CHINESE HERBAL MEDICINE AND PREDNISONE INCREASE PROPORTION OF SPLENIC CD4+CD25-FOXP3+ CELLS AND ALLEVIATE GLOMERULAR LESION IN MRL/LPR MICE

Objective: This study investigated the effects of Chinese herbal medicine and prednisone on CD4+FoxP3+ T cells (Tregs) and Th17 cells in the MRL/lpr mouse model of systemic lupus erythematosus. Methods: MRL/lpr mice were treated with herbal medicine (yin-nourishing and heat-clearing therapy), prednisone, and a combination of both for 7 weeks. The proportions of CD4+CD25+FoxP3+ cells, CD4+CD25-FoxP3+ cells, and CD4+IL-17+ cells in splenic mononuclear cell suspension were determined by flow cytometry. Histological slices of kidneys were stained by H&E, PAS, and Masson’s method. Activity indexes (AI) of glomerular lesions were scored. Results: The result showed that both herbal medicine and prednisone significantly increased the proportion of CD4+CD25-FoxP3+ cells (

A Longitudinal Analysis about the Effect of Air Pollution on Astigmatism for Children and Young Adults

Purpose: This study aimed to investigate the correlation between air pollution and astigmatism, considering the detrimental effects of air pollution on respiratory, cardiovascular, and eye health. Methods: A longitudinal study was conducted with 127,709 individuals aged 4-27 years from 9 cities in Guangdong Province, China, spanning from 2019 to 2021. Astigmatism was measured using cylinder values. Multiple measurements were taken at intervals of at least 1 year. Various exposure windows were used to assess the lagged impacts of air pollution on astigmatism. A panel data model with random effects was constructed to analyze the relationship between pollutant exposure and astigmatism. Results: The study revealed significant associations between astigmatism and exposure to carbon monoxide (CO), nitrogen dioxide (NO2), and particulate matter (PM2.5) over time. A 10 {\mu}g/m3 increase in a 3-year exposure window of NO2 and PM2.5 was associated with a decrease in cylinder value of -0.045 diopters and -0.017 diopters, respectively. A 0.1 mg/m3 increase in CO concentration within a 2-year exposure window correlated with a decrease in cylinder value of -0.009 diopters. No significant relationships were found between PM10 exposure and astigmatism. Conclusion: This study concluded that greater exposure to NO2 and PM2.5 over longer periods aggravates astigmatism. The negative effect of CO on astigmatism peaks in the exposure window of 2 years prior to examination and diminishes afterward. No significant association was found between PM10 exposure and astigmatism, suggesting that gaseous and smaller particulate pollutants have easier access to human eyes, causing heterogeneous morphological changes to the eyeball

Microbial traits determine soil C emission in response to fresh carbon inputs in forests across biomes

Soil priming is a microbial-driven process, which determines key soil–climate feedbacks in response to fresh carbon inputs. Despite its importance, the microbial traits behind this process are largely undetermined. Knowledge of the role of these traits is integral to advance our understanding of how soil microbes regulate carbon (C) emissions in forests, which support the largest soil carbon stocks globally. Using metagenomic sequencing and C-glucose, we provide unprecedented evidence that microbial traits explain a unique portion of the variation in soil priming across forest biomes from tropical to cold temperature regions. We show that microbial functional profiles associated with the degradation of labile C, especially rapid simple sugar metabolism, drive soil priming in different forests. Genes involved in the degradation of lignin and aromatic compounds were negatively associated with priming effects in temperate forests, whereas the highest level of soil priming was associated with β-glucosidase genes in tropical/subtropical forests. Moreover, we reconstructed, for the first time, 42 whole bacterial genomes associated with the soil priming effect and found that these organisms support important gene machinery involved in priming effect. Collectively, our work demonstrates the importance of microbial traits to explain soil priming across forest biomes and suggests that rapid carbon metabolism is responsible for priming effects in forests. This knowledge is important because it advances our understanding on the microbial mechanisms mediating soil–climate feedbacks at a continental scale.This work were financially supported by the National Natural Science Foundation of China (41907031), the Chinese Academy of Sciences “Light of West China” Program for Introduced Talent in the West, the National Natural Science Foundation of China (31570440, 31270484), the Key International Scientific and Technological Cooperation and Exchange Project of Shaanxi Province, China (2020KWZ-010), the 2021 First Funds for Central Government to Guide Local Science and Technology Development in Qinghai Province (2021ZY002), the i-LINK +2018 (LINKA20069) from CSIC, and a Ramón y Cajal grant from the Spanish Ministry of Science and Innovation (RYC2018-025483-I

Controlled synthesis of monodisperse gold nanorods with different aspect ratios in the presence of aromatic additives

This paper reports the synthesis of monodisperse gold nanorods (GNRs) via a simple seeded growth approach in the presence of different aromatic additives, such as 7-bromo-3-hydroxy-2-naphthoic acid (7-BrHNA), 3-hydroxy-2-naphthoic acid (HNA), 5-bromosalicylic acid (5-BrSA), salicylic acid (SA) or phenol (PhOH). Effects of the aromatic additives and hydrochloric acid (HCl) on the structure and optical properties of the synthesized GNRs were investigated. The longitudinal surface plasmon resonance (LSPR) peak wavelength of the resulting GNRs was found to be dependent on the aromatic additive in the following sequence: 5-BrSA (778 nm) > 7-BrHNA (706 nm) > SA (688 nm) > HNA (676 nm) > PhOH (638 nm) without addition of HCl, but this was changed to 7-BrHNA (920 nm) > SA (890 nm) > HNA (872 nm) > PhOH (858 nm) > 5-BrSA (816 nm) or 7-BrHNA (1005 nm) > PhOH (995 nm) > SA (990 nm) > HNA (980 nm) > 5-BrSA (815 nm) with the addition of HCl or HNO3 respectively. The LSPR peak wavelength was increased with the increasing concentration of 7-BrHNA without HCl addition, however, there was a maximum LSPR peak wavelength when HCl was added. Interestingly, the LSPR peak wavelength was also increased with amount of HCl added. The results presented here thus established a simple approach to synthesize monodisperse GNRs of different LSPR wavelength

Membrane lytic peptide-based molecular therapeutic for targeted anticancer treatment

Membrane lytic peptides are a novel class of anticancer agents which have the potential to overcome drug resistance. We aim to improve the selectivity, potency and pharmacokinetic profile of membrane lytic peptides in anticancer treatment and explore the underlying mechanism in this work. The first part is focused on selectivity mediated by tumor-associated protease. An 18 residue membrane lytic peptide was cyclized with a linker cleavable by tumor overexpressed MT1-MMP. The activity of peptide was suppressed upon cyclization and could be recovered upon enzymatic digestion. And MT1-MMP-positive cells were preferentially killed by the peptide. In the second part, we tried to improve the pharmacokinetic performance of lytic peptide with the strategy of polyvalency and polymeric therapeutics. A short amphipathic sequence (KW)3 was conjugated to dextran in multiple copies to afford a polyvalent conjugate Dex-(KW)3. The conjugate exhibited 500-fold potency enhancement compared to monomeric (KW)3 in MTT assay. No hemolytic activity was detected. Thermodynamic study revealed stronger membrane binding and deeper membrane penetration of Dex-(KW)3, which were attributed to the high local concentration of peptides on a nano-sized carrier. We further investigated the mechanism of how the conjugate affects cancer cells in the third part of this work. The membrane integrity and metabolic activity of cells were examined at different concentrations of conjugate. Membrane damage occurred at high concentration range. The decrease of metabolic activity began at low concentration when the plasma membrane was still intact. A dual-function mechanism was proposed and proven with a polyelectrolyte complex between Dex-(KW)3 and poly-γ-glutamic acid (PGA). The complexation neutralized the positive charge of Dex-(KW)3 and efficiently suppressed the plasma membrane lysing activity. But it did not change the intracellular activity of conjugate, namely decreasing the cell metabolic activity and mitochondrial membrane potential. We hypothesized the complex Dex-(KW)3/PGA was internalized and dissociate in the acidic environment of endosome. And it was supported by thermodynamic study, in which weaker binding between conjugate and PGA at pH 5.5 than at pH 7.4 was found. The complexation inhibited the effect on plasma membrane while maintained the intracellular activity. The strategy separates one effect from the other thus allows better understanding and control of the novel conjugate

Antitumor activity of a membrane lytic peptide cyclized with a linker sensitive to membrane type 1-matrix metalloproteinase

Membrane lytic peptides are a novel class of anticancer agents that have the potential to overcome drug resistance. The limited selectivity against cancer cells, however, presents a major hurdle for the application. We aim to exploit the proteolytic activity of tumor-associated matrix metalloproteinases (MMP) to mediate the cytotoxicity of these peptides. We designed a membrane lytic peptide cyclized with a linker cleavable by membrane type 1-MMP (MT1-MMP). We showed that the cyclic peptide could be restored to the linear state on MT1-MMP digestion, and it preferentially killed MMP-overexpressing cells above a threshold concentration. Circular dichroism indicated that cyclization resulted in a more rigid structure, making it more difficult for the lytic peptide to transit from random coil to alpha-helix in a membrane-mimicking environment. Selective membrane activity of the cyclic peptide was shown by comparing cytotoxicity results on RBC and two human breast cancer cell lines of different malignancy and MT1-MMP expression: highly invasive MDA-MB-435 and noninvasive MCF-7. Above a concentration of 5 mu mol/L, suppressed activity to MCF-7 and RBC was observed, whereas the toxicity against MDA-MB-435 was maintained. MMP inhibition experiments further showed that the membrane-lysing activity was enzyme dependent