferroptosis by inhibition of cystine uptake or dampening of GSH synthesis has been considered as a novel strategy for cancer therapy, while reversal of ferroptotic effect is able to delay progression of diverse disorders, such as cardiopathy, steatohepatitis, and acute kidney injury. The ubiquitin (Ub)-proteasome pathway (UPP) dominates the majority of intracellular protein degradation by coupling Ub molecules to the lysine residues of protein substrate, which is subsequently recognized by the 26S proteasome for degradation. Ubiquitination is crucially involved in a variety of physiological and pathological processes. Modulation of ubiquitination system has been exhibited to be a potential strategy for cancer treatment. Currently, more and more emerged evidence has demonstrated that ubiquitous modification is involved in ferroptosis and dominates the vulnerability to ferroptosis in multiple types of cancer. In this review, we will summarize the current findings of ferroptosis surrounding the viewpoint of ubiquitination regulation. Furthermore, we also highlight the potential effect of ubiquitination modulation on the perspective of ferroptosis-targeted cancer therapy.

Recent advances in enzymeless-based electrochemical sensors to diagnose neurodegenerative diseases.

The use of sensitive electrochemical sensors to detect biomarkers is an effective method for the early diagnosis of several neurodegenerative diseases (NDs), such as Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, etc. However, the commercialization of enzyme/aptamer-based sensors is still hampered owing to the historic drawbacks of biorecognition elements including high cost, poor stability, and complex integration technology. Non-enzymatic electrochemical sensors are more attractive compared to their traditional counterparts and can be widely harnessed owing to their low cost, high stability, sensitivity, and ease of miniaturization. This review summarizes recent research progress focusing on the construction of non-enzymatic electrochemical sensors and analyzes their present use in the early diagnosis of NDs. Additionally, this review addresses the limitations and challenges of the use of current non-enzymatic electrochemical sensor technologies for the diagnosis of NDs and highlights the possible directions for future research.

Preparation of graphene oxide (GO)/lanthanum coordination polymers for enhancement of bactericidal activity.

In this study, graphene oxide/lanthanum coordination polymer (GLCP) nanocomposites are prepared and their bactericidal activities against seven typical Pathogenic bacteria are evaluated. The GLCPs are fabricated through the electrostatic self-assembly of La ions on negatively charged graphene oxide (GO), followed by the stabilization of π-π stacking to ensure the formation of lanthanum coordination polymers on the GO surface. The morphologies and structures of the synthesized GLCPs are characterized using scanning electron microscopy (SEM), transmission electron microscopy (TEM), ultraviolet-visible (UV-vis) spectroscopy, Fourier transform infrared (FT-IR) spectroscopy, X-ray photoelectron spectroscopy (XPS) and thermogravimetric analysis (TGA). Moreover, the bactericidal effects of the well-coordinated GLCPs are investigated using the zone of inhibition and flat colony counting methods, as well as by determining the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). The five GLCPs synthesized in this study exhibit broad-spectrum antibacterial activities against seven typical Pathogenic bacteria. We believe that our study could serve as a starting point to prepare bactericidal materials for further applications.

Mitochondria-targeted high-load sound-sensitive micelles for sonodynamic therapy to treat triple-negative breast cancer and inhibit metastasis.

Breast cancer is the most common cancer among women worldwide, of which 10-20% accounts for triple-negative breast cancer (TNBC). TNBC is more aggressive, lacks an effective treatment target, and has a higher metastasis rate compared to other types of breast cancers. These characteristics result in poor therapeutic and prognostic outcomes in patients with TNBC. Sonodynamic therapy (SDT) is an emerging non-invasive procedure with high-tissue penetration properties to treat cancer. Therefore, we designed a new sonosensitizer, PEG-IR780@Ce6 for SDT, which showed excellent performance in inhibiting cancer cells and in simultaneously suppressing the migration and invasion of cancer cells. In vitro and in vivo experiments showed that PEG-IR780@Ce6 as a sonosensitizer could generate higher levels of reactive oxygen species (ROS) than IR780 and free Ce6 alone, thereby resulting in better anti-cancer effects. Besides, PEG-IR780@Ce6 inhibited the migration and invasion of MDA-MB-231 cells, both in vitro and in vivo, which indicated that it could suppress the metastasis of TNBC. Moreover, the long circulation time and the mitochondria-targeting ability of PEG-IR780@Ce6 guaranteed its accumulation in the tumor. In addition, both in vitro and in vivo experiments indicated the biocompatibility and biosafety of PEG-IR780@Ce6. In conclusion, our results collectively suggested that the newly designed sonosensitizer, PEG-IR780@Ce6, is a promising treatment option for TNBC with excellent therapeutic effects and low side effects.

Hollow Dodecahedra Graphene Oxide- Cuprous Oxide Nanocomposites With Effective Photocatalytic and Bactericidal Activity.

In this study, a kind of graphene oxide-cuprous oxide (GO-Cu2O) nanocomposites was fabricated with different morphologies to serve as a photocatalytic material for the degradation of organic/inorganic dyes under visible light and the bactericidal effect against pathogenic bacteria. The GO-Cu2O was prepared with solid cube and hollow dodecahedra morphologies through in-situ synthesis, and characterized by scanning electron microscopy (SEM), transmission electron microscope (TEM), X-ray diffraction (XRD), Raman, Ultraviolet and visible spectrophotometry (UV/vis), and Fourier transform infrared spectroscopy. In comparison with cubic GO-Cu2O, the absorption and degradation efficiency of the GO-Cu2O dodecahedra (GCD) composite in Methyl orange (MO), Rhodamine B (RhB), and phenol was higher owning to the more active sites for the simultaneous dye and light absorption of hollow structure. The antibacterial effect of the GO-Cu2O dodecahedra was examined by the flat colony counting method with an excellent bactericidal effect against pathogenic bacteria. The possible mechanism for the preparation of GCD possessing the enhancement of the visible-light photocatalytic and antibacterial efficiencies were also investigated.

Ferrocene-Encapsulated Zn Zeolitic Imidazole Framework (ZIF-8) for Optical and Electrochemical Sensing of Amyloid-ß Oligomers and for the Early Diagnosis of Alzheimer's Disease.

In this work, the ferrocene-encapsulated Zn zeolitic imidazole framework (ZIF-8) was prepared by the self-assembly of Zn ions and 2-methylimidazole and used for the dual detection of amyloid-beta oligomers (AßO), which is the main neuropathological hallmark of Alzheimer's disease. Ferrocene is an optically and electrochemically active signal which was successfully encapsulated inside of the ZIF-8 and released by the competitive coordination between Zn ions and AßO after being treated with AßO. The released ferrocene content was monitored by ultraviolet/visible spectrophotometry and cyclic voltammetry. The dual determination of AßO played a synergetic role in the quick qualitative and precise quantitative analyses in a wide detection range of 10-5 to 102 µM and good feasibility in artificial cerebrospinal fluid.

Monitoring of early diagnosis of Alzheimer's disease using the cellular prion protein and poly(pyrrole-2-carboxylic acid) modified electrode.

Amyloid-beta oligomers (AßΟ) are considered to be reliable biomarkers for the diagnosis of Alzheimer' disease (AD), and the cellular prion protein (PrPC) is identified as a receptor for AßO. We demonstrated a label and antibody-free electrochemical biosensor for the selective detection of AßO using an electrically conductive poly(pyrrole-2-carboxylic acid) (PPyCOOH) linking agent and PrPC receptor. In the fabrication of the biosensor, each step was characterized by electrochemical impedance spectroscopy and cyclic voltammetry. The developed PrPc/PPyCOOH biosensor exhibited extremely low detection limit of 10-4 pM with high sensitivity which is desirable for the early diagnosis of AD. The sensing performance was further confirmed by the mice infected with AD. The proposed sensor emerged as a promising tool for the early detection of AßO.

Graphene-spindle shaped TiO2 mesocrystal composites: facile synthesis and enhanced visible light photocatalytic performance.

Graphene (GR)-TiO2 mesocrystal composites were prepared by a facile template-free process based on the combination of sol-gel and solvothermal methods, and were characterized using field emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), high-resolution transmission electron microscopy (HRTEM), X-ray diffraction (XRD), Raman spectroscopy, UV-vis diffuse reflectance spectroscopy (UV-vis DRS), nitrogen absorption and electron spin resonance (ESR). Visible light photocatalytic performance of GR-TiO2 composites was evaluated for photocatalytic degradation of organic dye Rhodamine B. It was found that the amount of graphene oxide (GO) added obviously affects morphologies of TiO2 mesocrystals and photocatalytic activities of as-prepared nanocomposites. Composites prepared in the presence of different amounts of GO all exhibit higher photocatalytic activity than pure TiO2 mesocrystals and P25, the composite obtained by using 20mg GO presents the most uniform TiO2 mesocrystals in the composite and shows the highest photocatalytic efficiency. The mechanism for the generation of TiO2 mesocrystals in the GR-TiO2 composite is proposed and possible reasons for the enhancement in visible light photocatalytic efficiency are also discussed.