Highly flexible yet strain-insensitive conjugated polymer.

Imparting excellent electrical properties, mechanical robustness, suppleness, conduction stability during deformation, and self-healing to intrinsic conducting polymers is a challenging endeavor. The reversibly interlocked macromolecular networks (RILNs) approach is utilized to tackle this problem. Specifically, poly(3,4-ethylenedioxythiophene) (PEDOT) is mixed with flexible polysulfonic acid networks crosslinked by reversible Diels-Alder bonds, while rigid polyaniline networks crosslinked by reversible Schiff base bonds act as molecular staples. Owing to the joint actions of the doping effect of polyaniline on PEDOT, the specific interlocking architecture and synergy between the component materials, the electrical conductivity (59.3-980.5 S cm-1), tensile strength (8.4-81.6 MPa) and elongation at break (44.5-411.0%) of the resultant PEDOT/RILNs films is significantly tunable according to different usage scenarios by adjusting the PEDOT content from 1.48 to 22.24 wt%. More importantly, the electrical resistance of PEDOT/RILNs remains constant during not only a single large extension and deflection but also repeated stretching (up to 1500 cycles) and bending (up to 106 cycles). The built-in reversible covalent bonds enable the PEDOT/RILNs to autonomously restore damaged mechanical and electrical performance. These record-breaking results and the demonstration of self-powered sensor made of PEDOT/RILNs suggest that the proposed approach successfully satisfies various conflicting requirements of flexible electronics regarding the properties of conducting polymers.

Imparting Ultrahigh Strength to Polymers via a New Concept Strategy of Construction of up to Duodecuple Hydrogen Bonding among Macromolecular Chains.

Interconnecting macromolecules via multiple hydrogen bonds (H-bonds) can simultaneously strengthen and toughen polymers, but material synthesis becomes extremely difficult with increasing number of H-bonding donors and acceptors; therefore, most reports are limited to triple and quadruple H-bonds. Herein, this bottleneck is overcome by adopting a quartet-wise approach of constructing H-bonds instead of the traditional pairwise method. Thus, large multiple hydrogen bonds can be easily established, and the supramolecular interactions are further reinforced. Especially, when such multiple H-bond motifs are embedded in polymers, four macromolecular chains-rather than two as usual-are tied, distributing the applied stress over a larger volume and more significantly improving the overall mechanical properties. Proof-of-concept studies indicate that the proposed intermolecular multiple H-bonds (up to duodecuple) are readily introduced in polyurethane. A record-high tensile strength (105.2 MPa) is achieved alongside outstanding toughness (352.1 MJ m-3), fracture energy (480.7 kJ m-2), and fatigue threshold (2978.4 J m-2). Meantime, the polyurethane has acquired excellent self-healability and recyclability. This strategy is also applicable to nonpolar polymers, such as polydimethylsiloxane, whose strength (15.3 MPa) and toughness (50.3 MJ m-3) are among the highest reported to date for silicones. This new technique has good expandability and can be used to develop even more and stronger polymers.

Successful Management of Velopharyngeal Insufficiency in WAGR syndrome with Deletion of Chromosome 11p14.3.

Deletions in the 11p region can lead to severe outcomes, such as WAGR (Wilms tumor, aniridia, genitourinary anomalies, and mental retardation) syndrome. However, velopharyngeal insufficiency is little known, and its treatment guideline is yet to be established. Here, we present a velopharyngeal insufficiency case of a Korean patient with a 493kb deletion of chromosome 11p14.3. The patient was successfully managed with a posterior pharyngeal flap. Posterior pharyngeal flap should be considered in velopharyngeal insufficiency patients with WAGR syndrome.

Muscle Transcriptome Analysis of Mink at Different Growth Stages Using RNA-Seq.

Mink is a kind of small and precious fur animal resource. In this study, we employed transcriptomics technology to analyze the gene expression profile of mink pectoral muscle tissue, thereby elucidating the regulatory mechanisms underlying mink growth and development. Consequently, a total of 25,954 gene expression profiles were acquired throughout the growth and development stages of mink at 45, 90, and 120 days. Among these profiles, 2607 genes exhibited significant differential expression (|log2(fold change)| ≥ 2 and p_adj < 0.05). GO and KEGG enrichment analyses revealed that the differentially expressed genes were primarily associated with the mitotic cell cycle process, response to growth factors, muscle organ development, and insulin resistance. Furthermore, GSEA enrichment analysis demonstrated a significant enrichment of differentially expressed genes in the p53 signaling pathway at 45 days of age. Subsequent analysis revealed that genes associated with embryonic development (e.g., PEG10, IGF2, NRK), cell cycle regulation (e.g., CDK6, CDC6, CDC27, CCNA2), and the FGF family (e.g., FGF2, FGF6, FGFR2) were all found to be upregulated at 45 days of age in mink, which suggested a potential role for these genes in governing early growth and developmental processes. Conversely, genes associated with skeletal muscle development (PRVA, TNNI1, TNNI2, MYL3, MUSTN1), a negative regulator of the cell cycle gene (CDKN2C), and IGFBP6 were found to be up-regulated at 90 days of age, suggesting their potential involvement in the rapid growth of mink. In summary, our experimental data provide robust support for elucidating the regulatory mechanisms underlying the growth and development of mink.

Surgical correction of sunken upper eyelid with upper arcus marginalis release and precision fat distribution technique.

BACKGROUND: Sunken upper eyelids, characterized by hollowing in the upper orbital region, can contribute to an aged or fatigued appearance. We aim to report on the surgical technique and its effects, involving the release of the arcus marginalis of the upper eyelid and the precise distribution of orbital fat. METHODS: From December 2021 to March 2023, a total of 84 eyelids from 42 patients who underwent surgical correction for sunken upper eyelids, utilizing the upper arcus marginalis release and precision fat distribution technique, were included in this study. Preoperative and postoperative sunken depths were measured and statistically analyzed. Aesthetic satisfaction was assessed through patient questionnaires. RESULTS: Preoperative and postoperative sunken depths measured 9.2 ± 2.2 mm and 5.9 ± 2.3 mm, respectively. The mean improvement was 3.3 mm, a change of statistical significance. Aesthetic outcomes and patient satisfaction yielded favorable results. No major complications were observed during the follow-up period. CONCLUSION: The upper arcus marginalis release and orbital fat distribution technique demonstrated favorable outcomes in correcting sunken upper eyelids. This procedure ensures stable placement of orbital fat at the deepest sunken point, resulting in aesthetically pleasing and enduring results. This technique serves as a valuable alternative for patients with moderate to severe sunken eyelids.

Dynamic human exposure to airborne bacteria-associated antibiotic resistomes revealed by longitudinal personal monitoring data.

Airborne antibiotic-resistant bacteria (ARB) can critically impact human health. We performed resistome profiling of 283 personal airborne exposure samples from 15 participants spanning 890 days and 66 locations. We found a greater diversity and abundance of airborne bacteria community and antibiotic resistomes in spring than in winter, and temperature contributed largely to the difference. A total of 1123 bacterial genera were detected, with 16 genera dominating. Of which, 7/16 were annotated as major antibiotic resistance gene (ARG) hosts. The participants were exposed to a highly dynamic collection of ARGs, including 322 subtypes conferring resistance to 18 antibiotic classes dominated by multidrug, macrolide-lincosamide-streptogramin, ß-lactam, and fosfomycin. Unlike the overall community-level bacteria exposure, an extremely high abundance of specific ARG subtypes, including lunA and qacG, were found in some samples. Staphylococcus was the predominant genus in the bacterial community, serving as a primary bacterial host for the ARGs. The annotation of ARG-carrying contigs indicated that humans and companion animals were major reservoirs for ARG-carrying Staphylococcus. This study contextualized airborne antibiotic resistomes in the precision medicine framework through longitudinal personal monitoring, which can have broad implications for human health.

Ultrastrong bonding, on-demand debonding, and easy re-bonding of non-sticking materials enabled by reversibly interlocked macromolecular networks-based Janus-like adhesive.

Simultaneously gluing hydrophobic and hydrophilic materials is a highly desired but intractable task. Herein, we developed a facile strategy using reversibly interlocked macromolecular networks (ILNs) as an adhesive. As shown by the proof-of-concept assembly of glass/ILNs/fluoropolymer (i.e., a simplified version of a photovoltaic module), the sandwiched ILNs were stratified after hot-pressing owing to temporary decrosslinking enabled by the built-in reversible covalent bonds. The fragmented component networks were enriched near their respective thermodynamically favored substrates to form a Janus-like structure. Strong elaborate interfacial bespoke chemical bonds and mechanical interlocking were thus established accompanied by the reconstruction of ILNs after cooling, which cooperated with the robust cohesion of the core part of the ILNs resulting from topological entanglements and led to a record-high peeling strength of 64.86 N cm-1. Also, the ILN-based Janus-like adhesive possessed reversible recyclability, adhesivity and on-demand de-bondability. The molecular design detailed in this study serves as a guide for developing a high-performance smart adhesive that firmly bonds non-sticking materials. Compared with existing Janus adhesives, our ILNs-based adhesive not only shows extremely useful reversibility but also greatly simplifies the adhesion process with no surface treatment required.

F18:A-:B1 Plasmids Carrying blaCTX-M-55 Are Prevalent among Escherichia coli Isolated from Duck-Fish Polyculture Farms.

We determined the prevalence and molecular characteristics of blaCTX-M-55-positive Escherichia coli (E. coli) isolated from duck-fish polyculture farms in Guangzhou, China. A total of 914 E. coli strains were isolated from 2008 duck and environmental samples (water, soil and plants) collected from four duck fish polyculture farms between 2017 and 2019. Among them, 196 strains were CTX-M-1G-positive strains by PCR, and 177 (90%) blaCTX-M-1G-producing strains were blaCTX-M-55-positive. MIC results showed that the 177 blaCTX-M-55-positive strains were highly resistant to ciprofloxacin, ceftiofur and florfenicol, with antibiotic resistance rates above 95%. Among the 177 strains, 37 strains carrying the F18:A-:B1 plasmid and 10 strains carrying the F33:A-:B- plasmid were selected for further study. Pulse field gel electrophoresis (PFGE) combined with S1-PFGE, Southern hybridization and whole-genome sequencing (WGS) analysis showed that both horizontal transfer and clonal spread contributed to dissemination of the blaCTX-M-55 gene among the E. coli. blaCTX-M-55 was located on different F18:A-:B1 plasmids with sizes between ~76 and ~173 kb. In addition, the presence of blaCTX-M-55 with other resistance genes (e.g., tetA, floR, fosA3, blaTEM, aadA5 CmlA and InuF) on the same F18:A-:B1 plasmid may result in co-selection of resistance determinants and accelerate the dissemination of blaCTX-M-55 in E. coli. In summary, the F18:A-:B1 plasmid may play an important role in the transmission of blaCTX-M-55 in E. coli, and the continuous monitoring of the prevalence and transmission mechanism of blaCTX-M-55 in duck-fish polyculture farms remains important.

Genomic Insights into Global blaCTX-M-55-Positive Escherichia coli Epidemiology and Transmission Characteristics.

In recent years, blaCTX-M-55-positive Escherichia coli has been widely reported in multiple locations with an increasing trend in prevalence, yet few studies have comprehensively analyzed the transmission characteristics and epidemiological patterns of blaCTX-M-55-positive E. coli. Here, we constructed a blaCTX-M-55-positive E. coli global genomic data set as completely as possible and explored the epidemiology and potential impact of blaCTX-M-55-positive E. coli on a global scale by high-resolution bioinformatics methods. The results show that blaCTX-M-55-positive E. coli has spread widely worldwide, especially in Asia, with the rich sequence typing (ST) diversity and high proportion of auxiliary genome occupancy indicating a high degree of openness. The phylogenetic tree suggests that blaCTX-M-55-positive E. coli is frequently clonally transmitted between the three human-animal environments and often cotransmitted with fosA, mcr, blaNDM, and tet(X). The stable presence of InclI1 and InclI2 in different hosts from different sources suggests that this part of the plasmid drives the widespread transmission of blaCTX-M-55-positive E. coli. We inductively clustered all blaCTX-M-55 flanking environmental gene structures and obtained five types. Notably, "ISEcp1-blaCTX-M-55-orf477-(Tn2)" and "IS26(IS15DI)-hp-hp-blaCTX-M-55-orf477-hp-blaTEM-IS26-hp-IS26-Tn2" are dominant in "humans" and in "animals and related foods," respectively. Overall, our findings highlight the importance of whole-genome sequencing-based surveillance in exploring the transmission and evolution of blaCTX-M-55-positive E. coli in the context of "One Health," and they serve as a reminder to strengthen the surveillance of blaCTX-M-55-positive E. coli in order to address the potential risk of future large outbreaks. IMPORTANCE CTX-M-55 was first discovered in Thailand in 2004, and today, this enzyme is the most common CTX-M subtype in E. coli of animal origin in China. Thus, blaCTX-M-55-positive E. coli getting widely spread is a growing public health problem. Although prevalence surveys of blaCTX-M-55-positive E. coli in different hosts have been widely reported in recent years, they remain insufficient in "One Health" context and from a global comprehensive perspective. Here, we constructed a genomic database of 2144 blaCTX-M-55-positive E. coli and used bioinformatics methods to resolve the spread and evolution of blaCTX-M-55-positive E. coli. The results suggest a potential risk of rapid transmission of blaCTX-M-55-positive E. coli and that long-term continuous surveillance of blaCTX-M-55-positive E. coli should be emphasized.

The ß-catenin-LINC00183-miR-371b-5p-Smad2/LEF1 axis promotes adult T-cell lymphoblastic lymphoma progression and chemoresistance.

BACKGROUND: High-intensity chemotherapy regimens are often used in adult T-cell lymphoblastic lymphoma (T-LBL) patients. Nevertheless, the response rate remains unsatisfactory due to emergence of chemoresistance. Growing evidence has shown that long non-coding RNAs (lncRNAs) are involved in tumor progression and chemoresistance. Herein, we investigated the potential role of lncRNAs in T-LBLs. METHODS: RNAseq was used to screen and identify candidate lncRNAs associated with T-LBL progression and chemoresistance. Luciferase reporter assay was used to examine the binding of miR-371b-5p to the 3'UTR of Smad2 and LEF1, and the binding of TCF-4/LEF1 to the promoter of LINC00183. Chromatin immunoprecipitation assay was undertaken to analyze the connection between LEF1 and the LINC00183 promoter region. RNA immunoprecipitation assays were used to explore the mechanism whereby LINC00183 regulated miR-371b-5p. MTT and flow cytometry assays were used to measure apoptosis of T-LBL cells. RESULTS: LINC00183 was upregulated in T-LBL progression and chemoresistant tissues in both the Sun Yat-sen University Cancer Center dataset and the First Affiliated Hospital of Anhui Medical University dataset. High expression of LINC00183 was correlated with poorer overall survival and progression-free survival of T-LBL patients compared to those with low expression of LINC00183. Furthermore, miR-371b-5p was negatively regulated by LINC00183. In vivo and in vitro assays showed that LINC00183-mediated T-LBL chemoresistance depended on miR-371b-5p expression. The direct binding of miR-371b-5p to Smad2 and LEF1 was verified by luciferase assays. It was shown that TCF4/LEF1 could bind to the LINC00183 promoter site and increase its transcript level. Downregulation of miR-371b-5p led to increased expression of Smad2/LEF1, and in turn increased LINC00183 expression. Additionally, phospho-Smad2 promotes nuclear translocation of ß-catenin, LINC00183 downregulation decreased chemoresistance induced by ß-catenin and TGF-ß1 in T-LBL cells. CONCLUSION: We unraveled a ß-catenin-LINC00183-miR-371b-5p-Smad2/LEF1 feedback loop that promotes T-LBL progression and chemoresistance, indicating that LINC00183 may serve as a potential therapeutic target in T-LBLs.

Prevalence and molecular characteristics of mcr-1-positive Escherichia coli isolated from duck farms and the surrounding environments in coastal China.

The emergence of colistin-resistance is considered a threat to public health and colistin-resistant bacteria have recently been reported in animal, environmental and human sources. Whereas, the epidemic and dissemination of colistin-resistant bacteria in duck farms have not been surveyed, especially the surrounding environmental contamination from duck farms. We investigated the prevalence and molecular characteristics of mcr-1-positive E. coli from duck farms in coastal China. 360 mcr-1-positive E. coli isolates were collected from 1112 samples from duck farms and surrounding environments. The prevalence of mcr-1-positive E. coli in Guangdong province was higher than other two provinces we examined. PFGE analysis indicated clonal spread of mcr-1-positive E. coli between duck farms and surrounding environments, including water and soil. MLST analysis demonstrated that ST10 was more common than ST1011, ST117, and ST48. Phylogenomic analysis also suggested mcr-1-positive E. coli collected from distinct cities were assigned to the same lineage and mcr-1 was primarily located on IncI2 and IncHI2 plasmids. Genomic environment analysis showed mobile gene elements ISApl1 most likely plays a key role in the horizontal transmission of mcr-1. WGS further revealed that mcr-1 was found associated with 27 different ARGs. Our findings emphasize the urgent need for effective colistin resistance surveillance in humans, animals and the environment.

Sunlight Stimulated Photochemical Self-Healing Polymers Capable of Re-Bonding Damages up to a Centimeter Below the Surface Even Out of the Reach of the Illumination.

The development of photochemical self-healing polymers faces the the following bottlenecks: i) only the surface cracks can be restored and ii) materials' mechanical properties are lower. To break these bottlenecks, cross-linked poly(urethane-dithiocarbamate)s carrying photo-reversible dithiocarbamate bonds covalently linked to indole chromophores and benzyl groups are designed. The conjugated structure of the chromophore and benzyl enhances the addition reactivity of thiocarbonyl moiety and facilitates photo-cleavage of CS bond, so that transfer of the created radicals among dithiocarbamate linkages is promoted. Accordingly, reshuffling of the reversibly cross-linked networks via dynamic exchange between the activated dithiocarbamates is enabled in both surface layer and the interior upon exposure to the low-intensity ultraviolet (UV) light from the sun. It is found that the damages up to a centimeter below the surface can be effectively recovered in the sunshine, which greatly exceeds the maximum penetration distance of UV light (hundreds of microns). Besides, tensile strength and failure strain of the poly(urethane-dithiocarbamate) are superior to the reported photo-reversible polymers, achieving the record-high 33.8 MPa and 782.0% owing to the wide selectivity of soft/hard blocks, multiple interactions, and appropriate cross-linking architecture. The present work provides a novel paradigm of photo self-healing polymers capable of re-bonding cracks even out of the reach of the illumination.

Clinical Implication of E2F Transcription Factor 1 in Hepatocellular Carcinoma Tissues.

Background: To date, the clinical management of advanced hepatocellular carcinoma (HCC) patients remains challenging and the mechanisms of E2F transcription factor 1 (E2F1) underlying HCC are obscure. Materials and Methods: Our study integrated datasets mined from several public databases to comprehensively understand the deregulated expression status of E2F1. Tissue microarrays and immunohistochemistry staining was used to validate E2F1 expression level. The prognostic value of E2F1 was assessed. In-depth subgroup analyses were implemented to compare the differentially expressed levels of E2F1 in HCC patients with various tumor stages. Functional enrichments were used to address the predominant targets of E2F1 and shedding light on their potential roles in HCC. Results: We confirmed the elevated expression of E2F1 in HCC. Subgroup analyses indicated that elevated E2F1 level was independent of various stages in HCC. E2F1 possessed moderate discriminatory capability in differentiating HCC patients from non-HCC controls. Elevated E2F1 correlated with Asian race, tumor classification, neoplasm histologic grade, eastern cancer oncology group, and plasma AFP levels. Furthermore, high E2F1 correlated with poor survival condition and pooled HR signified E2F1 as a risk factor for HCC. Enrichment analysis of differentially expressed genes, coexpressed genes, and putative targets of E2F1 emphasized the importance of cell cycle pathway, where CCNE1 and CCNA2 served as hub genes. Conclusions: We confirmed the upregulation of E2F1 and explored the prognostic value of E2F1 in HCC patients. Two putative targeted genes (CCNE1 and CCNA2) of E2F1 were identified for their potential roles in regulating cell cycle and promote antiapoptotic activity in HCC patients.

The First High-quality Reference Genome of Sika Deer Provides Insights into High-tannin Adaptation.

Sika deer are known to prefer oak leaves, which are rich in tannins and toxic to most mammals; however, the genetic mechanisms underlying their unique ability to adapt to living in the jungle are still unclear. In identifying the mechanism responsible for the tolerance of a highly toxic diet, we have made a major advancement by explaining the genome of sika deer. We generated the first high-quality, chromosome-level genome assembly of sika deer and measured the correlation between tannin intake and RNA expression in 15 tissues through 180 experiments. Comparative genome analyses showed that the UGT and CYP gene families are functionally involved in the adaptation of sika deer to high-tannin food, especially the expansion of the UGT family 2 subfamily B of UGT genes. The first chromosome-level assembly and genetic characterization of the tolerance to a highly toxic diet suggest that the sika deer genome may serve as an essential resource for understanding evolutionary events and tannin adaptation. Our study provides a paradigm of comparative expressive genomics that can be applied to the study of unique biological features in non-model animals.

Metagenomic insights into the influence of mobile genetic elements on ARGs along typical wastewater treatment system on pig farms in China.

The wastewater treatment processes (WTP) on pig farms are heavily contaminated by antibiotic resistance genes (ARGs) and mobile genetic elements (MGEs) play an important role in shaping ARG profiles. Here we first employed metagenomic sequencing to follow the diversities and shifts of ARG associated mobile genetic elements (AAMGEs) including insertion sequences (ISs) and plasmids along the WTP for three pig farms in southeast China. The IS average relative abundance rose from the initial pig feces source to the wastewater storage lagoon (WSL) but decreased in the influent and rose in the effluent of the anaerobic digestor (AD). In contrast, plasmids were eliminated rapidly along this process. These results indicated that the AD reduced plasmid copies while IS abundance increased. We found a great diversity ISs, including IS91, ISNCY, IS630 and IS701, were large contributors to the transfer of multi-drug resistance. In addition, the tetracycline resistance genes co-occurred with a greater diversity of ISs than other ARG classes and this likely contributed to the high abundance of tetracycline resistance genes we found. The transfer of ARGs mediated by MGEs along the WTP of pig farms was a key contributor for the ARGs persistence in the environment of pig farms. Collectively, our findings demonstrated different fates for ISs and plasmids along the WTP for pig farms and suggested that AAMGE monitoring served as an important role in controlling ARGs in pig waste.

Tailored modular assembly derived self-healing polythioureas with largely tunable properties covering plastics, elastomers and fibers.

To impart self-healing polymers largely adjustable dynamicity and mechanical performance, here we develop libraries of catalyst-free reversible polythioureas directly from commodity 1,4-phenylene diisothiocyanate and amines via facile click chemistry based modular assembly. By using the amine modules with various steric hindrances and flexibilities, the reversible thiourea units acquire triggering temperatures from room temperature to 120 °C. Accordingly, the derived self-healable, recyclable and controlled degradable dynamically crosslinked polythioureas can take effect within wide temperature range. Moreover, mechanical properties of the materials can be tuned covering plastics, elastomers and fibers using (i) different assemble modules or (ii) solid-state stretching. Particularly, unidirectional stretching leads to the record-high tensile strength of 266 MPa, while bidirectional stretching provides the materials with biaxial strengths up to over 120 MPa. The molecular mechanism and technological innovations discussed in this work may benefit promotion and application of self-healing polymers towards greatly diverse demands and scenarios.

Transferability of tigecycline resistance: Characterization of the expanding Tet(X) family.

Tetracycline and its derivative tigecycline are clinical options against Gram-negative bacterial infections. The emergence of mobile Tet(X) enzymes that destruct tetracycline-type antibiotics is posing a big challenge to antibacterial therapy and food/environmental securities. Here, we present an update on a growing number of Tet(X) variants. We describe structure and action of Tet(X) enzyme, and discuss the evolutional origin. In addition, potential Tet(X) inhibitors are given. This mini-review might benefit better understanding of Tet(X)-mediated tigecycline resistance. This article is categorized under: Infectious Diseases > Genetics/Genomics/Epigenetics Infectious Diseases > Environmental Factors Infectious Diseases > Molecular and Cellular Physiology.