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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.

Blue crest between the wavelength of 460 nm and 480 nm was reported to present melatonin suppression effects, whereas effects of red light on circadian rhythm regulation remain unclear. Spectrum plays an important role in circadian rhythm regulation, yet a lot of researches focused on the correlated color temperature, although a correlated color temperature value corresponds to various possible spectrums. Here, we performed human factor experiments with 3 lamps on 17 participants, comprising 9 males and 8 females. Our results showed that spectrums with high blue intensity tended to cause abnormal regulations of melatonin and cortisol, while the abnormalities were likely to be compensated by the 606-635-nm red light, which was indispensable for the photo-biological effects concerning circadian rhythm regulation. Abnormal circadian rhythm regulation was also found to be influenced by the illuminance, as abnormalities were significant in 500 lux whereas they were likely to disappear in 250 lux, implying the existence of threshold doses to trigger abnormities concerning circadian rhythm regulation. Furthermore, circadian rhythm responses were distinct between males and females. Our work may have implications for the development of light source, as we suggest that lighting source designers should increase the 606-635-nm intensity for bed room luminaires to decrease melatonin suppression effects.

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.

Two high-speed countercurrent chromatography (HSCCC) modes were compared by separation of major alkaloids from crude extract of Picrasma quassioides. The conventional HSCCC separation was performed with a two-phase solvent system composed of petroleum ether–ethyl acetate–methanol–water (5:5:4.5:5.5, v/v/v/v) with 200 mg loading. pH-Zone-refining CCC was performed with two-phase solvent system composed of petroleum ether–ethyl acetate–n-butanol–water (3:2:7:9, v/v/v/v) where triethylamine (10 mM) was added to the upper organic stationary phase and hydrochloric acid (5 mM) was added to the lower aqueous phase with 2 g loading. From 2 g of crude extract, 87 mg of 5-methoxycanthin-6-one (a), 38 mg of 1-methoxy-β-carboline (b), 134 mg of 1-ethyl-4,8-dimethoxy-β-carboline (c), 74 mg of 1-ethoxycarbonyl-β-carboline (d), 56 mg of 1-vinyl-4,8-dimethoxy-β-carboline (e) and 26 mg of 1-vinyl-4-dimethoxy-β-carboline (f) were obtained with purities of over 97.0%. The results indicated that pH-zone-refining CCC is an excellent separations tool at the multigram level.

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.

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.

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.

pH-Zone refining counter-current chromatography was successfully applied to the preparative isolation and purification of six alkaloids from the ethanol extracts of Uncaria macrophylla Wall. Because of the low content of alkaloids (about 0.2%, w/w) in U. macrophylla Wall, the target compounds were enriched by pH-zone refining counter-current chromatography using a two-phase solvent system composed of petroleum ether–ethyl acetate–isopropanol–water (2:6:3:9, v/v), adding 10 mM triethylamine in organic stationary phase and 5 mM hydrochloric acid in aqueous mobile phase. Then pH-zone refining counter-current chromatography using the other two-phase solvent system was used for final purification. Six target compounds were finally isolated and purified by following two-phase solvent system composed of methyl tert-butyl ether (MTBE)–acetonitrile–water (4:0.5:5, v/v), adding triethylamine (TEA) (10 mM) to the organic phase and HCl (5 mM) to aqueous mobile phase. The separation of 2.8 g enriched total alkaloids yielded 36 mg hirsutine, 48 mg hirsuteine, 82 mg uncarine C, 73 mg uncarine E, 163 mg rhynchophylline, and 149 mg corynoxeine, all with purities above 96% as verified by HPLC Their structures were identified by electrospray ionization-mass spectrometry (ESI-MS) and 1H-NMR spectroscopy.

Avermectin fermentation residue (AFR) is rich in proteins, which can be depolymerized to value-added amino acids for in-plant reuse. The hydrochloric acid (HCl) hydrolysis is performed and investigated under different conditions, including HCl concentration, solid-liquid ratio, temperature, and time. The hydrolysis degree (HD) of 67.7% can be achieved. The empirical correlation of HD is established with a good practicability to control the HD and predict the experimental conditions. Solid-liquid reaction is confirmed to be dominant during the hydrolysis process. There are 17 kinds of amino acids in the hydrolysate, benefiting the reuse. Avermectin is not detected in the hydrolysate and AFR, and the mass of AFR is reduced by 53.8 wt%. This work provides a novel strategy for the environmentally friendly treatment and meanwhile the resource recovery of AFR. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

A label-free molecularly imprinted electrochemical sensor (MIECS) based on electropolymerized molecularly imprinted polymer (MIP) was developed for the determination of homocysteine (Hcy) in serum for the first time. MXene@AuNPs with layered structure was synthesized on the electrode by modifying MXene with gold nanoparticles (AuNPs). MIP based on dopamine hydrochloride (DA) were electropolymerized onto the surface of MXene@AuNPs modified electrode by molecular docking and quantum chemical calculations for specific recognition of Hcy. MXene@AuNPs as a carrier for immobilizing MIP steadily enhances the conductivity of the electrode (about 4.2-fold) and plays a crucial part in improving the detection sensitivity of MIECS. The results showed that the current response linearly decreased with the increasing concentration of Hcy in the detection range from 1 × 10−13 to 1 × 10−5 mol l−1, the limit of detection (LOD) and limit of quantification (LOQ) of 11.81 fmol l−1 and 39.49 fmol l−1, respectively. With favorable selectivity, stability, reproducibility and ruggedness, the developed MIECS was applied to the determination of Hcy in human serum samples with recoveries of 87.83%–92.58%. The proposed strategy has potential application for disease surveillance. [ABSTRACT FROM AUTHOR]

The present work describes a faithful strategy of dual-template molecularly imprinted polymers (MIP) to chiral recognize and quantify D-Cystine (D-Cys) and L-Cystine (L-Cys) at ultra-trace level through "vector method." Briefly, one has to saturate association D-Cys while analyzes L-Cys, and vice versa. Herein, the working electrode, magnetic glassy carbon (MGCE), was initially drop-coated with molybdenum disulfide-ionic liquid (MoS2-IL) dispersion liquid for large specific surface area and excellent electrical conductivity. After the working electrode was dried naturally, chitosan (CS) was electrodeposited on. And the strong electrostatic interactions between CS and Fe[(CN)6]3-/4- could further enhance the electric signal. Next, dual-template MIP dispersion liquid was drop-coated on the working electrode. Moreover, Fe3O4 nano-particles (NPs) was regard as the support skeleton material of dual-template MIP, which could significantly improve the bonding strength with MGCE. Herein, the proposed sensor demonstrated good analytical figures of merits with Differential Pulse Voltammetry (DPV), showing that the LOD of L-Cys and D-Cys were 0.7402 pg ml-1 and 0.6136 pg ml-1 respectively, with linear response ranges from 1 pg ml-1 to 12 pg ml-1 for both enantiomers. Furthermore, the proposed sensor exhibited great potential in chiral recognition and biochemical analysis. [ABSTRACT FROM AUTHOR]

Cytoglobin (Cygb), like other members of the globin family, is a nitric oxide (NO) dioxygenase, metabolizing NO in an oxygen (O2)-dependent manner. We examined the effect of modification of cysteine sulfhydryl groups of Cygb on its O2 binding and NO dioxygenase activity. The two cysteine sulfhydryls of Cygb were modified to form either an intramolecular disulfide bond (Cygb_SS), thioether bonds to N-ethylmaleimide (NEM; Cygb_SC), or were maintained as free SH groups (Cygb_SH). It was observed that the NO dioxygenase activity of Cygb only slightly changed (~ 25%) while the P50 of O2 binding to Cygb changed over four-fold with these modifications. Our results suggest that it is possible to separately regulate one Cygb function (such as O2 binding) without largely affecting the other Cygb functions (such as its NO dioxygenase activity). [ABSTRACT FROM AUTHOR]

Four geminal ionic liquids (GILs), namely, 1,4-bis(1,1'-butyl-3,3'- methylene- imidazolium)-benzene bis[(trifluoromethyl)sulfonyl]imide (BBMIB-NTf2), 1,4- bis(1,1'-butyl-3,3'-methylene-imidazolium)-benzene tetrafluoroborate (BBMIB-BF4), 1,4- bis(1,1'-butyl-3,3'-methylene-imidazolium)-benzene hexafluophosphate (BBMIB-PF6), and 1,4-bis(1,1'-methyl-3,3'-methylene-imidazolium)-benzene bis[(trifluoromethyl) sulfonyl] imide (BMMIB-NTf2), were synthesized. They were statically coated onto the inner walls of fused-silica capillary columns and used as stationary phases for gas chromatography. The evaluation of BBMIB-NTf2, BBMIB-BF4, BBMIB-PF6, and BMMIB-NTf2 as stationary phases is reported here for the first time. These new stationary phases exhibit efficiencies of at least 2.3 × 103 plates per meter. Abraham solvation parameter model was used to evaluate the solvation characteristics. The system constants indicated that the dipolarity/polarizability and the hydrogen-bond basicity play a major role among five molecular interactions between stationary phases and solute molecules. A fundamental understanding into the solvation characteristics of these GILs can be used as a guide to choosing the appropriate geminal ionic liquids for specific applications in various fields. The chromatographic separation performance was evaluated by a Grob test mixture, n-alkanes, alcohols, and aromatic isomers. Furthermore, the thermal stability was tested. The present results demonstrate that these geminal ionic liquids stationary phases possess excellent chromatographic separation performance and good thermal stability (at least up to 270 °C) and may be applicable as gas chromatography stationary phases for more application. [ABSTRACT FROM AUTHOR]

Liposomes have very similar structure to cell plasma membranes. Using liposomes as stationary phase in liquid chromatography (LC) or micellar electrokinetic chromatography (MEKC) has been demonstrated to be a good, dynamic method for the study of the interaction between cell membranes and important biomolecules. There has been no report on integrating plasma membrane proteins with phospholipids as pseudo-stationary phase in MEKC. In this paper, a novel mode of capillary electrophoresis (CE) is developed, that is, protein–liposome conjugate. This protein–liposome biomimetic membrane is demonstrated for the first time to be applicable as pseudo-stationary phase in MEKC. The protein is able to significantly improve chromatographic performance and stability. The experimental phenomena are further confirmed in terms of specific capacity factors and free binding energy. This new CE mode is used to investigate the interaction between dopamine transporter and dopamine–nomifensine. [ABSTRACT FROM AUTHOR]

Gold nanoparticle-based lateral flow immunoassays (AuNP LFIAs) are widely used point-of-care (POC) sensors for in vitro diagnostics. However, the sensitivity limitation of conventional AuNP LFIAs impedes the detection of trace biomarkers. Several studies have explored the size and shape factors of AuNPs and derivative nanohybrids, showing limited improvements or enhanced sensitivity at the cost of convenience and affordability. Here, we investigated surface chemistry on the sensitivity of AuNP LFIAs. By modifying surface ligands, a surface chemistry strategy involving weakly ionized AuNPs enables ultrasensitive naked-eye LFIAs (~100-fold enhanced sensitivity). We demonstrated how this surface chemistry-amplified immunoassay approach modulates nanointerfacial bindings to promote antibody adsorption and higher activity of adsorbed antibodies. This surface chemistry design eliminates complex nanosynthesis, auxiliary devices, or additional reagents while efficiently improving sensitivity with advantages: simplified fabrication process, excellent reproducibility and reliability, and ultrasensitivity toward various biomarkers. The surface chemistry using weakly ionized AuNPs represents a versatile approach for sensitizing POC sensors. [ABSTRACT FROM AUTHOR]