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The permeability of different strength grades of submerged non-dispersible concrete with different granulated slag admixtures in a saline soil environment simulated by different erosion solutions was investigated. The variation patterns of the chloride ion diffusion coefficient and pore characteristics were tested using NEL and MIP. The microscopic morphology of the specimens in different erosion environments and with slag doping was observed using SEM. The results showed that the impermeability of concrete in sulfate and complex salt environments was significantly reduced. The resistance of concrete to chloride ion penetration increased with the increase in strength grade, and the Cl− diffusion coefficient of C35 was 5–30% lower than those of C30 and C25 underwater non-dispersible concrete at 360 d. Meanwhile, the admixture of granulated blast-furnace slag optimized the pore size distribution and improved the matrix compactness and permeability. [ABSTRACT FROM AUTHOR]

Social isolation is a risk factor for multiple mood disorders. Specifically, social isolation can remodel the brain, causing behavioral abnormalities, including sociability impairments. Here, we investigated social behavior impairment in mice following chronic social isolation stress (CSIS) and conducted a screening of susceptible brain regions using functional readouts. CSIS enhanced synaptic inhibition in the anterior cingulate cortex (ACC), particularly at inhibitory synapses of cholecystokinin (CCK)-expressing interneurons. This enhanced synaptic inhibition in the ACC was characterized by CSIS-induced loss of presynaptic cannabinoid type-1 receptors (CB1Rs), resulting in excessive axonal calcium influx. Activation of CCK-expressing interneurons or conditional knockdown of CB1R expression in CCK-expressing interneurons specifically reproduced social impairment. In contrast, optogenetic activation of CB1R or administration of CB1R agonists restored sociability in CSIS mice. These results suggest that the CB1R may be an effective therapeutic target for preventing CSIS-induced social impairments by restoring synaptic inhibition in the ACC. [Display omitted] • CSIS enhances local inhibition in the ACC via influencing CCK-expressing interneurons • Excessive GABA release causally contributes to CSIS-induced social impairments • Loss of presynaptic CB1R in CCK-expressing interneurons drives inhibitory enhancement • Targeting CB1R corrects CSIS-induced social avoidance Guo et al. uncover cell-specific mechanisms in the anterior cingulate cortex that underlie the social impairments resulting from chronic social isolation and reveal a potential therapeutic strategy targeting the cannabinoid type-1 receptors (CB1Rs) to correct social avoidance. [ABSTRACT FROM AUTHOR]

A survey of the literature related to theoretical and experimental studies on stick–slip vibration in oilwell drillstring is carried out in this study. It aims to explain key concepts and present the existing methods for studying this phenomenon. After briefly describing the stick–slip vibration related problems, theoretical models for such phenomenon are discussed including both coupled and uncoupled models. Discussion for experimental investigations including both laboratory and field tests are hereinafter addressed. This study aims to summarize the literature related to the stick–slip vibration, and help researchers in understanding and suppressing such phenomenon. [ABSTRACT FROM AUTHOR]

Drilling is being used to access ever-deeper oil and gas reservoirs, thereby presenting various challenges to the design and operation of down-hole tools. Slip inserts are suspension devices that are used to lower the drill pipe into the borehole and lift it to the wellhead, and their performance determines the extended depth of the borehole. In this paper, based on the field and laboratory test of the slip system, parameter sensitivity analysis is applied to the performance of a slip insert to guide the design of the latter. First, a mechanical model is developed of the drill pipe with the slip insert acting on it, and the stress acting on the drill pipe is analyzed theoretically by regarding the drill pipe as a thick-walled cylinder. Next, a numerical model is established to investigate how the slip-insert structure influences the drill-pipe stress, wherein the drill-pipe diameter is 5″ and the axial load is 180 tons. Finally, the results of a series of numerical simulations are presented. For the present slip insert and drill pipe, the optimum slip-insert parameter values are a front-rake angle of 70°, a back-rake angle of 30°, a tooth height of 2 mm, and zero chamfer. [ABSTRACT FROM AUTHOR]

Hippocampal SIRT1 dysfunction and gene variation have previously been found potentially involved in depressive and anxiety disorders. However, the exact role of SIRT1 in post-traumatic stress disorder (PTSD) is not well understood. Here, we employed multiple genetic and pharmacological approaches targeting SIRT1 to verify the effects of SIRT1 on SPS-induced PTSD-like behaviors and its potential cellular and molecular mechanisms. We first demonstrated that Sirt1 knockout mice showed milder PTSD-like behavior after single prolonged stress (SPS) induction than wild type mice. Moreover, the expression of SIRT1 in the ventral CA1 (vCA1) region of hippocampus showed no significant changes following SPS induction, but the activity of SIRT1 enzyme was significantly increased post-SPS. Osmotic administration of EX527 in vCA1, a SIRT1 inhibitor, was shown to normalize the SIRT1 activity in SPS mice. Mechanically, EX527 rescued the acetylation of helix-loop-helix transcription factor 2 (NHLH2) and transcriptionally inhibited the increase of MAO-A expression in the vCA1, which thus suppressed the decomposition of the neurotransmitter serotonin into 5-hydroxydoleacetic acid (5-HIAA). Morphologically, Golgi staining showed that EX527 treatment improved the abnormal neuronal structure plasticity in the vCA1 region after SPS, including reversing the atrophic dendrites and the decreased dendritic spines. Finally, SIRT1 inhibitor effectively alleviated fear conditioning responses and anxiety-like behaviors. Our study first demonstrated that the development of PTSD-like behaviors was causatively related to the abnormal increase of SIRT1 activity in the ventral hippocampal CA1 region. And we also provided evidence that SIRT1 inhibition might exert therapeutic effects on PTSD by maintaining serotonin homeostasis through transcriptional inhibition of MAO-A, and thereby remodeled synaptic plasticity in the vCA1 region. • Sirt1 deletion increased resistance to PTSD-like stress stimuli in mice. • SIRT1 activity in ventral CA1 was negatively involved with PTSD. • EX527 protected 5-HT homeostasis in ventral CA1 of PTSD mice via inhibiting MAO-A. • EX527 remodeled synaptic plasticity in the ventral CA1 of PTSD mice. • SIRT1 inhibition alleviated PTSD symptoms in mice. [ABSTRACT FROM AUTHOR]

Abstract Mitochondria, as primary energy generators and Ca2+ biosensor, are dynamically coupled to neuronal activities, and thus play a role in neuroplasticity. Here we report that respiratory neuroplasticity induced by daily acute intermittent hypoxia (dAIH) evoked adaptive changes in the ultrastructure and postsynaptic distribution of mitochondria in the pre-Bötzinger complex (pre-BötC). The metabolic marker of neuronal activity, cytochrome c oxidase (CO), and dendritic mitochondria were examined in pre-BötC neurons of adult Sprague-Dawley rats preconditioned with dAIH, which is known to induce long-term facilitation (LTF) in respiratory neural activities. We performed neurokinin 1 receptor (NK1R) pre-embedding immunocytochemistry to define pre-BötC neurons, in combination with CO histochemistry, to depict ultrastructural alterations and CO activity in dendritic mitochondria. We found that the dAIH challenge significantly increased CO activity in pre-BötC neurons. Darkly CO-reactive mitochondria at postsynaptic sites in the dAIH group were much more prevalent than those in the normoxic control. In addition, the length and area of mitochondria were significantly increased in the dAIH group, implying a larger surface area of cristae for ATP generation. There was a fine, structural remodeling, notably enlarged and branching mitochondria or tapered mitochondria extending into dendritic spines. Mitochondrial cristae were mainly in parallel-lamellar arrangement, indicating a high efficiency of energy generation. Moreover, flocculent or filament-like elements were noted between the mitochondria and the postsynaptic membrane. These morphological evidences, together with increased CO activity, demonstrate that dendritic mitochondria in the pre-BötC responded dynamically to respiratory plasticity. Hence, plastic neuronal changes are closely coupled to active mitochondrial bioenergetics, leading to enhanced energy production and Ca2+ buffering that may drive the LTF expression. Highlights • dAIH challenge significantly increased CO activities in the pre-BötC. • Darkly CO reactive mitochondria were increased, and more in close proximity to synapses in dendrites after dAIH exposure. • The mean length and area of mitochondria were significantly increased in the dAIH group. • Mitochondria manifested fine structural remodeling, including locally enlarged or branchingand extending into the spines. [ABSTRACT FROM AUTHOR]

With the utilization of the hand-held equipment, Fourier transform infrared (FT-IR) spectroscopy is a promising analytical technique to minimize the time cost for the chemical identification of herbal materials. This research examines the feasibility of the hand-held FT-IR spectrometer for the on-site testing of herbal materials, using Lonicerae Japonicae Flos (LJF) and Lonicerae Flos (LF) as examples. Correlation-based linear discriminant models for LJF and LF are established based on the benchtop and hand-held FT-IR instruments. The benchtop FT-IR models can exactly recognize all articles of LJF and LF. Although a few LF articles are misjudged at the sub-class level, the hand-held FT-IR models are able to exactly discriminate LJF and LF. As a direct and label-free analytical technique, FT-IR spectroscopy has great potential in the rapid and automatic chemical identification of herbal materials either in laboratories or in fields. This is helpful to prevent the spread and use of adulterated herbal materials in time. [ABSTRACT FROM AUTHOR]

As an important tool for tripping of a drill-string, a drill-pipe (DP)-slip system directly affects both the service life of a DP and the target depth it can reach. In this paper, a finite element (FE) model programmed in ABAQUS is used to simulate interactions within a DP-slip system. For this model, materials, geometric dimensions, loads, and boundary conditions were determined from an actual DP-slip system. A special attention has been paid on the stress field of the slip insert and the DP focusing on the geometric parameter optimization of the slip insert with regards to the stress distribution, wherein factors like a longitudinal groove number in slip insert, a number of slip inserts, and a number of row spacing of slip inserts are considered. Numerical results show that the circumferential stress distribution and stress distribution in the direction of DP axis change for both the DP and slip insert and that the stresses of the inner surfaces are higher than that of the outer surfaces. Effects of geometric parameters of the slip insert on the stress distributions of both DP and slip insert are studied and the corresponding optimized values are obtained, which can be used when designing slip insert tools. • A finite element model was applied to analyze stresses within a DP-slip system. • A geometric optimization of slip inserts and row spacing was undertaken to minimize stresses. • The results suggest that stresses on the inner surfaces are higher than on the outer surfaces. [ABSTRACT FROM AUTHOR]

As an important tool for tripping of a drill-string, a drill-pipe (DP)-slip system directly affects both the service life of a DP and the target depth it can reach. In this paper, a finite element (FE) model programmed in ABAQUS is used to simulate interactions within a DP-slip system. For this model, materials, geometric dimensions, loads, and boundary conditions were determined from an actual DP-slip system. A special attention has been paid on the stress field of the slip insert and the DP focusing on the geometric parameter optimization of the slip insert with regards to the stress distribution, wherein factors like a longitudinal groove number in slip insert, a number of slip inserts, and a number of row spacing of slip inserts are considered. Numerical results show that the circumferential stress distribution and stress distribution in the direction of DP axis change for both the DP and slip insert and that the stresses of the inner surfaces are higher than that of the outer surfaces. Effects of geometric parameters of the slip insert on the stress distributions of both DP and slip insert are studied and the corresponding optimized values are obtained, which can be used when designing slip insert tools. • A finite element model was applied to analyze stresses within a DP-slip system. • A geometric optimization of slip inserts and row spacing was undertaken to minimize stresses. • The results suggest that stresses on the inner surfaces are higher than on the outer surfaces. [ABSTRACT FROM AUTHOR]

In our previous study, we demonstrated that fibroblast growth factor 2 (FGF2) administration alleviated posttraumatic stress disorder (PTSD) symptoms via an “astrocyte-related” mechanism. We further investigated the changes in the astrocytic glutamate transporters GLAST and GLT-1 and in JAK/STAT3 signaling (which is involved in astrocyte activation and GLAST/GLT-1 function) in single prolonged stress (SPS) model rats. High-performance liquid chromatography (HPLC), Western blot and immunohistochemistry analyses revealed a significant SPS-induced increase in the concentration of glutamate in the cerebrospinal fluid and decrease in GLAST/GLT-1 expression and JAK/STAT3 signaling. Treatment with FGF2 significantly alleviated GLAST/GLT-1 dysfunction, JAK/STAT3 signaling inhibition, and the behavioral abnormalities. The administration of the JAK/STAT pathway inhibitor AG490 blocked the effects of FGF2 on PTSD symptoms, astrocyte activation, and GLAST, but not GLT-1, expression in vivo and in vitro . Our findings suggest that astrocytic JAK/STAT signaling is associated with SPS-induced GLAST dysfunction and that FGF2 protects against PTSD symptoms by restoring astrocytic glutamate uptake via the JAK/STAT signaling pathway. [ABSTRACT FROM AUTHOR]

Abstract: Conducting polymers have been widely used in biomedical applications such as biosensors and tissue engineering but their non-degradability still poses a limitation. Therefore, great attention has been directed toward the recently developed degradable and electrically conductive polymers (DECPs). The different strategies for synthesis of degradable and conducting polymers containing conducting oligomers are summarized and discussed here as well as the influence of different macromolecular architectures such as linear, star-shaped, hyperbranched and cross-linked DECPs. Blends and composites of biodegradable and conductive polymers are also discussed. The developing trends and challenges with the design of DECPs are also presented. [Copyright &y& Elsevier]

Functionalizing aliphatic polyester hydrogels with an aniline oligomer is a means of achieving electrically conductive and degradable hydrogels. To lower the aniline oligomer content while maintaining a high conductivity and to overcome the acidic degradation product from polylactide reported in our previous work, a series of electroactive and degradable hydrogels based on polycaprolactone (PCL) hydrogels and carboxyl-capped aniline pentamer (CCAP) were synthesized by a simple coupling reaction at room temperature. The reaction was carried out between the hydroxyl groups of hydroxyethylmethacrylate in a photopolymerized glycidyl methacrylate (GMA)-functionalized PCL-poly(ethylene glycol)-PCL degradable network and carboxyl group of CCAP, using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide as water-condensing agent and 4-dimethylaminopyridine as catalyst. The electroactivity of the hydrogels was verified by cyclic voltammetry, which showed three pairs of redox peaks. The electrical conductivities and swelling ratios of these hydrogels were controlled by the CCAP content, the poly(ethylene glycol) molecular weight in the macromer, and the crosslinking density of the hydrogels. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011 [ABSTRACT FROM AUTHOR]

Abstract: A novel copolymer P(CS–Ma–DMAEMA) was synthesized with chitosan (CS), maleic anhydride (Ma) and 2-(dimethylamino)ethyl methacrylate (DMAEMA) by grafting and copolymerization. The copolymer obtained was analyzed by FT-IR, 1H NMR and UV, and the molecular weight and polydispersity were determined by gel permeation chromatography (GPC). The average size and distribution of copolymer micelles were determined by dynamic light scattering (DLS). Their aqueous solution properties and controlled coenzyme A delivery were also studied. It was found that the copolymer had temperature sensitivity and pH sensitivity. The factors affecting release behavior, such as concentration, pH and temperature were discussed in this paper. The higher concentration of the copolymer aqueous solution absorbed more coenzyme A than the lower one. The increasing temperature accelerated the drug release from the copolymer. The pH of the copolymer solution had significant impact on the release of coenzyme A. The results suggested that the novel copolymer could be used as drug delivery carrier. [Copyright &y& Elsevier]

Non-compressible hemorrhage control is a big challenge in both civilian life and the battlefield, causing a majority of deaths among all traumatic injury mortalities. Unexpected non-compressible bleeding not only happens in pre-hospital situations but also leads to a high risk of death during surgical processes throughout in-hospital treatment. Hemostatic materials for pre-hospital treatment or surgical procedures for non-compressible hemorrhage control have drawn more and more attention in recent years and several commercialized products have been developed. However, these products have all shown non-negligible limitations and researchers are focusing on developing more effective hemostatic materials for non-compressible hemorrhage control. Different hemostatic strategies (physical, chemical and biological) have been proposed and different forms (sponges/foams, sealants/adhesives, microparticles/powders and platelet mimics) of hemostatic materials have been developed based on these strategies. A summary of the requirements, state-of-the-art studies and commercial products of non-compressible hemorrhage-control materials is provided in this review with particular attention on the advantages and limitations of their emerging forms, to give a clear understanding of the progress that has been made in this area and the promising directions for future generations. [ABSTRACT FROM AUTHOR]

Background: Phenylalanine ammonia-lyase (PAL) serves as a key gateway enzyme, bridging primary metabolism and the phenylpropanoid pathway, and thus playing an indispensable role in flavonoid, anthocyanin and lignin biosynthesis. PAL gene families have been extensively studied across species using public genomes. However, a comprehensive exploration of PAL genes in Epimedium species, especially those involved in prenylated flavonol glycoside, anthocyanin, or lignin biosynthesis, is still lacking. Moreover, an in-depth investigation into PAL gene family evolution is warranted. Results: Seven PAL genes (EpPAL1-EpPAL7) were identified. EpPAL2 and EpPAL3 exhibit low sequence identity to other EpPALs (ranging from 61.09 to 64.38%) and contain two unique introns, indicating distinct evolutionary origins. They evolve at a rate ~ 10 to ~ 54 times slower compared to EpPAL1 and EpPAL4-7, suggesting strong purifying selection. EpPAL1 evolved independently and is another ancestral gene. EpPAL1 formed EpPAL4 through segmental duplication, which lead to EpPAL5 and EpPAL6 through tandem duplications, and EpPAL7 through transposed duplication, shaping modern EpPALs. Correlation analysis suggests EpPAL1, EpPAL2 and EpPAL3 play important roles in prenylated flavonol glycosides biosynthesis, with EpPAL2 and EpPAL3 strongly correlated with both Epimedin C and total prenylated flavonol glycosides. EpPAL1, EpPAL2 and EpPAL3 may play a role in anthocyanin biosynthesis in leaves. EpPAL2, EpPAL3, EpPAL6, and EpPAL7 might be engaged in anthocyanin production in petals, and EpPAL2 and EpPAL3 might also contribute to anthocyanin synthesis in sepals. Further experiments are needed to confirm these hypotheses. Novel insights into the evolution of PAL gene family suggest that it might have evolved from a monophyletic group in bryophytes to large-scale sequence differentiation in gymnosperms, basal angiosperms, and Magnoliidae. Ancestral gene duplications and vertical inheritance from gymnosperms to angiosperms likely occurred during PAL evolution. Most early-diverging eudicotyledons and monocotyledons have distinct histories, while modern angiosperm PAL gene families share similar patterns and lack distant gene types. Conclusions: EpPAL2 and EpPAL3 may play crucial roles in biosynthesis of prenylated flavonol glycosides and anthocyanins in leaves and flowers. This study provides novel insights into PAL gene family evolution. The findings on PAL genes in E. pubescens will aid in synthetic biology research on prenylated flavonol glycosides production. [ABSTRACT FROM AUTHOR]

Chaperonins Hsp60s are required for cellular vitality by assisting protein folding in an ATP-dependent mechanism. Although conserved, the human mitochondrial mHsp60 exhibits molecular characteristics distinct from the E. coli GroEL, with different conformational assembly and higher subunit association dynamics, suggesting a different mechanism. We previously found that the pathological mutant mHsp60V72I exhibits enhanced subunit association stability and ATPase activity. To provide structural explanations for the V72I mutational effects, here we determined a cryo-EM structure of mHsp60V72I. Our structural analysis combined with molecular dynamic simulations showed mHsp60V72I with increased inter-subunit interface, binding free energy, and dissociation force, all contributing to its enhanced subunit association stability. The gate to the nucleotide-binding (NB) site in mHsp60V72I mimicked the open conformation in the nucleotide-bound state with an additional open channel leading to the NB site, both promoting the mutant's ATPase activity. Our studies highlight the importance of mHsp60's characteristics in its biological function. [Display omitted] • The mHsp60 V72I mutation is linked to an increased subunit stability and ATPase activity • Cryo-EM structure and MD simulations explain the observed V72I allostery • Mutant's nucleotide-binding mimics the open conformation found in the NB-bound state • Mutant has a higher binding energy, dissociation force and smaller size than wildtype Syed et al. utilized biochemical characterization, cryo-EM, and molecular dynamics simulation to study the pathological V72I mutation in mitochondrial chaperonin Hsp60. They discovered that this mutation, although not located at the subunit interface or ATP-binding site, enhances subunit association and ATPase activity. [ABSTRACT FROM AUTHOR]

Eomecon chionantha Hance, an endemic species in China, has a long medical history in Chinese ethnic minority medicine and is known for its anti-inflammatory and analgesic effects. However, studies of E. chionantha are lacking. In this study, we investigated the characteristics of the E. chionantha chloroplast genome and determined the taxonomic position of E. chionantha in Papaveraceae via phylogenetic analysis. In addition, we determined molecular markers to identify E. chionantha at the molecular level by comparing the chloroplast genomes of E. chionantha and its closely related species. The complete chloroplast genomic information indicated that E. chionantha chloroplast DNA (178,808 bp) contains 99 protein-coding genes, 8 rRNAs, and 37 tRNAs. Meanwhile, we were able to identify a total of 54 simple sequence repeats through our analysis. Our findings from the phylogenetic analysis suggest that E. chionantha shares a close relationship with four distinct species, namely Macleaya microcarpa, Coreanomecon hylomeconoides, Hylomecon japonica, and Chelidonium majus. Additionally, using the Kimura two-parameter model, we successfully identified five hypervariable regions (ycf4-cemA, ycf3-trnS-GGA, trnC-GCA-petN, rpl32-trnL-UAG, and psbI-trnS-UGA). To the best of our knowledge, this is the first report of the complete chloroplast genome of E. chionantha, providing a scientific reference for further understanding of E. chionantha from the perspective of the chloroplast genome and establishing a solid foundation for the future identification, taxonomic determination and evolutionary analysis of this species. [ABSTRACT FROM AUTHOR]

Phosphorus, a crucial macronutrient essential for plant growth and development. Due to widespread phosphorus deficiency in soils, phosphorus deficiency stress has become one of the major abiotic stresses that plants encounter. Despite the evolution of adaptive mechanisms in plants to address phosphorus deficiency, the specific strategies employed by species such as Epimedium pubescens remain elusive. Therefore, this study observed the changes in the growth, physiological reponses, and active components accumulation in E. pubescensunder phosphorus deficiency treatment, and integrated transcriptome and miRNA analysis, so as to offer comprehensive insights into the adaptive mechanisms employed by E. pubescens in response to phosphorus deficiency across various stages of phosphorus treatment. Remarkably, our findings indicate that phosphorus deficiency induces root growth stimulation in E. pubescens, while concurrently inhibiting the growth of leaves, which are of medicinal value. Surprisingly, this stressful condition results in an augmented accumulation of active components in the leaves. During the early stages (30 days), leaves respond by upregulating genes associated with carbon metabolism, flavonoid biosynthesis, and hormone signaling. This adaptive response facilitates energy production, ROS scavenging, and morphological adjustments to cope with short-term phosphorus deficiency and sustain its growth. As time progresses (90 days), the expression of genes related to phosphorus cycling and recycling in leaves is upregulated, and transcriptional and post-transcriptional regulation (miRNA regulation and protein modification) is enhanced. Simultaneously, plant growth is further suppressed, and it gradually begins to discard and decompose leaves to resist the challenges of long-term phosphorus deficiency stress and sustain survival. In conclusion, our study deeply and comprehensively reveals adaptive strategies utilized by E. pubescens in response to phosphorus deficiency, demonstrating its resilience and thriving potential under stressful conditions. Furthermore, it provides valuable information on potential target genes for the cultivation of E. pubescens genotypes tolerant to low phosphorus. [ABSTRACT FROM AUTHOR]

Highlights: The design and application of conductive biomaterials for wound healing are comprehensively reviewed, including versatile conductive agents, the various forms of conductive wound dressings, and different in vivo applications. Three main strategies of which conductive biomaterials realizing their applications in wound healing and skin tissue engineering are discussed. The challenges and perspectives in designing multifunctional conductive biomaterials and further clinical translation are proposed. Conductive biomaterials based on conductive polymers, carbon nanomaterials, or conductive inorganic nanomaterials demonstrate great potential in wound healing and skin tissue engineering, owing to the similar conductivity to human skin, good antioxidant and antibacterial activities, electrically controlled drug delivery, and photothermal effect. However, a review highlights the design and application of conductive biomaterials for wound healing and skin tissue engineering is lacking. In this review, the design and fabrication methods of conductive biomaterials with various structural forms including film, nanofiber, membrane, hydrogel, sponge, foam, and acellular dermal matrix for applications in wound healing and skin tissue engineering and the corresponding mechanism in promoting the healing process were summarized. The approaches that conductive biomaterials realize their great value in healing wounds via three main strategies (electrotherapy, wound dressing, and wound assessment) were reviewed. The application of conductive biomaterials as wound dressing when facing different wounds including acute wound and chronic wound (infected wound and diabetic wound) and for wound monitoring is discussed in detail. The challenges and perspectives in designing and developing multifunctional conductive biomaterials are proposed as well. [ABSTRACT FROM AUTHOR]

Background and Purpose: Quercetin is a well‐known plant flavonoid with neuroprotective properties. Earlier work suggested it may relieve psychiatric disorders, cognition deficits and memory dysfunction through anti‐oxidant and/or radical scavenging mechanisms. In addition, quercetin modulated the physiological function of some ion channels. However, the detailed ionic mechanisms of the bioeffects of quercetin remain unknown. Experimental Approach Effects of quercetin on neuronal activities in the prefrontal cortex (PFC) and its ionic mechanisms were analysed by calcium imaging using mice bearing a green fluorescent protein, calmodulin, and M13 fusion protein and patch clamp in acute brain slices from C57BL/6 J mice and in HEK 293 cells. The possible ionic mechanism of action of quercetin on D‐amphetamine‐induced manic‐like effects in mice was explored with c‐fos staining and the open field behaviour test. Key Results: Quercetin reduced calcium influx triggered by PFC pyramidal neuronal activity. This effect involved increasing the rheobase of neuronal firing through decreasing membrane resistance following quercetin treatment. Spadin, a blocker of TREK‐1 potassium channels, also blocked the effect of quercetin on the membrane resistance and neuronal firing. Further, spadin blocked the neuroprotective effects of quercetin. The effects of quercetin on TREK‐1 channels could be mimicked by GF109203X, a protein kinase C inhibitor. In vivo, injection of quercetin relieved the manic hyperlocomotion in mice, induced by D‐amphetamine. This action was partly alleviated by spadin. Conclusion and Implications: TREK‐1 channels are a novel target for quercetin, by inhibiting PKC. This action could contribute to both the neuroprotective and anti‐manic‐like effects. [ABSTRACT FROM AUTHOR]

Degradable biomedical elastomers (DBE), characterized by controlled biodegradability, excellent biocompatibility, tailored elasticity, and favorable network design and processability, have become indispensable in tissue repair. This review critically examines the recent advances of biodegradable elastomers for tissue repair, focusing mainly on degradation mechanisms and evaluation, synthesis and crosslinking methods, microstructure design, processing techniques, and tissue repair applications. The review explores the material composition and cross-linking methods of elastomers used in tissue repair, addressing chemistry-related challenges and structural design considerations. In addition, this review focuses on the processing methods of two- and three-dimensional structures of elastomers, and systematically discusses the contribution of processing methods such as solvent casting, electrostatic spinning, and three-/four-dimensional printing of DBE. Furthermore, we describe recent advances in tissue repair using DBE, and include advances achieved in regenerating different tissues, including nerves, tendons, muscle, cardiac, and bone, highlighting their efficacy and versatility. The review concludes by discussing the current challenges in material selection, biodegradation, bioactivation, and manufacturing in tissue repair, and suggests future research directions. This concise yet comprehensive analysis aims to provide valuable insights and technical guidance for advances in DBE for tissue engineering. [ABSTRACT FROM AUTHOR]

There is still an urgent need to develop hydrogels with intelligent antibacterial ability to achieve on-demand treatment of infected wounds and accelerate wound healing by improving the regeneration microenvironment. We proposed a strategy of hydrogel wound dressing with bacteria-responsive self-activating antibacterial property and multiple nanozyme activities to remodel the regeneration microenvironment in order to significantly promote infected wound healing. Specifically, pH-responsive H2O2 self-supplying composite nanozyme (MSCO) and pH/enzyme-sensitive bacteria-responsive triblock micelles encapsulated with lactate oxidase (PPEL) were prepared and encapsulated in hydrogels composed of L-arginine-modified chitosan (CA) and phenylboronic acid-modified oxidized dextran (ODP) to form a cascade bacteria-responsive self-activating antibacterial composite hydrogel platform. The hydrogels respond to multifactorial changes of the bacterial metabolic microenvironment to achieve on-demand antibacterial and biofilm eradication through transformation of bacterial metabolites, and chemodynamic therapy enhanced by nanozyme activity in conjunction with self-driven nitric oxide (NO) release. The composite hydrogel showed 'self-diagnostic' treatment for changes in the wound microenvironment. Through self-activating antibacterial therapy in the infection stage to self-adaptive oxidative stress relief and angiogenesis in the post-infection stage, it promotes wound closure, accelerates wound collagen deposition and angiogenesis, and completely improves the microenvironment of infected wound regeneration, which provides a new method for the design of intelligent wound dressings. [ABSTRACT FROM AUTHOR]

Impaired extinction of fear memory is one of the most common symptoms in post‐traumatic stress disorder (PTSD), with limited therapeutic strategies due to the poor understanding of its underlying neural substrates. In this study, functional screening is performed and identified hyperactivity in the mediodorsal thalamic nucleus (MD) during fear extinction. Furthermore, the encoding patterns of the hyperactivated MD is investigated during persistent fear responses using multiple machine learning algorithms. The anterior cingulate cortex (ACC) is also identified as a functional downstream region of the MD that mediates the extinction of fear memory. The thalamocortical circuit is comprehensively analyzed and found that the MD‐ACC parvalbumin interneurons circuit is preferentially enhanced in PTSD mice, disrupting the local excitatory and inhibitory balance. It is found that decreased phosphorylation of the Kv3.2 channel contributed to the hyperactivated MD, primarily to the malfunctioning thalamocortical circuit. Using a lipid nanoparticle‐based RNA therapy strategy, channelopathy is corrected via a methoxylated siRNA targeting the protein phosphatase 6 catalytic subunit and restored fear memory extinction in PTSD mice. These findings highlight the function of the thalamocortical circuit in PTSD‐related impaired extinction of fear memory and provide therapeutic insights into Kv3.2‐targeted RNA therapy for PTSD. [ABSTRACT FROM AUTHOR]

This article explores the development of sensing materials and antibacterial materials that are responsive to antibiotics. Specifically, the use of supramolecular materials, particularly those based on macrocycles, has shown promise in detecting antibiotics and creating antibacterial materials. The article presents examples of macrocycles that have improved the detection responses and antibacterial effects of antibiotics. However, most macrocycles still rely on complex and time-consuming techniques for antibiotic detection. The article introduces a water-soluble tetraphenylene-based octacationic cage that can recognize and detect five β-lactam antibiotics, displaying fluorescence and an induced positive CD signal. The cage is non-toxic and exhibits good antimicrobial activity when combined with antibiotics. The authors propose that this cage could be used as a single-molecular platform for antibiotic detection and delivery while maintaining their antibacterial properties. This research offers new approaches for antibiotic detection and the creation of antimicrobial materials. [Extracted from the article]

Geum japonicum (Rosaceae) has been widely used in China as a traditional herbal medicine due to its high economic and medicinal value. However, the appearance of Geum species is relatively similar, making identification difficult by conventional phenotypic methods, and the studies of genomics and species evolution are lacking. To better distinguish the medicinal varieties and fill this gap, we carried out relevant research on the chloroplast genome of G. japonicum. Results show a typical quadripartite structure of the chloroplast genome of G. japonicum with a length of 156,042 bp. There are totally 131 unique genes in the genome, including 87 protein-coding genes, 36 tRNA genes, and 8 rRNA genes, and there were also 87 SSRs identified and mostly mononucleotide Adenine-Thymine. We next compared the plastid genomes among four Geum species and obtained 14 hypervariable regions, including ndhF, psbE, trnG-UCC, ccsA, trnQ-UUG, rps16, psbK, trnL-UAA, ycf1, ndhD, atpA, petN, rps14, and trnK-UUU. Phylogenetic analysis revealed that G. japonicum is most closely related to Geum aleppicum, and possibly has some evolutionary relatedness with an ancient relic plant Taihangia rupestris. This research enriched the genome resources and provided fundamental insights for evolutionary studies and the phylogeny of Geum. [ABSTRACT FROM AUTHOR]

Background: As the main pathological basis for various cardiovascular and cerebrovascular diseases, atherosclerosis has become one of the leading causes of death and disability worldwide. Emerging evidence has suggested that Rho GTPase Rnd3 plays an indisputable role in cardiovascular diseases, although its function in atherosclerosis remains unclear. Here, we found a significant correlation between Rnd3 and pyroptosis of aortic endothelial cells (ECs). Methods: ApoeKO mice were utilized as a model for atherosclerosis. Endothelium‐specific transgenic mice were employed to disrupt the expression level of Rnd3 in vivo. Mechanistic investigation of the impact of Rnd3 on endothelial cell pyroptosis was carried out using liquid chromatography tandem mass spectrometry (LC‐MS/MS), co‐immunoprecipitation (Co‐IP) assays, and molecular docking. Results: Evidence from gain‐of‐function and loss‐of‐function studies denoted a protective role for Rnd3 against ECs pyroptosis. Downregulation of Rnd3 sensitized ECs to pyroptosis under oxidized low density lipoprotein (oxLDL) challenge and exacerbated atherosclerosis, while overexpression of Rnd3 effectively prevented these effects. LC‐MS/MS, Co‐IP assay, and molecular docking revealed that Rnd3 negatively regulated pyroptosis signaling by direct interaction with the ring finger domain of tumor necrosis factor receptor‐associated factor 6 (TRAF6). This leads to the suppression of K63‐linked TRAF6 ubiquitination and the promotion of K48‐linked TRAF6 ubiquitination, inhibiting the activation of NF‐κB and promoting the degradation of TRAF6. Moreover, TRAF6 knockdown countered Rnd3 knockout‐evoked exacerbation of EC pyroptosis in vivo and vitro. Conclusions: These findings establish a critical functional connection between Rnd3 and the TRAF6/NF‐κB/NLRP3 signaling pathway in ECs, indicating the essential role of Rnd3 in preventing pyroptosis of ECs. [ABSTRACT FROM AUTHOR]

Wound with drug‐resistant bacterial infections has become a serious challenge for the healthcare system, and designing wound dressing to self‐adapt to the need of different stage of wound healing remains challenging. Herein, self‐adaptive wound dressings with multiple stimuli‐responsiveness and antibacterial activity are developed. Specifically, MoS2 carrying a reactive oxygen species (ROS) responsive nitric oxide (NO) release precursor L‐arginine (MSPA) is designed and incorporated into carboxymethyl chitosan/poly(N‐isopropylacrylamide) based cryogels (CMCS/PNIPAM) with multiple responsiveness (pH, near infrared (NIR), and temperature) to form self‐adaptive antibacterial cryogels that adapt to the therapeutic needs of different stages in infected wound healing. In response to the slightly acidic environment of bacterial infection, the cryogels assist the bacterial capture capacity through acid‐triggered protonation behavior, and effectively enhance the photodynamic antibacterial efficiency. Controllable on‐demand delivery of ROS, NO, and remote management of infected biofluid are achieved with NIR light as a trigger switch. The multiple stimuli‐responsive nanozyme‐based cryogels efficiently eliminate MRSA bacterial biofilm through NO assisted photodynamicand photothermal therapy (PDT&PTT). The multiple enzyme‐like activities of the cryogels effectively relieved oxidative damage. Notably, these cryogels effectively reduce wound infection, alleviated oxidative stress, and accelerate collagen deposition and angiogenesis in infected wounds, indicating that multiple stimuli‐responsive self‐adaptive wound dressings provide new ideas for infected wound treatment. [ABSTRACT FROM AUTHOR]

Key message: Key genes involved in metabolism and signalling of abscisic acid and gibberellins during Epimedium pseudowushanense B.L.Guo seed morphophysiological dormancy release were identified using phytochemistry, transcriptomics, and bioinformatic methods.Abstract: The molecular mechanism of seed morphophysiological dormancy of Epimedium pseudowushanense B.L.Guo. remains largely unknown. The endogenous abscisic acid (ABA) and gibberellin (GA) content of E. pseudowushanense seeds at three developmental stages were quantitatively determined. The results showed the levels of ABA in E. pseudowushanense seeds decreased during seed embryo growth and development, while levels of GA3 increased during seed embryo growth, and levels of GA4 increased during seed dormancy release and seed sprouting. A high-throughput sequencing method was used to determine the E. pseudowushanense seed transcriptome. The transcriptome data were assembled as 178,613 unigenes and the numbers of differentially expressed unigenes between the seed development stages were compared. Computer analysis of reference pathways revealed that 12 candidate genes were likely to be involved in metabolism and signalling of ABA and GAs. The expression patterns of these genes were revealed by real-time quantitative PCR. Phylogenetic relationships among the deduced E. pseudowushanense proteins and their homologous proteins in other plant species were analysed. The results indicated that EpNCED1, EpNCED2, EpCYP707A1, and EpCYP707A2 are likely to be involved in ABA biosynthesis and catabolism. EpSnRK2 is likely implicated in ABA signalling during seed dormancy. EpGA3ox is likely to be involved in GA biosynthesis. EpDELLA1 and EpDELLA2 are likely implicated in GA signalling. This study is the first to provide the E. pseudowushanense seed transcriptome and the key genes involved in metabolism and signalling of ABA and GAs, and it is valuable for studies on the mechanism of seed morphophysiological dormancy. [ABSTRACT FROM AUTHOR]

Conducting polymers and biodegradable polylactide (PLA) scaffolds are both promising biomaterials applied in bone tissue engineering. It is necessary to develop a composite scaffold combining their properties of osteogenic differentiation promotion and three-dimension matrix. To conquer the problem of poor processability of conductive polymers, we use a novel in-situ polymerization/thermal induced phase separation (TIPS) method to fabricate conductive nanofibrous PLA scaffolds with well-distributed polyaniline (PANI) nano-structures. The simple preparation technique provides the possibility to scale-up production of these conductive nanofibrous composite scaffolds. The scaffold structure and content of in-situ formed polyaniline nanoparticles was thoroughly characterized with 1 H NMR, FT-IR, XPS, TGA, SEM and UV–vis, and the conductivity/electrochemical properties of the composite scaffolds were controlled with varied feed ratios of aniline to PLA. Meanwhile, the good cytocompatibility of these composite scaffolds was evaluated by culturing bone marrow derived mesenchymal stem cells (BMSCs) on them. The effect of conductive nanofibrous scaffolds on osteogenic differentiation was studied with expression levels of alkaline phosphatase (Alp), osteocalcin (Ocn) and runt-related transcription factor 2 (Runx2) during the culture of BMSCs for three weeks. The calcium mineralization of BMSCs is determined by alizarin red staining. These results indicated that a moderate content of PANI in the conductive nanofibrous scaffolds significantly promoted osteogenic differentiation of BMSCs for engineering bone tissues. [ABSTRACT FROM AUTHOR]

Acetylcholinesterase (AChE) is a key target for the current symptomatic treatment of Alzheimer's disease, and galantamine is a clinical anticholinesterase drug with transiently acting characteristic and good selectivity for AChE. The present theoretical‐experimental work improves the drug's residence time without reducing the inhibition effect, thus providing a crucial breakthrough for modifying the inhibitor of AChE with better kinetic behavior. The static binding and dynamic delivery properties acquired from atomic view reveal that the galantamine simply occupies a catalytic anionic site, and its release from AChE needs only ∼8.6 kcal/mol. Both of these may cause the short residence time of galantamine. The hotspots and most favorable transport mechanism are identified, and the hydrogen bond and aromatic stacking interactions are observed to play crucial roles for galantamine binding and release in AChE. The typical peripheral anionic site arisen at the delivery process would provide another key occupation to enhance the anti‐release ability for inhibitors. The compound with "specific‐ring‐chain‐ring" framework with detailed beneficial modification scheme is summarized, which may improve the residence time of the inhibitor in AChE. The thermodynamic and dynamic properties of galantamine derivatives are also studied. Based on dictamnine, a natural alkaloid, two novel eligible derivatives are designed, synthesized and evaluated, which verifies our prediction. Multiple computational approaches and experimental combinations probably provide a train of thought from both static and dynamic views to modify or design appropriate inhibitors on the basis of specific binding and transportation features. [ABSTRACT FROM AUTHOR]

Camptotheca acuminata Decne., the main source of camptothecin (CPT), has received increasing attention for its remarkable antitumor activity. Many CPT derivatives are clinically used as effective anticancer agents worldwide. However, their biosynthesis mechanism remains unclear, and uncovering this pathway would greatly facilitate development of alternative CPT production methods to replace current inefficient plant‐derived ones. The expression of >30,000 genes was accurately quantified using unique molecular identifier RNA sequencing in 10 C. acuminata tissues, and 7854 proteins from five tissues were quantified with label‐free quantitative proteomics. Fifteen full‐length transcriptomes were sequenced with long‐read Oxford Nanopore Technologies, and 5692 alternative splicing events were discovered among 4746 genes. Integrated transcriptome and proteome analysis provided novel insights into CPT biosynthesis and its hierarchical regulation. Five cytochrome P450s and three O‐methyltransferases were considered as candidates involved in the biosynthesis of CPT and its derivatives, while 15 transcription factors potentially regulating CPT biosynthesis were screened. These findings provide important clues for elucidating the biosynthetic mechanisms of CPT and its derivatives and substantially contribute to the future production of these anticancer agents with synthetic biology. The generated large‐scale multiomics data also provide valuable resources for investigating the functional genomics of the most important CPT‐producing plant species–C. acuminata. [ABSTRACT FROM AUTHOR]

Epimedium pseudowushanense B.L.Guo, a light-demanding shade herb, is used in traditional medicine to increase libido and strengthen muscles and bones. The recognition of the health benefits of Epimedium has increased its market demand. However, its resource recycling rate is low and environmentally dependent. Furthermore, its natural sources are endangered, further increasing prices. Commercial culture can address resource constraints of it.Understanding the effects of environmental factors on the production of its active components would improve the technology for cultivation and germplasm conservation. Here, we studied the effects of light intensities on the flavonoid production and revealed the molecular mechanism using RNA-seq analysis. Plants were exposed to five levels of light intensity through the periods of germination to flowering, the flavonoid contents were measured using HPLC. Quantification of epimedin A, epimedin B, epimedin C, and icariin showed that the flavonoid contents varied with different light intensity levels. And the largest amount of epimedin C was produced at light intensity level 4 (I4). Next, the leaves under the treatment of three light intensity levels (“L”, “M” and “H”) with the largest differences in the flavonoid content, were subjected to RNA-seq analysis. Transcriptome reconstruction identified 43,657 unigenes. All unigene sequences were annotated by searching against the Nr, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. In total, 4008, 5260, and 3591 significant differentially expressed genes (DEGs) were identified between the groups L vs. M, M vs. H and L vs. H. Particularly, twenty-one full-length genes involved in flavonoid biosynthesis were identified. The expression levels of the flavonol synthase, chalcone synthase genes were strongly associated with light-induced flavonoid abundance with the highest expression levels found in the H group. Furthermore, 65 transcription factors, including 31 FAR1, 17 MYB-related, 12 bHLH, and 5 WRKY, were differentially expressed after light induction. Finally, a model was proposed to explain the light-induced flavonoid production. This study provided valuable information to improve cultivation practices and produced the first comprehensive resource for E. pseudowushanense transcriptomes. [ABSTRACT FROM AUTHOR]

Injectable self-healing hydrogel dressing with multifunctional properties including anti-infection, anti-oxidative and conductivity promoting wound healing process will be highly desired in wound healing application and its design is still a challenge. We developed a series of injectable conductive self-healed hydrogels based on quaternized chitosan-g-polyaniline (QCSP) and benzaldehyde group functionalized poly(ethylene glycol)-co-poly(glycerol sebacate) (PEGS-FA) as antibacterial, anti-oxidant and electroactive dressing for cutaneous wound healing. These hydrogels presented good self-healing, electroactivity, free radical scavenging capacity, antibacterial activity, adhesiveness, conductivity, swelling ratio, and biocompatibility. Interestingly, the hydrogel with an optimal crosslinker concentration of 1.5 wt% PEGS-FA showed excellent in vivo blood clotting capacity, and it significantly enhanced in vivo wound healing process in a full-thickness skin defect model than quaternized chitosan/PEGS-FA hydrogel and commercial dressing (Tegaderm™ film) by upregulating the gene expression of growth factors including VEGF, EGF and TGF-β and then promoting granulation tissue thickness and collagen deposition. Taken together, the antibacterial electroactive injectable hydrogel dressing prolonged the lifespan of dressing relying on self-healing ability and significantly promoted the in vivo wound healing process attributed to its multifunctional properties, meaning that they are excellent candidates for full-thickness skin wound healing. [ABSTRACT FROM AUTHOR]

In the context of climate change, freshwater shrinkage and industrialization, human diseases are increasing due to water pollution by toxic chemicals and pathogenic bacteria, calling for advanced methods to treat contaminated water. Here we review piezocatalysis, an overlooked method to degrade organic pollutants and inhibit bacteria. Recent research shows that the properties of piezoelectric materials have remarkably progressed due to a high surface area and a built-in electric field at the nanolevel. This induces an efficient charge carrier generation, which allows fast reaction mediated by reactive oxygen species. We discuss bacterial growth, methods for water treatment and the piezocatalytic mechanism with focus on charge generation, cavitation and bacterial inactivation by reactive oxygen species. We present applications to the removal of dyes and pathogenic bacteria. [ABSTRACT FROM AUTHOR]

Gynostemma is an important medicinal and food plant of the Cucurbitaceae family. The phylogenetic position of the genus Gynostemma in the Cucurbitaceae family has been determined by morphology and phylogenetics, but the evolutionary relationships within the genus Gynostemma remain to be explored. The chloroplast genomes of seven species of the genus Gynostemma were sequenced and annotated, of which the genomes of Gynostemma simplicifolium, Gynostemma guangxiense and Gynostemma laxum were sequenced and annotated for the first time. The chloroplast genomes ranged from 157,419 bp (Gynostemma compressum) to 157,840 bp (G. simplicifolium) in length, including 133 identical genes: 87 protein-coding genes, 37 tRNA genes, eight rRNA genes and one pseudogene. Phylogenetic analysis showed that the genus Gynostemma is divided into three primary taxonomic clusters, which differs from the traditional morphological classification of the genus Gynostemma into the subgenus Gynostemma and Trirostellum. The highly variable regions of atpH-atpL, rpl32-trnL, and ccsA-ndhD, the repeat unilts of AAG/CTT and ATC/ATG in simple sequence repeats (SSRs) and the length of overlapping regions between rps19 and inverted repeats(IRb) and between ycf1 and small single-copy (SSC) were found to be consistent with the phylogeny. Observations of fruit morphology of the genus Gynostemma revealed that transitional state species have independent morphological characteristics, such as oblate fruit and inferior ovaries. In conclusion, both molecular and morphological results showed consistency with those of phylogenetic analysis. [ABSTRACT FROM AUTHOR]

It is an outstanding solution for protecting the environment using manufactured sand instead of natural river sand in concrete. In this paper, tunnel granite muck was processed into low carbon, coarse and fine aggregates, and low carbon aggregates were used to prepare bridge concrete. Meanwhile, the mechanical properties, anti-permeability, and frost resistance of concrete were investigated. The results demonstrated that the concrete prepared using low carbon aggregate had higher mechanical properties than concrete prepared using river sand. The chloride ion penetration resistance of concrete using low carbon aggregate is better than that of concrete using river sand, and frost resistance has been improved. [ABSTRACT FROM AUTHOR]

Prenylated flavonol glycosides in Epimedium plants, as key medicinal components, are known to have great pharmaceutical activities for human health. Among the main prenylated flavonol glycosides, the modification mechanism of different sugar moieties is still not well understood. In the current study, a novel prenylated flavonol rhamnoside xylosyltransferase gene (EpF3R2″XylT) was cloned from E. pubescens, and the enzymatic activity of its decoding proteins was examined in vitro with different prenylated flavonol rhamnoside substrates and different 3-O-monosaccharide moieties. Furthermore, the functional and structural domains of EpF3R2″XylT were analyzed by bioinformatic approaches and 3-D protein structure remodeling. In summary, EpF3R2″XylT was shown to cluster with GGT (glycosyltransferase that glycosylates sugar moieties of glycosides) through phylogenetic analysis. In enzymatic analysis, EpF3R2″XylT was proven to transfer xylose moiety from UDP-xylose to prenylated flavonol rhamnoside at the 2″-OH position of rhamnose. The analysis of enzymatic kinetics showed that EpF3R2″XylT had the highest substrate affinity toward icariin with the lowest Km value of 75.96 ± 11.91 mM. Transient expression of EpF3R2″XylT in tobacco leaf showed functional production of EpF3R2″XylT proteins in planta. EpF3R2″XylT was preferably expressed in the leaves of E. pubescens, which is consistent with the accumulation levels of major prenylflavonol 3-O-triglycoside. The discovery of EpF3R2″XylT will provide an economical and efficient alternative way to produce prenylated flavonol trisaccharides through the biosynthetic approach. [ABSTRACT FROM AUTHOR]

Paradoxical sleep deprivation (PSD) is prevalent in modern society, and impaired memory is one of its serious consequences. The pathogenic mechanism is still unclear, and the therapeutic strategies for PSD are limited. Here, we found that quercetin treatment ameliorated memory impairments caused by PSD in a dose-dependent manner in an animal model. Quercetin could restore the dynamic changes of the gamma band while the animals performed novel object recognition (NOR) tasks as determined by electroencephalogram analysis. Morphological analysis showed that quercetin, by targeting the hippocampal CA1 region, strikingly ameliorated the overactivation of microglia induced by PSD. Mechanistically, quercetin inhibited the toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), and nuclear factor kappa-b (NF-κB) cascade, which is critical for abnormal microglial activation following PSD stress. Our results provided experimental evidence for the therapeutic effects of quercetin on PSD-related memory impairments by suppressing TLR4/MyD88/NF-κB signaling that mediated abnormal microglia activation in the hippocampus. [Display omitted] • Quercetin ameliorated memory impairment induced by PSD stress in a dose-dependent manner. • Quercetin restored the dynamics of the gamma band in PSD mice while the mice performed novel object recognition. • Quercetin significantly alleviated microglia activation caused by PSD. • Quercetin inhibited the abnormal activation of microglia by suppressing the TLR4/MyD88/NF-κB pathway. [ABSTRACT FROM AUTHOR]

Owing to the high depth of tissue penetration, non‐invasiveness, and controllability, ultrasound (US)‐mediated sonodynamic therapy (SDT) has shown broad application prospects for tumor treatment. However, the electron‐hole separation inefficiency of sonosensitizers and the tumor hypoxia remain two major challenges limiting the effect of SDT. Here, ultrafine photoetched bismuth vanadate (BiVO4) nanorods modified with DSPE‐PEG2000 (PEBVO@PEG NRs) were fabricated to achieve in situ self‐supply of oxygen (O2) and reactive oxygen species (ROS) for hypoxic tumor therapy. The photoetching approach could enhance the charge separation by inducing enriched oxygen vacancies on the surface of BiVO4, thereby improving the generation efficiency of ROS and O2. The PEBVO@PEG overcome the main obstacles of traditional sonosensitizers in the SDT process and show promising sonodynamic therapeutic effects, thus providing new strategies for improving the performance of sonosensitizer and hypoxic tumor elimination. [ABSTRACT FROM AUTHOR]

Owing to the high depth of tissue penetration, non‐invasiveness, and controllability, ultrasound (US)‐mediated sonodynamic therapy (SDT) has shown broad application prospects for tumor treatment. However, the electron‐hole separation inefficiency of sonosensitizers and the tumor hypoxia remain two major challenges limiting the effect of SDT. Here, ultrafine photoetched bismuth vanadate (BiVO4) nanorods modified with DSPE‐PEG2000 (PEBVO@PEG NRs) were fabricated to achieve in situ self‐supply of oxygen (O2) and reactive oxygen species (ROS) for hypoxic tumor therapy. The photoetching approach could enhance the charge separation by inducing enriched oxygen vacancies on the surface of BiVO4, thereby improving the generation efficiency of ROS and O2. The PEBVO@PEG overcome the main obstacles of traditional sonosensitizers in the SDT process and show promising sonodynamic therapeutic effects, thus providing new strategies for improving the performance of sonosensitizer and hypoxic tumor elimination. [ABSTRACT FROM AUTHOR]

[Display omitted] The design of conductive hydrogels integrating anti-fatigue, high sensitivity, strong mechanical property and good sterilization performance remains a challenge. We innovatively introduced metal coordination in covalently crosslinked Pluronic F-127 micelle network and synthesized nanocomposite conductive tough hydrogel through the combination of covalent crosslinking, metal coordination and silver nanowire reinforcement. Compared with pure diacylated PF127 hydrogel (PF127), the tensile strength of PF-AA-AM-Al3+/Ag0.25 hydrogel reaching 1.4 MPa was about 10 times than that of PF127. The toughness of PF-AA-AM-Al3+/Ag0.25 reaches 1.88 MJ/m3. Compared with PF-AA-AM-Al3+, the introduction of silver nanowires increased the fatigue life of PF-AA-AM-Al3+/Ag0.25 by 200% (31837 cycles), 170% (12804 cycles) and 1022% (511 cycles) under 100%, 120% and 150% ultimate tensile strains, respectively. Besides, the PF-AA-AM-Al3+/Ag0.25 showed strain sensitivity to small deformation (Gauge factor = 2.42) in wearable tests on hands and knees. In addition, the PF-AA-AM-Al3+/Ag0.25 had good cytocompatibility and antibacterial performance that bacteria killing ratio of 98% to S. aureus and 99% to E. coli. Finally, a viscoelastic numerical constitutive model was established based on finite element method to study the damage failure history of the material. Comparative analysis showed that local stress concentration was the main factor leading to the failure of hydrogel. [ABSTRACT FROM AUTHOR]

Myelination of Schwann cells (SCs) is critical for the success of peripheral nerve regeneration, and biomaterials that can promote SCs' neurotrophin secretion as scaffolds are beneficial for nerve repair. Here we present a biomaterials-approach, specifically, a highly tunable conductive biodegradable flexible polyurethane by polycondensation of poly(glycerol sebacate) and aniline pentamer, to significantly enhance SCs' myelin gene expression and neurotrophin secretion for peripheral nerve tissue engineering. SCs are cultured on these conductive polymer films, and the biocompatibility of these films and their ability to enhance myelin gene expressions and sustained neurotrophin secretion are successfully demonstrated. The mechanism of SCs' neurotrophin secretion on conductive films is demonstrated by investigating the relationship between intracellular Ca 2+ level and SCs' myelination. Furthermore, the neurite growth and elongation of PC12 cells are induced by adding the neurotrophin medium suspension produced from SCs-laden conductive films. These data suggest that these conductive degradable polyurethanes that enhance SCs' myelin gene expressions and sustained neurotrophin secretion perform great potential for nerve regeneration applications. [ABSTRACT FROM AUTHOR]

Myotube formation is crucial to restoring muscular functions, and biomaterials that enhance the myoblast differentiation into myotubes are highly desirable for muscular repair. Here, we report the synthesis of electroactive, ductile, and degradable copolymers and their application in enhancing the differentiation of myoblasts to myotubes. A hyperbranched ductile polylactide (HPLA) was synthesized and then copolymerized with aniline tetramer (AT) to produce a series of electroactive, ductile and degradable copolymers (HPLAAT). The HPLA and HPLAAT showed excellent ductility with strain to failure from 158.9% to 42.7% and modulus from 265.2 to 758.2 MPa. The high electroactivity of the HPLAAT was confirmed by UV spectrometer and cyclic voltammogram measurements. These HPLAAT polymers also showed improved thermal stability and controlled biodegradation rate compared to HPLA. Importantly, when applying these polymers for myotube formation, the HPLAAT significantly improved the proliferation of C2C12 myoblasts in vitro compared to HPLA. Furthermore, these polymers greatly promoted myogenic differentiation of C2C12 cells as measured by quantitative analysis of myotube number, length, diameter, maturation index, and gene expression of MyoD and TNNT. Together, our study shows that these electroactive, ductile and degradable HPLAAT copolymers represent significantly improved biomaterials for muscle tissue engineering compared to HPLA. [ABSTRACT FROM AUTHOR]

Skin has strong self-regenerative capacity, while severe skin defects do not heal without appropriate treatment. Therefore, in order to cover the wound sites and hasten the healing process, wound dressings are required. Hydrogels have emerged as one of the most promising candidates for wound dressings because of their hydrated and porous molecular structure. Chitosan (CS) with biocompatibility, oxygen permeability, hemostatic and antimicrobial properties is beneficial for wound treatment and it can generate self-healing hydrogels through reversible crosslinks, from dynamic covalent bonding, such as Schiff base bonds, boronate esters, and acylhydrazone bonds, to physical interactions like hydrogen bonding, electrostatic interaction, ionic bonding, metal-coordination, host–guest interactions, and hydrophobic interaction. Therefore, various chitosan-based self-healing hydrogel dressings have been prepared in recent years to cope with increasingly complex wound conditions. This review's objective is to provide comprehensive information on the self-healing mechanism of chitosan-based hydrogel wound dressings, discuss their advanced functions including antibacterial, conductive, anti-inflammatory, anti-oxidant, stimulus-responsive, hemostatic/adhesive and controlled release properties, further introduce their applications in the promotion of wound healing in two categories: acute and chronic (infected, burn and diabetic) wounds, and finally discuss the future perspective of chitosan-based self-healing hydrogel dressings for wound healing. [Display omitted] • The design strategies for chitosan-based self-healing hydrogels are discussed. • Chitosan-based self-healing hydrogel dressings are categorized according to functions in detail. • The employment of chitosan-based self-healing hydrogel wound dressings in various wounds are expounded. • Future outlook for chitosan-based self-healing hydrogel wound dressings is proposed. [ABSTRACT FROM AUTHOR]

[Display omitted] • Microchannel-aligned cryogel was formed via unidirectional freezing technique. • These cryogels exhibited good oxygen generation and delivery function. • These cryogels showed good antibacterial property against MRSA. • Cryogels significantly promoted healing of MRSA-infected diabetic wound. Wounds in diabetic patients suffer from bacterial infection, reduced angiogenesis, and inadequate oxygen supply, which prolong healing time and form chronic wounds. Long-term hypoxia is one of the main causes of delayed wound healing. Therefore, it is particularly urgent to develop new dressings with oxygen release and antibacterial properties for the infected diabetic wound. In this paper, we developed oxygen-releasing and macrochannel-aligned cryogels based on acylhydrazone bond cross-linking between the adipic dihydrazide grafted hyaluronic acid (AHA) and oxidized dextran (OD). The aligned macroporous structure of cryogels formed by the unidirectional freezing technique is favorable for the release of oxygen. The incorporated calcium peroxide (CPO) can react with water to produce oxygen and hydrogen peroxide (H 2 O 2), which can provide good antibacterial properties, while excess H 2 O 2 can be decomposed into oxygen by catalase (CAT), achieving oxygen release for up to 10 days. The macrochannel-aligned cryogels have suitable mechanical properties, oxygen release property, good biological property, and antibacterial property resulting from H 2 O 2 release. In the MRSA-infected diabetic full-thickness defect wound model, compared to the commercial dressing, the cryogel showed excellent bactericidal property and better wound healing by providing oxygen, regulating inflammation, accelerating collagen deposition, and promoting granulation tissue formation and vascularization. In brief, this study developed an efficient oxygen-releasing and antibacterial cryogel with an aligned macroporous structure, which may provide a new strategy for the management of chronic hypoxic infected diabetic wounds. [ABSTRACT FROM AUTHOR]

The "Janus" feature/structure inspired by the ancient Roman double-sided protector is prominent in the field of materials science due to its unique "asymmetric" concept and flexible and adjustable characteristics. The emergence of numerous biomaterials based on Janus properties/structures provides a different approach to material design for complex biomedical scenarios. Gel materials with excellent water absorption, flexibility and biocompatibility in various biomedical applications have greatly increased, and the structural design and functional integration of gels have reached some bottleneck. The Janus properties/structures completely subvert the traditional concept of "homogeneous gel" and break the limitation of "two-sided consistency" in biomedical gels. The concept of "two-sided asymmetry" led by "Adhesion-antiadhesion properties" and "hydrophilic-hydrophobic properties" has emerged and expanded the broad biomedical application prospects of Janus gels. In this review, we first summarize the various structural characteristics of Janus gel materials and the preparation technology of these gels, and explore the secret behind Janus structures from the raw materials and design concepts. Secondly, different kinds of asymmetries, including "hydrophilic-hydrophobic properties", "Adhesion-antiadhesion properties", structural heterogeneity and other unusual asymmetry, are discussed to show the relationship between Janus characteristics and structure. The applications of advanced Janus gels in biomedical fields such as tissue repair, anti-adhesion, substance delivery, hemostasis and human activity sensing are emphatically reviewed. In addition, the latest challenges and possible future direction of Janus gel are proposed. [Display omitted] [ABSTRACT FROM AUTHOR]

Highlights: Mussel and brown algae inspired dual-bionic bioadhesive cross-linked by dynamic bonds exhibits good self-healing capacity and sufficient adhesive strength. And the adhesive hydrogel shows temperature-dependent reversible adhesive behavior, and could achieve fault-tolerate adhesive application and repeated tissue adhesion. The coordination interaction between ferric ions and protocatechualdehyde equips the hydrogel with photothermal antibacterial effect. The injectable adhesive with antioxidation and good hemostatic effect shows promising application in tissue sealant and wound closure. Hydrogels with multifunctionalities, including sufficient bonding strength, injectability and self-healing capacity, responsive-adhesive ability, fault-tolerant and repeated tissue adhesion, are urgently demanded for invasive wound closure and wound healing. Motivated by the adhesive mechanism of mussel and brown algae, bioinspired dynamic bonds cross-linked multifunctional hydrogel adhesive is designed based on sodium alginate (SA), gelatin (GT) and protocatechualdehyde, with ferric ions added, for sutureless post-wound-closure. The dynamic hydrogel cross-linked through Schiff base bond, catechol-Fe coordinate bond and the strong interaction between GT with temperature-dependent phase transition and SA, endows the resulting hydrogel with sufficient mechanical and adhesive strength for efficient wound closure, injectability and self-healing capacity, and repeated closure of reopened wounds. Moreover, the temperature-dependent adhesive properties endowed mispositioning hydrogel to be removed/repositioned, which is conducive for the fault-tolerant adhesion of the hydrogel adhesives during surgery. Besides, the hydrogels present good biocompatibility, near-infrared-assisted photothermal antibacterial activity, antioxidation and repeated thermo-responsive reversible adhesion and good hemostatic effect. The in vivo incision closure evaluation demonstrated their capability to promote the post-wound-closure and wound healing of the incisions, indicating that the developed reversible adhesive hydrogel dressing could serve as versatile tissue sealant. [ABSTRACT FROM AUTHOR]

Oligosaccharides, which exist widely in herbs, present diverse important pharmacological activities. However, the complexity of oligosaccharides seriously challenges their profiling, quality control, and elucidation of activity. In this paper, a novel oligosaccharide analytical method based on a new derivatization pretreatment and ultra-performance liquid chromatography coupled with high resolution tandem mass spectrometry (UPLC–HRMS) procedure was developed to rapidly profile and identify the oligosaccharides of Epimedium . Oligosaccharides are easily derivatized by 2,4-bis(diethylamino)-6-hydrazino-1,3,5-triazine under convenient and mild conditions. Without any further purification steps, oligosaccharides were analyzed by an established UPLC–HRMS/MS method with high sensitivity, good separation efficiency and speed. Benefitting from the derivatization, the oligosaccharides generated a response in the MS two orders of magnitude higher than that of the free oligosaccharide. Oligosaccharides of 52 Epimedium samples were profiled and identified based on the high-resolution mass spectral data. A total of 66 oligosaccharide compounds detected in 52 Epimedium herbs were relatively quantified and statistically processed by principal component analysis (PCA). The 52 Epimedium herbs could be classified into different species based on their oligosaccharide composition and content. Thirteen oligosaccharide compounds demonstrated potential as markers for Epimedium species classification, and their structures were preliminarily identified using MS/MS spectra. [ABSTRACT FROM AUTHOR]

Maternal exposure to anesthetic agents could impose significant neurocognitive risks on the developing brain of infants. Myelin produced by oligodendrocytes (OLs) is essential for the development of brain. However, the concrete effect of general anesthesia on the development and myelination of OLs is still elusive. In this study, we aim to investigate postnatal myelination and neural behavior after maternal exposure to sevoflurane. Pregnant C57BL/6 J mice (gestational day 15.5) were anesthetized with 2.5% sevoflurane (in 97.5% O 2) for 6 h. Cognitive function and motor coordination of the offspring mice were evaluated with novel object recognition, Morris water maze and accelerating rotarod tests. Myelination and development of hippocampal OLs were analyzed with immunohistochemistry, qRT-PCR, western blotting and electron microscopy. The functionality of myelin was measured with electrophysiology. Our results showed that sevoflurane anesthesia during the gestational period induced cognitive and motor impairments in offspring mice, accompanied with damages of myelin structure and down regulations of myelin-associated genes and proteins (including MBP, Olig1, PDGFRα, Sox10, etc.). The development and maturation of OLs were suppressed, and the axonal conduction velocity was declined. These results demonstrated that maternal sevoflurane exposure could induce detrimental effects on cognitive and motor functions in offspring, which might be associated with disrupted myelination of OLs in the hippocampus. • Maternal sevoflurane exposure causes cognitive and motor disorders in offspring mice. • Sevoflurane exposure in prenatal period impairs myelin structure in the hippocampus. • Development of oligodendrocytes is suppressed in the hippocampus of postnatal mice. • Axonal conduction velocity is declined following prenatal sevoflurane anesthesia. [ABSTRACT FROM AUTHOR]