Predictive value of miR-636 in patients with acute myocardial infarction undergoing percutaneous coronary intervention and its bioinformatics analysis.

BACKGROUND: MicroRNAs (miRNAs) play an important role in the pathogenesis of cardiovascular diseases such as acute myocardial infarction (AMI). Percutaneous coronary intervention (PCI) is currently the most direct and effective procedure to treat AMI, but the occurrence of postoperative cardiovascular events (MACE) affects patients' quality of life. The objective of this study was to identify a new biomarker that could provide a theoretical basis for the prevention of MACE in patients with AMI undergoing PCI. METHODS: 142 AMI patients who underwent PCI and 130 healthy volunteers were selected as study subjects. Detection of miR-636 expression level by fluorescence quantitative PCR. ROC, Kaplan-Meier and Cox regression analyses were applied to evaluate the diagnostic and prognostic value of miR-636 for AMI. The miR-636 target genes were predicted and enriched for GO function and KEGG pathway. RESULTS: MiR-636 expression levels were elevated in patients with AMI. ROC curve analysis showed that miR-636 had a feasible diagnostic value in distinguishing AMI patients from healthy controls miR-636 expression levels were elevated in patients who developed MACEs. ROC results showed that miR-636 had significant diagnostic value in differentiating AMI patients with and without MACEs after PCI treatment. GO and KEGG enrichment analyses showed that miR-636 may transmit information to vesicles formed by the cell membrane. CONCLUSIONS: MiR-636 expression serves as a biomarker for diagnosing AMI and predicting the occurrence of MACE after PCI.

Managing spatio-temporal heterogeneity of susceptibles by embedding it into an homogeneous model: A mechanistic and deep learning study.

Accurate prediction of epidemics is pivotal for making well-informed decisions for the control of infectious diseases, but addressing heterogeneity in the system poses a challenge. In this study, we propose a novel modeling framework integrating the spatio-temporal heterogeneity of susceptible individuals into homogeneous models, by introducing a continuous recruitment process for the susceptibles. A neural network approximates the recruitment rate to develop a Universal Differential Equations (UDE) model. Simultaneously, we pre-set a specific form for the recruitment rate and develop a mechanistic model. Data from a COVID Omicron variant outbreak in Shanghai are used to train the UDE model using deep learning methods and to calibrate the mechanistic model using MCMC methods. Subsequently, we project the attack rate and peak of new infections for the first Omicron wave in China after the adjustment of the dynamic zero-COVID policy. Our projections indicate an attack rate and a peak of new infections of 80.06% and 3.17% of the population, respectively, compared with the homogeneous model's projections of 99.97% and 32.78%, thus providing an 18.6% improvement in the prediction accuracy based on the actual data. Our simulations demonstrate that heterogeneity in the susceptibles decreases herd immunity for ~37.36% of the population and prolongs the outbreak period from ~30 days to ~70 days, also aligning with the real case. We consider that this study lays the groundwork for the development of a new class of models and new insights for modelling heterogeneity.

Prenatal diagnosis of monozygotic twins with phenotypic differences in chromosome 17q12 deletion syndrome.

We present a case study highlighting prenatal ultrasound findings in monozygotic twins with chromosome 17q12 deletion syndrome. Fetus A exhibited bilateral fetal pyelectasis and talipes equinovarus, while fetus B showed hyperechogenic kidneys. Despite sharing the same de novo variant, the twins displayed distinct clinical phenotypes, suggesting the presence of non-genetic factors influencing the phenotypic variability of this syndrome. This case represents the first documented instance of prenatally identified identical twins affected by 17q12 deletion syndrome.

Simulation-Directed Construction of Bamboo-Forest-Like Heat Conduction Networks to Enhance Silicon Rubber Composites' Heat Conduction Properties.

Highly vertically thermally conductive silicon rubber (SiR) composites are widely used as thermal interface materials (TIMs) for chip cooling. Herein, inspired by water transport and transpiration of Moso bamboo-forests extensively existing in south China, and guided by filler self-assembly simulation, bamboo-forest-like heat conduction networks, with bamboo-stems-like vertically aligned polydopamine-coated carbon fibers (VA-PCFs), and bamboo-leaves-like horizontally layered Al2O3(HL-Al2O3), are rationally designed and constructed. VA-PCF/HL-Al2O3/SiR composites demonstrated enhanced heat conduction properties, and their through-plane thermal conductivity and thermal diffusivity reached 6.47 W (mK)-1 and 3.98 mm2 s-1 at 12 vol% PCF and 4 vol% Al2O3 loadings, which are 32% and 38% higher than those of VA-PCF (12 vol%) /SiR composites, respectively. The heat conduction enhancement mechanisms of VA-PCF/HL-Al2O3 networks on their SiR composites are revealed by multiscale simulation: HL-Al2O3 bridges the separate VA-PCF heat flow channels, and transfers more heat to the matrix, thereby increasing the vertical heat flux in composites. Along with high volume resistivity, low compression modulus, and coefficient of thermal expansion, VA-PCF/HL-Al2O3/SiR composites demonstrate great application potential as TIMs, which is proven using multiphysics simulation. This work not only makes a meaningful attempt at simulation-driven biomimetic material structure design but also provides inspiration for the preparation of TIMs.

Engineering probiotic Escherichia coli Nissle 1917 to block transfer of multiple antibiotic resistance genes by exploiting a type I CRISPR-Cas system.

Many multidrug-resistant (MDR) bacteria have evolved through the accumulation of antibiotic resistance genes (ARGs). Although the potential risk of probiotics as reservoirs of ARGs has been recognized, strategies for blocking the transfer of ARGs while using probiotics have rarely been explored. The probiotic Escherichia coli Nissle 1917 (EcN) has long been used for treating intestinal diseases. Here, we demonstrate frequent transfer of ARGs into EcN both in vitro and in vivo, raising concerns about its potential risk of accumulating antibiotic resistance. Given that no CRISPR-Cas system was found in natural EcN, we integrated the type I-E CRISPR-Cas3 system derived from E. coli BW25113 into EcN. The engineered EcN was able to efficiently cleave multiple ARGs [i.e., mcr-1, blaNDM-1, and tet(X)] encoding enzymes for degrading last-resort antibiotics. Through co-incubation of EcN expressing Cas3-Cascade and that expressing Cas9, we showed that the growth of the former strain outcompeted the latter strain, demonstrating a better clinical application prospect of EcN expressing the type I-E CRISPR-Cas3 system. In the intestine of a model animal (i.e., zebrafish), the engineered EcN exhibited immunity against the transfer of CRISPR-targeted ARGs. Our work equips EcN with immunity against the transfer of multiple ARGs by exploiting the exogenous type I-E CRISPR-Cas3 system, thereby reducing the risk of the spread of ARGs while using it as a probiotic chassis for generating living therapeutics. IMPORTANCE: To reduce the development of antibiotic resistance, probiotics have been considered as a substitute for antibiotics. However, probiotics themselves are reservoirs of antibiotic resistance genes (ARGs). This study introduces a new strategy for limiting the spread of ARGs by engineering the typical probiotic strain Escherichia coli Nissle 1917 (EcN), which has been used for treating intestinal diseases and developed as living therapeutics. We also demonstrate that the type I CRISPR-Cas system imposes a lower growth burden than the type II CRISPR-Cas system, highlighting its promising clinical application potential. Our work not only provides a new strategy for restricting the transfer of ARGs while using probiotics but also enriches the genetic engineering toolbox of EcN, paving the way for the safe use and development of probiotics as living therapeutics.

Two colistin resistance-producing Aeromonas strains, isolated from coastal waters in Zhejiang, China: characteristics, multi-drug resistance and pathogenicity.

Introduction: Aeromonas spp. are ubiquitous inhabitants of ecosystems, and many species are opportunistically pathogenic to humans and animals. Multidrug-resistant (MDR) Aeromonas species have been widely detected in hospitals, urban rivers, livestock, and aquatic animals. Results: In this study, we identified two Aeromonas isolates, namely Aeromonas veronii 0728Q8Av and Aeromonas caviae 1029Y16Ac, from coastal waters in Zhejiang, China. Both isolates exhibited typical biochemical characteristics and conferred MDR to 11 kinds of antibiotics, remaining susceptible to ceftazidime. Whole-genome sequencing revealed that both isolates harbored multiple antibiotic resistance genes (ARGs) and several mobile genetic elements (MGEs) on the chromosomes, each containing a resistance genomic island (GI), a typical class 1 integron, a transposon, and various insertion sequences (ISs). Most ARGs were situated within the multiple resistance GI, which contained a class 1 integron and a transposon in both Aeromonas isolates. Furthermore, a chromosomal mcr-3.16 gene was identified in A. veronii 0728Q8Av, while a chromosomal mcr-3.3 was found in A. caviae 1029Y16Ac. Both mcr-3 variants were not located within but were distanced from the multidrug resistance GI on the chromosome, flanking by multiple ISs. In addition, a mcr-3-like was found adjacent to mcr-3.16 to form a tandem mcr-3.16-mcr-3-like-dgkA structure; yet, Escherichia coli carrying the recombinants of mcr-3-like did not exhibit resistance to colistin. And an incomplete mcr-3-like was found adjacent to mcr-3.3 in A. caviae 1029Y16Ac, suggesting the possibility that mcr-3 variants originated from Aeromonas species. In vivo bacterial pathogenicity test indicated that A. veronii 0728Q8Av exhibited moderate pathogenicity towards infected ayu, while A. caviae 1029Y16Ac was non-virulent. Discussion: Thus, both Aeromonas species deserve further attention regarding their antimicrobial resistance and pathogenicity.

In vivo fitness of sul gene-dependent sulfonamide-resistant Escherichia coli in the mammalian gut.

The widespread sulfonamide resistance genes sul1, sul2, and sul3 in food and gut bacteria have attracted considerable attention. In this study, we assessed the in vivo fitness of sul gene-dependent sulfonamide-resistant Escherichia coli, using a murine model. High fitness costs were incurred for sul1 and sul3 gene-dependent E. coli strains in vivo. A fitness advantage was found in three of the eight mice after intragastric administration of sul2 gene-dependent E. coli strains. We isolated three compensatory mutant strains (CMSs) independently from three mice that outcompeted the parent strain P2 in vivo. Whole-genome sequencing revealed seven identical single nucleotide polymorphism (SNP) mutations in the three CMSs compared with strain P2, an additional SNP mutation in strain S2-2, and two additional SNP mutations in strain S2-3. Furthermore, tandem mass tag-based quantitative proteomic analysis revealed abundant differentially expressed proteins (DEPs) in the CMSs compared with P2. Of these, seven key fitness-related DEPs distributed in two-component systems, galactose and tryptophan metabolism pathways, were verified using parallel reaction monitoring analysis. The DEPs in the CMSs influenced bacterial motility, environmental stress tolerance, colonization ability, carbohydrate utilization, cell morphology maintenance, and chemotaxis to restore fitness costs and adapt to the mammalian gut environment.IMPORTANCESulfonamides are traditional synthetic antimicrobial agents used in clinical and veterinary medical settings. Their long-term excessive overuse has resulted in widespread microbial resistance, limiting their application for medical interventions. Resistance to sulfonamides is primarily conferred by the alternative genes sul1, sul2, and sul3 encoding dihydropteroate synthase in bacteria. Studying the potential fitness cost of these sul genes is crucial for understanding the evolution and transmission of sulfonamide-resistant bacteria. In vitro studies have been conducted on the fitness cost of sul genes in bacteria. In this study, we provide critical insights into bacterial adaptation and transmission using an in vivo approach.