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Biomedical subjects

Yali Liu

Publications and source records attributed to Yali Liu.

16 recordsLinked to original sources

In vitro activity of contezolid and other comparators against clinical Staphylococcus and Enterococcus: a multicenter study in China.

OBJECTIVE: To evaluate the in vitro activity of contezolid against clinical Staphylococcus and Enterococcus isolates from across China, and compare its performance with linezolid and other key agents. METHODS: A total of 2510 non-duplicate Gram-positive cocci isolates were collected from 70 hospitals in seven Chinese regions. Minimum inhibitory concentrations (MICs) were determined using broth microdilution (BMD) per CLSI guidelines. MIC50/90 values, susceptibility rates, cumulative MIC curves and MIC distribution agreement between contezolid and linezolid were assessed. Linezolid-resistant isolates and contezolid-resistant isolates-defined as those based on CLSI 2025 linezolid breakpoints-underwent whole-genome sequencing and comprehensive screening for known oxazolidinone resistance determinants, including acquired resistance genes, 23S rRNA mutations and amino acid substitutions in ribosomal proteins L3, L4 and L22. RESULTS: Contezolid exhibited potent in vitro activity, with >99% of isolates inhibited at ≤4 mg/L and showed lower MIC50/90 than linezolid, with a consistently left-shifted cumulative MIC distribution. Cohen's kappa analysis supporting enhanced activity of contezolid. Notably, we report for the first time clinical isolates with contezolid MICs up to 16 mg/L. Whole-genome analysis of 14 linezolid-resistant isolates (including five resistant to contezolid) revealed universal presence of optrA, cfr, fexA and other resistance genes, alongside domain V 23S rRNA mutations and substitutions in ribosomal proteins L3 and L4, supporting a shared genetic basis and potential cross-resistance between the two agents. CONCLUSIONS: Contezolid demonstrated potent and consistent activity against drug-resistant Gram-positive cocci, supporting its potential as a therapeutic alternative to linezolid. Further studies are needed to confirm resistance mechanisms and clinical utility.

Microbial Sensitivity Tests↗

C6ORF120 regulates hepatic lipid metabolism through PPAR signaling pathway in metabolic dysfunction-associated steatotic liver disease.

Background Emerging evidence indicates that C6ORF120 is highly expressed in the liver and may modulate immune responses in various hepatic disorders. However, its role in hepatic lipid metabolism and metabolic dysfunction-associated steatotic liver disease (MASLD) is unexplored. This study aimed to elucidate the effects and potential mechanisms of C6ORF120 on hepatic lipogenesis. Methods C6ORF120 expression in MASLD was assessed using patient serum and the Gene Expression Omnibus (GEO) database. A high-fat diet-induced MASLD model was established in C6orf120-KO rats. Fatty acid-induced lipid accumulation models were generated in primary hepatocytes, HepG2 and Huh7 cells. These models were employed to investigate the effects of C6ORF120 on hepatic lipogenesis and MASLD progression. Results C6ORF120 expression was significantly upregulated in MASLD patients and obese rat models. Genetic deletion of C6ORF120 markedly alleviated high-fat diet-induced steatosis in the liver of rats. In vitro, C6orf120 gene deficiency attenuated lipid accumulation and suppressed key lipogenic genes (such as fatty acid synthase (Fasn), phospho-acetyl coenzyme carboxylase (p-ACC), sterol regulatory element binding protein-1c (Srebp1c)) in primary hepatocytes and HepG2 cells. Conversely, C6ORF120 overexpression increased lipid accumulation in HepG2 cells. RNA sequencing analysis showed that lipid metabolism pathway and peroxisome proliferators activated receptor (PPAR) signaling pathway were significantly altered in the liver of C6orf120-KO rats. We demonstrated that C6ORF120 may regulate lipid metabolism through the hepatic PPARα, which is involved in fatty acid production and lipid oxidation. Further, we found that serum C6ORF120 expression was correlated with clinical indicators in patients with MASLD. Conclusion This study preliminarily revealed a novel function for C6ORF120 in hepatic lipid metabolism via affecting the PPAR pathway. The result identifies C6ORF120 as a novel regulator of hepatic lipid metabolism through PPARα-dependent mechanisms, offering potential therapeutic targets for MASLD.

Lipid Metabolism↗

Differential methylation of a retrotransposon upstream of a MYB gene causes variegation of lettuce leaves, which is abolished by the presence of an (AT)5 repeat in the promoter.

Variegation, a common phenomenon in plants, can be the result of several genetic, developmental, and physiological factors. Leaves of some lettuce cultivars exhibit dramatic red variegation; however, the genetic mechanisms underlying this variegation remain unknown. In this study, we cloned the causal gene for variegation on lettuce leaves and elucidated the underlying molecular mechanisms. Genetic analysis revealed that the polymorphism of variegated versus uniformly red leaves is caused by an "AT" repeat in the promoter of the RLL2A gene encoding a MYB transcription factor. Complementation tests demonstrated that the RLL2A allele (RLL2AV) with (AT)n repeat numbers other than five led to variegated leaves. RLL2AV was expressed in the red spots but not in neighboring green regions. This expression pattern was in concert with a relatively low level of methylation in a retrotransposon inserted in -761 bp of the gene in the red spots compared to high methylation of the retrotransposon in the green region. The presence of (AT)5 in the promoter region, however, stabilized the expression of RLL2A, resulting in uniformly red leaves. In summary, we identified a novel promoter mechanism controlling variegation through inconsistent levels of methylation and showed that the presence of a simple sequence repeat of specific size could stabilize gene expression.

Promoter Regions, Genetic↗

Adaptation for Staphylococcus aureus to hosts via insertion mutation in the accessory gene regulator agrC gene: decreased virulence and enhanced persistence capacity.

UNLABELLED: Staphylococcus aureus is an important human pathogen due to its vast array of virulence factors regulated by multiple regulatory mechanisms, including the accessory gene regulator. In this study, two S. aureus strains were simultaneously isolated from the blood of a febrile patient, belonging to the same clone, designated as 23H with a complete hemolytic phenotype, and 23B, exhibiting an incomplete hemolytic phenotype. The genomic comparison between strains 23B and 23H revealed that 23B had a single adenine base insertion at position 923 in the agrC gene, leading to a functional loss of the encoded AgrC. Experimental findings showed that strain 23B had decreased hemolytic activity, lower cytotoxicity against human alveolar epithelial A549 cells and in the Galleria mellonella model, and a reduced ability to survive intracellularly after infecting macrophages, in comparison to 23H. Conversely, 23B exhibited enhanced biofilm formation, greater adherence to A549 cells, and increased persistence in the face of vancomycin and daptomycin treatment. Transcriptomic analysis revealed that 23B upregulated surface protein-encoding genes while simultaneously reducing the expression levels of virulence factors, highlighting the intricate regulatory adjustments facilitating its persistence and reducing pathogenic potential. ATP assay results indicated that 23B maintained elevated ATP levels during the exponential phase yet exhibited reduced levels in the stationary phase when compared with 23H. Our findings suggested that the mutation in the agrC gene of S. aureus results in diminished virulence but markedly enhances persistence. This mutated strain warrants clinical attention because it may lead to treatment failures and persist in patients. IMPORTANCE: In clinical antimicrobial therapy, bacterial strains often develop resistance to antimicrobial agents. Additionally, mutations in their gene regulatory networks can increase their persistence, especially in immunocompromised patients. This study identified an insertion mutation in the accessory gene regulator, agrC gene, carried by a Staphylococcus aureus strain isolated from the blood of a febrile patient, leading to the functional loss of AgrC. Further research revealed that despite the reduced virulence of the mutated strain, it significantly bolstered the capacity to adapt and endure within the host during prolonged infections. This was evidenced by increased adhesion and biofilm formation capabilities, development of antimicrobial tolerance, and decreased ATP levels linked to persistence. Therefore, monitoring these mutations in S. aureus is crucial clinically, as they can complicate treatment strategies.

Staphylococcus aureus↗

Reusable platinum nanoparticle modified boron doped diamond microelectrodes for oxidative determination of arsenite.

Boron doped diamond (BDD) macro- and microelectrodes were modified by electrodeposition of platinum nanoparticles using a multipotential step electrodeposition technique and used for the oxidative determination of arsenite, As(III). The formation of Pt nanoparticles was evident from cyclic voltammetry measurement, whereas AFM and SEM revealed the size and size distribution of deposited Pt nanoparticles. Raman spectroscopy illustrated a correlation between the typical BDD signature and the number of platinum deposition cycles. Linear sweep voltammetry performed with the modified BDD microelectrode outperformed its macrocounterpart and resulted in very low detecting currents with enhanced signal-to-noise ratios. With linearity up to 100 ppb and a detection limit of 0.5 ppb, the electrochemical system was applicable for processing tap and river water samples. Over 150 repetitive runs could be performed, and electrochemical etching of platinum allowed the reuse of the BDD microelectrode. The presence of copper and chloride ions, the two most severe interferents at levels commonly found in groundwater, did not interfere with the assay.

Arsenites↗

Metallic nanoparticle-carbon nanotube composites for electrochemical determination of explosive nitroaromatic compounds.

Metal nanoparticles (Pt, Au, or Cu) together with multiwalled and single-walled carbon nanotubes (MWCNT and SWCNT) solubilized in Nafion have been used to form nanocomposites for electrochemical detection of trinitrotoluene (TNT) and several other nitroaromatics. Electrochemical and surface characterization by cyclic voltammetry, AFM, TEM, SEM, and Raman spectroscopy confirmed the presence of metal nanoparticles on CNTs. Among various combinations tested, the most synergistic signal effect was observed for the nanocomposite modified glassy carbon electrode (GC) containing Cu nanoparticles and SWCNT solubilized in Nafion. This combination provided the best sensitivity for detecting TNT and other nitroaromatic compounds. Adsorptive stripping voltammetry for TNT resulted in a detection limit of 1 ppb, with linearity up to 3 orders of magnitude. Selectivity toward the number and position of the nitro groups in different nitroaromatics was very reproducible and distinct. Reproducibility of the TNT signal was within 7% (n = 8) from one electrode preparation to another, and the response signal was stable (+/-3.8% at 95% confidence interval) for 40 repeated analyses with 10 min of preconditioning. The Cu-SWCNT-modified GC electrode was demonstrated for analysis of TNT in tap water, river water, and contaminated soil.

Chromatography, Gas↗

Incorporating time-dependent covariates in survival analysis using the LVAR method.

In survival analysis, use of the Cox proportional hazards model requires knowledge of all covariates under consideration at every failure time. Since failure times rarely coincide with observation times, time-dependent covariates (covariates that vary over time) need to be inferred from the observed values. In this paper, we introduce the last value auto-regressed (LVAR) estimation method and compare it to several other established estimation approaches via a simulation study. The comparison shows that under several time-dependent covariate processes this method results in a smaller mean square error when considering the time-dependent covariate effect.

Computer Simulation↗

Electrochemical determination of arsenite using a gold nanoparticle modified glassy carbon electrode and flow analysis.

A flow analysis electrochemical system has been developed, characterized, and optimized for the determination of arsenite (As(III)). Sensitivity was significantly improved by the electrochemical deposition of gold nanoparticles on a dual glassy carbon electrode, which was inserted into a cross-flow thin-layer electrochemical cell. The electrochemical system was linear up to 15 ppb with a detection limit of 0.25 ppb. Gold deposition was evident from cyclic voltammetry measurements, whereas atomic force microscopy and scanning electron microscopy revealed the size and distribution of deposited gold nanoparticles. The size and density of the nanoparticles were related to the gold salt concentration, deposition time, and potential as well as the electrode position. The response to arsenite was directly related to the frequency, increment, and amplitude of the square wave voltammetry as well as the deposition time and potential. Estimated reproducibility was +/-1.1% at 95% confidence interval for 40 repeated analyses of 8 ppb arsenite during continuous analysis. The reproducibility was far superior if the electrochemical reduction of arsenite was performed in nitric acid instead of hydrochloric or sulfuric acid. The electrochemical system was applicable for analysis of spiked arsenic in mineral water containing a significant amount of various ion elements.

Arsenites↗

A colorimetric method for point mutation detection using high-fidelity DNA ligase.

The present study reported proof-of-principle for a genotyping assay approach that can detect single nucleotide polymorphisms (SNPs) through the gold nanoparticle assembly and the ligase reaction. By incorporating the high-fidelity DNA ligase (Tth DNA ligase) into the allele-specific ligation-based gold nanoparticle assembly, this assay provided a convenient yet powerful colorimetric detection that enabled a straightforward single-base discrimination without the need of precise temperature control. Additionally, the ligase reaction can be performed at a relatively high temperature, which offers the benefit for mitigating the non-specific assembly of gold nanoparticles induced by interfering DNA strands. The assay could be implemented via three steps: a hybridization reaction that allowed two gold nanoparticle-tagged probes to hybrid with the target DNA strand, a ligase reaction that generates the ligation between perfectly matched probes while no ligation occurred between mismatched ones and a thermal treatment at a relatively high temperature that discriminate the ligation of probes. When the reaction mixture was heated to denature the formed duplex, the purple color of the perfect-match solution would not revert to red, while the mismatch gave a red color as the assembled gold nanoparticles disparted. The present approach has been demonstrated with the identification of a single-base mutation in codon 12 of a K-ras oncogene that is of significant value for colorectal cancers diagnosis, and the wild-type and mutant type were successfully scored. To our knowledge, this was the first report concerning SNP detection based on the ligase reaction and the gold nanoparticle assembly. Owing to its ease of operation and high specificity, it was expected that the proposed procedure might hold great promise in practical clinical diagnosis of gene-mutant diseases.

Cell Line↗

Light-assisted synthesis of Pt-Zn porphyrin nanocomposites and their use for electrochemical detection of organohalides.

Pt-Zn porphyrin nanocomposites have been synthesized using zinc porphyrin and dihydrogen hexachloroplatinate in the presence of light and ascorbic acid. TEM and AFM imaging revealed that Pt nanoparticles with an average diameter of approximately 3.5 nm were embedded within the Zn porphyrin matrix. The glassy carbon electrode was modified with Nafion-stabilized Pt-Zn porphyrin nanocomposites and used for dehalogenation of carbon tetrachloride, chloroform, pentachlorophenol, chlorobenzene, and hexachlorobenzene as five test models. The Pt-Zn porphyrin nanocomposite-modified electrode exhibited catalytic activity for the reduction of organohalides at -1.0 V versus Ag/AgCl. Raman signatures confirmed the dehalogenation of chlorobenzene by the nanocomposite-modified electrode. The above two aliphatic and three aromatic organohalides had detection limits of 0.5 microM with linearity up to 8 microM. The modified electrode was good for at least 80 repeated measurements of 4 microM chlorobenzene with a storage stability of 1 month at room temperature. The deactivation of the electrode activity was associated with the loss of platinum nanoparticles from the nanocomposite structure.

Electrochemistry↗

Electrophoretic separation of aniline derivatives using fused silica capillaries coated with acid treated single-walled carbon nanotubes.

This paper reports on a new strategy for coating fused silica capillaries based on the ionic adsorption of acid treated single-walled carbon nanotubes (SWCNTs) on a poly(diallydimethylammonium chloride)-modified fused silica surface. The coated capillaries were used to demonstrate their performance for baseline separation of a mixture of seven nitrogen-containing aromatic compounds compared to capillary zone electrophoresis. This combined layer formed a coating material that could be useful for improvement of the selectivity of the solutes in an electrical field. We reasoned that the interaction of the solutes and the modified capillary wall occurred mainly via ionic interactions with the charged moieties of CNTs. The single-walled CNT modified capillaries were very stable and could be used for over 200 repeated analyses without compromising its analytical performance.

Aniline Compounds↗

Oxidation, deformation, and destruction of carbon nanotubes in aqueous ceric sulfate.

A simple wet chemical method involving only ultrasonic processing in dilute ceric sulfate (CS) was used to functionalize carbon nanotubes (CNTs). Unexpectedly, single-walled and multiwalled carbon nanotubes (SWCNTs and MWCNTs) were cut, oxidized, and disintegrated by sonication in 0.1 N CS for 2-5 h. Transmission electron microscopy (TEM), atomic force microscopy (AFM), X-ray photoelectron spectroscopy (XPS), X-ray diffraction spectroscopy (XRD), Raman scattering, and photoacoustic Fourier transform infrared spectroscopy (FTIR) were used to probe wall damage during the chemical processing. Cyclic voltammetry and impedance spectroscopy were used to evaluate the conductivity of the CS-treated CNTs. This one-step process resulted in the destruction of SWCNTs to produce nonconducting amorphous carbon. MWCNTs were oxidized and converted to graphitic materials and amorphous carbon with retained conductivity.

Electric Conductivity↗

Impedance sensing of DNA binding drugs using gold substrates modified with gold nanoparticles.

Interfacial interactions between immobilized DNA probes and DNA-specific sequence binding drugs were investigated using impedance spectroscopy toward the development of a novel biosensing scheme. The impedance measurements are based on the charge-transfer kinetics of the [Fe(CN)6]3-/4- redox couple. Compared to bare gold surfaces, the immobilization of DNA and then the DNA-drug interaction on electrode surfaces altered the capacitance and the interfacial electron resistance and thus diminished the charge-transfer kinetics by reducing the active area of the electrode or by preventing the redox species from approaching the electrode. Electrochemical deposition of gold nanoparticles on a gold electrode surface showed significant improvement in sensitivity. DNA-capped gold nanoparticles on electrodes act as selective sensing interfaces with tunable sensitivity due to higher amounts of DNA probes and the concentric orientation of the DNA self-assembled monolayer. The specificity of the interactions of two classical minor groove binders, mythramycin, a G-C specific-DNA binding anticancer drug, netropsin, an A-T specific-DNA binding drug and an intercalator, nogalamycin on AT-rich DNA-modified substrate and GC-rich DNA-modified substrate are compared. Using gold nanoparticle-deposited substrates, impedance spectroscopy resulted in a 20-40-fold increase in the detection limit. Arrays of deposited gold nanoparticles on gold electrodes offered a convenient tool to subtly control probe immobilization to ensure suitably adsorbed DNA orientation and accessibility of other binding molecules.

DNA↗

An animal model of SARS produced by infection of Macaca mulatta with SARS coronavirus.

A new SARS animal model was established by inoculating SARS coronavirus (SARS-CoV) into rhesus macaques (Macaca mulatta) through the nasal cavity. Pathological pulmonary changes were successively detected on days 5-60 after virus inoculation. All eight animals showed a transient fever 2-3 days after inoculation. Immunological, molecular biological, and pathological studies support the establishment of this SARS animal model. Firstly, SARS-CoV-specific IgGs were detected in the sera of macaques from 11 to 60 days after inoculation. Secondly, SARS-CoV RNA could be detected in pharyngeal swab samples using nested RT-PCR in all infected animals from 5 days after virus inoculation. Finally, histopathological changes of interstitial pneumonia were found in the lungs during the 60 days after viral inoculation: these changes were less marked at later time points, indicating that an active healing process together with resolution of an acute inflammatory response was taking place in these animals. This animal model should provide insight into the mechanisms of SARS-CoV-related pulmonary disease and greatly facilitate the development of vaccines and therapeutics against SARS.

Animals↗

Electrochemical biosensing platforms using platinum nanoparticles and carbon nanotubes.

Platinum nanoparticles with a diameter of 2-3 nm were prepared and used in combination with single-wall carbon nanotubes (SWCNTs) for fabricating electrochemical sensors with remarkably improved sensitivity toward hydrogen peroxide. Nafion, a perfluorosulfonated polymer, was used to solubilize SWCNTs and also displayed strong interactions with Pt nanoparticles to form a network that connected Pt nanoparticles to the electrode surface. TEM and AFM micrographs illustrated the deposition of Pt nanoparticles on carbon nanotubes whereas cyclic voltammetry confirmed an electrical contact through SWCNTs between Pt nanoparticles and the glassy carbon (GC) or carbon fiber backing. With glucose oxidase (GOx) as an enzyme model, we constructed a GC or carbon fiber microelectrode-based biosensor that responds even more sensitively to glucose than the GC/GOx electrode modified by Pt nanoparticles or CNTs alone. The response time and detection limit (S/N = 3) of this biosensor was determined to be 3 s and 0.5 microM, respectively.

Aspergillus niger↗

Determination of median nerve somatosensory evoked potentials in 27 patients with hemiplegia.

Twenty-seven in-patients with hemiplegia following brain injury were studied by using upper extremity median nerve somatosensory evoked patentials (SVEP), Brunnstrom assessment in hemiplegic hand and assessment of the patients' activities of daily lioing (ADL) (Barthel index). The upper extremity median nerve SEP on the affected and normal sides was determined. By using Kovindha standard, upper extremity median nerve SEP was graded in accordance with N20. The correlation between the differences of SEP N20 amplitude and the latencies on the both sides and the Barthel index scores was analyzed. A Spearman correlation analysis was made between the median nerve SEP N20 grades and Brunnstrom stages in hand or ADL on the affected side. The results showed that upper extremity median nerve SEP grades were positively correlated with those of the Brunnstrom stages in hand (r1 = 0.6925, P1 < 0.01). The correlation coefficient between SEP N20 grades and patients' ADL grades was r2 = 0.5015, P2 < 0.01. It was concluded that upper extremity median nerve SEP could be used as a sensitive electrophysiological predictor to clinically assess hemiplegic hand function. SEP N20 might play a role in predicting the ADL of the patients with hemiplegia to some extent, but could not be used as a sensitive predictor to directly observe and predict the ADL of the patients.

Adult↗