Search

Background: Keloid is a disease characterized by proliferation of fibrous tissue after the healing of skin tissue, which seriously affects the daily life of patients. However, the clinical treatment of keloids still has limitations, that is, it is not effective in controlling keloids, resulting in a high recurrence rate. Thus, it is urgent to identify new signatures to improve the diagnosis and treatment of keloids. Method: Bulk RNA seq and scRNA seq data were downloaded from the GEO database. First, we used WGCNA and MEGENA to co-identify keloid/immune-related DEGs. Subsequently, we used three machine learning algorithms (Randomforest, SVM-RFE, and LASSO) to identify hub immune-related genes of keloid (KHIGs) and investigated the heterogeneous expression of KHIGs during fibroblast subpopulation differentiation using scRNA-seq. Finally, we used HE and Masson staining, quantitative reverse transcription-PCR, western blotting, immunohistochemical, and Immunofluorescent assay to investigate the dysregulated expression and the mechanism of retinoic acid in keloids. Results: In the present study, we identified PTGFR, RBP5, and LIF as KHIGs and validated their diagnostic performance. Subsequently, we constructed a novel artificial neural network molecular diagnostic model based on the transcriptome pattern of KHIGs, which is expected to break through the current dilemma faced by molecular diagnosis of keloids in the clinic. Meanwhile, the constructed IG score can also effectively predict keloid risk, which provides a new strategy for keloid prevention. Additionally, we observed that KHIGs were also heterogeneously expressed in the constructed differentiation trajectories of fibroblast subtypes, which may affect the differentiation of fibroblast subtypes and thus lead to dysregulation of the immune microenvironment in keloids. Finally, we found that retinoic acid may treat or alleviate keloids by inhibiting RBP5 to differentiate pro-inflammatory fibroblasts (PIF) to mesenchymal fibroblasts (MF), which further reduces collagen secretion. Conclusion: In summary, the present study provides novel immune signatures (PTGFR, RBP5, and LIF) for keloid diagnosis and treatment, and identifies retinoic acid as potential anti-keloid drugs. More importantly, we provide a new perspective for understanding the interactions between different fibroblast subtypes in keloids and the remodeling of their immune microenvironment. [ABSTRACT FROM AUTHOR]

Background: This meta-analysis investigated the influence of exercise on cognitive function in people living with diabetes. Methods: Stringent criteria for literature inclusion and exclusion were defined. Searches were conducted across four English databases to gather randomized controlled trials investigating exercise interventions for cognitive function in people living with diabetes. Outcome indicators from 1193 subjects across 12 articles were analyzed using RevMan 5.4 software. Results: Exercise intervention demonstrated the ability to mitigate cognitive decline in people living with diabetes, with a combined effect size (standardized mean difference) of 0.91, 95% CI: 0.28, 1.54, P < 0.00001. The intervention effect showed significant modulation by intervention content (I2 = 95%), intervention duration (I2 = 95%), intervention frequency (I2 = 95%), and intervention cycle (I2 = 96%). Among these factors, multi-component exercise, sessions >40 minutes, exercise frequency >4 times per week, and sustained exercise for >6 months were paramount, all with P < 0.05. Conclusion: Exercise intervention emerges as a viable strategy for delaying cognitive decline in people living with diabetes. Its efficacy is subject to modulation by various variables. Optimal intervention includes multi-component exercise, individual sessions lasting 40–60 minutes, exercising >4 times a week, and continuous exercise for over 6 months. [ABSTRACT FROM AUTHOR]

Based on the land economic density of 892 town units, the spatial pattern of the land economic density in Zhejiang Province is analyzed using the coefficient of variation, spatial classification, and spatial correlation methods, and the influencing factors are analyzed using a spatial regression model. The results are as follows: (1) The coefficients of variation were 2.6 and 3.1 in 2014 and 2019, respectively, indicating that the degree of imbalance of the town's industrial economy at the county level increased. (2) The distribution of the high-level agglomeration areas was characterized by one core area and two sub-core areas. The main core area was located at the junction of Hangzhou City, Shaoxing City, and Jiaxing City, and the two sub-core areas were located in Yuyao City and the main urban area of Ningbo City. In addition, several small-scale agglomeration areas composed of medium and high-level units were distributed in Wenzhou City. (3) The high-value agglomeration and low-value agglomeration distribution in the spatial correlation patterns was identified using the spatial auto-correlation method. The hot spots and sub-hot spots were distributed in Northern Zhejiang, and the cold spots formed a large-scale agglomeration in Quzhou City, Lishui City, Taizhou City, and several other cities in Southern Zhejiang. (4) Compared with the county scale, the spatial scope of the high-level areas in Northern Zhejiang shrunk significantly at the township scale, and the high-level agglomeration areas along the southeast coast changed into a cluster of several townships. (5) According to the geographically weighted regression (GWR) model, the importance of influencing factors is as follows: population density > regional area > industrial output value per capita > total population > proportion of secondary and tertiary personnel > total employees. [ABSTRACT FROM AUTHOR]

Fabricating highly oriented 2D nanosheet arrays is crucial for boosting their performance in electronics, catalysis, optics, and energy conversion, while it remains a challenge due to the high surface energy often leads to random aggregation or interlaced structure. In this study, it is found that the exposed facet of Fe2O3 can greatly influence the interface growth arrangement of bimetallic hydroxide (NiCo(OH)2) nanosheets. The NiCo(OH)2 nanosheets tend to parallel‐standing on the cubic and spindle Fe2O3 while random‐ and interlaced‐standing on the Fe2O3 hexagonal nanoplates and microspheres. The theoretical simulation further indicates the orientation of deposited hydroxide sheets is decided explicitly by the interfacial lattice match/mismatch. Compared to the common interlaced structure of nanosheets, the parallel‐standing nanosheet arrays reduce grain boundaries and improve the charge transfer efficiency. As a result, the derived NiCoP cages exhibit a promising oxygen evolution reaction performance with an overpotential of 255 mV at 10 mA cm−2, and the maximum current density of 400 mA cm−2 with the overpotential of 319 mV. [ABSTRACT FROM AUTHOR]

The massive use of fossil fuels releases a great amount of CO2, which substantially contributes to the global warming. For the global goal of putting CO2 emission under control, effective utilization of CO2 is particularly meaningful. Electrocatalytic CO2 reduction reaction (eCO2RR) has great potential in CO2 utilization, because it can convert CO2 into valuable carbon‐containing chemicals and feedstock using renewable electricity. The catalyst design for eCO2RR is a key challenge to achieving efficient conversion of CO2 to fuels and useful chemicals. For a typical heterogeneous catalyst, surface and interface engineering is an effective approach to enhance reaction activity. Herein, the development and research progress in CO2 catalysts with focus on surface and interface engineering are reviewed. First, the fundaments of eCO2RR is briefly discussed from the reaction mechanism to performance evaluation methods, introducing the role of the surface and interface engineering of electrocatalyst in eCO2RR. Then, several routes to optimize the surface and interface of CO2 electrocatalysts, including morphology, dopants, atomic vacancies, grain boundaries, surface modification, etc. are reviewed and representative examples are given. At the end of this review, we share our personal views in future research of eCO2RR. [ABSTRACT FROM AUTHOR]

Developing a highly active, durable, and low-platinum-based electrocatalyst for the cathodic oxygen reduction reaction (ORR) is for breaking the bottleneck of large-scale applications of proton exchange membrane fuel cells (PEMFCs). Herein, ultrafine PtZn intermetallic nanoparticles with low Pt-loading and trace germanium (Ge) involvement confined in the nitrogen-doped porous carbon (Ge-L 10 -PtZn@N-C) are reported. The Ge-L 10 -PtZn@N-C exhibit superior ORR activity with a mass activity of 3.04 A mg -1 Pt and specific activity of 4.69 mA cm -2 , ≈12.2- and 10.2-times improvement compared to the commercial Pt/C (20%) at 0.90 V in 0.1 m KOH. The cathodic catalyst Ge-L 10 -PtZn@N-C assembled in the PEMFC shows encouraging peak power densities of 316.5 (at 0.86 V) and 417.2 mW cm -2 (at 0.91 V) in alkaline and acidic fuel-cell, respectively. The combination of experiment and density functional theory calculations (DFT) results robustly reveal that the participation of trace Ge can not only trigger a "growth site locking effect" to effectively inhibit nanoparticle growth, bring miniature nanoparticles, enhance dispersion uniformity, and achieve the exposure of the more electrochemical active site, but also effectively modulates the electronic structure, hence optimizing the adsorption/desorption of the oxygen intermediates., (© 2023 Wiley‐VCH GmbH.)

Two-dimensional (2D) PdSe 2 film has the characteristics of adjustable bandgap, high carrier mobility, and high stability. Photodetector (PD) based on 2D PdSe 2 exhibits wide spectral self-driving features, demonstrating enormous potential in the field of optical detection. Here, we design and fabricate PdSe 2 /Si heterojunction PDs with various thicknesses of the PdSe 2 films from 10 to 35 nm. Due to the enhancement of light absorption capacity and built-in electric field of heterojunction, the photodetector with thicker PdSe 2 film can generate more photo-generated carriers and effectively separate them to form a large photocurrent, thus showing more excellent photodetection performance. The responsivity and specific detectivity of the PdSe 2 /Si PDs with 10 nm, 20 nm, and 35 nm PdSe 2 films are 2.12 A W -1 and 6.72 × 10 9 Jones, 6.17 A W -1 and 1.95 × 10 10 Jones, and 8.02 A W -1 and 2.54 × 10 10 Jones, respectively (808 nm illumination). The PD with 35 nm PdSe 2 film exhibits better performance than the other two PDs, with the rise/fall times of 15.8 μ s/138.9 μ s at f = 1 kHz and the cut-off frequency of 8.6 kHz. Furthermore, we demonstrate that the properties of PdSe 2 /Si PD array have excellent uniformity and stability at room temperature and shows potential for image sensing in the UV-vis-NIR wavelength range., (© 2023 IOP Publishing Ltd.)

Background: Smad7 is protective in a mouse model of rheumatoid arthritis. Here we investigated whether Smad7-expressing CD4 + T cells and the methylation of Smad7 gene in CD4 + T cells contribute to the disease activity of RA in patients., Methods: Peripheral CD4 + T cells were collected from 35 healthy controls and 57 RA patients. Smad7 expression by CD4 + T cells were determined and correlated with the clinical parameters of RA including RA score and serum levels of IL-6, CRP, ESR, DAS28-CRP, DAS28-ESR, Swollen joints and Tender joints. Bisulfite sequencing (BSP-seq) was used to determine the DNA methylation in Smad7 promoter (-1000 to +2000) region in CD4 + T cells. In addition, a DNA methylation inhibitor, 5-Azacytidine (5-AzaC), was added to CD4 + T cells to examine the possible role of Smad7 methylation in CD4 + T cell differentiation and functional activity., Results: Compared to the heath controls, Smad7 expression was significantly decreased in CD4 + T cells from RA patients and inversely correlated with the RA activity score and serum levels of IL-6 and CRP. Importantly, loss of Smad7 in CD4 + T cell was associated with the alteration of Th17/Treg balance by increasing Th17 over the Treg population. BSP-seq detected that DNA hypermethylation occurred in the Smad7 promoter region of CD4 + T cells obtained from RA patients. Mechanistically, we found that the DNA hypermethylation in the Smad7 promoter of CD4 + T cells was associated with decreased Smad7 expression in RA patients. This was associated with overreactive DNA methyltransferase (DMNT1) and downregulation of the methyl-CpG binding domain proteins (MBD4). Inhibition of DNA methylation by treating CD4 + T cells from RA patients with 5-AzaC significantly increased Smad7 mRNA expression along with the increased MBD4 but reduced DNMT1 expression, which was associated with the rebalance in the Th17/Treg response., Conclusion: DNA hypermethylation at the Smad7 promoter regions may cause a loss of Smad7 in CD4 + T cells of RA patients, which may contribute to the RA activity by disrupting the Th17/Treg balance., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Hu, Xu, He, Shan, Zhou, Wang, Bai, Shang, Nie, Pan, Lan and Wang.)

The massive use of fossil fuels releases a great amount of CO 2 , which substantially contributes to the global warming. For the global goal of putting CO 2 emission under control, effective utilization of CO 2 is particularly meaningful. Electrocatalytic CO 2 reduction reaction (eCO 2 RR) has great potential in CO 2 utilization, because it can convert CO 2 into valuable carbon-containing chemicals and feedstock using renewable electricity. The catalyst design for eCO 2 RR is a key challenge to achieving efficient conversion of CO 2 to fuels and useful chemicals. For a typical heterogeneous catalyst, surface and interface engineering is an effective approach to enhance reaction activity. Herein, the development and research progress in CO 2 catalysts with focus on surface and interface engineering are reviewed. First, the fundaments of eCO 2 RR is briefly discussed from the reaction mechanism to performance evaluation methods, introducing the role of the surface and interface engineering of electrocatalyst in eCO 2 RR. Then, several routes to optimize the surface and interface of CO 2 electrocatalysts, including morphology, dopants, atomic vacancies, grain boundaries, surface modification, etc., are reviewed and representative examples are given. At the end of this review, we share our personal views in future research of eCO 2 RR., (© 2022 Wiley-VCH GmbH.)

The intracellular triterpene yield from Ganoderma atrum was enhanced by optimization based on single-factor experiments, Plackett-Burman experimental design (PBED) and response surface methodology (RSM) under liquid fermentation conditions. The optimal medium composition (g·L-1) was glucose (46.0), bean cake powder (30.2), KH2PO4 (2.0), CaCl2 (3.0), MgSO4 (1.5), FeSO4 (0.2), and pH 6.0. Under the optimal conditions, the highest triterpene yield of 0.527 g·L-1 was obtained, which was 4.705-fold higher than before optimization. The fermented powder that was collected from the optimal medium was subjected to simulated gastrointestinal digestion, with differences resulting from extraction in different digestive juices (purified water, simulated gastric digestive juice, simulated gastrointestinal digestive juice). The content of triterpenes and polysaccharides increased, except for total phenol content. In terms of the antioxidant activity, the 1,1-diphenyl-2-picrylhydrazyl radical 2,2-diphenyl-1-(2,4,6-trinitrophenyl) hydrazyl (DPPH+⋅) scavenging activity gradually decreased whereas the 2, 2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS+⋅) scavenging activity first decreased and then increased. In terms of enzyme viability, the activity of α-amylase (α-AL) and α-glucosidase (α-GC) in the digestive juices decreased dramatically. The main bioactive components of G. atrum and their bioactivity in digestive juices were evaluated, providing a reference for the effective use of fermented power from G. atrum.

Objective: To investigate the effects of shikonin (SKN) on M1 and M2 polarization of macrophages both and ., Methods: Collagen-induced arthritis (CIA) in male DBA/1 mice were treated with a dose of 4 mg/kg/day of SKN for 23 d ( = 6/group). The histopathology of inflamed joints in CIA mice was evaluated to test the anti-arthritic effect of SKN. M1/M2 polarization of macrophages induced by lipopolysaccharide (LPS) and interferon (IFN)-γ or interleukin (IL)-4 and IL-13, were used to assess the effect of SKN (0.05, 0.1, and 0.2 μM). The effect of SKN on the protein expression of nitric oxide synthase, arginase, CD68, and CD206 was evaluated using western blot analysis., Results: The results of this study revealed that SKN delayed the arthritis feet symptom score, reduced the incidence rate of arthritis, and relieved the inflammation of joints in CIA mice. SKN inhibited M1 macrophage polarization but did not affect M2 macrophage polarization in the joints of CIA mice. Moreover, SKN inhibited M1 polarization induced by LPS and IFN-γ, but did not affect M2 polarization induced by IL-4 and IL-13., Conclusion: These findings suggest that SKN alleviated CIA through inhibiting M1 macrophage polarization and has great potential as a new drug for RA treatment.

Insulin is produced and secreted by pancreatic β cells in the pancreas, which plays a key role in maintaining euglycemia. Insufficient secretion or deficient usage of insulin is the main cause of diabetes mellitus (DM). Drug therapy and islets transplantation are classical treatments for DM. Pancreatic β cell replacement therapy could help patients to get rid of drugs and alleviate the problem of lacking in transplantable donors. Pancreatic β-like cells can be acquired by cell reprogramming techniques or directed induction of stem cell differentiation. These cells are proved to be functional both in vitro and in vivo . Some hospitals have already performed clinical trials for pancreatic β cell replacement therapy. Functional pancreatic β-like cells, which obtained from in vitro pathway, could be a reliable source of cell therapy for treating DM. In this review, the approaches of obtaining pancreatic β cells are summarized and the remaining problems are discussed. Some thoughts are provided for further acquisition and application of pancreatic β cells.