Triple-layered core-shell fiber dressings with enduring platelet conservation and sustained growth factor release abilities for chronic wound healing.

Platelet-rich plasma (PRP) is one of the most popular biomaterials in regenerative medicine. However, the difficulties encountered in its preservation, and the requirement for on-demand preparation severely limit its application. In addition, its rapid degradation in the wound microenvironment makes the sustained release of growth factors impossible and finally reduces the therapeutic effect on chronic wounds. Here, a multifunctional dressing based on triple-layered core-shell fibers for loading and enduring preservation of PRP was developed using a one-step coaxial bioprinting technique combined with freeze-drying. The platelets were effectively dispersed and immobilized in the core layer of the fiber, leading to a sustained release of growth factors from the PRP. The rate of release can be controlled by adjusting the triple-layered core-shell structure. Simultaneously, the triple-layered core-shell structure can reduce the deactivation of PRP during freezing and storage. The experimental findings suggest that PRP exhibits sustained activity, facilitating the process of wound healing even after a storage period of 180 days. Furthermore, the protective mechanism of PRP by the triple-layered core-shell fiber was investigated, and the conditions for freeze-drying and storage were optimized, further enhancing the long-term storability of PRP. As a result, the multifunctional core-shell fiber dressings developed in this study offer a novel approach for sustained growth factor release and the enduring preservation of active PRP.

The optimized carbapenem inactivation method for objective and accurate detection of carbapenemase-producing Acinetobacter baumannii.

The modified carbapenem inactivation method (mCIM) recommended by the Clinical and Laboratory Standards Institute is not applicable for detecting carbapenemases in Acinetobacter baumannii. Four currently reported phenotypic detection methods, namely, the modified Hodge test, the mCIM, the adjusted mCIM, and the simplified carbapenem inactivation method (sCIM), did not perform well in our 90 clinical A. baumannii isolates. Thus, the minimal inhibitory concentrations (MICs) of carbapenems and the existence and expression of carbapenemase-encoding genes were detected to explain the results. According to the E-test, which was more accurate than the VITEK 2 system, 80.0 and 41.1% were resistant to imipenem (IPM) and meropenem (MEM), respectively, and 14.4 and 53.3% exhibited intermediate resistance, respectively. Five ß-lactamase genes were found, of which blaOXA-51-like, blaTEM, and blaOXA-23-like were detected more frequently in 85 non-susceptible strains. The expression of blaOXA-23-like was positively correlated with the MIC values of IPM and MEM. Therefore, an improved approach based on the mCIM, designated the optimized CIM (oCIM), was developed in this study to detect carbapenemases more accurately and reproducibly. The condition was improved by evaluating the factors of A. baumannii inoculum, incubation broth volume, and MEM disk incubation time. Obvious high sensitivity (92.94%) and specificity (100.00%) were obtained using the oCIM, which was cost-effective and reproducible in routine laboratory work.

Mineralogical characteristics of root iron plaque and its functional mechanism for regulating Cr phytoextraction of hyperaccumulator Leersia hexandra Swartz.

Leersia hexandra Swartz (L. hexandra) is a promising hyperaccumulator for Cr pollution remediation, but whether its Cr phytoextraction is subject to the root surface-attached iron plaque (IP) remains unclear. In this research, the natural and artificial IPs were proven to be comprised of small amounts of exchangeable Fe as well as carbonate Fe, and dominantly Fe minerals involving amorphous two-line ferrihydrite (Fh), poorly crystalline lepidocrocite (Le) and highly crystalline goethite (Go). The Fe content in the artificial IPs augmented with increasing induced Fe(II) concentration, and the 50 mg/L Fe(II) led to the identical Fe content and different component proportions of artificial IP (Fe50) and natural IP. Fh was consisted of highly aggregated nanoparticles, and the aging of Fh caused its phase conversion to rod-like Le and Go. The Cr(VI) adsorption results of Fe minerals corroborated the coordination of Cr(VI) onto the Fh surface and the significantly greater equilibrium Cr(VI) adsorption amount of Fh over Le and Go. The greatest Cr(VI) reduction capacity of Fh among three Fe minerals was found to be related to its most abundant surface-adsorbed Fe(II) content. The results of hydroponic experiment of L. hexandra showed that the presence of IP facilitated the Cr(VI) removal by L. hexandra during the cultivation period of 10-45 days, and consequently, compared to the Fe0 group (without IP), around 60% of increase in the Cr accumulation of shoots was achieved by Fe50 group. The findings of this work are conductive to furthering our understanding of IP-regulated Cr phytoextraction of L. hexandra.

Biomimetic three-layer hierarchical scaffolds for efficient water management and cell recruitment.

Taking inspiration from the structures of roots, stems and leaves of trees in nature, a biomimetic three-layered scaffold was designed for efficient water management and cell recruitment. Using polycaprolactone (PCL) and polyacrylonitrile (PAN) as raw materials, radially oriented nanofiber films and multistage adjustable nanofiber films were prepared through electrospinning technology as the base skin-friendly layer (roots) and middle unidirectional moisture conductive material (stems), the porous polyurethane foam was integrated as the outer moisturizing layer (leaves). Among which, radially oriented nanofiber films could promote the directional migration of fibroblasts and induce cell morphological changes. For the spatially hierarchically nanofiber films, the unidirectional transport of liquid was effectively realized. While the porous polyurethane foam membrane could absorb 9 times its weight in biofluid and retain moisture for up to 10 h. As a result, the biomimetic three-layered scaffolds with different structures can promote wound epithelization and drain biofluid while avoiding wound inflammation caused by excessive biofluid, which is expected to be applied in the field of skin wounds.

Progranulin from different gliocytes in the nucleus accumbens exerts distinct roles in FTD- and neuroinflammation-induced depression-like behaviors.

BACKGROUND: Neuroinflammation in the nucleus accumbens (NAc) is well known to influence the progression of depression. However, the molecular mechanisms triggering NAc neuroinflammation in depression have not been fully elucidated. Progranulin (PGRN) is a multifunctional growth factor that is linked to the innate immune response and inflammation, and PGRN plays a key role in neurodegenerative diseases such as frontotemporal dementia (FTD). Here, the purpose of this study was to validate whether PGRN was involved in the NAc neuroinflammation-promoted depressive-like phenotype. METHODS: A NAc neuroinflammation-relevant depression-like model was established using wild-type (WT) and PGRN-knockout (KO) mice after NAc injection with lipopolysaccharide (LPS), and various behavioral tests related to cognition, social recognition, depression and anxiety were performed with WT and PGRNKO mice with or without NAc immune challenge. RT‒PCR, ELISA, western blotting and immunofluorescence staining were used to determine the expression and function of PGRN in the neuroinflammatory reaction in the NAc after LPS challenge. The morphology of neurons in the NAc from WT and PGRNKO mice under conditions of NAc neuroinflammation was analyzed using Golgi-Cox staining, followed by Sholl analyses. The potential signaling pathways involved in NAc neuroinflammation in PGRNKO mice were investigated by western blotting. RESULTS: Under normal conditions, PGRN deficiency induced FTD-like behaviors in mice and astrocyte activation in the NAc, promoted the release of the inflammatory cytokines interleukin (IL)-6 and IL-10 and increased dendritic complexity and synaptic protein BDNF levels in the NAc. However, NAc neuroinflammation enhanced PGRN expression, which was located in astrocytes and microglia within the NAc, and PGRN deficiency in mice alleviated NAc neuroinflammation-elicited depression-like behaviors, seemingly inhibiting astrocyte- and microglia-related inflammatory reactions and neuroplasticity complexity in the NAc via the p38 and nuclear factor of kappa (NF-κB) signaling pathways present in the NAc after neuroinflammation. CONCLUSIONS: Our results suggest that PGRN exerts distinct function on different behaviors, showing protective roles in the FTD-like behavior and detrimental effects on the neuroinflammation-related depression-like behavior, resulting from mediating astrocyte and microglial functions from the NAc in different status.

Exploring the Visual Space Structure of Oil Painting Based on Visual Importance.

For present and future design, research on visual-spatial language and the mastery of its fundamental concepts is extremely valuable. Since a more comprehensive research system has not yet been established to investigate the aesthetics of visual form and its significance, the research fields of spatial color and spatial structure relationships are currently relatively unique. The visual forms of design will be fundamentally affected by the diverse development of the design thinking ideology, and the expansion of design language will become a given. Design thinking and methods are significantly impacted by the emphasis on digital technology in online media. Design is no longer restricted to the arrangement of two-dimensional planes thanks to the visual space of oil paintings; three-dimensional space and time organization structures are combined with visual elements, and content layout evolves from static layout to dynamic interactive layout. In order to better understand visual space and intuition, this study begins by examining the structure of visual space in oil paintings. It does this by using artistic psychology and spatial space as research hints. The experimental results demonstrate that the depth-aware image quality evaluation algorithm in this study consumes more time than the MSEPF + 30 algorithm and the MSEPF + 50 algorithm by 12 ms and 15 ms, respectively, while the time consumption of individual particles is increased by 0.08 ms and 0.04 ms, respectively. This algorithm can thus meet the real-time requirements. As a result, it is anticipated that this study will address more comprehensive and detailed data as well as theoretical underpinnings that will be helpful in the study of painting art.

Alterations in gut microbiota affect behavioral and inflammatory responses to methamphetamine in mice.

RATIONALE AND OBJECTIVES: Methamphetamine (METH) is a highly addictive and widely abused drug that causes severe neuroinflammation in the human brain. The gut microbiota has a tremendous impact on the core symptoms of neuropsychiatric disorders via the microbiota-gut-brain (MGB) axis. However, it is not clear whether alterations in the gut microbiota are involved in METH exposure. METHODS: We established a mouse model with chronic, escalating doses of METH exposure. Intervene in gut microbiota with antibiotics to observe the changes of locomotor activity caused by METH exposure in mice. qPCR and 16S rRNA gene sequencing were used to analyze the gut microbiota profiles. In addition, we tested the levels of inflammatory factors in the nucleus accumbens (NAc), prefrontal cortex (mPFC), hippocampus (HIp), and spleen. Finally, short-chain fatty acids (SCFAs) were supplemented to determine the interaction between behavior changes and the structure of gut microbiota. RESULTS: In this research, METH increased the locomotor activity of mice, while antibiotics changed the effect. Antibiotics enhanced the expression of pro-inflammatory cytokines in mPFC, HIp, and spleen of METH-exposed mice. METH altered the gut microbiota of mice after antibiotic treatment, such as Butyricicoccus and Roseburia, which are related to butyrate metabolism. Supplementation with SCFAs changed the behavior of METH-exposed mice and decreased Parabacteroides and increased Lactobacillus in METH-exposed mice gut. CONCLUSIONS: This research showed that antibiotics affected the behavior of METH-exposed mice and promoted inflammation. Our findings suggest that SCFAs might regulate METH-induced gut microbiota changes and behavior.

Dopamine D3 receptor signaling alleviates mouse rheumatoid arthritis by promoting Toll-like receptor 4 degradation in mast cells.

Dopamine receptors are involved in several immunological diseases. We previously found that dopamine D3 receptor (D3R) on mast cells showed a high correlation with disease activity in patients with rheumatoid arthritis, but the mechanism remains largely elusive. In this study, a murine collagen-induced arthritis (CIA) model was employed in both DBA/1 mice and D3R knockout mice. Here, we revealed that D3R-deficient mice developed more severe arthritis than wild-type mice. D3R suppressed mast cell activation in vivo and in vitro via a Toll-like receptor 4 (TLR4)-dependent pathway. Importantly, D3R promoted LC3 conversion to accelerate ubiquitin-labeled TLR4 degradation. Mechanistically, D3R inhibited mTOR and AKT phosphorylation while enhancing AMPK phosphorylation in activated mast cells, which was followed by autophagy-dependent protein degradation of TLR4. In total, we found that D3R on mast cells alleviated inflammation in mouse rheumatoid arthritis through the mTOR/AKT/AMPK-LC3-ubiquitin-TLR4 signaling axis. These findings identify a protective function of D3R against excessive inflammation in mast cells, expanding significant insight into the pathogenesis of rheumatoid arthritis and providing a possible target for future treatment.

Dopamine D3 receptor in the nucleus accumbens alleviates neuroinflammation in a mouse model of depressive-like behavior.

We recently reported that dopamine D3 receptor (D3R) was involved in inflammation-related depression. Nucleus accumbens (NAc) inflammation is implicated in the development and progression of depression, but its regulatory mechanism remains largely unknown. In a mouse model of NAc neuroinflammation induced by bilateral NAc injection of lipopolysaccharide (LPS), we observed that NAc neuroinflammation triggered depressive-like behaviors, and D3R expression decline and microglial activation in the NAc. A selective knockdown of D3R in the NAc elicited depressive-like behaviors, while re-expression of D3R in the NAc of global D3RKO mice alleviated depressive-like behaviors induced by D3R deficiency. D3R downregulation in the NAc shifted microglia toward a proinflammatory state, which was validated with cultured mouse microglial cultures. Further in vitro results demonstrated that D3R inhibition induced microglia to enter a proinflammatory state primarily through the Akt signaling pathway. In conclusion, our results suggest that D3R expression in the NAc may inhibit microglial proinflammatory responses in the NAc, thus alleviating NAc neuroinflammation and subsequent depressive-like behaviors through the Akt signaling pathway.

Curcumin alleviates imiquimod-induced psoriasis in progranulin-knockout mice.

Recent advances have revealed that progranulin (PGRN) is related to the aetiology of psoriasis. Moreover, curcumin, a compound derived from turmeric, has been proposed as a potential therapeutic approach in psoriasis-like dermatitis, but it is still unclear whether curcumin affects the development of psoriasis-like skin lesions under PGRN-deficient conditions. Therefore, in this study, we developed a mouse model of psoriatic skin lesions using topical application of imiquimod (IMQ) in both wild type and PGRN-knockout mice to test this possibility. We observed that PGRN deficiency not only increased proinflammatory cytokine IL-17A levels and aggravated psoriasis-like damaged appearance and epidermal thickening but also directly mediated changes in keratinocyte proliferation (Krt 14, cyclinD1 and c-Myc) and differentiation (Krt 10 and Filaggrin) associated gene expression following IMQ challenge, compared to those in the control group. Furthermore, curcumin treatment (50 mg/kg and 200 mg/kg, intragastrically) for 21 consecutive days suppressed the IMQ exposure-induced increase in PGRN expression. Importantly, curcumin treatment significantly alleviated the PGRN deficiency-induced exacerbation of psoriatic appearance, histological features and keratinocyte proliferation after IMQ exposure. In summary, these results demonstrate the direct regulation of PGRN in keratinocyte proliferation and differentiation in psoriatic lesions and demonstrate the protective effect of curcumin on PGRN deficiency-induced psoriatic skin lesion exacerbation.

Microglial activation contributes to depressive-like behavior in dopamine D3 receptor knockout mice.

We previously demonstrated that the dopamine D3 receptor (D3R) inhibitor, NGB2904, increases susceptibility to depressive-like symptoms, elevates pro-inflammatory cytokine expression, and alters brain-derived neurotrophic factor (BDNF) levels in mesolimbic dopaminergic regions, including the medial prefrontal cortex (mPFC), nucleus accumbens (NAc), and ventral tegmental area (VTA) in mice. The mechanisms by which D3R inhibition affects neuroinflammation and onset of depression remain unclear. Here, using D3R-knockout (D3RKO) and congenic wild-type C56BL/6 (WT) mice, we demonstrated that D3RKO mice displayed depressive-like behaviors, increased tumornecrosisfactor-α (TNF-α), interleukin-1ß (IL-1ß), and IL-6 levels, and altered BDNF expression in selected mesolimbic dopaminergic regions. D3R expression was localized to astrocytes or microglia in the mPFC, NAc, and VTA in WT mice. D3RKO mice exhibited a large number of Iba1-labelled microglia in the absence of glial fibrillary acidic protein (GFAP)-labelled astrocytes in mesolimbic dopaminergic brain areas. Inhibition or ablation of microglia by minocycline (25 mg/kg and 50 mg/kg) or PLX3397 (40 mg/kg) treatment ameliorated depressive-like symptoms, alterations in pro-inflammatory cytokine levels, and BDNF expression in the indicated brain regions in D3RKO mice. Minocycline therapy alleviated the increase in synaptic density in the NAc in D3RKO mice. These findings suggest that microglial activation in selected mesolimbic reward regions affects depressive-like behaviors induced by D3R deficiency.