Photoelectrochemical Biosensor for Histone Deacetylase Sirt1 Detection Based on Polyaspartic Acid-Engaged and Triggered Redox Cycling Amplification and Enhanced Photoactivity of BiVO4 by Gold Nanoparticles and SnS2.

A photoelectrochemical (PEC) biosensor was established for histone deacetylase Sirt1 detection based on the polyaspartic acid (PASP)-mediated redox cycling amplification and Sirt1 catalysis deacetylation-triggered recognition of the deacetylated substrate peptide, using PASP as the recognition reagent. After BiVO4 was composited with gold nanoparticles and SnS2, the photoactivity of the composite was greatly enhanced due to the matched energy band structure. Under the catalysis of Sirt1 enzyme, the acetylated substrate peptide was deacetylated to obtain a positive peptide, which was recognized by negative PASP. In addition to the recognition function, PASP also played other triple roles. First, PASP interacted with the positive peptide to form a double-stranded structure, which led to the electrode interface changing from irregular to regular, resulting in an improved PEC response. Second, PASP was involved into redox cycle amplification due to its reduction to dehydroascorbic acid. Further, it was used for repeated preparation of ascorbic acid to provide electron donors. This process enhanced the PEC response. Third, based on the matched energy band with BiVO4, PASP effectively improved the photoactivity of BiVO4. With multiplex signal amplification, the PEC biosensor showed a wide linear range (1.83-1830 pM) and high detection sensitivity with a low detection limit of 0.732 pM (S/N = 3). The applicability of this method was evaluated by studying the effects of a known inhibitor of nicotinamide and the heavy metal ions of Cd2+ and Pb2+ on Sirt1 enzyme activity, and the results showed that this method not only provided a new platform for screening Sirt1 enzyme inhibitors but also provided new biomarkers for evaluating the ecotoxicological effects of environmental pollutants.

Oncogenic transmembrane protein 158 drives the PI3K/Akt signaling pathway to accelerate gastric cancer cell growth.

Gastric cancer (GC) is a serious threat to human health and an important cause of cancer-related death. Herein, we evaluated the influence of transmembrane protein 158 (TMEM158) on GC cell growth. According to Genomic Spatial Event (GSE) and The Cancer Genome Atlas (TCGA) databases, TMEM158 content is amplified in GC tissues. The diagnostic value of TMEM158 expression in GC is huge. GC sufferers with high expression of TMEM158 were associated with poor overall survival. In addition, TMEM158 content was increased in GC cells. TMEM158 promoted GC cell proliferation by modulating the PI3K/Akt signaling pathway. Lack of TMEM158 reduced GC tumor growth. Collectively, TMEM158 accelerated GC cell proliferation by modulating the PI3K/Akt signaling pathway, making it a prospective biomarker for survival in GC patients.

Antibody-free photoelectrochemical strategy for simultaneous detection of methylated RNA, METTL3/METTL14 protein and MazF protein based on enhanced photoactivity of MoSe2-BiOI nanocomposite.

Taking advantages of the catalytic activity of METTL3/METTL14 protein towards adenine methylation in RNA sequence and the specific digestion activity of MazF protein towards unmethylated RNA sequence containing ACA bases, a novel photoelectrochemical biosensor was constructed for simultaneous detection of RNA methylation, METTL3/METTL14 protein and MazF protein. MoSe2-BiOI nanocomposite was prepared and considered as photoactive material, catalytic hairpin assembly strategy and in situ generation of electron donors catalyzed by polyaspartic acid-loaded alkaline phosphatase technique were employed as signal amplification. Under the optimum conditions, the detection ranges of methylated RNA, METTL3/METTL14 protein and MazF protein were 0.001-50 nM, 0.001-25 ng/µL, and 0.001-10 U/mL, respectively. The corresponding detection limits were 0.46 pM, 0.51 pg/µL and 0.42 U/µL with S/N = 3. In addition, the effect of drugs and composite pollutants on the activities of MazF proteins was assessed, proving the applicability of the developed method in the field of drug screening for MazF-related diseases. Moreover, the effects of pollutants on the activity of METTL3/METTL14 were also preliminarily explored, providing new information on pathogenic mechanism of pollutants.

One-pot synthesis of 2D Ag/BiOCl/Bi2O2CO3 S-scheme heterojunction with oxygen vacancy for photocatalytic disinfection of Fusarium graminearum in vitro and in vivo.

2D Ag/BiOCl/Bi2O2CO3 S-scheme heterojunction was prepared with oxygen vacancy (OVs) via one-pot hydrothermal method. The XRD and XPS analysis indicated the synthesized sample contained Ag nanoparticles (AgNPs) instead of Ag ions. The SEM and HRTEM pictures showed that BiOCl/Bi2O2CO3 nanosheets were modified with AgNPs. Compared with AgNPs, BiOCl, and Bi2O2CO3, Ag/BiOCl/Bi2O2CO3 exhibited highly photocatalytic inactivation of pathogenic fungi (Fusarium graminearum) due to the wide light absorption range and S-scheme heterojunction structure, which improved the production and transfer of photogenerated carrier, and enhanced the separation of photogenerated e-/h+ pairs. In addition, the improved photocatalytic disinfection against Fusarium graminearum of Ag/BiOCl/Bi2O2CO3 was verified in Sedeveria Letizia plant. Furthermore, active species capture assay and ESR experiments disclosed the involvement of OVs, h+, ∙O2-, ∙OH, and -for Fusarium graminearum destruction during photocatalysis process. The S-scheme heterojunction was proved via oxygen vacancy, which was extensively beneficial to increase charge transmission and separation efficiency. Our work proposed Ag/BiOCl/Bi2O2CO3 was an efficient and ecological fungicide to inactive Fusarium graminearum in vitro and vivo for crop disease.

Photoelectrochemical biosensor for DNA demethylase detection based on enzymatically induced double-stranded DNA digestion by endonuclease-exonuclease system and Bi4O5Br2-Au/CdS photoactive material.

A novel photoelectrochemical (PEC) biosensor for the detection of DNA demethylase MBD2 was developed based on Bi4O5Br2-Au/CdS photosensitive material. Bi4O5Br2 was firstly modified with gold nanoparticles (AuNPs), following with the modification onto the ITO electrode with CdS to realize the strong photocurrent response as a result of AuNPs had good conductibility and the matched energy between CdS and Bi4O5Br2. In the presence of MBD2, double-stranded DNA (dsDNA) on the electrode surface was demethylated, which triggered the digestion activity of endonuclease HpaII to cleave dsDNA and induced the further cleavage of the dsDNA fragment by exonuclease III (Exo III), causing the release of biotin labeled dsDNA and inhibiting the immobilization of streptavidin (SA) onto the electrode surface. As a results, the photocurrent was increased greatly. However, in the absence of MBD2, HpaII digestion activity was inhibited by DNA methylation modification, which further caused the failure in the release of biotin, leading to the successful immobilization of SA onto the electrode to realize a low photocurrent. The sensor had a detection of 0.3-200 ng/mL and a detection limit was 0.09 ng/mL (3σ). The applicability of this PEC strategy was assessed by studying the effect of environmental pollutants on MBD2 activity.

Antibody-free photoelectrochemical biosensor for DNA carboxylation detection based on SnS2@Ti3C2 heterojunction.

As an important epigenetic modification, 5-carboxycytosine (5caC) played an important role in gene regulation, cell differentiation and growth. 5caC existed in many cells and tissues, but it was highly similar to the structure of other cytosine derivatives and had less content in the genome. Therefore, it was urgent to develop a sensitive and highly selective trace biosensor to detect 5caC. A novel photoelectrochemical biosensor was fabricated for 5-carboxy-2'-deoxycytidine-5'-triphosphate (5cadCTP) detection, where SnS2@Ti3C2 nanocomposite was employed as photoactive material, polyethyleneimine was used as 5cadCTP recognition and capture reagent, and Ru(NH3)63+ was used as photosensitizer for signal amplification. Due the good conductivity of Ti3C2 MXene and the matched energy band between Ti3C2 MXene and SnS2, SnS2@Ti3C2 nanocomposite presented strong photoactivity, which was beneficial to the high detection sensitivity. For specific recognition of 5cadCTP, the covalent interaction of -NH2 in 5cadCTP with -COOH on the substrate electrode was used, which was beneficial to the high detection selectivity. A broad linear relationship between photocurrent and 5cadCTP concentration was observed ranging from 1 pM to 0.2 µM. The low detection limit of 260 fM was achieved. The developed method has high detection specificity and can even distinguish 5caC with its derivatives. In addition, the applicability was evaluated by detecting the content change of 5caC in the genomic DNA of rice seedlings after cultured with environmental pollutants. This work provides a novel platform for 5cadCTP detection, and it can also be applied to detect other cytosine derivatives with suitable recognition strategies.

Investigation of the effect of antibiotics on 5-formylcytosine content in mazie seedling tissues based on photoelectrochemical biosensor.

Given the improved photoactivity of Bi2S3 by MXene, an article photoelectrochemical biosensor was designed for 5-formyl-2'-deoxycytidine (5fdCTP) detection, where Bi2S3: MXene was selected as photoactive material, polydopamine was used as solid electron donor and 5fdCTP capture reagent, calcined ZIF-8(C-ZIF-8) was chosen as the artificial enzyme. With the catalyzed by C-ZIF-8, 4-chloro-1-naphthol was allegro oxidized by H2O2 to form the insoluble benzo-4-chlorohexadienone, and then deposited on the surface of the electrode, Resulting in a decrease of the PEC response. Under the optimum conditions, the sensor has a linear range of 0.001-200 nM and a detection limit of 0.51 pM (3σ). The suitability of the developed method was appraised by investigating the effect of antibiotics on 5fdCTP content in the genomic DNA of the roots of maize seedlings. As a new detection platform, the application of this approach can be expanded to investigative the impact of other pollutants on the content of 5fdCTP in plant or animal tissues, explore the feasibility of 5fdCTP as a new indicator for the ecotoxicological effect of pollutants, and the photoelectrochemical method as a new assessment technique for the ecotoxicological effects of pollutants.

MXene Enhanced Photoactivity of Bi2O3/Bi2S3 Heterojunction with G-wire Superstructure for Photoelectrochemical Detection of TET1 Protein.

Ten-eleven translocation 1 (TET1) protein has the potential to accelerate the oxygenation of 5-methylcytosine to 5-hydroxymethylcytosine (5hmC); then the -CH2OH of 5hmC can further covalently react with -SH catalyzed by M.HhaI methyltransferase. A brand-new photoelectrochemical (PEC) detection technique for the TET1 protein was created in light of this. For this objective, the Bi2O3/Bi2S3 heterojunction was first prepared by a one-pot hydrothermal method and served for photosensitive materials. For further enhancing the photoactivity, Bi2O3/Bi2S3 was blended with MXene to form an energy band-matched structure, thus improving the migration kinetics of photogenerated carriers. For achieving a high sensitivity of detection, a DNA Walker incorporated with the nicking endonuclease (Nb.BbvCI enzyme)-assisted signal amplification strategy was presented to output exponential G-quadruplex fragments. Self-assembly of the free G-quadruplex sequence into a G-wire superstructure with the assistance of Mg2+ provided more loading sites for MB and amplified the PEC signal. The linear range of the biosensor was 0.1-10 µg/mL with a detection limit of 0.024 µg/mL (S/N = 3) for TET1 protein under optimal experimental conditions. The suitability of the proposed method was evaluated by inhibitor screening experiments and the influence of environmental degradation on the activity of TET1 protein.

The Impact of the Duration of Cardiac Troponin I Elevation on the Clinical Prognosis as Well as Incidence of New-Onset Atrial Fibrillation Respectively in Elderly Non-ST-Elevation Acute Myocardial Infarction Patients without PCI.

OBJECTIVE: This study aimed to investigate the impact of the duration of cardiac troponin I (TnI) elevation on the prognosis and incidence of new-onset atrial fibrillation (NOAF) in elderly patients with non-ST-elevation acute myocardial infarction (NSTE-AMI). METHODS: A total of 383 NSTE-AMI patients ≥75 years old were enrolled in this study and divided into two groups: in 194 cases, the duration of TnI elevation was ≥14 days (group 1), and in 189 cases, the duration of TnI elevation was <14 days (group 2). The patients were followed up for 60 months. The effect of TnI on prognosis was studied by cohort. The primary endpoint was a composite endpoint of cardiovascular death, reinfarction, ischemic stroke, and hospitalization for heart failure, and the secondary endpoint was all-cause death. A case-control study design was adopted to analyze the influencing factors of NOAF occurrence in Group 1 and Group 2. RESULTS: The median duration of follow-up was 26 months. Multivariate Cox's regression analysis revealed that the duration of TnI elevation ≥14 days and diuretic use were independent variables of the major composite endpoint (p < 0.01 for both), and the left ventricular ejection fraction and the duration of TnI elevation ≥14 days were independent related variables of all-cause death (p < 0.05). The duration of TnI elevation ≥14 days was correlated with the occurrence of NOAF, but, in the multivariate logistic regression model, only uric acid and high-sensitivity C-reactive protein were independently associated with NOAF (p < 0.05). CONCLUSION: The duration of TnI elevation ≥14 days was the independent correlation factor of the major composite endpoint and all-cause death; high sensitivity C-reactive protein and uric acid are independent risk factors for NOAF.

Collaborative care intervention for patients with chronic heart failure: A systematic review and meta-analysis.

INTRODUCTION: Patients with chronic heart failure (HF) show many symptoms that worsen the quality of life (QoL). Collaborative care intervention (CCI) aims to improve the QoL and symptoms by integrating psychosocial and palliative strategies in chronic care. METHODS: The PubMed, EMBASE, and Cochrane library databases were searched from inception to September 2018. The included studies were used to determine pooled standard mean differences (SMDs) and associated 95% confidence intervals (CIs). The data were assessed by fixed- and random effects models, respectively. RESULTS: Twenty-one studies including 2999 patients with chronic heart failure were included. The results showed significantly improved QoL in the CCI group compared with the routine care group (SMD = 0.60, 95%CI 0.27-0.94, Pheterogeneity < .001, I = 94.1%). The patients who received face-to-face interventions experienced a significant improvement (SMD = 0.54, 95%CI 0.24-0.85, Pheterogeneity < .001, I = 88.7%) in terms of QoL compared with those administered only telephone interventions. Furthermore, significantly improved anxiety level (SMD = 0.33, 95%CI 0.12-0.55, Pheterogeneity = .612, I = 0%) and 6-min walk test (SMD = 0.46, 95%CI 0.29-0.64, Pheterogeneity = .458, I = 0%) were found in the CCI group compared with the routine care group. CONCLUSION: These findings confirmed that collaborative care intervention effectively improves the quality of life as well as psychological (anxiety) and physical (6-min walk test) functions in patients with chronic heart failure compared with routine care. Furthermore, face-to-face interventions show a greater improvement of QoL compared with telephone-only interventions.

Oncogenic transmembrane protein 158 drives the PI3K/Akt signaling pathway to accelerate gastric cancer cell growth

Gastric cancer (GC) is a serious threat to human health and an important cause of cancer-related death. Herein, we evaluated the influence of transmembrane protein 158 (TMEM158) on GC cell growth. According to Genomic Spatial Event (GSE) and The Cancer Genome Atlas (TCGA) databases, TMEM158 content is amplified in GC tissues. The diagnostic value of TMEM158 expression in GC is huge. GC sufferers with high expression of TMEM158 were associated with poor overall survival. In addition, TMEM158 content was increased in GC cells. TMEM158 promoted GC cell proliferation by modulating the PI3K/Akt signaling pathway. Lack of TMEM158 reduced GC tumor growth. Collectively, TMEM158 accelerated GC cell proliferation by modulating the PI3K/Akt signaling pathway, making it a prospective biomarker for survival in GC patients.

The structures, cytotoxicity, apoptosis and molecular docking controlled by the aliphatic chain of palladium(II) complexes.

A new series of Pd(II) complexes derived from benzenealkyl dicarboxylate ligands, [Pd(Ln)(phen)] (phen=2,9-dimethyl-1,10-phenanthroline, complex 1: L1=phenylmalonate; complex 2: L2=benzylmalonate; complex 3: L3=(2-phenylethyl)malonate; complex 4: L4=(3-phenylpropyl)malonate) have been synthesized under room temperature condition. These complexes contain a long dicarboxylate aliphatic chain. They were characterized by elemental analysis, infrared spectroscopy, single crystal X-ray diffraction. The binding of complexes with fish sperm DNA (FS-DNA) was investigated by UV absorption and fluorescence spectra. Gel electrophoresis assay demonstrated the ability of the complexes to cleave the pBR322 plasmid DNA. The cytotoxic activity of the complexes was tested against two different cancer cell lines, HeLa and HL-60. Cytotoxic activity studies showed the four complexes exhibited significant cancer cell inhibitory rate. Further flow cytometry experiments showed that the cytotoxic Pd(II) complexes induced apoptosis of HL-60 tumor cell lines. The molecular dynamic simulations and docking methods were used to predict the DNA binding affinity of Pd(II) complexes by the resulting relative binding energy of complexes with DNA -6.01, -6.25, -7.24 and -7.59 kcal/mol, while with DNA-topoisomerase I (Topo I) -7.98, -9.25, -10.2 and -11.5 kcal/mol, respectively. The good visualization images supported with the experimental results of structure-activity relationship between cytotoxicity and carbon chain length.