Investigation of G-Quadruplex DNA-Mediated Charge Transport for Exploring DNA Oxidative Damage in Telomeres.

The human telomeric DNA 3' single-stranded overhang comprises tandem repeats of the sequence d(TTAGGG), which can fold into the stable secondary structure G-quadruplex (G4) and is susceptible to oxidative damage due to the enrichment of G bases. 8-Oxoguanine (8-oxoG) formed in telomeric DNA destabilizes G4 secondary structures and then inhibits telomere functions such as the binding of G4 proteins and the regulation of the length of telomeres. In this work, we developed a G4-DNA self-assembled monolayer electrochemical sensing interface using copper-free click chemistry based on the reaction of dibenzocyclooctyl with azide, resulting in a high yield of DNA tethers with order and homogeneity surfaces, that is more suitable for G-quadruplex DNA charge transport (CT) research. At high DNA coverage density surfaces, G-quadruplex DNA is 4 times more conductive than double-stranded DNA owing to the well-stacked aromatic rings of G-quartets acting as good charge transfer channels. The effect of telomeric oxidative damage on G-quadruplex-mediated CT is investigated. The accommodation of 8-oxoG at G sites originally in the syn or anti conformation around the glycosyl bond in the nonsubstituted hTel G-quadruplex causes structural perturbation and a conformational shift, which disrupts the π-stack, affecting the charge transfer and attenuating the electrochemical signal. The current intensity was found to correlate with the amount of 8-oxodG, and the detection limit was estimated to be approximately one lesion in 286 DNA bases, which can be converted into 64.7 fmol on the basis of the total surface DNA coverage. The improved G4-DNA order and homogeneity sensing interface represent a major step forward in this regard, providing a reliable and controlled electrochemical platform for the accurate measurement and diagnosis of G4-DNA oxidative damage.

Intra-Individual Variation in Disease-Specific IgG Fc Glycoform Ratios to Monitor the Disease Progression of Lung Cancer.

Aberrant protein glycosylation is an active pathological alteration related to the progression of cancers. The speed of progression varies among individuals, increasing the difficulties of prognosis assessment. Hence, evaluating variation in glycosylation using patients themselves as their own controls is a potential way to reduce the impact of individual differences on progression monitoring. Here, following a longitudinal follow-up study involving 125 lung cancer (LC) patients with progressive disease, we isolated disease-specific IgG from serum using polyacrylamide gel electrophoresis, obtained IgG glycoform ratios using mass spectrometry, and then set a fold-change cutoff of 1.5 to utilize the intra-individual variation in IgG glycosylation to monitor PD. We found that the serial monitoring of 15 types of glycoform ratios provided an effective way for monitoring LC progression. Over 1.5-fold changes in glycoform ratios relative to the first observed value were detected in 117 of 125 LC patients (93.6%). Our established method predicted LC progression 55.8 (IQR 31.1-90.1) weeks earlier than imaging examination did. In summary, intra-individual variation in IgG glycoform ratios is useful to monitor LC progression, expanding our knowledge about the relationship between IgG glycosylation and cancer prognosis. The raw data files are available via the ProteomeXchange Consortium with the identifier PXD037541.

Mesoporous PtIr alloy single-particle: A novel SECM-tip for in situ monitoring NO of single-cell.

As a vital factor in cell metabolism, nitric oxide (NO) is associated with nitrosative stress and subsequent inflammations and diseases. In situ, real-time NO monitoring is challenging due to its relative trace concentration and fast diffusion in cell. Scanning electrochemical microscopy (SECM) is suited uniquely for single-cell analysis, and its electrochemical response to targets can be further enhanced by improving the interfacial properties of its tip. Here, an ultramicroelectrodes (UMEs) modification strategy based on bimetallic single-particle was proposed for the first time. This mesoporous platinum/iridium alloy single-particle (mPtIr SP) interface using micelle-assisted electrodeposition was characterized by scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS). And the nucleation kinetic progress which can be defined as "oil-in-water-like" electrodeposition was discussed in detail. The high sensitivity (203.86 µA/µM·cm2) and good selectivity for NO detection benefits from the high catalysis of the PtIr alloy and the high mass transfer properties of the porous interface. In particular, this novel UME can real-time monitor NO release from a single MCF-7 cell stimulated by perfluorooctanoic acid (PFOA), providing new ideas for contaminant toxicity assessment, health diagnostics, and disease treatment.

Deep learning-based solution for smart contract vulnerabilities detection.

This paper aims to explore the application of deep learning in smart contract vulnerabilities detection. Smart contracts are an essential part of blockchain technology and are crucial for developing decentralized applications. However, smart contract vulnerabilities can cause financial losses and system crashes. Static analysis tools are frequently used to detect vulnerabilities in smart contracts, but they often result in false positives and false negatives because of their high reliance on predefined rules and lack of semantic analysis capabilities. Furthermore, these predefined rules quickly become obsolete and fail to adapt or generalize to new data. In contrast, deep learning methods do not require predefined detection rules and can learn the features of vulnerabilities during the training process. In this paper, we introduce a solution called Lightning Cat which is based on deep learning techniques. We train three deep learning models for detecting vulnerabilities in smart contract: Optimized-CodeBERT, Optimized-LSTM, and Optimized-CNN. Experimental results show that, in the Lightning Cat we propose, Optimized-CodeBERT model surpasses other methods, achieving an f1-score of 93.53%. To precisely extract vulnerability features, we acquire segments of vulnerable code functions to retain critical vulnerability features. Using the CodeBERT pre-training model for data preprocessing, we could capture the syntax and semantics of the code more accurately. To demonstrate the feasibility of our proposed solution, we evaluate its performance using the SolidiFI-benchmark dataset, which consists of 9369 vulnerable contracts injected with vulnerabilities from seven different types.

Plantamajoside alleviates hypoxia-reoxygenation injury through integrin-linked kinase/c-Src/Akt and the mitochondrial apoptosis signaling pathways in H9c2 myocardial cells.

Myocardial ischemia-reperfusion injury(MIRI) is one of the common complications after myocardial infarction surgery, Oxidative stress is among the main mechanisms of myocardial ischemia-reperfusion injury. Plantamajoside (PMS), the main effective ingredient in the genus Plantain, has been reported to possess an antioxidation, anti-inflammatory and anti-apoptosis role. However, whether PMS can attenuate myocardial ischemia-reperfusion injury is not yet known. Herein, we explored the effects of PMS on hypoxia-reoxygenation (H/R) injury in H9c2 cardiomyocytes and the underling molecular mechanisms of the treatment. Network pharmacological analysis screened the top 31 key genes in the treatment of MIRI disease treated with PMS, and the result of molecular docking further illustrated the roles that the PMS play in the treatment of MIRI through its interference with integrin-linked kinase (ILK) target protein. PMS was not cytotoxic in the concentration range of 5-40 µM and increased cell survival after H/R injury in a concentration-dependent manner without affecting proliferation or growth. PMS significantly reduced the levels of lactate dehydrogenase, malonic dialdehyde, reactive oxygen species and cell apoptosis, and increased soperoxide dismutase activity compared with those of the H/R injury group. PMS promoted the protein and mRNA expression of ILK and Bcl-2, the protein expression of p-Akt, and reduced the protein and mRNA expression of Bax, Caspase-3, and Cytochrome c, the protein expression of p-c-Src. PMS has protective effects against H/R injury in H9c2 cells, and its protective mechanism may be related to reactive oxygen species clearance, activation of the ILK/c-Src/Akt pathway and inhibition of the mitochondrial apoptosis.

Bioferment residue: TG-FTIR study and cocombustion in a MSW incineration plant.

With fast development of industry large quantities of hazardous waste are produced in China. Today, incineration plays an important role in the disposal of hazardous waste. Co-incineration of some types of hazardous wastes with municipal solid waste (MSW) has been suggested in the Proposed Standards for Pollutants for MSW combustors in China, published in 2010. According to this proposal, coincinerated hazardous waste should have similar combustion characteristics with MSW, such as bioferment residue (HW02-276-001-02 in China Hazardous Waste List). In this study, residue from the production of hydrochloride salt spectinomycin, a bioferment process, was studied by thermogravimetric analysis (TGA) coupled with Fourier transform infrared (TG-FTIR) analysis. In TGA, the sample attains its final weight before 800 °C. No gaseous pollutants evolve in large amount during FTIR analysis. During test runs at a MSW incineration plant in Jinhua, Zhejiang Province, bioferment residue was added to MSW at a rate of 24 ton/day and fed to the circulated fluidized bed (CFB) incineration system with capacity of 500 ton/day MSW. The operating parameters and emissions were monitored. The system performance was obviously not affected by addition of bioferment residue to MSW/coal and the pollutant emissions met the Chinese standard, with or without addition of bioferment into feedstock.

Native ambient mass spectrometry of intact protein assemblies directly from Escherichia coli colonies.

Here, we demonstrate that by combining electroporation with native ambient mass spectrometry, it is possible to detect intact non-covalent protein complexes directly from bacterial colonies growing on agar. Homodimers HdeA and HdeB were identified, together with the 50 kDa Mn-bound superoxide dismutase homodimer, in addition to some previously undetected monomeric proteins.

Effectiveness and safety of treating carotid atherosclerotic plaques with the method of nourishing qi, promoting blood circulation and expelling phlegm: A systematic review and meta-analysis.

Objectives: This meta-analysis aimed at evaluating the effectiveness and safety of Chinese medicine (TCM), which nourished qi, promoted blood circulation, and expelled phlegm (YQHXZT), in treating carotid atherosclerosis (CAS) from an immunological perspective. Background: The incidence of CAS has been increasing and tends to be younger. Although western medicine is effective, there are some limitations. TCM has certain advantages over the multichannel and multitarget treatment strategies in slowing down the process of CAS. However, there is no comprehensive review in this field. Methods: Nine databases were searched from January, 2012, to September, 2022. After applying the inclusion and exclusion criteria to the RCTs, research quality evaluation and data extraction were conducted, and a meta-analysis of the articles was performed. The GRADE was used to assess the quality of the evidence. Results: Fourteen RCTs involving 1,191 patients were identified. The results indicated that the experimental group was more effective in improving carotid intima-media thickness (CIMT)[SMD = -0.97, 95%CI(-.30,-0.65), p < 0.00001], reducing carotid plaque area [SMD = -1.98, 95%CI(-3.06,-0.89), p = 0.0003], lowering hs-CRP [SMD = -1.33, 95%CI(-1.59,-1.06), p < 0.00001] and LDL-C levels [SMD = -0.60, 95%CI(-0.83,-0.38), p < 0.00001]. Moreover, the experimental group was superior to peak systolic blood flow velocity (PSV) [SMD = -0.37, 95%CI(-0.59,-0.16), p = 0.0007], clinical efficacy [RR = 1.64, 95% CI (1.39, 1.94), p < 0.00001] and plaque area efficacy [RR = 1.36, 95% CI (1.22, 1.52), p < 0.0001]. The adverse reactions were not statistically significant in the two groups [RD = -0.01, 95% CI (-0.04.0.01), p = 0.17]. The results of grade evaluation suggested that the outcome indicators LDL-C, hs-CRP, plaque area efficacy, PSV, and adverse events were moderate. CIMT, plaque reduction area, and TCM clinical efficacy were low-quality. Conclusion: The combination of YQHXZT can alleviate the process of CAS by inhibiting the thickening of CIMT, reducing plaque area and lowering hs-CRP and LDL-C levels. The mechanism may possibly be related to reducing lipid deposition and inhibiting the inflammatory response. Besides, the combination did not increase the risk of adverse effects. However, more well-designed RCTs are needed in the future. Systematic review registration: CRD42022360529, https://www.crd.york.ac.uk/prospero/.

Effectiveness and Safety of Treating Negative Emotions after PCI from the Perspective of Qi and Blood: A Systematic Review and Meta-Analysis.

Background: Many patients undergoing PCI have been reported to suffer from psychological distress and negative emotions. Several lines of evidence have indicated that PCI patients with negative emotions are particularly vulnerable to myocardial reperfusion injury when they face psychological challenges. As proven by clinical trials and research, traditional Chinese medicine (TCM) has certain advantages in alleviating psychological symptoms in PCI patients. The level of evidence for TCM is not yet high. There is no existing systematic review to evaluate the effectiveness and safety of TCM in post-PCI patients. Methods: PubMed, EMBASE, Cochrane Library, Web of Science, CNKI, VIP, Wanfang Database, and CBM were searched to identify randomized controlled trials (RCTs) that treated negative emotions after PCI using qi and blood cotherapy. The search period was from database inception to March 1, 2022. After applying the inclusion and exclusion criteria to the RCTs, research quality evaluation and data extraction were conducted, and a meta-analysis of the articles was performed using Revman 5.3 and Stata 12.1. Results: A total of 14 RCTs involving 1314 patients were included. Meta-analysis results indicated that compared with the anti-anxiety and depression medications group, the qi-blood harmony group was more effective in clinical outcomes (RR = 1.19, 95% CI (1.13, 1.25), P < 0.00001), maintaining the stability of angina pectoris (SMD = 0.65, 95% CI (0.29, 1.01), P=0.0004), increasing the degree of patients' satisfaction (SMD = 0.95, 95% CI (0.25, 1.65), P=0.008), reducing the frequency of attacks (SMD = 0.64, 95% CI (0.11, 1.18), P=0.02), and the incidence of adverse reactions (RR = 0.54, 95% CI (0.43, 0.68), P < 0.00001). The HAMA and HAMD scores were significantly lower after treatment, and there was no significant difference between the two groups (HAMA: RR = 1.03, 95% CI (0.95, 1.12), P=0.4). The efficacy of the two groups was comparable. In terms of reduction of the HAMD score, after sensitivity analysis, the literature by Liang was found to be significantly influencing the results, and after excluding the results of Liang, the qi-blood harmony group was superior to the Western medicine group for reducing the HAMD score (RR = 1.12, 95% CI (1.01, 1.24), P < 0.05), which was significantly different. The results of this review, combined with the grade evaluation, suggest that the HAMA posttreatment score reduction, the efficacy of TCM treatment, and the incidence of adverse reactions were supported by moderate evidence, and the HAMD posttreatment score reduction and the SAQ score were supported by low-quality evidence. Conclusion: Treating negative emotions after PCI based on the idea of "harmonization of qi and blood" can effectively improve the clinical efficacy, the stability of angina pectoris and the degree of patient satisfaction, and can reduce the frequency of angina attacks and the incidence of adverse events. There was no significant difference between the two groups for reductions in the HAMA and HAMD scores. However, more high-quality, large sample, multicentre RCTs are still needed for further verification. PROSPERO Registration Number: PROSPERO CRD42022313169.

Application of Multi-Dimensional Intelligent Visual Quantitative Assessment System to Evaluate Hand Function Rehabilitation in Stroke Patients.

Background: Hand dysfunction is one of the main symptoms of stroke patients, but there is still a lack of accurate hand function assessment systems. This study focused on the application of the multi-dimensional intelligent visual quantitative assessment system (MDIVQAS) in the rehabilitation assessment of hand function in stroke patients and evaluate hand function rehabilitation in stroke patients. Methods: Eighty-two patients with stroke and unilateral hand dysfunction were evaluated by MDIVQAS. Cronbach's Alpha coefficient was used to assess the internal consistency of MDIVQAS; the F-test is used to assess the differences in MDIVQAS for multiple repeated measures. Spearman's analysis was used to identify correlations of MDIVQAS with other assessment systems. t-tests were used to identify differences in outcomes assessed with MDIVQAS in patients before and after treatment. p < 0.05 were considered significant. Results: (1) Cronbach's Alpha coefficient of MDIVQAS in evaluating hand's function > 0.9. (2) There was no significant difference between the other repeated measurements, except for thumb rotation in MDIVQAS. (3) MDIVQAS had a significant correlation with other assessment systems (r > 0.5, p < 0.01). (4) There were significant differences in the evaluation of hand function in patients before and after treatment using MDIVQAS. Conclusion: The MDIVQAS system has good reliability and validity in the evaluation of stroke hand function, and it can also better evaluate the treatment effect.

Association of serum total fatty acids with type 2 diabetes.

BACKGROUND: Type 2 diabetes (T2D), a typical metabolic disease, is closely associated with serum free fatty acids. But the association between serum total fatty acids (TFAs, free fatty acids plus esterified fatty acids) and T2D has not been reported. METHODS: Serum esterified fatty acids were hydrolyzed under alkaline conditions, and serum TFAs were extracted after acidizing. Fourteen of serum TFAs in 1,828 serum samples, including 543 controls, 655 prediabetes, and 630 T2D patients, were simultaneously quantified based on the calibration curves of 8 fatty acids using matrix-assisted laser desorption/ionization-Fourier transform ion cyclotron resonance mass spectrometry (MALDI-FTICR MS). RESULTS: Correlation analysis revealed strong correlations among serum TFAs and ratios of the TFAs in T2D patients compared with controls or prediabetes both in males and females. Receiver operating characteristic analysis indicated that a panel including fasting plasma glucose, glycosylated hemoglobin type A1c, gamma-glutamyltransferase, triglyceride, C18:1, and C20:3, has a good capability to distinguish prediabetes from T2D, with the sensitivity of 87.0%, the specificity of 91.0%, and the area under curve (AUC) of 0.96. CONCLUSIONS: In this study, rapid, absolute, and simultaneous quantification of serum TFAs was performed using MALDI-FTICR MS. C18:1 and C20:3 were significantly correlated with prediabetes and T2D.

Monitoring novel modified hemoglobin using mass spectrometry contributes to accurate blood glucose management of the Han Chinese population.

BACKGROUND: The goal of this study was to detect novel modified forms of hemoglobin using mass spectrometry (MS) and to investigate the effect of modified hemoglobin on HbA1c and fasting plasma glucose (FPG). METHODS: This study was conducted on 1200 subjects aged >25 years. Hemoglobin from the above-mentioned subjects was detected using direct-infusion electrospray ionization-MS, and HbA1c and FPG were measured according to the manufacturer's instructions. Regression analysis was performed to estimate the correlations and interactions among HbA1c, FPG, and modified hemoglobin. RESULTS: Multiple modified forms (α1, α2, α3, ß1, ß2, and ß3) of hemoglobin were observed using MS. Statistical analyses indicated that modified hemoglobin was significantly correlated with FPG (p ≤ .01). The association of FPG with α1% (p = .021) and ß3% (p < .001) values was independent of HbA1c% and other modified forms of hemoglobin. Interaction analyses implied two significant interaction effects of HbA1c% with gender (ß = -0.184, p = .007) and α3% (ß = -0.104, p < .001) on FPG. The relationship between HbA1c% and FPG was stronger in males than in females, and a decreased level of α3% also affected the association of HbA1c% and FPG. CONCLUSIONS: This MS-based method is an effective tool for monitoring glycated forms of hemoglobin than traditional approaches. For the Han Chinese population, multiple-glycated hemoglobin affects the association of FPG with HbA1c%, and the correlation between FPG and HbA1c% in females is different from that in males. These data suggest that the HbA1c criteria for the diagnosis and monitoring of diabetes should be established according to genders and modified types of hemoglobin.