Supramolecular Sequential Light-Harvesting Systems for Constructing White LED Device and Latent Fingerprint Imaging.

The fabrication of supramolecular light-harvesting systems (LHS) with sequential energy transfer is of significance in utilizing light energy. In this study, we report the non-covalent self-assembly of a sequential LHS by pillar[5]arene-based host-guest interaction in water and its applications in white light-emitting diode (LED) device and latent fingerprint imaging. The host-guest complex WP5 ⊃ ${ \supset }$ G self-assembles into nanoparticles in water and shows enhanced aggregation-induced emission (AIE) effect. The nanoparticles can be further used to construct sequential LHS with fluorescent dyes 4,7-di(2-thienyl)-benzo[2,1,3]thiadiazole (DBT) and sulforhodamine 101 (SR101). Impressively, the system shows white-light emission when the molar ratio of WP5 ⊃ ${ \supset }$ G/DBT/SR101 is 1100/2/16. The material can be coated on a LED bulb to achieve white-light emission. In addition, the sequential LHS exhibit multicolor fluorescence including red emission, which have been successfully applied to high-resolution imaging of latent fingerprints. Therefore, we demonstrated a general strategy for the construction of sequential LHS in water based on macrocyclic host-guest interaction and explored its multi-functional applications in white-light LED device and imaging of latent fingerprints, which will promote future development and application of supramolecular LHSs.

Self-assembly of amphiphilic asymmetric comb-like copolymers with responsive rigid side chains.

Amphiphilic asymmetric comb-like copolymers (AACCs) exhibit distinct self-assembly behaviours due to their unique architecture. However, the synthetic difficulties of well-defined AACCs have prohibited a systematic understanding of the architecture-morphology relationship. In this work, we conducted dissipative particle dynamics simulations to investigate the self-assembly behaviours of AACCs with responsive rigid side chains in selective solvents. The effects of side chain length, number of branches, and spacers on the morphology of aggregates were investigated by mapping out morphology diagrams. Besides, the numbers and surface areas of aggregates clearly depicted the morphological transitions during the self-assembly process. Moreover, the rod-to-coil conformation transitions were simulated to explore the stimuli-responsive behaviour of the AACCs with responsive rigid side chains by adjusting the bond angle parameter of the rigid chains. The results indicated that without the support of the rigid chains, the assembly structure collapsed, leading to the tube-to-channelized micelles and one-compartment-to-multicompartment vesicle morphology transformations. The simulation results are consistent with earlier experimental results, which can provide theoretical guidance for assembly toward desired nanostructures.

Characterization of the complete mitochondrial genome of Paecilomyces variotii and comparative evolutionary mitochondriomics of 36 fungi.

BACKGROUD: Paecilomyces variotii has important economic value in stimulating crop growth, biodegradation, and other aspects. Up to now, there are no research reports on its mitochondrial genome. METHODS AND RESULTS: The mitochondrial genome of Paecilomyces variotii was determined with the next-generation sequencing method (Illumina, NovaSeq), and its characteristics were analyzed using various bioinformatics approaches. The length of complete mitochondrial genome sequence of P. variotii is 40,965 bp and consists of 14 protein-coding genes, 2 ribosomal RNA genes, 1 ribosomal protein S3 gene, 26 transport RNA genes. The results of phylogenetics analysis using Bayesian inference and Maximum likelihood methods showed that P. variotii belongs to the Eurotiales order in the Thermoascaceae family, and 9 genera within the Eurotiomycetes class were effectively distinguished with high support rates (bootstrap value > 92% and posterior probabilities > 99%). The analysis of synonymous substitution rates and nonsynonymous substitution rates indicated that the Ka/Ks values of the 14 PCGs in the mitochondrial genomes of the two orders in the Eurotiomycetes class ranged from 0 to 0.4333. CONCLUSIONS: This study revealed the structural and sequence information characteristics of the mitochondrial genome of P. variotii, and the phylogenetic results strongly support its classification within the family Thermoascaceae, consistent with traditional morphological taxonomy studies. The 14 PCGs in the mitochondrial genomes of the two orders in the Eurotiomycetes class are subject to strong purifying (negative) selection. The results of this research provides an important molecular basis for the development of genomics, evolutionary genetics and molecular markers of P. variotii in the future.

Comparison Between Drug-Coated Balloon and Stents in Large De Novo Coronary Artery Disease: A Systematic Review and Meta-Analysis of RCT Data.

PURPOSE: Although a number of studies involving small-vessel de novo coronary disease showed clinical benefits of drug-coated balloons (DCB), the role of DCB in large vessel lesions is still unclear. METHODS: We searched main electronic databases for randomized controlled trials (RCTs) comparing DCB with stents for large vessel de novo coronary artery disease. The primary endpoint was major cardiovascular adverse events (MACE), composite cardiovascular death (CD), myocardial infarction (MI), or target lesion revascularization (TLR). RESULTS: This study included 7 RCTs with 770 participants. DCB were associated with a marked risk reduction in MACE [Risk Ratio (RR): 0.48; 95% confidence interval [CI]: 0.24 to 0.97; P = 0.04], TLR (RR: 0.53; 95% CI: 0.25 to 1.14; P = 0.10), and late lumen loss [standard mean difference (SMD): -0.57; 95% CI: -1.09 to -0.05; P = 0.03] as compared with stents. There is no significant difference in MI (RR: 0.58; 95% CI: 0.21 to 1.54; P = 0.27), CD (RR: 0.33; 95% CI: 0.06 to 1.78; P = 0.19), and minimal lumen diameter (SMD: -0.34; 95% CI: -0.72 to 0.05; P = 0.08) between groups. In subgroup analyses, the risk reduction of MACE persisted in patients with chronic coronary syndrome (RR: 0.25; 95% CI: 0.07 to 0.89; P = 0.03), and patients receiving DCB vs. bare metal stent (RR: 0.19; 95% CI: 0.05 to 0.73; P = 0.01). In addition, there was no significant difference between the DCB group and the drug eluting stent group for MACE (RR: 0.69; 95% CI: 0.30 to 1.60; P = 0.38). CONCLUSION: DCB may be an effective therapeutic option in patients with large vessel de novo coronary artery disease.

Automated detection and segmentation of pleural effusion on ultrasound images using an Attention U-net.

BACKGROUND: Ultrasonic for detecting and evaluating pleural effusion is an essential part of the Extended Focused Assessment with Sonography in Trauma (E-FAST) in emergencies. Our study aimed to develop an Artificial Intelligence (AI) diagnostic model that automatically identifies and segments pleural effusion areas on ultrasonography. METHODS: An Attention U-net and a U-net model were used to detect and segment pleural effusion on ultrasound images of 848 subjects through fully supervised learning. Sensitivity, specificity, precision, accuracy, F1 score, the receiver operating characteristic (ROC) curve, and the area under the curve (AUC) were used to assess the model's effectiveness in classifying the data. The dice coefficient was used to evaluate the segmentation performance of the model. RESULTS: In 10 random tests, the Attention U-net and U-net 's average sensitivity of 97% demonstrated that the pleural effusion was well detectable. The Attention U-net performed better at identifying negative images than the U-net, which had an average specificity of 91% compared to 86% for the U-net. Additionally, the Attention U-net was more accurate in predicting the pleural effusion region because its average dice coefficient was 0.86 as opposed to the U-net's average dice coefficient of 0.82. CONCLUSIONS: The Attention U-net showed excellent performance in detecting and segmenting pleural effusion on ultrasonic images, which is expected to enhance the operation and application of E-FAST in clinical work.

Nomogram to differentiate benign and malignant thyroid nodules in the American College of Radiology Thyroid Imaging Reporting and Data System level 5.

OBJECTIVES: To develop and validate a nomogram for differentiating benign and malignant thyroid nodules of American College of Radiology (ACR) Thyroid Imaging Reporting and Data System (TI-RADS) level 5 (TR5) and improving the performance of the guideline. METHODS: From May 2018 to December 2019, 640 patients with TR5 nodules were retrospectively included in the primary cohort. Univariate and multivariable analyses were performed to determine the risk factors for thyroid cancer. A nomogram was established on the basis of multivariable analyses; the performance of the nomogram was evaluated with respect to discrimination, calibration, and clinical usefulness. The nomogram model was also compared to the ACR score model. External validation was performed and the independent validation cohort contained 201 patients from April 2021 to January 2022. RESULTS: Multivariable analyses showed that age, tumour location, multifocality, concomitant Hashimoto's disease, neck lymph node status reported by ultrasound (US) and ACR score were the independent risk factors for thyroid cancer (all p < .05). The nomogram showed good discrimination, with an area under the curve (AUC) of 0.786 (95% confidence interval [CI]: 0.742-0.830) and 0.712 (95% CI: 0.615-0.809) in the primary cohort and external validation cohort, respectively. Decision curve analysis demonstrated the clinical usefulness of the model. Compared to the ACR score model, the nomogram showed higher AUC (0.786 vs. 0.626, p < .001) and specificity (0.783 vs. 0.391). CONCLUSIONS: The presented nomogram model, based on age, tumour features and ACR score, can differentiate benign and malignant thyroid nodules in TR5 and had a high specificity.

Fluorescent Nanoassemblies in Water Exhibiting Tunable LCST Behavior and Responsive Light Harvesting Ability.

Responsive fluorescent nanomaterials have been received considerable attention in recent years. In this work, a bola-type amphiphilic molecule, CSO, was synthesized which contains a hydrophobic cyanostilbene core and hydrophilic oligo(ethylene glycol) (OEG) coils at both sides. The cyanostilbene group is aggregation-induced emission (AIE) active, while the OEG coils are thermo-responsive. As a result, the CSO molecules can self-assemble into blue-fluorescent nanoassemblies with lower critical solution temperature (LCST) behavior in aqueous media. It is noteworthy that the LCST behavior can be reversibly regulated with changes in concentration and the introduction of K+ . Intriguingly, fluorescence of CSO assembly shows a blue-shift upon heating. Finally, by employing CSO as a light capturing antenna and energy donor, an artificial light harvesting system with tunable emission and thermo-responsive characteristics was fabricated. This study not only demonstrates an integrated approach to create responsive fluorescent nanomaterials, but also shows great potential for producing luminescent materials and mimicking photosynthesis in nature.

Selective C(sp3)-S Bond Cleavage of Thioethers to Build Up Unsymmetrical Disulfides.

The selective C(sp3)-S bond cleavage of thioethers was first developed to prepare unsymmetrical disulfides by using electrophilic halogenation reagents. In this strategy, NBS (N-bromosuccinimide) achieves selective furfuryl C(sp3)-S bond cleavage of furfuryl alkylthioethers at room temperature. Meanwhile, NFSI (N-fluorobenzenesulfonimide) enables selective methyl C(sp3)-S bond cleavage of aryl and alkyl methylthioethers at an elevated temperature. Notably, the substrate scope investigation indicates that the order of selectivity of the C-S bond cleavage is furfuryl C(sp3)-S > benzyl C(sp3)-S > alkyl C(sp3)-S > C(sp2)-S bond. Moreover, this practical and operationally simple strategy also provides an important complementary way to access various unsymmetrical disulfides with excellent functional group tolerances and moderate to good yields.

LINC00115 regulates lung adenocarcinoma progression via sponging miR-154-3p to modulate Sp3 expression.

The most commonly diagnosed and most lethal subtype of lung cancer is lung adenocarcinoma (LUAD). Therefore, more detailed understanding of the potential mechanism and identification of potential targets of lung adenocarcinoma is needed. A growing number of reports reveals that long non-coding RNAs (lncRNAs) play crucial roles in cancer progression. In present study, we found that lncRNA LINC00115 was upregulated in LUAD tissues and cells. Functional studies revealed that LINC00115 knockdown inhibits the proliferation, growth, invasion, and migration of LUAD cells. Mechanically, we indicated that miR-154-3p is target microRNA of LINC00115, and the effect of downregulated LINC00115 on LUAD cells was partially reversed by the miR-154-3p antisense oligonucleotide (ASO-miR-154-3p). Further investigation revealed that Specificity protein 3 (Sp3) directly interacted with miR-154-3p, and the Sp3 level was positively correlated with the LINC00115 expression. Rescue experiments further showed that Sp3 overexpression partially restored the effect of downregulated LINC00115 on LUAD cells. Similarly, in vivo experiments confirmed that downregulated LINC00115 inhibited xenograft growth and Sp3 expression. Our results demonstrated that LINC00115 knockdown inhibited LUAD progression via sponging miR-154-3p to modulate Sp3 expression. These data indicate that the LINC00115/miR-154-3p/Sp3 axis can be a potential therapeutic target of LUAD.

[Application of Droplet-Based Microfluidics in Microbial Research].

Droplet-based microfluidics is a technology that generates and manipulates highly uniform droplets, ranging from picoliter to nanoliter droplets, in microchannels under precise control. In biological research, each droplet can be used to encapsulate a small group of cells or even a single cell, and then serve as an individual container for biochemical reaction, which is well suited for high-throughput and high-resolution biochemical analysis. In the field of microbial research, from cultivation and identification of microbes to the investigation of the spatiotemporal dynamics of microbial communities, from precise quantitation of microbiota to systematic study of microbial interactions, and from the isolation of rare and unculturable microbes to the development of genetically engineered strains, droplet microfluidic technology has played an important promotional role in all these aspects. Droplet microfluidics shows potential for becoming a basic tool for exploring single-cell microbes in microbiological research. In this review, we gave a brief overview of the technical basis of droplet microfluidics. Then, we presented its latest applications in microbial research and had some discussions, aiming to provide a reference for relevant research on microorganisms.

S-glutathionylation proteome profiling reveals a crucial role of a thioredoxin-like protein in interspecies competition and cariogenecity of Streptococcus mutans.

S-glutathionylation is an important post-translational modification (PTM) process that targets protein cysteine thiols by the addition of glutathione (GSH). This modification can prevent proteolysis caused by the excessive oxidation of protein cysteine residues under oxidative or nitrosative stress conditions. Recent studies have suggested that protein S-glutathionylation plays an essential role in the control of cell-signaling pathways by affecting the protein function in bacteria and even humans. In this study, we investigated the effects of S-glutathionylation on physiological regulation within Streptococcus mutans, the primary etiological agent of human dental caries. To determine the S-glutathionylated proteins in bacteria, the Cys reactive isobaric reagent iodoacetyl Tandem Mass Tag (iodoTMT) was used to label the S-glutathionylated Cys site, and an anti-TMT antibody-conjugated resin was used to enrich the modified peptides. Proteome profiling identified a total of 357 glutathionylated cysteine residues on 239 proteins. Functional enrichment analysis indicated that these S-glutathionylated proteins were involved in diverse important biological processes, such as pyruvate metabolism and glycolysis. Furthermore, we studied a thioredoxin-like protein (Tlp) to explore the effect of S-glutathionylation on interspecies competition between oral streptococcal biofilms. Through site mutagenesis, it was proved that glutathionylation on Cys41 residue of Tlp is crucial to protect S. mutans from oxidative stress and compete with S. sanguinis and S. gordonii. An addition rat caries model showed that the loss of S-glutathionylation attenuated the cariogenicity of S. mutans. Taken together, our study provides an insight into the S-glutathionylation of bacterial proteins and the regulation of oxidative stress resistance and interspecies competition.

Deep learning for emergency ascites diagnosis using ultrasonography images.

PURPOSE: The detection of abdominal free fluid or hemoperitoneum can provide critical information for clinical diagnosis and treatment, particularly in emergencies. This study investigates the use of deep learning (DL) for identifying peritoneal free fluid in ultrasonography (US) images of the abdominal cavity, which can help inexperienced physicians or non-professional people in diagnosis. It focuses specifically on first-response scenarios involving focused assessment with sonography for trauma (FAST) technique. METHODS: A total of 2985 US images were collected from ascites patients treated from 1 January 2016 to 31 December 2017 at the Shenzhen Second People's Hospital. The data were categorized as Ascites-1, Ascites-2, or Ascites-3, based on the surrounding anatomy. A uniform standard for regions of interest (ROIs) and the lack of obstruction from acoustic shadow was used to classify positive samples. These images were then divided into training (90%) and test (10%) datasets to evaluate the performance of a U-net model, utilizing an encoder-decoder architecture and contracting and expansive paths, developed as part of the study. RESULTS: Test results produced sensitivity and specificity values of 94.38% and 68.13%, respectively, in the diagnosis of Ascites-1 US images, with an average Dice coefficient of 0.65 (standard deviation [SD] = 0.21). Similarly, the sensitivity and specificity for Ascites-2 were 97.12% and 86.33%, respectively, with an average Dice coefficient of 0.79 (SD = 0.14). The accuracy and area under the curve (AUC) were 81.25% and 0.76 for Ascites-1 and 91.73% and 0.91 for Ascites-2. CONCLUSION: The results produced by the U-net demonstrate the viability of DL for automated ascites diagnosis. This suggests the proposed technique could be highly valuable for improving FAST-based preliminary diagnoses, particularly in emergency scenarios.

Schisandrin B inhibits α-melanocyte-stimulating hormone-induced melanogenesis in B16F10 cells via downregulation of MAPK and CREB signaling pathways.

Schisandrin B (Sch B), a lignan compound in Schisandra, possesses antioxidant, anti-inflammatory, and antiobesity activities. The effect of Sch B on melanogenesis and molecular mechanisms are still unknown. Therefore, we aimed to investigate the antimelanogenic effects of Sch B on α-melanocyte-stimulating hormone-induced B16F10 cells and elucidate the underlying molecular mechanisms. We found that Sch B significantly suppressed melanin content and mushroom tyrosinase (TYR) activity. Sch B treatment decreased the expression of TYR, melanocyte-inducing transcription factor (MITF), tyrosinase-related protein (TRP) 1, and TRP2. Moreover, Sch B modulated the phosphorylation of p38, extracellular-regulated protein kinase, c-Jun N-terminal kinase, and cAMP-response element binding protein (CREB), implying that these pathways may be involved in suppressing melanogenesis. Furthermore, we found that Sch B decreased melanogenesis by downregulating MITF and melanogenic enzymes via MAPK and CREB pathways. Overall, these findings indicate that Sch B has the potential use in whitening.

Demystifying the Dark Web Opioid Trade: Content Analysis on Anonymous Market Listings and Forum Posts.

BACKGROUND: Opioid use disorder presents a public health issue afflicting millions across the globe. There is a pressing need to understand the opioid supply chain to gain new insights into the mitigation of opioid use and effectively combat the opioid crisis. The role of anonymous online marketplaces and forums that resemble eBay or Amazon, where anyone can post, browse, and purchase opioid commodities, has become increasingly important in opioid trading. Therefore, a greater understanding of anonymous markets and forums may enable public health officials and other stakeholders to comprehend the scope of the crisis. However, to the best of our knowledge, no large-scale study, which may cross multiple anonymous marketplaces and is cross-sectional, has been conducted to profile the opioid supply chain and unveil characteristics of opioid suppliers, commodities, and transactions. OBJECTIVE: We aimed to profile the opioid supply chain in anonymous markets and forums via a large-scale, longitudinal measurement study on anonymous market listings and posts. Toward this, we propose a series of techniques to collect data; identify opioid jargon terms used in the anonymous marketplaces and forums; and profile the opioid commodities, suppliers, and transactions. METHODS: We first conducted a whole-site crawl of anonymous online marketplaces and forums to solicit data. We then developed a suite of opioid domain-specific text mining techniques (eg, opioid jargon detection and opioid trading information retrieval) to recognize information relevant to opioid trading activities (eg, commodities, price, shipping information, and suppliers). Subsequently, we conducted a comprehensive, large-scale, longitudinal study to demystify opioid trading activities in anonymous markets and forums. RESULTS: A total of 248,359 listings from 10 anonymous online marketplaces and 1,138,961 traces (ie, threads of posts) from 6 underground forums were collected. Among them, we identified 28,106 opioid product listings and 13,508 opioid-related promotional and review forum traces from 5147 unique opioid suppliers' IDs and 2778 unique opioid buyers' IDs. Our study characterized opioid suppliers (eg, activeness and cross-market activities), commodities (eg, popular items and their evolution), and transactions (eg, origins and shipping destination) in anonymous marketplaces and forums, which enabled a greater understanding of the underground trading activities involved in international opioid supply and demand. CONCLUSIONS: The results provide insight into opioid trading in the anonymous markets and forums and may prove an effective mitigation data point for illuminating the opioid supply chain.

Locomotion Mode Recognition for Walking on Three Terrains Based on sEMG of Lower Limb and Back Muscles.

Gait phase detection on different terrains is an essential procedure for amputees with a lower limb assistive device to restore walking ability. In the present study, the intent recognition of gait events on three terrains based on sEMG was presented. The class separability and robustness of time, frequency, and time-frequency domain features of sEMG signals from five leg and back muscles were quantitatively evaluated by statistical analysis to select the best features set. Then, ensemble learning method that combines the outputs of multiple classifiers into a single fusion-produced output was implemented. The results obtained from data collected from four human participants revealed that the light gradient boosting machine (LightGBM) algorithm has an average accuracy of 93.1%, a macro-F1 score of 0.929, and a calculation time of prediction of 15 ms in discriminating 12 different gait phases on three terrains. This was better than traditional voting-based multiple classifier fusion methods. LightGBM is a perfect choice for gait phase detection on different terrains in daily life.

Using system dynamics to assess the complexity of rural toilet retrofitting: Case study in eastern China.

Rural toilet retrofitting (RTR) is a complex, dynamic system that is affected by many factors and the positive/negative feedback relationships between subsystems and variables. Traditional technologies and management methods face challenges in fundamentally describing and solving problems in RTR. To bridge this gap, this study utilizes system dynamics and causal loop diagrams to explain such problems based on data collected from the stakeholders of the RTR in Jiaozhou from 2018 to 2019. Specifically, this study examines the RTR system from the perspectives of household users, wastewater treatment plants, local governments, grassroots promoters, operation and maintenance personnel, toilet supplier and construction teams, and fecal sludge end users. The factors and processes involved in RTR are identified, and the feedback and relationships among its major stakeholders are established. Results show that the motivation of farmers to engage in RTR is a key variable that affects their final decisions regarding retrofitting and maintaining toilet functions. Meanwhile, the important variables related to the feedback and relationships among the major stakeholders of RTR are mostly focused on policies, subsidies, technology, satisfaction, and cooperation. A scientific analysis method and the updated RTR plan for toilet revolution are then formulated to promote the implementation of RTR in developing countries.

Protective Effects of L-Theanine on IPEC-J2 Cells Growth Inhibition Induced by Dextran Sulfate Sodium via p53 Signaling Pathway.

L-theanine is a nonprotein amino acid found in tea leaves and has been widely used as a safe food additive in beverages or foods because of its varied bioactivities. The aim of this study was to reveal the in vitro gastrointestinal protective effects of L-theanine in DSS-induced intestinal porcine enterocyte (IPEC-J2) cell models using molecular and metabolic methods. Results showed that 2.5% dextran sulfate sodium (DSS) treatment inhibited the cell proliferation of IPEC-J2 and blocked the normal operation of the cell cycle, while L-theanine pretreatment significantly preserved these trends to exert protective effects. L-theanine pre-treatment also up-regulated the EGF, CDC2, FGF2, Rb genes and down-regulated p53, p21 proliferation-related mRNA expression in DSS-treated cells, in accompany with p53 signaling pathway inhibition. Meanwhile, metabolomics analysis revealed that L-theanine and DSS treated IPEC-J2 cells have different metabolomic profiles, with significant changes in the key metabolites involved in pyrimidine metabolism and amino acid metabolism, which play an important role in nucleotide metabolism. In summary, L-theanine has a beneficial protection in DSS-induced IPEC-J2 cells via promoting proliferation and regulating metabolism disorders.

Schisandrin B attenuates bleomycin-induced pulmonary fibrosis in mice through the wingless/integrase-1 signaling pathway.

Purpose/Aim: Pulmonary fibrosis (PF) is characterized by the progressive and ultimately fatal accumulation of fibroblasts and extracellular matrix in the lung that distorts its architecture and compromises its function.Objective: The present study investigated the potential protective effects of schisandrin B (Sch B) on the Wingless/Integrase-1 (Wnt) signaling pathway in attenuating inflammation and oxidative stress in ICR mice.Methods: Sixty healthy ICR mice were randomly divided into the following groups: control group, bleomycin (BLM) group, Sch B low dose (Sch B-L) group, Sch B medium dose (Sch B-M) group, Sch B high dose (Sch B-H) group, and dexamethasone (DXM) group. The expression of transforming growth factor (TGF)-ß1 was examined by ELISA. In addition, the levels of superoxide dismutase (SOD), hydroxyproline (HYP), and the total antioxidant capacity (T-AOC) were determined. The protein and mRNA levels of matrix metalloproteinase 7 (MMP7) and ß-catenin in mice were analyzed by western blot and quantitative real -quantitative time PCR (qRT-PCR), respectively.Results: Lung tissues from the BLM group exhibited significantly more inflammatory changes and a significantly greater number of collagen fibers than lung tissues from the control group. In addition, the lung tissues from these BLM-treated mice exhibited slightly increased MMP7 and ß-catenin protein expression. Lung tissues from the Sch B-H group exhibited fewer inflammatory changes and fewer collagen fibers than lung tissues from the BLM group. Furthermore, the lung tissues from the Sch B-H mice exhibited decreased HYP and TGF-ß1 levels, but increased SOD and T-AOC levels.Conclusions: The present study provided evidence that Sch B may be a potential therapeutic agent for the treatment of PF.

Signal Transduction of Streptococci by Cyclic Dinucleotide Second Messengers.

Since the discovery of cyclic dimeric guanosine 3',5'-monophosphate (c-di-GMP) in 1987, the role of cyclic dinucleotides in signal pathways has been extensively studied. Many receptors and effectors of cyclic dinucleotides have been identified which play important roles in cellular processes. Example of such effectors include cyclic dimeric adenosine 3',5'-monophosphate (c-di-AMP)-binding proteins and endoplasmic reticulum membrane adaptor. Accumulating evidence indicate that cyclic dinucleotides act as second messengers that not only regulate the bacterial physiological processes but also affect host immune responses during infections. Streptococci species, which produce cyclic dinucleotides, are responsible for many human diseases. Numerous studies suggest that the cyclic dinucleotides are vital in signal transduction pathways as second messengers and influence the progression of infectious diseases. Here, we provide an overview of the molecular principles of cyclic dinucleotides synthesis and degradation and discuss recent progress on streptococcal signal transduction pathways by cyclic dinucleotide second messengers and their role in regulating host immune reaction. This review will provide a better understanding of the molecular mechanisms of streptococcal cyclic dinucleotide second messengers thereby revealing novel targets for preventing infections.

Schisandrin B inhibits TGF-ß1-induced epithelial-mesenchymal transition in human A549 cells through epigenetic silencing of ZEB1.

Purpose/Aim: More and more evidences suggest that airway remodeling of fibrotic lung diseases may be associated with epithelial-mesenchymal transition (EMT) of human A549 cells induced by transforming growth factor (TGF)-ß1. Schisandrin B (Sch B) is the highest content of dibenzocyclooctadiene lignans in Schisandra chinensis. In this study, we assessed the inhibitory influences of Sch B on TGF-ß1-stimulated EMT in human A549 cells. Materials and Methods: The influences of Sch B on cell viability, invasion and metastasis in TGF-ß1-induced human A549 cells were detected by MTT, wound healing and transwell invasion assays. The expression levels of α-SMA, E-cadherin, ZEB1 and Twist1 were examined by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blot. The enrichment of H3K4me3 and H3K9me3 at the ZEB1 promoter was determined by ChIP analysis. Results: Experimental results showed that Sch B increased the expression of the epithelial phenotype marker E-cadherin and inhibited the expression of the mesenchymal phenotype marker α-SMA during EMT induced by TGF-ß1. The enhancement in invasion and migration of TGF-ß1-induced A549 cells was inhibited by Sch B. Sch B also repressed the expression of ZEB1 transcription factor in EMT, by increasing the enrichment of H3K9me3 at the ZEB1 promoter to repress its transcription while the expression of the Twist1 transcription factor was unaffected. Conclusions: Our data suggest that Sch B can prevent TGF-ß1-stimulated EMT in A549 cells through epigenetic silencing of ZEB1, which may be clinically related to the efficient treatment of EMT-associated fibrotic diseases.