Dynamic simulation and experimental studies of molecularly imprinted label-free sensor for determination of milk quality marker.

Bovine serum albumin (BSA) has emerged as a biomarker for mammary gland health and cow quality, being recognized as a significant allergenic protein. In this study, a novel flexible molecular imprinted electrochemical sensor by surface electropolymerization using pyrrole (Py) as functional monomer, which can be better applied to the detection of milk quality marker BSA. Based on computational results, with regard to all polypyrrole (PPy) conformations and amino-acid positions within the protein, the BSA molecule remained firmly embedded into PPy polymers with no biological changes. The molecular imprinted electrochemical sensor displayed a broad linear detection range from 1.0 × 10-4 to 50 ng·mL-1 (R2 = 0.995) with a low detection limit (LOD) of 4.5 × 10-2 pg·mL-1. Additionally, the sensor was highly selective, reproducible, stable and recoverable, suggesting that it might be utilized for the evaluation of milk quality.

Effects of simulated microgravity on current generation of electrochemically active bacteria: Insights from case-control study using random positioning machine.

Electrochemically active bacteria (EAB) exhibit promising prospects for space exploration and life support systems. However, the effects of the space environment on EAB are unclear. In this study, the effects of simulated microgravity on the current generation of mixed-culture EAB were illustrated, and the underlying mechanism was elucidated. The results demonstrated that the electrochemical activity of mixed-culture EAB was enhanced, which was mainly due to the enrichment of Geobacter and the increase in EAB biomass. Additionally, the genes and proteins of the biofilm changed obviously under simulated microgravity conditions, including: I) genes related to signal transfer, II) genes related to cell wall synthesis, and III) genes related to riboflavin synthesis. This study first revealed the enrichment in EAB abundance, the increase in EAB biomass, and the promotion of current generation under simulated microgravity.

KAT8-catalyzed lactylation promotes eEF1A2-mediated protein synthesis and colorectal carcinogenesis.

Aberrant lysine lactylation (Kla) is associated with various diseases which are caused by excessive glycolysis metabolism. However, the regulatory molecules and downstream protein targets of Kla remain largely unclear. Here, we observed a global Kla abundance profile in colorectal cancer (CRC) that negatively correlates with prognosis. Among lactylated proteins detected in CRC, lactylation of eEF1A2K408 resulted in boosted translation elongation and enhanced protein synthesis which contributed to tumorigenesis. By screening eEF1A2 interacting proteins, we identified that KAT8, a lysine acetyltransferase that acted as a pan-Kla writer, was responsible for installing Kla on many protein substrates involving in diverse biological processes. Deletion of KAT8 inhibited CRC tumor growth, especially in a high-lactic tumor microenvironment. Therefore, the KAT8-eEF1A2 Kla axis is utilized to meet increased translational requirements for oncogenic adaptation. As a lactyltransferase, KAT8 may represent a potential therapeutic target for CRC.

A ratiometric molecular imprinted electrochemiluminescence sensor based on enhanced luminescence of CdSe@ZnS quantum dots by MXene@NaAsc for detecting uric acid.

An unlabeled ratiometric molecular imprinted electrochemiluminescence sensor was developed for the determination of trace uric acid, based on MXene@NaAsc nanocomposites, CdSe@ZnS quantum dots and molecularly imprinted polymer composites modified glass carbon electrode. MXene@NaAsc stably enhanced the electron transfer and improved electrochemiluminescence intensity by acting as a base platform and signal amplifier for CdSe@ZnS quantum dots. Specific molecular imprinting cavities based on electropolymerization with o-phenylenediamine were formed to specifically identify uric acid. Combining the good sensitivity of electrochemiluminescence and the excellent selectivity of molecularly imprinted polymer, the ratio of optical signal and electrical signal was used as a comprehensive signal to achieve the detection of uric acid. Based on this, uric acid was detected in the range from 1 × 10-10 to 1 × 10-4 mol/L with the LOD of 18.13 pmol/L (S/N = 3). The developed sensor with easy preparation, great selectivity and excellent sensitivity could successfully detect uric acid in human serum.

The Complex Network of ADP-Ribosylation and DNA Repair: Emerging Insights and Implications for Cancer Therapy.

ADP-ribosylation is a post-translational modification of proteins that plays a key role in various cellular processes, including DNA repair. Recently, significant progress has been made in understanding the mechanism and function of ADP-ribosylation in DNA repair. ADP-ribosylation can regulate the recruitment and activity of DNA repair proteins by facilitating protein-protein interactions and regulating protein conformations. Moreover, ADP-ribosylation can influence additional post-translational modifications (PTMs) of proteins involved in DNA repair, such as ubiquitination, methylation, acetylation, phosphorylation, and SUMOylation. The interaction between ADP-ribosylation and these additional PTMs can fine-tune the activity of DNA repair proteins and ensure the proper execution of the DNA repair process. In addition, PARP inhibitors have been developed as a promising cancer therapeutic strategy by exploiting the dependence of certain cancer types on the PARP-mediated DNA repair pathway. In this paper, we review the progress of ADP-ribosylation in DNA repair, discuss the crosstalk of ADP-ribosylation with additional PTMs in DNA repair, and summarize the progress of PARP inhibitors in cancer therapy.

Molecularly imprinted polymer coating-assisted CsPbBr3 perovskite quantum dots/TiO2 inverse opal heterojunctions for the photoelectrochemical detection of cholesterol.

Photoelectrochemical sensors have outstanding advantages including high sensitivity and miniaturization for outdoor use. Recently, perovskite quantum dots have attracted significant attention due to their high photoluminescence quantum yield. Nonetheless, there is still a strong need to improve their performance in challenging aqueous biological applications. In this paper, based on the molecularly imprinted polymer encapsulation of CsPbBr3 perovskite quantum dot/TiO2 inverse opal heterojunction structures, linear photoelectrochemical detection of cholesterol in aqueous solution was obtained without the involvement of an enzyme. The attenuation of photocurrent intensity under intermittent irradiation within 900 s (45 on/off cycles) was only 8.6%, demonstrating the superior stability of CsPbBr3 based sensor here. At the same time, the minimum detection limit of 1.22 × 10-9 mol L-1 in buffer conditions was lower than that reported for cholesterol photoelectric sensors. It has also been shown that the photoelectrochemical sensor of CsPbBr3 here outperformed that of CH3NH3PbBr3, which is another important member of the perovskite family. Finally, the proposed photoelectrochemical sensor platform was successfully applied in the determination of cholesterol in challenging serum with satisfactory recovery. The synergism among CsPbBr3 perovskite quantum dots, TiO2 inverse opal structure and imprinted polymer has led to greatly improved water stability, super selectivity and sensitivity, thus promoting the development of perovskite-based biological sensors.

A chiral multi-shelled mesoporous carbon nanospheres used for high-resolution gas chromatography separations.

Herein, a chiral multishelled mesoporous carbon nanospheres (MCNs) with unique spiral multishelled hollow mesoporous chiral structure is synthesized; the MCNs can be used as stationary phases for high-resolution gas chromatography (GC) and have good separation capacity. The successful preparation of MCNs is verified by a variety of characterizations. In addition, the MCNs-coated capillary column shows excellent separation performance for n-alkanes, n-alcohols, aromatic compounds, and esters, and it has a faster analysis time than the HP-5 commercial capillary column. The chromatography separation performance for various isomers and racemates of the MCNs stationary phase was evaluated, and it showed good separation capability for amino acid derivatives. The MCNs-coated capillary column has been demonstrated to present good reproducibility and stability. In summary, all of the chromatography experiments in this work indicate that this new stationary phase of the MCNs has good application potential for GC capillary separation.

Topological insulator Bi2Se3 based electrochemical aptasensors for the application of sensitive detection of interferon-γ.

Interferon-γ (IFN-γ) is one of the crucial inflammatory cytokines as an early indicator of multiple diseases. A fast, simple, sensitive and reliable IFN-γ detection method is valuable for early diagnosis and monitoring of treatment. In this work, we creatively developed an electrochemical aptasensor based on the topological material Bi2Se3 for sensitive IFN-γ quantification. The high-quality Bi2Se3 sheet was directly exfoliated from a single crystal, which immobilized the synthesized IFN-γ aptamer. Under optimal conditions, the electrochemical signal revealed a wide linear relation along with the logarithmic concentration of IFN-γ from 1.0 pg mL-1 to 100.0 ng mL-1, with the limit of detection as low as 0.5 pg mL-1. The topological material Bi2Se3 with Dirac surface states improved the electrochemical signal/noise ratio and thus the sensitivity of the sensors. Furthermore, this electrochemical aptasensor exhibited excellent specificity and stability, which could be attributed to the large-scale smooth surface of the Bi2Se3 sheet with few defects decreasing the non-specific absorption. The developed biosensor has the same good performance as the ELISA method for detecting the real serum samples. Our work demonstrates that the developed electrochemical aptasensors based on topological materials have great potential in the field of clinical determination.

Fundus-Vascular Responses to Color Deviation Caused by Non-Oxidative Blue Filtering.

Aims: Short-wavelength blue light damaged retina by the oxidative stress in the retinal pigment epithelial (RPE) cells. Filtering blue light from screen could reduce blue hazard, whereas it inevitably altered color-gamut coverage and color-deviation level. Although abnormal fundus-vascular density (FVD) sometimes indicated fundus disease, few researchers noticed its responses to the variation of color-gamut coverage and color-deviation level. Methods: In this study, we performed cellular experiments and analyzed the RPE cell viabilities (CVs) in spectrums with different blue (455-475 nm) ratios to describe the corresponding oxidative-stress levels. Further, we investigated the effects of color-gamut and deviation on FVD variations during the screen-watching task using human factor experiments with 30 participants (university students, including 17 males and 13 females, 21 to 30 years old). Results: RPE CVs were similar in different spectrums, implying that non-oxidative blue filtering hardly contributed to CV improvement. Color-deviation level seems to induce more significant effects on the visual function compared to color-gamut coverage, and MTF and FVD presents similar variation trends during the visual task. Conclusion: Oxidative-free blue filtering contributed little to decrease retinal oxidative stress yet caused color-deviation increase, which caused significant FVD reduction.

Chiral hydrogen-bonded organic frameworks used as a chiral stationary phase for chiral separation in gas chromatography.

Hydrogen-bonded organic frameworks (HOFs) are two dimensional (2D) or three dimensional (3D) porous crystalline materials constructed by Hydrogen bond interaction. In recent years, a variety of functional HOF materials have been successfully synthesized and used in structural identification, environmental pollutant removal, chiral resolution, drug delivery, fluorescence sensing, etc. Here, we first reported that a HOF to coated capillary column for high-resolution gas chromatographic separation of a wide range of analytes, including n-alkanes, n-alcohols, polycyclic aromatic hydrocarbons, and positional isomers, especially for racemates, the HOFs column showed excellent separation repeatability and reproducibility. The relative standard deviation (RSD) values for the retention times were in the range of 0.37-2.43% for run to run (n = 3), 0.38-2.51% for day-to-day (n = 3), and 0.31-2.54% for column-to-column (n = 3), respectively. Moreover, we applied density-functional theory to calculate the adsorption of enantiomers in HOF structures. This work proved that the HOFs had great application prospects as stationary phase in gas chromatography.

Nucleic Acid Sensing Pathways in DNA Repair Targeted Cancer Therapy.

The repair of DNA damage is a complex process, which helps to maintain genome fidelity, and the ability of cancer cells to repair therapeutically DNA damage induced by clinical treatments will affect the therapeutic efficacy. In the past decade, great success has been achieved by targeting the DNA repair network in tumors. Recent studies suggest that DNA damage impacts cellular innate and adaptive immune responses through nucleic acid-sensing pathways, which play essential roles in the efficacy of DNA repair targeted therapy. In this review, we summarize the current understanding of the molecular mechanism of innate immune response triggered by DNA damage through nucleic acid-sensing pathways, including DNA sensing via the cyclic GMP-AMP synthase (cGAS), Toll-like receptor 9 (TLR9), absent in melanoma 2 (AIM2), DNA-dependent protein kinase (DNA-PK), and Mre11-Rad50-Nbs1 complex (MRN) complex, and RNA sensing via the TLR3/7/8 and retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs). Furthermore, we will focus on the recent developments in the impacts of nucleic acid-sensing pathways on the DNA damage response (DDR). Elucidating the DDR-immune response interplay will be critical to harness immunomodulatory effects to improve the efficacy of antitumor immunity therapeutic strategies and build future therapeutic approaches.

A molecularly imprinted electrochemical sensor with tunable electrosynthesized Cu-MOFs modification for ultrasensitive detection of human IgG.

Human IgG is one of the most important immunoglobulins in the human body. The present study described the fabrication of four kinds of layer-by-layer structures of copper metal-organic frameworks (Cu-MOFs) on the working electrode by electrodeposition, which were then applied as an electrochemical sensor for the sensitive determination of IgG in serum. First, MOFs synthesized using different deposition potentials are expected to have varied morphology and properties. Herein, four copper MOFs (Cu-MOFs) were electrosynthesized by a simple and direct reduction approach. The as-synthesized Cu-MOFs exhibit varied morphology and electrocatalytic behavior. Then, IgG was employed as a template in the electropolymerization of pyrrole-imprinted films on the surface of glassy carbon electrodes. Finally, the template protein was removed to form a molecularly imprinted film with the capability to qualitatively and quantitatively signaling of IgG. Under optimized conditions, the sensor for IgG exhibits a wide detection range of 0.01-10 ng mL-1 with a limit of detection (LOD) of 3 pg mL-1 (S/N = 3). Besides, other parameters including the selectivity, reproducibility (RSD 3.6%), and recovery rate (95.2-102.0%) are all satisfactory. The practicability of the sensor was verified by detecting IgG in human serum samples, which indicated that the sensor was suitable for potential clinical applications.

Dual selective sensor for exosomes in serum using magnetic imprinted polymer isolation sandwiched with aptamer/graphene oxide based FRET fluorescent ignition.

The selective and sensitive detection of cancerous exosomes in serum is critical for early disease diagnosis and improved prognosis. Previous exosome-related research has been limited by a lack of well-understanding in exosomes as well as the challenging background interference of body fluid. Molecularly imprinted polymers (MIPs) and nucleic acid aptamers can be regarded as the two alternatives to antibodies. When using imprinted polymer technology, comprehensive and precise information about the target constituents is not required. In this study, a novel kind of dual selective fluorescent nanosensor for the poorly characterized exosomes was constructed by integrating magnetic MIP selective exosome capture sandwiched with an aptamer/graphene oxide fluorescence resonance energy transfer system (FRET) based selective 'turn-on' exosome labeling heterogeneously. The overall strategy performance was successively evaluated using lysozyme and exosomes as targets. Good linearity and high sensitivity achieved were demonstrated. The LOD of exosomal detection in serum was 2.43 × 106 particles/mL, lower than other immunology based detection methods. The discrimination between serum from breast cancer patients and healthy people was also primarily studied. In conclusion, the developed sensor with outstanding selectivity, high detection sensitivity, simplicity, low cost, and wide applicability for known or unknown targets present significant potential in challenging clinical diagnosis.

A novel real-time TMAO detection method based on microbial electrochemical technology.

Trimethylamine N-oxide (TMAO) is considered to be a novel biomarker of cardiovascular diseases. However, the traditional TMAO detection method has failed to meet the requirements of real-time and point-of-care tests. Herein, a novel TMAO detection method based on microbial electrochemical technology is established, which realizes the direct conversion of TMAO concentration into electrical signals. Attached Shewanella loihica PV-4 was first proven to be capable of simultaneous inward extracellular electron transfer and TMAO reduction. The TMAO detection method showed a wide linear range of 0 to 250 µM, a high sensitivity of 23.92 µA/mM, and a low limit of detection of 5.96 µM. In addition, the TMAO detection process was accomplished within 600 s, with an acceptable accuracy of 90% in the real serum, showing high feasibility in clinical applications.

A chiral metal-organic cage used as the stationary phase for gas chromatography separations.

Chiral metal-organic cages (MOCs) are a new type of porous materials with unique molecular recognition ability, which have received research attention as a chiral stationary phase (CSP) for gas chromatography (GC). Herein, we report the detailed investigation of a chiral MOC ([Cu12(LPA)12(H2O)12], PA = L-phenylalanine, MOC-PA) as a novel stationary phase for GC separations. The MOC-PA capillary column exhibited a high-resolution performance for a wide range of analytes, including n-alkanes, n-alcohols, esters, aromatic compounds and the Grob mixture, positional isomers and racemates. In particular, MOC-PA coated column displayed good resolution and performance for amino acid derivatives. Moreover, the MOC-PA column showed excellent separation repeatability and reproducibility. The relative standard deviation (RSD) values for the retention times were in the range of 0.16-0.30% for run to run (n = 3), 0.31-0.77% for day-to-day (n = 3), and 3.6-4.7% for column-to-column (n = 3), respectively. The experimental results showed that MOC-PA had great potential as a GC stationary phase.

Chiral amorphous metal-organic polyhedra used as the stationary phase for high-resolution gas chromatography separations.

Herein, we describe a new chiral amorphous metal-organic polyhedra used as the stationary phase for high-resolution gas chromatography (GC). The chiral stationary phase was coated onto a capillary column via a dynamic coating process and investigated for a variety of compounds. The experimental results showed that the chiral stationary phase exhibits good selectivity for linear alkanes, linear alcohols, polycyclic aromatic hydrocarbons, isomers, and chiral compounds. In addition, the column has the advantages of high column efficiency and short analysis time. The present work indicated that amorphous metal-organic polyhedra have great potential for application as a new type of stationary phase for GC.

An RNA Metabolism and Surveillance Quartet in the Major Histocompatibility Complex.

At the central region of the mammalian major histocompatibility complex (MHC) is a complement gene cluster that codes for constituents of complement C3 convertases (C2, factor B and C4). Complement activation drives the humoral effector functions for immune response. Sandwiched between the genes for serine proteinase factor B and anchor protein C4 are four less known but critically important genes coding for essential functions related to metabolism and surveillance of RNA during the transcriptional and translational processes of gene expression. These four genes are NELF-E (RD), SKIV2L (SKI2W), DXO (DOM3Z) and STK19 (RP1 or G11) and dubbed as NSDK. NELF-E is the subunit E of negative elongation factor responsible for promoter proximal pause of transcription. SKIV2L is the RNA helicase for cytoplasmic exosomes responsible for degradation of de-polyadenylated mRNA and viral RNA. DXO is a powerful enzyme with pyro-phosphohydrolase activity towards 5' triphosphorylated RNA, decapping and exoribonuclease activities of faulty nuclear RNA molecules. STK19 is a nuclear kinase that phosphorylates RNA-binding proteins during transcription. STK19 is also involved in DNA repair during active transcription and in nuclear signal transduction. The genetic, biochemical and functional properties for NSDK in the MHC largely stay as a secret for many immunologists. Here we briefly review the roles of (a) NELF-E on transcriptional pausing; (b) SKIV2L on turnover of deadenylated or expired RNA 3'→5' through the Ski-exosome complex, and modulation of inflammatory response initiated by retinoic acid-inducible gene 1-like receptor (RLR) sensing of viral infections; (c) DXO on quality control of RNA integrity through recognition of 5' caps and destruction of faulty adducts in 5'→3' fashion; and (d) STK19 on nuclear protein phosphorylations. There is compelling evidence that a dysregulation or a deficiency of a NSDK gene would cause a malignant, immunologic or digestive disease.

Combination of Three Functionalized Temperature-Sensitive Chromatographic Materials for Serum Protein Analysis.

We have developed a methodology to capture acidic proteins, alkaline proteins, and glycoproteins separately in mouse serum using a combination of three functionalized temperature-responsive chromatographic stationary phases. The temperature-responsive polymer poly(N-isopropylacrylamide) was attached to the stationary phase, silica. The three temperature-responsive chromatographic stationary phase materials were prepared by reversible addition-fragmentation chain transfer polymerization. Alkaline, acidic, and boric acid functional groups were introduced to capture acidic proteins, alkaline proteins, and glycoproteins, respectively. The protein enrichment and release properties of the materials were examined using the acidic protein, bovine serum albumin; the alkaline protein, protamine; and the glycoprotein, horseradish peroxidase. Finally, the three materials were used to analyze mouse serum. Without switching the mobile phase, the capture and separation of mouse serum was achieved by the combination of three temperature-responsive chromatographic stationary phase materials. On the whole, 313 proteins were identified successfully. The number of different proteins identified using the new method was 1.46 times greater than the number of proteins that has been identified without applying this method. To our knowledge, this method is the first combinatorial use of three functionalized temperature-responsive chromatographic stationary phase silica materials to separate proteins in mouse serum.

Magnetic Fluorescence Molecularly Imprinted Polymer Based on FeOx/ZnS Nanocomposites for Highly Selective Sensing of Bisphenol A.

In this study, magnetic fluorescence molecularly imprinted polymers were fabricated and used for the selective separation and fluorescence sensing of trace bisphenol A (BPA) in environmental water samples. The carboxyl-functionalized FeOx magnetic nanoparticles were conjugated with mercaptoethylamine-capped Mn2+ doped ZnS quantum dots to prepare magnetic FeOx and ZnS quantum dot nanoparticles (FeOx/ZnS NPs). Additionally, molecular imprinting on the FeOx/ZnS NPs was employed to synthesize core-shell molecularly imprinted polymers. The resulting nanoparticles were well characterized using transmission electron microscopy, Fourier transform infrared spectra, vibrating sample magnetometer and fluorescence spectra, and the adsorption behavior was investigated. Binding experiments showed that the molecularly imprinted FeOX/ZnS NPs (FeOx/ZnS@MIPs) exhibited rapid fluorescent and magnetic responses, and high selectivity and sensitivity for the detection of bisphenol A (BPA). The maximum adsorption capacity of FeOx/ZnS@MIPs was 50.92 mg·g-1 with an imprinting factor of 11.19. Under optimal conditions, the constructed fluorescence magnetic molecularly imprinted polymers presented good linearity from 0 to 80 ng mL-1 with a detection limit of 0.3626 ng mL-1 for BPA. Moreover, the proposed fluorescence magnetic polymers were successfully applied to on-site magnetic separation and real-time fluorescence analysis of target molecule in real samples.

[Preparation and adsorption characteristics of lysozyme-imprinted polymer membrane].

In this work, a novel polymer membrane molecularly imprinted on a silanized glass substrate was prepared. Lysozyme was chosen as the template protein, and acrylamide and N,N'-methylenebisacrylamide were used as the functional monomer and crosslinking agent, respectively. The adsorption equilibrium time, maximum adsorption capacity, specific recognition ability, reusability, and application of the prepared lysozyme-imprinted polymer membrane were investigated experimentally. The prepared polymer membrane exhibited special recognition ability and could quickly adsorb lysozyme. Under optimal conditions, the adsorption equilibrium time of the prepared polymer membrane for lysozyme was 5 min, and the adsorption behavior conformed to the Langmuir adsorption model; the theoretical maximum adsorption capacity was 42.5 mg/g, and the adsorption capacity for an egg sample was 30 mg/g. Additionally, the polymer membrane showed a high selectivity toward the template protein, lysozyme, and exhibited no obvious adsorption of several interfering proteins; the imprinting factor was 3.0. The maximum adsorption capacity of the polymer membrane decreased by 5% after being reused five times. The polymer membrane was used for the adsorption of lysozyme in samples, and good results were obtained. This strategy has potential for the separation and enrichment of target proteins in complex biological samples.