Browse Articles

Unveiling the anti-inflammatory mechanism of exogenous hydrogen sulfide in Kawasaki disease based on network pharmacology and experimental validation

Wastewater based genomic surveillance key to population level monitoring of AmpC/ESBL producing Escherichia coli

Abstract Antimicrobial resistance (AMR) is a serious threat to global public health, but obtaining representative data on AMR for healthy human populations is difficult. Here, we leverage the power of whole genome sequencing (WGS) to screen AmpC- and extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli from 77 composite samples obtained from 10 wastewater treatment plants across Finland. We found a high abundance of multidrug-resistant AmpC/ESBL-producing E. coli and significant differences in the diversity of AMR genes between the sampled cities. The in silico analysis of 73 short-read genome sequences shows the clonally diverse isolates consisting of 30 sequence types (STs), including the globally distributed pandemic ST131 clone. The CTX-M ESBL genes were detected in 86.3% (63/73) of the isolates concurrently with the blaTEM-1 (31.5%, 23/73) and blaOXA-1 (9.6%, 7/73) genes. The most prevalent ESBL genes were blaCTX-M-15 (46.6%, 34/73), blaCTX-M-27 (16.4%, 12/73), blaCTX-M-14 (4.1%, 3/73), and blaCTX-M-55 (4.1%, 3/73). Two isolates harboured the carbapenemase resistance gene, blaKPC-2 and blaNDM-1, respectively. In addition, WGS predicted phenotypic resistance against aminoglycosides, beta-lactams, cephalosporins, quinolones, sulfonamides, carbapenems, and polymyxins. The diversity of antibiotic- and stress-resistance genes correlated with the clinical incidence reported in the Finnish AMR report. Core-genome MLST revealed two wastewater genomic clusters but no genomic clusters among human and wastewater ST131 isolates. Our findings suggest the circulation of distinct clonal lineages of AmpC/ESBL-producing E. coli across Finland, with variations in AMR gene diversity and abundance by wellbeing service county. Also, our findings underscore the fact that wastewater surveillance could be key to population-level monitoring of AmpC/ESBL-producing Escherichia coli and can serve as complementary data to guide public health decisions. We propose longitudinal WGS-based epidemiology as an economically feasible approach for global AMR surveillance, pathogen evolution, and prediction of AMR.

Ginsenoside Rg1 regulating inflammatory response and bone-remodeling through Keap1/Nrf2 signaling pathway in rats with periodontitis

Integrating bioinformatics and metabolomics to identify potential biomarkers of hypertensive nephropathy

YKL-40 inhibits melanoma progression and metastasis by inducing immune cell infiltration in a mouse model

Initial findings creating a temperature prediction model using vibroacoustic signals originating from tissue needle interactions

Abstract This research explores the acquisition and analysis of vibroacoustic signals generated during tissue-tool interactions, using a conventional aspiration needle enhanced with a proximally mounted MEMS audio sensor, to extract temperature information. Minimally invasive temperature monitoring is critical in thermotherapy applications, but current methods often rely on additional sensors or simulations of typical tissue behavior. In this study, a commercially available needle was inserted into water-saturated foams with temperatures ranging from 25 to 55 °C, varied in 5° increments. Given that temperature affects the speed of sound, water’s heat capacity, and the mechanical properties of most tissues, it was hypothesized that the vibroacoustic signals recorded during needle insertion would carry temperature-dependent information. The acquired signals were segmented, processed, and analyzed using signal processing techniques and a deep learning algorithm. Results demonstrated that the audio signals contained distinct temperature-dependent features, enabling temperature prediction with a root mean squared error of approximately 3 °C. We present these initial laboratory findings, highlighting significant potential for refinement. This novel approach could pave the way for a real-time, minimally invasive method for thermal monitoring in medical applications.

Machine learning analysis identified NNMT as a potential therapeutic target for hepatocellular carcinoma based on PCD-related genes

Synergetic simplified super-twisting algorithm control for stability enhancement of PV/BESS-based DC microgrid

Disruption of tryptophan metabolism by high-fat diet-triggered maternal immune activation promotes social behavioral deficits in male mice

BOOST: a robust ten-fold expansion method on hour-scale

Targeting the ceramidase ACER3 attenuates cholestasis in mice by mitigating bile acid overload via unsaturated ceramide-mediated LXRβ signaling transduction

Abstract Bile acid overload critically drives the pathogenesis of cholestatic liver injury (CLI). While ceramide metabolism has garnered increasing interest in liver research, the role of ceramides in CLI remains unclear. This study investigates the function of alkaline ceramidase 3 (ACER3)-catalyzed hydrolysis of unsaturated ceramides in CLI. Using clinical specimens, this work finds that ACER3 expression is upregulated in the cholestatic liver and positively correlated with the severity of CLI in patients. Acer3 ablation increases ceramide(d18:1/18:1) and attenuates bile duct ligation-induced CLI in female mice with reduced hepatic necrosis, inflammation, and fibrosis. However, it does not significantly impact CLI in male mice. Moreover, ceramide(d18:1/18:1) treatment attenuates CLI in wild-type female mice. Similarly, ACER3 knockdown and ceramide(d18:1/18:1) treatment prevent lithocholic-acid-induced cell death in human-liver-derived HepG2 cells. Mechanistically, ceramide(d18:1/18:1) binds the ligand binding domain of the liver X receptor β, acting as an agonist to activate its transcriptional functions. This activation upregulates sulfotransferase 2A1-catalyzed bile acid sulfation, normalizes bile acid metabolism, and restores lipogenesis, thereby reducing bile acid overload in hepatocytes to attenuate CLI. Our findings uncover the role of ceramide(d18:1/18:1)-liver X receptor β signaling in mitigating bile acid overload in the cholestatic liver, offering mechanistic insights and suggesting therapeutic potential for targeting ACER3 and ceramide(d18:1/18:1) for CLI.

A nanovaccine for immune activation and prophylactic protection of atherosclerosis in mouse models

Swapping rice for alternative cereals can reduce climate-induced production losses and increase farmer incomes in India

Screening the human druggable genome identifies ABHD17B as an anti-fibrotic target in hepatic stellate cells

Multimodal histopathologic models stratify hormone receptor-positive early breast cancer

Molecular glues of the regulatory ChREBP/14-3-3 complex protect beta cells from glucolipotoxicity

Post heat treatment optimization of cold spray additive manufactured Inconel 718

A finite element with statistical analysis study to investigate the electrical performance of composite insulators under water droplet impact

Analyzing coastal dynamics by means of multi-sensor satellite imagery at the East Frisian Island of Langeoog, Germany

Abstract Monitoring coastal dynamics is critical for the effective protection of coastal environments. Satellite remote sensing data offers significant potential to support this monitoring while also addressing the considerable challenges posed by the rapidly changing environmental conditions in coastal regions, such as tidal levels and currents. These challenges are particularly pronounced in meso- and macrotidal coastal areas. The goal of this study is to evaluate the effectiveness of a multi-sensor satellite remote sensing-based approach to assess coastal dynamics in a mesotidal environment, using the Island of Langeoog, Germany, as a case study. This approach also addresses the often limited availability of in-situ data in such regions. We employed high-resolution (HR) and medium-resolution (MR) optical data, alongside very high-resolution (VHR) Synthetic Aperture Radar (SAR) data, to detect coastal changes by analyzing several proxies, including the migration of sand bars, waterline position, dune toe location, and the extent of dry sandy coastal areas. To achieve this, we assessed and integrated thresholding and classification methods based on their suitability for specific sensors and proxies. Our findings demonstrate that combining different sensor types enables a more comprehensive analysis of various proxies of coastal dynamics. We successfully extracted instantaneous waterlines and identified migrating sand bars, linking these results to shoreline positions. Furthermore, our analysis revealed the direct influence of replenishment measures on beach conditions and suggested a stabilizing effect on the protective dune system. The findings display the uncertainties due to wave run-up and short-term variations in water level associated with analyzing dynamic meso-tidal sandy beach areas. Our results underscore the significant potential of multi-sensor data integration and diverse methodological approaches for supporting coastal protection authorities assessing the state of beaches.

Crystallographic and geochemical responses of giant clams on turbid reefs

Abstract Marine calcifying organisms on coral reefs face significant threats from various anthropogenic stressors. To better understand how these organisms will respond to a rapidly changing ocean, it is crucial to investigate their biomineralization across different reef environments. Despite their resilience and potential as conservation hotspots, turbid reefs—projected to expand throughout the 21st century—remain understudied, including a limited knowledge of biomineralization processes within these environments. Herein, for the first time, we assess the crystallographic and geochemical signatures of aragonite giant clam shells Tridacna squamosa from high and low turbid reefs in the Coral Triangle. Shell composition is strongly influenced by turbidity and biominerals formed in a high turbid reef show a more organized crystal orientation and significantly lower element-to-calcium ratios (magnesium/calcium, strontium/calcium). We hypothesize that these variations are driven by physiological changes related to the trophic flexibility of T. squamosa , utilizing both autotrophic and heterotrophic mechanisms. Observed differences may have implications for biomechanical and defense responses of shells, important in their ability to survive future change.