Rigid Fe(III) Chelate with Phosphonate Pendants: A Stable and Effective Extracellular MRI Contrast Agent.

A novel Fe(III) complex, Fe-tBPCDTA, was synthesized and explored as a potential contrast agent for MRI. Compared to established agents like Fe-EDTA and Fe-tCDTA, Fe-tBPCDTA exhibited moderate relaxivity (r1 = 1.17 s-1·mmol-1) due to its enhanced second-sphere mechanism. It also displayed improved kinetic inertness, lower cytotoxicity, and enhanced redox stability. In vivo studies demonstrated its function as an extracellular fluid agent, providing tumor contrast comparable to that of Gd-DTPA at a higher dosage. Complete renal clearance occurred within 24 h. These findings suggest Fe-tBPCDTA as a promising candidate for further development as a safe and effective extracellular MRI contrast agent.

Photocatalytic, Oxidative Cleavage of C-C Bond in Lignin Models and Native Lignin.

It is challenging to realize the selective C-C bond cleavage of lignin ß-O-4 linkages for production of high-value aromatic chemicals due to its intrinsic inertness and complex structure. Here we report a light-driven, chlorine-radical-based protocol to realize the oxidative C-C bond cleavage in various lignin model compounds catalyzed by commercially available TPT and CaCl2, achieving high conversion and good to high product yields at room temperature. Mechanistic studies reveal that the preferential activation of Cß-H bond facilitates the oxidation and C-C bond cleavage of lignin ß-O-4 model via chlorine radical. Furthermore, this method is also applicable to the depolymerization of natural lignin extracts, furnishing the aromatic oxygenates from the cleavage of Cα-Cß bonds. This study provides experimental foundations to the depolymerization and valorization of lignin into high value-added aromatic compounds.

Chromosome-level genome assembly and annotation of eel goby (Odontamblyopus rebecca).

The eel gobies fascinate researchers with many important features, including its unique body structure, benthic lifestyle, and degenerated eyes. However, genome assembly and exploration of the unique genomic composition of the eel gobies are still in their infancy. This has severely limited research progress on gobies. In this study, multi-platform sequencing data were generated and used to assemble and annotate the genome of O. rebecca at the chromosome-level. The assembled genome size of O. rebecca is 918.57 Mbp, which is similar to the estimated genome size (903.03 Mbp) using 17-mer. The scaffold N50 is 41.67 Mbp, and 23 chromosomes were assembled using Hi-C technology with a mounting rate of 99.96%. Genome annotation indicates that 53.29% of the genome is repetitive sequences, and 22,999 protein-coding genes are predicted, of which 21,855 have functional annotations. The chromosome-level genome of O. rebecca will not only provide important genomic resources for comparative genomic studies of gobies, but also expand our knowledge of the genetic origin of their unique features fascinating researchers for decades.

Crohn's disease: an update.

Crohn's disease (CD) is a chronic, relapsing and remitting inflammatory bowel disease (IBD) that is increasing in incidence and prevalence globally. Management aims to achieve endoscopic healing, symptom resolution and improvement in quality of life. Therapeutic approaches in CD vary depending on disease phenotype. Thiopurines are important in steroid-sparing maintenance therapy, while anti-tumour necrosis factor agents play a fundamental role, especially in fistulising CD. Suboptimal response to these medications may require escalation to other immunosuppressive and biologic therapies, and surgical intervention is still required in a proportion of patients. Tailoring treatment to target specific patient phenotypes, disease severity and patient wishes is becoming more feasible with the growing array of therapeutic options in CD.

Elucidating the role of nicotinamide N-methyltransferase-p53 axis in the progression of chronic kidney disease.

Background: Chronic kidney disease (CKD) is a significant global health issue characterized by progressive loss of kidney function. Renal interstitial fibrosis (TIF) is a common feature of CKD, but current treatments are seldom effective in reversing TIF. Nicotinamide N-methyltransferase (NNMT) has been found to increase in kidneys with TIF, but its role in renal fibrosis is unclear. Methods: Using mice with unilateral ureteral obstruction (UUO) and cultured renal interstitial fibroblast cells (NRK-49F) stimulated with transforming growth factor-ß1 (TGF-ß1), we investigated the function of NNMT in vivo and in vitro. Results: We performed single-cell transcriptome sequencing (scRNA-seq) on the kidneys of mice and found that NNMT increased mainly in fibroblasts of UUO mice compared to sham mice. Additionally, NNMT was positively correlated with the expression of renal fibrosis-related genes after UUO injury. Knocking down NNMT expression reduced fibroblast activation and was accompanied by an increase in DNA methylation of p53 and a decrease in its phosphorylation. Conclusions: Our findings suggest that chronic kidney injury leads to an accumulation of NNMT, which might decrease p53 methylation, and increase the expression and activity of p53. We propose that NNMT promotes fibroblast activation and renal fibrosis, making NNMT a novel target for preventing and treating renal fibrosis.

Climate Adaptation and Drift Shape the Genomes of Two Eel-Goby Sister Species Endemic to Contrasting Latitude.

Deciphering the role of climate adaptation in generating genetic divergence and hence speciation is a central question in evolution. Comparisons of genomes of closely related species spanning selective climate gradients are particularly informative in discerning the signatures of selection and thereby providing valuable information concerning the role of climate adaptation in speciation. Here we re-sequenced 99 genomes of the two sister eel-goby species Odontamblyopus lacepedii and O. rebecca, which are endemic to tidal mudflats spanning contrasting latitude gradients, to estimate the influence of divergent climate selection on shaping genome-wide patterns of divergence. The results indicated that genome-wide differentiation between the two species was evident (genome-wide FST = 0.313). Against a background of high baseline genomic divergence, 588 and 1202 elevated divergent loci were detected to be widespread throughout their genomes, as opposed to focused within small islands of genomic regions. These patterns of divergence may arise from divergent climate selection in addition to genetic drift acting through past glacial segregation (1.46 million years ago). We identified several candidate genes that exhibited elevated divergence between the two species, including genes associated with substance metabolism, energy production, and response to environmental cues, all putative candidates closely linked to thermal adaptation expected from the latitude gradient. Interestingly, several candidates related to gamete recognition and time of puberty, and also exhibited elevated divergence, indicating their possible role in pre-zygote isolation and speciation of the two species. Our results would expand our knowledge on the roles of latitude climate adaptation and genetic drift in generating and maintaining biodiversity in marine teleosts.

Genome Sequencing Provides Novel Insights into Mudflat Burrowing Adaptations in Eel Goby Taenioides sp. (Teleost: Amblyopinae).

Amblyopinae is one of the lineage of bony fish that preserves amphibious traits living in tidal mudflat habitats. In contrast to other active amphibious fish, Amblyopinae species adopt a seemly more passive lifestyle by living in deep burrows of mudflat to circumvent the typical negative effects associated with terrestriality. However, little is known about the genetic origin of these mudflat deep-burrowing adaptations in Amblyopinae. Here we sequenced the first genome of Amblyopinae species, Taenioides sp., to elucidate their mudflat deep-burrowing adaptations. Our results revealed an assembled genome size of 774.06 Mb with 23 pseudochromosomes anchored, which predicted 22,399 protein-coding genes. Phylogenetic analyses indicated that Taenioides sp. diverged from the active amphibious fish of mudskipper approximately 28.3 Ma ago. In addition, 185 and 977 putative gene families were identified to be under expansion, contraction and 172 genes were undergone positive selection in Taenioides sp., respectively. Enrichment categories of top candidate genes under significant expansion and selection were mainly associated with hematopoiesis or angiogenesis, DNA repairs and the immune response, possibly suggesting their involvement in the adaptation to the hypoxia and diverse pathogens typically observed in mudflat burrowing environments. Some carbohydrate/lipid metabolism, and insulin signaling genes were also remarkably alterated, illustrating physiological remolding associated with nutrient-limited subterranean environments. Interestingly, several genes related to visual perception (e.g., crystallins) have undergone apparent gene losses, pointing to their role in the small vestigial eyes development in Taenioides sp. Our work provide valuable resources for understanding the molecular mechanisms underlying mudflat deep-burrowing adaptations in Amblyopinae, as well as in other tidal burrowing teleosts.

Low-Temperature-Tolerant Strain-Sensing Flexible Composite for Soft Body Armor.

Developing soft body armor with sensing characteristics in various application scenarios is a challenge but important for creating a peaceful world and personal safety, whereas existing materials suffer from indefinite protective effects and stimulus response at subzero temperatures in the long term. Herein, an anti-freezing and flexible puncture-resistance composite with strain-sensing ability is developed by compounding a NaCl-soaked poly(vinyl alcohol) (PVA)/sodium alginate (SA)/glycerol (Gly) hydrogel (PSGN hydrogel) with Kevlar fabric. After freezing-thawing treatment once and NaCl immersion for 10 h, the Kevlar/PSGN-10 composite has excellent puncture-resistance properties and linear, rapid response, wide band, and stable strain-sensing behaviors at 25 and -30 °C. The composite's maximum puncturing force and energy dissipation at -30 °C are 53.92 N and 370 mJ, respectively, increased by 285 and 302% compared with neat Kevlar fabric. The flexibility reduction and the mass addition of the Kevlar/PSGN-10 composite are merely 19 and 40%, respectively, showing superior wearable comfortability and protection efficiency. The composites also reveal remarkable strain-sensing abilities at -30 °C (linear strain sensitivity with GF = 0.27 and R2 = 0.981, a wide working frequency range of 0.16-1.3 Hz, and sensing stability for 1500 cycles). Moreover, the composite could respond to multipart body motion directly, including fingers, elbows, wrists, and knees. Consequently, the Kevlar/PSGN composite developed in this paper is promising for intelligent soft body armor at various temperatures.

Catalytic Modification of Porous Two-Dimensional Ni-MOFs on Portable Electrochemical Paper-Based Sensors for Glucose and Hydrogen Peroxide Detection.

Rapid and accurate detection of changes in glucose (Glu) and hydrogen peroxide (H2O2) concentrations is essential for the predictive diagnosis of diseases. Electrochemical biosensors exhibiting high sensitivity, reliable selectivity, and rapid response provide an advantageous and promising solution. A porous two-dimensional conductive metal-organic framework (cMOF), Ni-HHTP (HHTP = 2,3,6,7,10,11-hexahydroxytriphenylene), was prepared by using a one-pot method. Subsequently, it was employed to construct enzyme-free paper-based electrochemical sensors by applying mass-producing screen-printing and inkjet-printing techniques. These sensors effectively determined Glu and H2O2 concentrations, achieving low limits of detection of 1.30 µM and 2.13 µM, and high sensitivities of 5573.21 µA µM-1 cm-2 and 179.85 µA µM-1 cm-2, respectively. More importantly, the Ni-HHTP-based electrochemical sensors showed an ability to analyze real biological samples by successfully distinguishing human serum from artificial sweat samples. This work provides a new perspective for the use of cMOFs in the field of enzyme-free electrochemical sensing, highlighting their potential for future applications in the design and development of new multifunctional and high-performance flexible electronic sensors.

Ultra-strong tungsten refractory high-entropy alloy via stepwise controllable coherent nanoprecipitations.

High-performance refractory alloys with ultrahigh strength and ductility are in demand for a wide range of critical applications, such as plasma-facing components. However, it remains challenging to increase the strength of these alloys without seriously compromising their tensile ductility. Here, we put forward a strategy to "defeat" this trade-off in tungsten refractory high-entropy alloys by stepwise controllable coherent nanoprecipitations (SCCPs). The coherent interfaces of SCCPs facilitate the dislocation transmission and relieve the stress concentrations that can lead to premature crack initiation. As a consequence, our alloy displays an ultrahigh strength of 2.15 GPa with a tensile ductility of 15% at ambient temperature, with a high yield strength of 1.05 GPa at 800 °C. The SCCPs design concept may afford a means to develop a wide range of ultrahigh-strength metallic materials by providing a pathway for alloy design.

Direct synthesis of sila-benzoazoles through hydrosilylation and rearrangement cascade reaction of benzoazoles and silanes.

Sila-isosteres have attracted increasing attention due to their potential application in a variety of fields and their different properties compared to their carbon-containing analogs. However, the preparation of these silicon-containing compound remains challenging and thus the development of alternative synthetic methodologies is desirable. Here, we employ B(C6F5)3 as catalyst to enable the synthesis of highly functionalized sila-benzoazoles via hydrosilylation and rearrangement cascade reaction of benzoazoles and commercially available silanes. This strategy also exhibits remarkable features such as 100% atom-economy, good functional group tolerance, broad substrate scope, easy scale-up and good catalytic performance, demonstrating its potential application in sila-isostere synthesis.

Adolescents and Adults With Congenital Heart Disease: Why Are They Lost to Follow-Up?

Almost 90% of infants with congenital heart disease (CHD) now reach adulthood but require long-term surveillance to recognize and manage residual and/or evolving lesions. Yet many are lost to follow-up. A scoping review identified four specific domains that pose barriers to consistent follow-up. There are multiple issues associated with transition from pediatric to adult care which included-the lack of a seamless transfer, the establishment of a new trusting relationship, promoting the right balance of patient autonomy and addressing knowledge gaps. Additional issues related to logistic problems of time, distance, cost, and the availability of specialized care, are further compounded by the psychosocial factors and the heterogeneity of the cardiac abnormality affecting our patients. Further study of all these issues is warranted to improve ongoing engagement.

Reversible Iron Oxyfluoride (FeOF)-Graphene Composites as Sustainable Cathodes for High Energy Density Lithium Batteries.

Two large barriers are impeding the wide implementation of electric vehicles, namely driving-range and cost, primarily due to the low specific energy and high cost of mono-valence cathodes used in lithium-ion batteries. Iron is the ideal element for cathode materials considering its abundance, low cost and toxicity. However, the poor reversibility of (de)lithiation and low electronic conductivity prevent iron-based high specific energy multi-valence conversion cathodes from practical applications. In this work, a sustainable FeOF nanocomposite is developed with extraordinary performance. The specific capacity and energy reach 621 mAh g-1 and 1124 Wh kg-1 with more than 100 cycles, which triples the specific capacity, and doubles the specific energy of current mono-valence intercalation LiCoO2 . This is the result of an effective approach, combing the nanostructured FeOF with graphene, realized by making the (de)lithiation reversible by immobilizing FeOF nanoparticles and the discharge products over the graphene surface and providing the interparticle electric conduction. Importantly, it demonstrates that introducing small amount of graphene can create new materials with desired properties, opening a new avenue for altering the (de)lithiation process. Such extraordinary performance represents a significant breakthrough in developing sustainable conversion materials, eventually overcoming the driving range and cost barriers.

Comparative Transcriptome Analyses Provide New Insights into the Evolution of Divergent Thermal Resistance in Two Eel Gobies.

Adaptation to thermal conditions in tidal mudflats always involves tolerating frequent fluctuations and often extreme environmental temperatures. Regulation of gene expression plays a fundamental role in the evolution of these thermal adaptations. To identify the key gene regulatory networks associated with the thermal adaptation, we investigated the capability of cold tolerance, as well as the transcriptomic changes under cold stress in two mudflat inhabitants (Odontamblyopus lacepedii and O. rebecca) with contrasting latitude affinity. Our results revealed a remarkable divergent capacity of cold tolerance (CTmin: 0.61 °C vs. 9.57 °C) between the two gobies. Analysis of transcriptomic changes under cold stress unveiled 193 differentially expressed genes exhibiting similar expression profiles across all tissues and species, including several classic metabolic and circadian rhythm molecules such as ACOD and CIART that may represent the core cold response machinery in eel gobies. Meanwhile, some genes show a unique expression spectrum in the more cold-tolerant O. lacepedii suggesting their roles in the enhanced cold tolerance and hence the extreme thermal adaptations. In addition, a weighted gene co-expression network analysis (WGCNA) revealed a subset of metabolic hub genes including MYH11 and LIPT2 showing distinct down-regulation in O. lacepedii when exposed to cold stress which highlights the role of reduced energy consumption in the enhanced cold tolerance of eel gobies. These findings not only provide new insights into how mudflat teleosts could cope with cold stress and their potential evolutionary strategies for adapting to their thermal environment, but also have important implications for sound management and conservation of their fishery resources in a scenario of global climate warming in the marine realm.

Metabonomic identification of serum biomarkers related to heat stress tolerance of sheep.

Heat stress is considered as a limiting factor for sheep production; it is necessary to screen for sheep breeds with heat tolerance. This study was to compare the serum metabolomes of Hu sheep and Dorper sheep and identify potential biomarkers related to heat stress. The results revealed that the respiratory rate, heart rate, and rectal temperature of Dorper sheep were significantly higher than those of Hu sheep. Compared to Dorper sheep, the serum activities of total antioxidant capacity and glutathione peroxidase in Hu sheep were significantly higher, while the concentration of malondialdehyde was lower. Metabolomics analysis identified 107 differential serum metabolites. The pathways enriched from the altered serum metabolites between the two breeds were mainly involved in protein metabolism, carbohydrate metabolism, and lipid metabolism. The levels of antioxidant- and energy-related metabolites were higher in the serum of Hu sheep than that of Dorper sheep; however, the levels of lipid catabolism- and inflammation-related were higher in the serum of Dorper sheep. The results indicate that Hu sheep had better heat stress resistance capability than Dorper sheep. Moreover, high levels of metabolites in the serum of Hu sheep are potential biomarkers for heat stress tolerance, including l-methionine, s-adenosylmethionine, and nicotinuric acid.

Parametric Study on Low-Velocity Impact (LVI) Damage and Compression after Impact (CAI) Strength of Composite Laminates.

A full-scale model for predicting low-velocity impact (LVI) damage and compression after impact (CAI) strength was established based on a subroutine of the material constitutive relationship and the cohesive elements. The dynamic responses of the laminate under impact load and damage propagation under a compressive load were presented. The influences of impact energy and ply thickness on the impact damage and the CAI strength were predicted. The predicted results were compared with the experimental ones. It is shown that the predicted value of the CAI strength is in good agreement with the experimental result. As the impact energy reaches a certain value, the CAI strength no longer decreases with the increase in the impact energy. Decreasing the ply thickness can effectively improve the damage resistance and CAI strength.

Preparation and performance study of a reactive polyurethane hot-melt adhesive/CS-Fe3O4 magnetic nanocomposite film/fabric.

Magnetic nanoparticles are attracting significant attention for their wide application as biomaterials and magnetic storage materials. As an environmentally friendly adhesive, reactive polyurethane hot-melt adhesive (PUR) is a biocompatible polymer with a wide range of applications. In this paper, chitosan (CS)-surface-modified magnetic Fe3O4 nanoparticles were synthesized by the sol-gel method. Surface modification of the Fe3O4 nanoparticles with CS enhanced their mechanical properties in PUR. The nanoparticles were characterized by Fourier transform infrared (FTIR) and X-ray diffraction (XRD) analyses, while their surface morphology was elucidated using scanning electron microscopy (SEM) and projection electron microscopy (TEM) techniques. Subsequently, PUR/CS-Fe3O4 magnetic nanocomposite films were prepared using an in situ method, wherein different amounts of CS-surface-modified magnetic Fe3O4 nanoparticles were doped into the PUR and coated on the films. The thermal, UV resistance and mechanical properties of the PUR/CS-Fe3O4 magnetic nanocomposite films were investigated by TGA, UV spectrometer and tensile testing. CS-Fe3O4 nanoparticles were successfully prepared using the sol-gel method and CS to modify the surface of the Fe3O4 nanoparticles. The results show that the mechanical properties and UV resistance of PUR/CS-Fe3O4 magnetic nanocomposites are improved by almost 50%, so the constructed PUR/CS-Fe3O4 magnetic nanocomposites have good UV-resistant properties and mechanical properties. The as-synthesized CS-Fe3O4 magnetic nanocomposites show great potential for application to mechanical and textile development.

The multifaceted role of the SASP in atherosclerosis: from mechanisms to therapeutic opportunities.

BACKGROUND: The global population of older individuals is growing, and ageing is a key risk factor for atherosclerotic cardiovascular diseases. Abnormal accumulation of senescent cells can cause potentially deleterious effects on the organism with age. As a vital marker of cellular senescence, the senescence-associated secretory phenotype (SASP) is a novel mechanism to link cellular senescence with atherosclerosis. MAIN BODY: In this review, we concretely describe the characteristics of the SASP and its regulation mechanisms. Importantly, we provide novel perspectives on how the SASP can promote atherosclerosis. The SASP from different types of senescent cells have vital roles in atherosclerosis progression. As a significant mediator of the harmful effects of senescent cells, it can play a pro-atherogenic role by producing inflammation and immune dysfunction. Furthermore, the SASP can deliver senescence signals to the surrounding vascular cells, gradually contributing to the development of atherosclerosis. Finally, we focus on a variety of novel therapeutic strategies aimed to reduce the burden of atherosclerosis in elderly individuals by targeting senescent cells and inhibiting the regulatory mechanisms of the SASP. CONCLUSION: This review systematically summarizes the multiple roles of the SASP in atherosclerosis and can contribute to the exploration of new therapeutic opportunities.

Long non-coding RNA H19 promotes leukocyte inflammation in ischemic stroke by targeting the miR-29b/C1QTNF6 axis.

AIMS: Inflammatory processes induced by leukocytes are crucially involved in the pathophysiology of acute ischemic stroke. This study aimed to elucidate the inflammatory mechanism of long non-coding RNA (lncRNA) H19-mediated regulation of C1q and tumor necrosis factor 6 (C1QTNF6) by sponging miR-29b in leukocytes during ischemic stroke. METHODS: H19 and miR-29b expression in leukocytes of patients with ischemic stroke and rats with middle cerebral artery occlusion were measured by real-time polymerase chain reaction. H19 siRNA and miR-29b antagomir were used to knock down H19 and miR-29b, respectively. We performed in vivo and in vitro experiments to determine the impact of H19 and miR-29b on C1QTNF6 expression in leukocytes after ischemic injury. RESULTS: H19 and C1QTNF6 upregulation, as well as miR-29b downregulation, was detected in leukocytes of patients with stroke. Moreover, miR-29b could bind C1QTNF6 mRNA and repress its expression, while H19 could sponge miR-29b to maintain C1QTNF6 expression. C1QTNF6 overexpression promoted the release of IL-1ß and TNF-α in leukocytes, further exacerbated blood-brain barrier disruption, and aggravated the cerebral ischemic injury. CONCLUSIONS: Our findings confirm that H19 promotes leukocyte inflammation by targeting the miR-29b/C1QTNF6 axis in cerebral ischemic injury.

Tribological Performance of Diamond Films with Different Roughnesses of Silicon Nitride Substrates and Carbon Source Concentrations.

Diamond films were deposited on silicon nitride (Si3N4) substrates with three different roughnesses using the method of hot-filament chemical vapor deposition (HFCVD). The tribological properties of the film were studied by changing the deposition time, deposition distance, and methane (CH4) concentration. The friction coefficient, delamination threshold load, and wear rate of the diamond films were tested and calculated using the reciprocating friction and wear test under dry friction conditions. The results show that, when the deposition time is 12 h, the bonding force of the film is the lowest and the friction coefficient is the largest (0.175, 0.438, and 0.342); the deposition distance has little effect on the friction performance. The friction coefficients (0.064, 0.107, and 0.093) of nano-diamond films (NCD) prepared at a 40 sccm CH4 concentration are smaller than those of micro-diamond films (MCD) prepared at a 16 sccm CH4 concentration. The load thresholds before delamination of Ra 0.4 µm substrate diamond film are as high as 40 N and 80 N, whereas the diamond films deposited on Ra 0.03 µm substrates have lower wear rates (4.68 × 10-4 mm3/mN, 5.34 × 10-4 mm3/mN) and low friction coefficients (0.119, 0.074, 0.175, and 0.064). Within a certain load range, the deposition of a diamond film on a Ra 0.03 µm Si3N4 substrate significantly reduces the friction coefficient and improves wear resistance. Diamond film can improve the friction performance of a workpiece and prolong its service life.