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Injectable hyaluronic acid (HA) hydrogel plays an important role in dermal filling. However, conventional HA dermal fillers mostly lack bio‐functional diversity and frequently cause adverse reactions because of the chemical stiffness of highly modified degree and crosslinker residues. In this study, polylactic acid (PLA) was embedded into HA hydrogel as a bioactive substance and 1,4‐butanediol diglycidyl ether was used as a crosslinker to prepare the HA/PLA composite hydrogel with enhanced biocompatibility and biological performance. We aimed to investigate the properties of HA/PLA composite hydrogels as dermal fillers by assessing the rheological properties, surface microstructure, enzymolysis stability, swelling ratio, degradation rate, cytotoxicity, and anti‐wrinkle effect on photo‐aged skin. The results showed that the stability and stiffness of the composite hydrogel decreased with an increasing amount of PLA, while the in vivo safety of the HA/PLA hydrogel was enhanced, showing no adverse reactions such as edema, redness, or swelling. Moreover, the composite hydrogel with 2 wt% PLA exhibited excellent anti‐wrinkle effects, showing the highest collagen production. Thus, the PLA‐embedded HA composite hydrogel showed potential as a dermal filler with high safety, easy injectability, and excellent anti‐wrinkle effects. [ABSTRACT FROM AUTHOR]

Sand liquefaction triggered by earthquakes is a devastating geological disaster and has emerged as an engaging topic in earthquake engineering. With an enhanced understanding of pure sand liquefaction promoted by laboratory research, there is a growing concern, following filed investigations, over the influence of fine particles on the liquefaction potential of sand containing inclusions. Efforts have been devoted to clarifying the significance of certain physical indicators (e.g., plasticity index, particle shape and gradation characteristics), and fruitful conclusions can be found in the published literature. However, the relationship between the content of fine particles and the cyclic degradation in liquefaction process seems still unclear. To fill this knowledge gap, three sets of cyclic triaxial tests were performed on various sand–fines mixtures with the dry tamping method. The experimental results revealed that (i) fine particles provided a negative contribution to the global soil structure; (ii) however, the damping ratio measured from the obtained stress–strain loops manifested its independence from the fines content during cyclic degradation. In this paper, we propose a shearing mechanism on the microscopic scale to explain the above contrasting observations. For a given soil fabric, the fine particles around sand-to-sand contact points probably break strong force chains, intensifying the threat of liquefaction. By contrast, these fines play the same role in favouring relative sliding between sand grains during both the loading and unloading stages. As the maximum stored energy and the energy loss per cycle are amplified with the same scaling factor, the damping ratio, defined as the ratio between them, should display a macroscopic invariance in triaxial tests. [ABSTRACT FROM AUTHOR]

Few studies on anti-inflammatory drugs with indole groups have been published. This is the first study that demonstrates the anti-inflammatory effects of indole derivative XCR-5a in vitro and in vivo. This study aimed to discover more anti-inflammatory drugs with indole groups and investigate their anti-inflammatory mechanisms. First, a series of indole derivatives was synthesized, then screened for XCR-5a, a compound with anti-inflammatory effects. Second, the in vitro production of IL-1β, IL-6, TNF-α, inducible nitric oxide synthase (iNOS), and cyclo-oxygenase-2 (COX-2) in lipopolysaccharide (LPS)-induced primary cells of mice pretreated with XCR-5a was determined using qPCR and ELISA. Finally, the effect of XCR-5a on LPS-induced NF-κB signaling activation was determined by Western blotting. An in vivo mouse sepsis model was established. In mouse lung tissue, the production of IL-1β, IL-6, and TNF-α was determined and H&E staining was performed. Our findings showed that XCR-5a could suppress the production of LPS-induced IL-1β, IL-6, and TNF-α, as well as mRNA expression of iNOS and COX-2. Pretreatment with XCR-5a inhibited the LPS-induced inflammatory response in septic mice in vivo by decreasing pro-inflammatory cytokines production in serum and reducing immune cell infiltration. Mechanistically, XCR-5a suppressed LPS-induced activation of the NF-κB signaling pathway. XCR-5a has anti-inflammatory effects in vitro and in vivo. Therefore, XCR-5a could be a potential drug candidate for the treatment of inflammatory diseases. [ABSTRACT FROM AUTHOR]

Pt-free composite counter electrode (CE) composed of La2O3 was successfully synthesized by a simple pyrolysis of Lanthanum acetate hydrate (La(CH3COO)3·xH2O) in a high-temperature solid phase. Furthermore, three proportion composite catalysts of La2O3@MWCNTs based on La2O3 and multiwall carbon nanotubes (MWCNTs) were prepared and characterized as Pt-free catalysts for CE in dye-sensitized solar cells (DSSCs). The morphology and structure of La2O3@MWCNT composites were determined by scanning electron microscopy and X-ray diffraction. The electrochemical performance of La2O3@MWCNT composite catalysts for CEs was determined by photocurrent-voltage measurements, cyclic voltammetry, electrochemical impedance spectroscopy, and Tafel polarization. The experimental results showed that the power conversion efficiencies of 5.20, 5.12, and 4.70% were obtained for La2O3: MWCNTs with mass ratios of 5:1, 3:1, and 1:1 as counter electrode towards the reduction of I3−/I− ions respectively in the encapsulation of DSSC batteries, which were higher than that of MWCNTs (3.94%) and La2O3 (0.77%) electrode under the similar conditions. The enhanced electrode performance was attributed to relatively larger surface area and higher conductivity of La2O3@MWCNT composite catalysts. [ABSTRACT FROM AUTHOR]

Non-alcoholic fatty liver disease (NAFLD), which affects approximately one-third of the general population, has become a global health problem. Thus, more effective treatments for NAFLD are urgently required. In the present study, high levels of C-C motif ligand 19 (CCL19), signaling pathways such as Toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB), and proinflammatory factors including interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were detected in NAFLD patients, thereby indicating that there may be an association between CCL19 and these factors in NAFLD progression. Using a high-fat diet (HFD), the present study generated a Sprague-Dawley rat model of NAFLD, which displayed dyslipidemia with increased levels of plasma aspartate aminotransferase, alanine aminotransferase, total cholesterol and triglyceride. Dyslipidemia, liver histopathology and gene expression analyses indicated that the NAFLD model was successfully induced by HFD, and metformin and berberine (BBR) were effective treatments for NAFLD. HFD-induced CCL19 levels and associated factors were markedly reduced by the two drug treatments. In addition, metformin or BBR alone significantly promoted adenosine monophosphate-activated protein kinase (AMPK) phosphorylation, which was inhibited by HFD. These results demonstrated that metformin and BBR could improve NAFLD, which may be via the activation of AMPK signaling, and the high expression of CCL19 in NAFLD was significantly reduced by metformin and BBR. It could be inferred that inhibition of CCL19 may be an effective treatment for NAFLD. [ABSTRACT FROM AUTHOR]

Macromolecular crowding and confinement are two factors that potentially affect protein structure and function in a complex cellular environment. The confinement effect on the structure and function of holoCaM [Ca2+-loaded calmodulin (CaM)], a two-domain protein involved in many calcium-mediated signaling pathways, has been investigated previously. However, little is known about how macromolecular crowding affects holoCaM structure and function. Here, the structure-function correlations of holoCaM are investigated in macromolecular crowded environments. It was found that macromolecular crowding impacts its structure and function mildly. The major conformational states are still extended conformation with inter-domain separation in crowded environment as well as those in dilute solution, but the population of transiently compact conformation increases compared to dilute solution. Furthermore, macromolecular crowding facilitates the binding of CaM with AcN19 peptide (CaM-bind domain of α- syn). This study provides a direct comparison for macromolecular crowding and confinement effects on protein structure and function, which helps to understand chemistry regulation in living cells. [ABSTRACT FROM AUTHOR]

Inflammation is a biological process closely related to different kinds of diseases, such as cancer and metabolic diseases. Therefore, effective control of the occurrence and development of inflammation is of great significance for disease prevention and control. Recently, 2-substituted indoles have gradually become a research hotspot because of their stability and pharmacological activity. Here we synthesized a series of compound containing 2-substituted indoles and investigated XCR-7a's role in inflammatory response. Our data show that XCR-7a can inhibit the production of inflammatory cytokines interleukin-1 beta (IL-1β), interleukin-6 (IL-6) and inflammatory mediator cyclooxygenase-2 (COX-2) induced by lipopolysaccharide (LPS) in mouse peritoneal macrophages. Also, XCR-7a has a protective effect on LPS-induced inflammatory response in mice. Mechanically, we found that XCR-7a could inhibit the phosphorylation of c-Fos induced by LPS, which suggested that the protective effect of XCR-7a on inflammation was related to its negative regulation to phosphorylation of c-Fos. Briefly, our results demonstrated that XCR-7a could be expected to be a potential drug for controlling inflammation. XCR-7a had anti-inflammatory activities in vitro and in vivo, and might be a potential therapeutic candidate for LPS-induced sepsis. [Display omitted] • XCR-7a inhibits LPS-induced inflammatory cytokines in mouse peritoneal macrophages. • XCR-7a relieves LPS-induced sepsis in mice. • XCR-7a suppresses LPS-induced c-Fos phosphorylation. [ABSTRACT FROM AUTHOR]

Background: PCSK9 MaB (Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitor) may reduce the occurrence of major adverse cardiovascular events (MACEs) in patients diagnosed with acute coronary syndrome (ACS). In this meta-analysis, we conducted a thorough compilation of evidence from established clinical studies to evaluate PCSK9 MaB's capacity to control blood lipid levels and prevent MACEs in ACS patients., Methods: We conducted searches on Pubmed, Embase, the Cochrane Library, and Web of Science to identify relevant articles. Data from ACS patients were extracted using a standardized format for aggregating data. We calculated the risk ratio (RR) for MACE and assessed changes in blood lipid parameters. All statistical analyses were performed using RevMan., Results: 11 articles representing 5 trials were included in our systematic review and meta-analysis. When compared to a placebo, PCSK9 MaB significantly reduced the risk of MACEs ( I 2 = 0%, p = 0.63, RR [95% CI] = 0.88 [0.81, 0.97], p < 0.01) and the recurrence rate of ACS ( I 2 = 45%, p = 0.18, RR [95% CI] = 0.89 [0.83, 0.95], p < 0.01). Additionally, PCSK9 MaB notably reduced low-density lipoprotein cholesterol (LDL-C) levels (SMD [95% CI] = -2.12 [-2.32, -1.92], p < 0.01) and Apolipoprotein B (ApoB) levels (SMD [95% CI] = -1.83 [-2.48, -1.18], p < 0.01). Importantly, there were no significant differences in adverse reactions between the PCSK9 MaB group and the control group., Conclusions: PCSK9 MaB, whether used as a standalone treatment or in combination with other therapies, can effectively inhibit PCSK9. It substantially lowers key blood lipid parameters, including low-density lipoprotein (LDL), ApoB, and triglycerides, all without giving rise to notable safety concerns., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2024 The Author(s). Published by IMR Press.)

Neutrophil extracellular traps (NETs), a network of DNA histone complexes and proteins released by activated neutrophils, have been demonstrated to be associated with inflammation, infection related immune response and tumorigenesis in previous reports. However, the relationship between NETs related genes and breast cancer remains controversial. In the study, we retrieved transcriptome data and clinical information of BRCA patients from The Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) datasets. The expression matrix of neutrophil extracellular traps (NETs) related genes was generated and consensus clustering was performed by Partitioning Around Medoid (PAM) to classify BRCA patients into two subgroups (NETs high group and NETs low group). Subsequently, we focus on the differentially expressed genes (DEGs) between the two NETs-related subgroups and further explored NETs enrichment related signaling pathways by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. In addition, we constructed a risk signature model by LASSO Cox regression analysis to evaluate the association between riskscore and prognosis. Even more, we explored the landscape of the tumor immune microenvironment and the expression of immune checkpoints related genes as well as HLA genes between two NETs subtypes in breast cancer patients. Moreover, we found and validated the correlation of different immune cells with risk score, as well as the response to immunotherapy in different subgroups of patients was detected by Tumor Immune Dysfunction and Exclusion (TIDE) database. Ultimately, a nomogram prognostic prediction model was established to speculate on the prognosis of breast cancer patients. The results suggest that high riskscore is associated with poor immunotherapy response and adverse clinical outcomes in breast cancer patients. In conclusion, we established a NETs-related stratification system that is beneficial for guiding the clinical treatment and predicting prognosis of BRCA., 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 Zhao and Xie.)

IκBα is a critical protein that inhibits NF-κB nuclear translocation and impairs NF-κB-mediated signaling. The abundance of IκBα determines the activation and restoration of the inflammatory response. However, posttranslational regulation of IκBα remains to be fully understood. In this study, we identified ubiquitin-specific protease 39 (USP39) as a negative regulator in the NF-κB inflammatory response by stabilizing basal IκBα. The expression of USP39 in macrophages was reduced under LPS-induced inflammation. Knockdown or knockout of USP39 in macrophages significantly increased the expression and secretion of proinflammatory cytokines upon exposure to LPS or Escherichia coli, whereas reexpression of exogenous USP39 in USP39-deficient macrophages rescued the effect. Moreover, USP39-defective mice were more sensitive to LPS or E. coli-induced systemic sepsis. Mechanistically, USP39 interacted with and stabilized IκBα by reducing K48-linked polyubiquination of IκBα. Taken together, to our knowledge, our study for the first time revealed the inhibitory function of USP39 in the NF-κB inflammatory response, providing a previously unknown mechanism for control of inflammatory cytokine induction in the cellular anti-inflammatory response., (Copyright © 2023 by The American Association of Immunologists, Inc.)

Educational revisions facilitate the relief of teacher stress by means of enhancing school organizational conditions. However, limited research has explored the effects of school organizational conditions on teacher stress in China. Using a sample of 734 primary and secondary school teachers from 30 provinces or municipalities of China, this study examined the effects of school organizational conditions on teacher stress in China, with a particular focus on the mediating role of psychological resilience and moderating role of perceived COVID-19 crisis strength. The results demonstrated that school organizational conditions were negatively associated with teacher stress. Furthermore, psychological resilience partially mediated the relation between school organizational conditions and teacher stress. In addition, perceived COVID-19 crisis strength significantly moderated the direct and indirect relations between school organizational conditions and teacher stress. The relations between school organizational conditions and teacher stress and between school organizational conditions and psychological resilience were stronger for teachers who perceived low levels of COVID-19 crisis strength. However, the indirect relation between psychological resilience and stress was stronger for teachers who perceived high levels of COVID-19 crisis strength. Implications have been provided accordingly., 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 Fu, Ouyang, Liu, Xu, Wang, Ye and Zhao.)

Background: Polycystic ovary syndrome (PCOS), one of the most common endocrine diseases in women of childbearing age, has been found to be accompanied by changes in the gut microbiota. The Bu Shen Yang Xue formula (BSYXF) is a traditional Chinese medicine widely used for the treatment of PCOS. This study aimed to investigate whether the protective effects of β-sitosterol, the main active ingredient of BSYXF, on PCOS was mediated by regulating gut microbiota. Methods: The presence of β-sitosterol in BSYXF was detected by liquid chromatography-mass spectrometry. The PCOS-like mouse model was induced by dehydroepiandrosterone. The fecal supernatant of β-sitosterol-treated mice was prepared for fecal microbiota transplantation (FMT). Body weight and wet weight of the uterus and ovary of the mice were recorded for organ index calculation. Hematoxylin and eosin stain was used to assess the endometrial morphology and microenvironment changes. Expression of endometrial receptivity markers cyclooxygenase-2 (COX-2), Integrin α νβ 3, leukemia inhibitory factor (LIF), and homeobox A10 (HOXA10) in the endometrium were determined by immunohistochemistry and western blot analysis. Enzyme-linked immunosorbent assay was employed to detect the expression of follicle stimulating hormone (FSH), luteinizing hormone (LH), progesterone (P), and testosterone (T) in the serum. The diversity of gut microbiota was examined by 16S rDNA gene sequencing. Results: With the treatment of β-sitosterol and β-sitosterol - FMT, the uterine index of PCOS-like mice increased, the ovarian index decreased, levels of COX-2, LH and T decreased, and levels of Integrin α νβ 3, LIF, HOXA10, FSH, and P increased. Under β-sitosterol treatment, the structure of the gut microbiota in PCOS-like mice was also changed. Conclusion: β-sitosterol regulates the endometrial receptivity of PCOS and harmonizes the sex hormone balance, which may be related to the changes in the structure and composition of gut microbiota, thus affecting the pathological process of PCOS., 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 © 2021 Yu, Cao, Huang, Liu, Lu and Zhao.)

There is still no resolution for arterial remodeling related with hypertension, though hypertension treatment has access to a number of pharmacological agents. The present study aimed at investigating the prevention of Cyathula officinalis Kuan's roots ( C. officinalis Kuan) against in arterial remodeling in vitro . Spontaneously hypertensive rats (SHRs) were intragastrically administered 3, 6 or 12 g/kg C. officinalis Kuan or normal saline or enalapril (2.5 mg/kg) once a day for 8 weeks. Hematoxylin and eosin were used to measure blood pressure and stain carotid and arota. The serum concentration of nitric oxide (NO) was measured by NO assay kit (nitrate reductase method). The endothelin-1 transcriptional level, endothelial NO synthase of endothelium as well as angiotensin II receptor type 1 (AT1R) of aorta and carotid was tested by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and the protein level in aorta was also measured by western blotting. The blood pressure in SHR+enalapril, SHR+3 g/kg, SHR+6 g/kg and SHR+12 g/kg C. officinalis Kuan groups was significantly decreased at 4, 6 and 8 weeks post-treatment compared with SHR group. Different doses of C. officinalis Kuan and enalapril treatment showed aortic wall thinness and strengthened NO serum level, but made no impact on the transcriptional level of AT1R in aorta or endothelial NO synthase in carotid. It is suggested by such results that therapy by C. officinalis Kuan is able to fight against arterial remodeling, thus may provide a new means to treat arterial remodeling caused by hypertension.