Triptolide alleviates acute gouty arthritis caused by monosodium urate crystals by modulating macrophage polarization and neutrophil activity.

The present study focused on the efficacy and role of triptolide (TPL) in relieving symptoms of acute gouty arthritis (AGA) in vivo and in vitro. The effects of TPL in AGA were investigated in monosodium urate (MSU)-treated rat ankles, RAW264.7 macrophages, and neutrophils isolated from mouse peritoneal cavity. Observation of pathological changes in the ankle joint of rats. Enzyme-linked immunosorbent assay and real-time quantitative polymerase chain reaction (RT-qPCR) were performed to detect the expression levels of inflammatory factors and chemokines. The levels of the indicators of macrophage M1/M2 polarization, and the mechanistic targets of Akt and rapamycin complex 2, were determined via western blotting and RT-qPCR. The expression levels of CD86 and CD206 were detected using immunohistochemistry. Neutrophil migration was observed via air pouch experiments in vivo and Transwell cell migration assay in vitro. Myeloperoxidase (MPO) and Neutrophil elastase (NE) release was analyzed by via immunohistochemistry and immunofluorescence. The expression levels of beclin-1, LC3B, Bax, Bcl-2, and cleaved caspase-3 in neutrophils were determined via western blotting and immunofluorescence. Neutrophil apoptosis was detected using the terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Our results suggest that TPL inhibited inflammatory cell infiltration in rat ankle joints and inflammatory factor and chemokine secretion in rat serum, regulated macrophage polarization through the PI3K/AKT signaling pathway, suppressed inflammatory factor and chemokine expression in neutrophils, and inhibited neutrophil migration, neutrophil extracellular trap formation, transitional autophagy, and apoptosis. This suggests that TPL can prevent and treat MSU-induced AGA by regulating macrophage polarization through the PI3K/Akt pathway and modulating neutrophil activity.

A single-domain protein catenane of dihydrofolate reductase.

A single-domain protein catenane refers to two mechanically interlocked polypeptide rings that fold synergistically into a compact and integrated structure, which is extremely rare in nature. Here, we report a single-domain protein catenane of dihydrofolate reductase (cat-DHFR). This design was achieved by rewiring the connectivity between secondary motifs to introduce artificial entanglement and synthesis was readily accomplished through a series of programmed and streamlined post-translational processing events in cells without any additional in vitro reactions. The target molecule contained few exogenous motifs and was thoroughly characterized using a combination of ultra-performance liquid chromatography-mass spectrometry, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, protease cleavage experiments and ion mobility spectrometry-mass spectrometry. Compared with the linear control, cat-DHFR retained its catalytic capability and exhibited enhanced stability against thermal or chemical denaturation due to conformational restriction. These results suggest that linear proteins may be converted into their concatenated single-domain counterparts with almost identical chemical compositions, well-preserved functions and elevated stabilities, representing an entirely new horizon in protein science.

Tanshinone IIA Improves Acute Gouty Arthritis in Rats through Regulating Neutrophil Activation and the NLRP3 Inflammasome.

Objectives: To investigate the prevention and treatment effect of tanshinone IIA (TIIA) on acute gouty arthritis (AGA) and its mechanism. Methods: The anti-AGA effect of TIIA was observed in vivo and in vitro. Neutrophils were isolated from the abdominal cavity of mice, and the anti-AGA effect of TIIA was investigated in a rat model of MSU-induced AGA. The pathological changes of the ankle joint tissues were assessed by H&E. Cytokine and chemokine expression were determined by ELISA and RT-qPCR. The NLRP3 inflammasome pathway protein levels in the ankle joint tissues were evaluated via western blotting. Neutrophil migration was evaluated in air pouch and transwell assays. Immunohistochemistry and immunofluorescence analysis evaluate the release of myeloperoxidase (MPO), neutrophil elastase (NE), and citrullination of histone H3 (CitH3). Beclin-1 and LC3B expressions were determined using western blotting and immunofluorescence. Key Findings. Treatment with TIIA alleviated synovial hyperplasia and neutrophil infiltration, regulated cytokine and chemokine expressions, and inhibited NLRP3 activation in AGA rats, neutrophil migration, MPO, NE, and CitH3 expression, and LC3B and Beclin-1 protein expression. Conclusions: These results demonstrate that TIIA can effectively enhance AGA by focusing on the neutrophils and NLRP3 inflammasome, demonstrating that TIIA may act as a potential helpful agent for AGA.

Severe community-acquired pneumonia caused by Chlamydia pecorum.

Chlamydia pecorum is a zoonotic pathogen. Here, we report the first case of human infection with C. pecorum. A man aged 51 years with high fever and dry cough was diagnosed with severe community-acquired pneumonia and respiratory failure. C. pecorum was found responsible for the infection, which was detected from bronchoalveolar lavage fluid through metagenomic next-generation sequencing. C. pecorum infection was further identified by quantitative polymerase chain reaction and complement fixation test. The patient's condition improved rapidly after targeted treatment. He was a farmer with diabetes mellitus and had a history of close contact with sheep, which might result in C. pecorum infection. Our report could provide a direction for the diagnosis and treatment of human C. pecorum pneumonia.

Tanshinone IIA Ameliorates Nonalcoholic Steatohepatitis in Mice by Modulating Neutrophil Extracellular Traps and Hepatocyte Apoptosis.

Salvia miltiorrhiza Bunge, a traditional Chinese medicine, is widely used in the treatment of a variety of diseases and syndromes. Tanshinone IIA (TIIA), a phenanthrenequinone-class derivative extracted from S. miltiorrhiza, is one of its main active components and has anti-inflammatory effects on various tissues and cells. This study aimed to investigate the beneficial effects of TIIA on nonalcoholic steatohepatitis (NASH) induced in mice using a methionine choline deficiency (MCD) diet and the underlying mechanism of these. Our results reveal that TIIA remarkably ameliorated hepatic steatosis and inflammation and decreased the serum levels of liver dysfunction markers while increasing the levels of serum total cholesterol and triglycerides in MCD-fed mice. TIIA significantly reduced mRNA levels of the inflammatory factors TNF-α, IL-6, and TGF-ß. Similarly, TIIA inhibited caspase-3 and Bax-mediated apoptosis in MCD-fed mice. Together, our data indicate that TIIA inhibits the formation of MPO and CitH3 in neutrophil extracellular traps and inhibits apoptosis mediated by caspase-3 and Bax in hepatocytes, thereby mitigating inflammatory progression in an MCD diet-induced NASH mouse model.

Tanshinone IIA regulates the TGF-ß1/Smad signaling pathway to ameliorate non-alcoholic steatohepatitis-related fibrosis.

Tanshinone IIA (TIIA) is a major component extracted from the traditional herbal medicine Salvia miltiorrhiza and has been indicated to play a role in the treatment of organ fibrosis. However, the evidence supporting its antifibrotic effect is insufficient and the underlying mechanism is unclear. To investigate the therapeutic effect of TIIA on non-alcoholic steatohepatitis-related fibrosis (NASH-F), the present study used a methionine choline deficiency diet to induce NASH-F in rats, and explored the effect of TIIA on the transforming growth factor-ß1 (TGF-ß1)/Smad signaling pathway. Wistar rats were randomly divided into control, NASH-F and TIIA groups. After 8 weeks of treatment, the levels of serum markers associated with liver function and fibrosis were measured, liver fat vacuoles and inflammation were assessed by haematoxylin and eosin staining, and liver fibrosis was assessed by Masson's trichrome staining. TGF-ß1, Smad2, Smad3, Smad7 and α-smooth muscle actin (α-SMA) mRNA expression, and TGF-ß1, Smad2/3, phosphorylated (p)-Smad2/3, Smad7 and α-SMA protein levels were determined. The results revealed that TIIA could remarkably ameliorate liver fat vacuoles and inflammation in NASH-F rats, and could decrease the levels of serum aspartate aminotransferase, alanine aminotransferase, total bilirubin, total bile acid, hyaluronic acid, type Ⅳ collagen, laminin and type III collagen, while increasing the levels of total cholesterol and triglycerides; however, this was not statistically significance. TIIA markedly suppressed the increased TGF-ß1, Smad2, Smad3 and α-SMA mRNA expression levels observed in the liver of NASH-F rats, while it increased the mRNA expression level of Smad7. Similarly, TIIA suppressed the increased TGF-ß1, p-Smad2/3 and α-SMA protein levels observed in the liver of NASH-F rats, while it increased the protein expression level of Smad7 in vitro and in vivo. TIIA had no significant cytotoxic effect at 10, 20, 40 and 80 µmol/l on human LX-2 cell. In conclusion, the findings of the present study indicated that TIIA alleviated NASH-F by regulating the TGF-ß1/Smad signaling pathway. TIIA may be a useful tool in the prevention and treatment of NASH-F.

Genetically engineered materials: Proteins and beyond.

Information-rich molecules provide opportunities for evolution. Genetically engineered materials are superior in that their properties are coded within genetic sequences and could be fine-tuned. In this review, we elaborate the concept of genetically engineered materials (GEMs) using examples ranging from engineered protein materials to engineered living materials. Protein-based materials are the materials of choice by nature. Recent progress in protein engineering has led to opportunities to tune their sequences for optimal material performance. Proteins also play a central role in living materials where they act in concert with other biological components as well as nonbiological cofactors, giving rise to living features. While the existing GEMs are often limited to those constructed by building blocks of biological origin, being genetically engineerable does not preclude nonbiologic or synthetic materials, the latter of which have yet to be fully explored.

Elemental mercury sensing by synchronously sweeping two multimode diode lasers.

We propose a sum-frequency-generation (SFG) laser-based elemental mercury sensing method by mixing two low-cost multimode diode lasers (MDLs). The wavelengths of the two MDLs are synchronously scanned, which enlarges the whole coverage range of wavelength and improves the measurement stability. Correlation spectroscopy was used to eliminate the impact of environmental change and enhance and trace the absorption signal of the sample accurately. A novel data processing method was employed to extract the weak absorption signals from the background efficiently. A sensitivity of ${0.1}\;\unicode{x00B5} {{\rm g/m}^3}$0.1µg/m3 (11 ppt) was achieved for 1-m path length and 10-s integration time. The sensing range was efficiently increased up to ${200}\;\unicode{x00B5} {{\rm g/m}^3}$200µg/m3 using a calibration curve based on a new mathematical analytical formula. Real-time monitoring of the mercury volatilization and diffusion process was experimentally demonstrated with a time resolution of 10 s. The performance of the system shows great practical value for the detection of elemental mercury in industrial applications.

Acupuncture Alleviates Rheumatoid Arthritis by Immune-Network Modulation.

Rheumatoid arthritis (RA) is a chronic, systemic autoimmune inflammatory and debilitating disease that involves the systemic imbalance of the immune network. Previous studies have shown that acupuncture can help treat RA. However, its specific mechanisms are not fully understood. Thus, the present study was designed to clarify the mechanisms of acupuncture acted on RA via immune network modulation using complete Freund's adjuvant (CFA)-induced arthritic rats. Results revealed that manual acupuncture (MA) could alleviate the inflammation and pain of infected joints. Moreover, MA could effectively stimulate the innate immune cytokines (IL-1[Formula: see text], IL-1[Formula: see text], IL-6, IL-7, IL-18, TNF-[Formula: see text]) and adaptive immunity cytokines (IL-2, IL-12, IFN-[Formula: see text], IL-4, IL-5, IL-10, IL-13, IL-17) as the main part of the immune response and repaired damage of RA. These complex immunomodulatory processes were analyzed quantitatively by cell-cell communication (CCC) networks. The CCC networks demonstrated that the immune networks were enhanced with the development of RA, while MA enhanced the immune networks in the early stage to act on RA and promoted the immune-network to a normal level at the late stage. Moreover, we found that monocyte/macrophage and endothelial cells were the key cells of innate immunity and body cells; TH1, TH2 and B cells were the key cells of adaptive immunity, which were also the main target cells for MA regulation.

Detection of gaseous elemental mercury using a frequency-doubled green diode laser.

We demonstrate a second-harmonic-generation (SHG) based method for the detection of gaseous elemental mercury by using a newly available green diode laser. Multimode ultraviolet radiation at 253.7 nm is generated through a process of SHG. Correlation spectroscopy is introduced into the scheme to guarantee the measurement accuracy. The limit of detection achieved is 0.6 µg/m3 (0.07 ppb) for 1-m pathlength and 10-s integration time. The measurement accuracy is estimated to be 1.2%. The linear response range is estimated to be 0~60 µg/m2 (6.7 ppb·m), within which the linearity error is less than 1%. Real-time monitoring of mercury volatilization is demonstrated with a time resolution of 1 s. The results of performance characterization show that the proposed method has great potentials for mercury sensing in environmental and industrial fields.

Newspaper coverage of tobacco issues: an analysis of print news in Chinese cities, 2008-2011.

OBJECTIVE: The purpose of this study was to determine to what extent Chinese media coverage of tobacco issues in 17 Chinese cities comprises messaging known to motivate healthy behaviour. METHODS: This study involved a content analysis of 4821 articles that contained at least one full paragraph focused on tobacco issues from newspapers published in cities that participated in the Tobacco-Free City-Gates Tobacco Control Project in China between 1 January 2008 and 30 June 2011. RESULTS: The number of tobacco-focused articles increased over the study period. The number of articles varied considerably among different newspapers and cities. Education, prevention and cessation programs (35%) were the most frequent theme. There was also considerable variation in the volume of coverage each month. News articles were the most frequent article type (70%). The majority of the articles (72%) were positive for tobacco control. There were significant differences between party newspapers and local newspapers in prominence, article type, slant and fear appeal. One quarter (n=729) of the articles mentioned the severity of tobacco use, while only 10% of the articles referred to susceptibility to the threat. CONCLUSIONS: The coverage of events was predominantly positive toward tobacco control. However, media reports could better support tobacco control efforts if they did a better job at provoking an emotional response to the harms of tobacco use and promoting a sense among smokers that they can succeed in quitting smoking.