Technical advancements and protocol optimization of diffusion-weighted imaging (DWI) in liver

An area of rapid advancement in abdominal MRI is diffusion-weighted imaging (DWI). By measuring diffusion properties of water molecules, DWI is capable of non-invasively probing tissue properties and physiology at cellular and macromolecular level. The integration of DWI as part of abdominal MRI exam allows better lesion characterization and therefore more accurate initial diagnosis and treatment monitoring. One of the most technical challenging, but also most useful abdominal DWI applications is in liver and therefore requires special attention and careful optimization. In this article, the latest technical developments of DWI and its liver applications are reviewed with the explanations of the technical principles, recommendations of the imaging parameters, and examples of clinical applications. More advanced DWI techniques, including Intra-Voxel Incoherent Motion (IVIM) diffusion imaging, anomalous diffusion imaging, and Diffusion Kurtosis Imaging (DKI) are discussed

Anomalous wavefront control via nonlinear acoustic metasurface through second-harmonic tailoring and demultiplexing

We propose a nonlinear acoustic metasurface concept by exploiting the nonlinearity of the locally resonant unit cells formed by curved beams. The analytical model is established to explore the nonlinear phenomenon, specifically the second-harmonic generation (SHG) of the acoustic waveguide and validated through numerical and experimental studies. Novel nonlinear acoustic metasurfaces are developed to demultiplex different frequency components and achieve anomalous wavefront control of SHG in the transmitted region. To this end, we demonstrate wave steering, wave focusing, and self-bending propagation. Our results show that the proposed nonlinear metasurface provides an effective and efficient platform to achieve significant SHG, and separate different harmonic components for wavefront control of individual harmonics. Overall, this study offers new avenues to harness nonlinear effects for acoustic wavefront tailoring and develops new potential toward advanced technologies to manipulate acoustic waves

TextPainter: Multimodal Text Image Generation with Visual-harmony and Text-comprehension for Poster Design

Text design is one of the most critical procedures in poster design, as it relies heavily on the creativity and expertise of humans to design text images considering the visual harmony and text-semantic. This study introduces TextPainter, a novel multimodal approach that leverages contextual visual information and corresponding text semantics to generate text images. Specifically, TextPainter takes the global-local background image as a hint of style and guides the text image generation with visual harmony. Furthermore, we leverage the language model and introduce a text comprehension module to achieve both sentence-level and word-level style variations. Besides, we construct the PosterT80K dataset, consisting of about 80K posters annotated with sentence-level bounding boxes and text contents. We hope this dataset will pave the way for further research on multimodal text image generation. Extensive quantitative and qualitative experiments demonstrate that TextPainter can generate visually-and-semantically-harmonious text images for posters.Comment: Accepted to ACM MM 2023. Dataset Link: https://tianchi.aliyun.com/dataset/16003

Differential Dopamine D1 and D3 Receptor Modulation and Expression in the Spinal Cord of Two Mouse Models of Restless Legs Syndrome

Restless Legs Syndrome (RLS) is often and successfully treated with dopamine receptor agonists that target the inhibitory D3 receptor subtype, however there is no clinical evidence of a D3 receptor dysfunction in RLS patients. In contrast, genome-wide association studies in RLS patients have established that a mutation of the MEIS1 gene is associated with an increased risk in developing RLS, but the effect of MEIS1 dysfunction on sensorimotor function remain unknown. Mouse models for a dysfunctional D3 receptor (D3KO) and Meis1 (Meis1KO) were developed independently, and each animal expresses some features associated with RLS in the clinic, but they have not been compared in their responsiveness to treatment options used in the clinic. We here confirm that D3KO and Meis1KO animals show increased locomotor activities, but that only D3KO show an increased sensory excitability to thermal stimuli. Next we compared the effects of dopaminergics and opioids in both animal models, and we assessed D1 and D3 dopamine receptor expression in the spinal cord, the gateway for sensorimotor processing. We found that Meis1KO share most of the tested behavioral properties with their wild type (WT) controls, including the modulation of the thermal pain withdrawal reflex by morphine, L-DOPA and D3 receptor (D3R) agonists and antagonists. However, Meis1KO and D3KO were behaviorally more similar to each other than to WT when tested with D1 receptor (D1R) agonists and antagonists. Subsequent Western blot analyses of D1R and D3R protein expression in the spinal cord revealed a significant increase in D1R but not D3R expression in Meis1KO and D3KO over WT controls. As the D3R is mostly present in the dorsal spinal cord where it has been shown to modulate sensory pathways, while activation of the D1Rs can activate motoneurons in the ventral spinal cord, we speculate that D3KO and Meis1KO represent two complementary animal models for RLS, in which the mechanisms of sensory (D3R-mediated) and motor (D1R-mediated) dysfunctions can be differentially explored

Identification and characterization of a novel chromosomal aminoglycoside 3’-O-phosphotransferase, APH(3′)-Id, from Kluyvera intermedia DW18 isolated from the sewage of an animal farm

BackgroundAminoglycosides, as important clinical antimicrobials, are used as second-line drugs for treating multidrug-resistant tuberculosis or combined with β-lactam drugs for treating severe infections such as sepsis. Aminoglycoside-modifying enzyme (AME) is the most important mechanism of aminoglycoside resistance and deserves more attention.MethodsThe bacterium Kluyvera intermedia DW18 was isolated from the sewage of an animal farm using the conventional method. The agar dilution method was used to determine the minimum inhibitory concentrations (MICs) of antimicrobials. A novel resistance gene was cloned, and the enzyme was expressed. The kinetic parameters were measured by a SpectraMax M5 multifunctional microplate reader. Bioinformatic analysis was performed to reveal the genetic context of the aph(3′)-Id gene and its phylogenetic relationship with other AMEs.ResultsA novel aminoglycoside 3′-O-phosphotransferase gene designated aph(3′)-Id was identified in K. intermedia DW18 and shared the highest amino acid identity of 77.49% with the functionally characterized aminoglycoside 3′-O-phosphotransferase APH(3′)-Ia. The recombinant plasmid carrying the novel resistance gene (pMD19-aph(3′)-Id/E. coli DH5α) showed 1,024-, 512-, 128- and 16-fold increased MIC levels for kanamycin, ribostamycin, paromomycin and neomycin, respectively, compared with the reference strain DH5α. APH(3′)-Id showed the highest catalytic efficiency for ribostamycin [kcat/Km of (4.96 ± 1.63) × 105 M−1/s−1], followed by paromomycin [kcat/Km of (2.18 ± 0.21) × 105 M−1/s−1], neomycin [kcat/Km of (1.73 ± 0.20) × 105 M−1/s−1], and kanamycin [kcat/Km of (1.10 ± 0.18) × 105 M−1/s−1]. Three conserved functional domains of the aminoglycoside phosphotransferase family and ten amino acid residues responsible for the phosphorylation of kanamycin were found in the amino acid sequence of APH(3′)-Id. No mobile genetic element (MGE) was discovered surrounding the aph(3′)-Id gene.ConclusionIn this work, a novel aminoglycoside 3’-O-phosphotransferase gene designated aph(3′)-Id encoded in the chromosome of the environmental isolate Kluyvera intermedia DW18 was identified and characterized. These findings will help clinicians select effective antimicrobials to treat infections caused by pathogens with this kind of resistance gene

Retrospective analysis of 217 fatal intoxication autopsy cases from 2009 to 2021: temporal trends in fatal intoxication at Tongji center for medicolegal expertise, Hubei, China

This retrospective analysis of fatal intoxication case autopsies was performed at Tongji Center for Medicolegal Expertise in Hubei (TCMEH) from 2009 to 2021 to obtain up-to-date information on intoxication cases. The objective was to describe important data about evolving patterns in intoxication occurrences, enhance public safety policies, and assist forensic examiners and police in more efficient handling of such cases. Analyses based on sex, age, topical exposure routes, toxic agents, and mode of death were performed using 217 records of intoxication cases collected from TCMEH as a sample, and the results were compared with reports previously published (from 1999 to 2008) from this institution. Deaths from intoxications occurred at a higher rate in males than in females and were most common among individuals aged 30–39 years. The most frequent method of exposure was oral ingestion. The causative agents of deadly intoxications have changed when compared to the data from the previous 10 years. For instance, deaths from amphetamine overdoses are becoming more prevalent gradually, whereas deaths due to carbon monoxide and rodenticide intoxication have declined dramatically. In 72 cases, pesticides continued to be the most frequent intoxication cause. A total of 60.4% of the deaths were accidental exposure. Men died from accidents at a higher rate than women, although women were more likely to commit suicide. Particular focus is needed on the use of succinylcholine, cyanide, and paraquat in homicides

BlaPSZ-1, a novel AmpC gene identified from a Pantoea isolate

BackgroundPantoea species of the family Erwiniaceae are well-known plant pathogens and animal and human conditional pathogens. Due to the widespread and continuous use of antimicrobials, multidrug-resistant strains continue to emerge, making clinical treatment difficult; therefore, there is an increasing need to clarify the mechanisms of drug resistance.MethodsA rabbit anal fecal sample was collected by a swab and the streak plate method was used to isolate single colonies. The standard agar dilution method was used to determine the minimum inhibitory concentrations (MICs) against antimicrobials. The complete genome sequence of the bacterium was obtained using Next-Generation Sequencing platforms. The potential resistance gene was annotated based on the Comprehensive Antibiotic Resistance Database (CARD) and verified by molecular cloning. The β-lactamase PSZ-1 was expressed via the pCold I expression vector and its enzyme kinetic parameters were analyzed. The genetic environment and evolutionary process of the novel resistance gene-related sequences were analyzed by bioinformatic methods.ResultsThe isolate Pantoea endophytica X85 showed some degree of resistance to penicillins as well as cephalosporins. A novel AmpC resistance gene, designated blaPSZ-1 in this research, was identified to be encoded in the plasmid (pPEX85) of P. endophytica X85. BlaPSZ-1 showed resistance to penicillins and several first-, second-and third-generation cephalosporins as well as aztreonam, but it did not show resistance to the fourth-generation cephalosporins or carbapenems tested. Enzyme kinetic assays revealed that it could hydrolyze amoxicillin, penicillin G, cephalothin, and cefazolin, and its hydrolytic activity could be strongly inhibited by the inhibitor avibactam, which was generally consistent with antimicrobial susceptibility testing results. No hydrolytic activity was observed for third-generation cephalosporins or aztreonam.ConclusionIn this study, a novel AmpC β-lactamase gene, designated blaPSZ-1, was characterized and it was encoded in the plasmid of the bacterium P. endophytica X85. It shows resistance to penicillins and several cephalosporins. The discovery of novel drug resistance mechanisms can help guide the scientific use of drugs in animal husbandry and clinical practice, effectively avoiding the abuse of antimicrobials and thus preventing the further development and spread of bacterial resistance