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Hepatotoxicity caused by the anticancer medication oxaliplatin (OXA) significantly restricts its clinical use and raises the risk of liver damage. Huaier, a fungus found in China, has been demonstrated to have various beneficial effects in adjuvant therapy for cancer. However, the preventive impact of Huaier against OXA-induced hepatotoxicity is still unknown. The potential molecular pathways behind the hepatoprotective activity of Huaier against OXA-induced hepatotoxicity were investigated in the current study Mice were intraperitoneally injected with 10 mg/kg of OXA once a week for six consecutive weeks to establish a liver injury model. Huaier (2 g/kg, 4 g/kg, and 8 g/kg) was administered weekly to mice by gavage for six weeks. Commercial kits were used to determine the contents of glutathione, catalase, superoxide dismutase, and malondialdehyde. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting were used to assess the impact of Huaier therapy on the expression of the PI3K pathway. Huaier exhibited a good protective effect on OXA-induced hepatotoxicity in a dose-dependent manner, which was connected to the suppression of oxidative stress, according to the results of biochemical index detection and histological staining analysis. In addition, Huaier could counteract the OXA-induced suppression of the PI3K/AKT signaling pathway. Moreover, the hepatoprotective effect and PI3K activation of Huaier were eradicated by LY294002. These findings imply that by decreasing oxidative stress, Huaier can minimize OXA-induced liver injury, establishing the groundwork for Huaier to lessen chemotherapy-induced hepatotoxicity in clinical practice.

Abstract Skin fibrosis is characterized by the excessive accumulation of extracellular matrix (ECM) caused by fibrotic disorders of the skin. In recent years, ECM stiffness has emerged as a prominent mechanical cue that precedes skin fibrosis and drives its progression by promoting fibroblasts activation. However, how stiffness influences fibroblasts activation for skin fibrosis progression remains unknown. Here, we report a positive feedback loop mediated by the mechanosensitive ion channel Piezo1 and aberrant tissue mechanics in driving skin fibrosis. Piezo1 is upregulated in fibrotic skin in both humans and mice. Piezo1 knockdown dermal fibroblasts lose their fibroproliferative phenotypes despite being grown on a stiffer substrate. We show that Piezo1 acts through the Wnt2/Wnt11 pathway to mechanically induce secretion of C-C motif chemokine ligand 24 (CCL24, also known as eotaxin-2), a potent cytokine associated with fibrotic disorders. Importantly, adeno-associated virus (AAV)-mediated Piezo1 knockdown ameliorated the progression of skin fibrosis and skin stiffness in mice. Overall, increased matrix stiffness promotes skin fibrosis through the inflammatory Piezo1-Wnt2/Wnt11-CCL24 pathway. In turn, a stiffer skin microenvironment increases Piezo1 expression to exacerbate skin fibrosis aggression. Therefore, targeting Piezo1 represents a strategy to break the positive feedback loop between fibroblasts mechanotransduction and aberrant tissue mechanics in skin fibrosis.

Chronic wounds and scar formation are widespread due to limited suitable remedies. The macrophage is a crucial regulator in wound healing, controlling the onset and termination of inflammation and regulating other processes related to wound healing. The current breakthroughs in developing new medications and drug delivery methods have enabled the accurate targeting of macrophages in oncology and rheumatic disease therapies through clinical trials. These successes have cleared the way to utilize drugs targeting macrophages in various disorders. This review thus summarizes macrophage involvement in normal and pathologic wound healing. It further details the targets available for macrophage intervention and therapeutic strategies for targeting the behavior of macrophages in tissue repair and regeneration.

HPV (Human papillomavirus) affects 600,000 people worldwide each year. Almost all cervical cancers are associated with a past HPV infection. In particular, the positivity to the high-risk type HPV16 is detected in most of the invasive cervical cancers. FDA has approved prophylactic vaccines that protect against new HPV16 infections, but do not induce immunity in those patients with established infections or neoplasms. To date, no therapeutic vaccine targeting HPV16-associated lesions has been authorized. We have developed an mRNA-based vaccine against the HPV16 late oncoproteins E6 and E7, which are abundantly and exclusively expressed in high-grade squamous intraepithelial lesions (HSILs), a stage of the cervical disease that precedes the progression to carcinoma. Our in vitro and in vivo studies demonstrated that the translated mRNA is functional and elicits an antigen-specific adaptive immune response. Upon immunization with the vaccine, mice with HPV16+ lesions exhibited tumor growth inhibition, extension of lifespan, and development of a protective immune memory. In light of these results and the remarkable clinical success of mRNA vaccines against SARS-CoV2, we believe that our mRNA-based therapeutic vaccine has the potential to offer a non-invasive treatment alternative to the current standard of care for HPV16+ HSILs.

To develop green finance and ensure the goal of carbon peaking and carbon neutrality, China set up the pilot zones for green finance reform and innovation in 2017. We empirically tested the policy effect of the pilot zones with data from 2010 to 2019 for prefecture-level cities in China. The study shows that the pilot zones have induced an effect on regional green technology innovation, reflected in the application and acquisition of both green invention patents and green utility patents, and the promotion effect is better for green utility patents than green invention patents, which is supported by the robustness test using PSM-DID. This study provides theoretical support and empirical evidence for evaluating the policy effects of the pilot zones and provides a reference for the differentiated formulation of green financial policies.

In this study, a compact combined reaction mechanism for diesel-biodiesel-gasoline mixtures (CDBG) is developed, comprising n-heptane, methyl butanoate (MB) and methyl decanoate (MD) as well as toluene and isooctane to represent the combustion characteristics of diesel, biodiesel and gasoline fuels, respectively. The mechanisms are separately reduced prior to combining by means of directed relation graph (DRG), directed relation graphs with error propagation (DRGEP) and full species sensitivity analysis (FSSA). The reduced mechanisms are then combined, and extensive validations are carried out for closed homogenous reactor application under the following conditions: T = 600–1700 K, P = 1–50 atm, and equivalence ratios (Φ) of 0.25–1.5 (156 setups in total). To boost the accuracy of the CDBG mechanism, cross-reaction analysis is performed to identify the important intermediate species and reactions. The identified species and reactions are subsequently integrated into the CDBG mechanism, resulting in significant improvements in ID timings up to 30%, 18% and 16% for the CDBG sub-mechanisms of diesel, biodiesel and gasoline, respectively. In addition, Arrhenius rate constant optimisation is also employed to further improve the ignition behaviour of the proposed kinetic mechanism. The results revealed that the dual implementation of the cross-reaction analysis and Arrhenius rate constant optimisation diminished the maximum associated errors considerably, down to 14.6%, 16.9% and 14.9% for the CDBG sub-mechanisms of diesel, biodiesel and gasoline, respectively. Concisely, the best results achieved at T = 600–1700 K were P = 41 atm and Φ=1, P = 1,4 atm and Φ=1, and P = 50 bar and Φ=0.3 for diesel, biodiesel and gasoline surrogates, respectively.

Biodiesel combustion in diesel engines is associated with reduced carbon monoxide, particulate matter and unburned hydrocarbons emissions, but several concerns remain including carbon deposition, low thermal efficiency and elevated nitrogen oxides production. To this end, the incorporation of gasoline additive has been proposed as a solution to the drawbacks posed by biodiesel. Integrated chemical kinetics-computational fluid dynamics combustion modelling is a widely used tool to understand the combustion characteristics of new fuel mixtures. This study provides a thorough review of the advances gained in the field of combustion modelling for gasoline-biodiesel mixtures. A thorough appraisal of gasoline surrogate mechanisms such as the primary reference fuel, toluene primary reference fuel and multi-component mechanisms is presented. Developments in the biodiesel surrogate mechanisms such as methyl-butanoate, methyl-hexanoate, methyl-heptanoate, methyl-octanoate, and methyl-decanoate are also discussed. Furthermore, this study also presents a wide-reaching analysis of the modelling results looking into the effects of gasoline addition on the combustion characteristics of gasoline-biodiesel mixtures. From the modelling studies reviewed, the addition of gasoline brings about an increase in the ignition delay timing, in-cylinder pressure and heat release rate (at high temperatures). Also, the rise in gasoline fraction (at low temperatures) leads to the reduction in the combustion duration, nitrogen oxides and soot emissions, but increased carbon monoxide and hydrocarbons emissions. Finally, increased gasoline fraction improves the fuelling economy (at high temperatures) and the combustion stability (at low temperatures).

We performed molecular dynamics simulations of the high voltage pulse explosion of single aluminum wires with the energy ratio of 0.6 in vacuum and studied the role of wire radial dimension. Simulation results show that large-diameter wires having a large material depth and a small specific surface can maintain a higher deposition energy density and effectively reduce the influence of the radial difference in thermodynamic parameters, leading to higher explosion velocity and a lower vaporization rate in the large-diameter wire. The most significant effect is that the larger diameter wire has a longer explosion development time. In addition, the propagation and reflection of the rarefaction waves in the wire result in two explosion regimes: the spinodal decomposition propagating inward from the surface and the cavitation boiling from the center to the surface. Increasing the diameter will increase the domination range of the spinodal decomposition mechanism.

Preterm birth is still a major health problem and maternal inflammation has been shown to play a role. The combination of maternal inflammation and neonatal hyperoxia contributes to epigenetic changes that influence gene expression and the development of bronchopulmonary dysplasia (BPD). We have previously demonstrated suppression of miR-29b and increases in DNA methylation in infants with severe BPD and in our mouse model of maternal inflammation and neonatal hyperoxia exposure. The present studies further explored epigenetic changes in the murine model to include histone methylation. We identified a global suppression of histone methylation in exposed mice and validated decreases in expression in well-defined histone modifications, specifically H3K4me3, H3K27me3, H3K36me2, H3K79me2, and H4K20me3. We further tested the hypothesis that restoration of miR-29b expression would restore the histone methylation marks. Using lipid nanoparticle delivery of miR-29b, partial to full methylation was reestablished for H3K4me3, H3K27me3, and H4K20me3; all tri-methylation marks. To identify the causes of decreased methylation in exposed mice, we measured commonly identified methylases and demethylases. We found a decreased expression of SUV40H2, a methylase primarily associated with H4K20me3. Further studies are needed to identify the causes for the decreased global histone methylation and potential therapeutic opportunities.

Traditional Chinese medicine (TCM) preparations are widely used for healthcare and clinical practice. So far, the methods commonly used for quality evaluation of TCM preparations mainly focused on chemical ingredients. The biological ingredient analysis of TCM preparations is also important because TCM preparations usually contain both plant and animal ingredients, which often include some mis-identified herbal materials, adulterants or even some biological contaminants. For biological ingredient analysis, the efficiency of DNA extraction is an important factor which might affect the accuracy and reliability of identification. The component complexity in TCM preparations is high, and DNA might be destroyed or degraded in different degrees after a series of processing procedures. Therefore, it is necessary to establish an effective protocol for DNA extraction from TCM preparations. In this study, we chose a classical TCM preparation, Liuwei Dihuang Wan (LDW), as an example to develop a TCM-specific DNA extraction method. An optimized cetyl trimethyl ammonium bromide (CTAB) method (TCM-CTAB) and three commonly-used extraction kits were tested for extraction of DNA from LDW samples. Experimental results indicated that DNA with the highest purity and concentration was obtained by using TCM-CTAB. To further evaluate the different extraction methods, amplification of the second internal transcribed spacer (ITS2) and the chloroplast genome trnL intron was carried out. The results have shown that PCR amplification was successful only with template of DNA extracted by using TCM-CTAB. Moreover, we performed high-throughput 454 sequencing using DNA extracted by TCM-CTAB. Data analysis showed that 3–4 out of 6 prescribed species were detected from LDW samples, while up to 5 contaminating species were detected, suggesting TCM-CTAB method could facilitate follow-up DNA-based examination of TCM preparations.

Although Traditional Chinese Medicine (TCM) preparations have long history with successful applications, the scientific and systematic quality assessment of TCM preparations mainly focuses on chemical constituents and is far from comprehensive. There are currently only few primitive studies on assessment of biological ingredients in TCM preparations. Here, we have proposed a method, M-TCM, for biological assessment of the quality of TCM preparations based on high-throughput sequencing and metagenomic analysis. We have tested this method on Liuwei Dihuang Wan (LDW), a TCM whose ingredients have been well-defined. Our results have shown that firstly, this method could determine the biological ingredients of LDW preparations. Secondly, the quality and stability of LDW varies significantly among different manufacturers. Thirdly, the overall quality of LDW samples is significantly affected by their biological contaminations. This novel strategy has the potential to achieve comprehensive ingredient profiling of TCM preparations. [ABSTRACT FROM AUTHOR]