Sentiment Diffusion of Social Inequality in Microblogs: A Case Study of “Migrant Worker” in Sina Weibo

Migrant workers constitute the main city workforce in China. However, they are the victims of social inequality. Sina Weibo is one of the most important channels for people to share information and public opinions. In order to study into the sentiment diffusion of social inequality over Sina Weibo, we collected a huge number of root microblogs and reposts based on the search query “Migrant Worker”. With applying the sentiment tendency analysis tool provided by Baidu AI, we were able to capture the sentiment flipping process. We found that most microblog users tended to follow the previous users’ sentiment polarity. But the intensity of the sentiment polarity would always get weaken

Three “hotspots” important for adenosine A2B receptor activation: a mutational analysis of transmembrane domains 4 and 5 and the second extracellular loop

G protein-coupled receptors (GPCRs) are a major drug target and can be activated by a range of stimuli, from photons to proteins. Despite the progress made in the last decade in molecular and structural biology, their exact activation mechanism is still unknown. Here we describe new insights in specific regions essential in adenosine A2B receptor activation (A2BR), a typical class A GPCR. We applied unbiased random mutagenesis on the middle part of the human adenosine A2BR, consisting of transmembrane domains 4 and 5 (TM4 and TM5) linked by extracellular loop 2 (EL2), and subsequently screened in a medium-throughput manner for gain-of-function and constitutively active mutants. For that purpose, we used a genetically engineered yeast strain (Saccharomyces cerevisiae MMY24) with growth as a read-out parameter. From the random mutagenesis screen, 12 different mutant receptors were identified that form three distinct clusters; at the top of TM4, in a cysteine-rich region in EL2, and at the intracellular side of TM5. All mutant receptors show a vast increase in agonist potency and most also displayed a significant increase in constitutive activity. None of these residues are supposedly involved in ligand binding directly. As a consequence, it appears that disrupting the relatively “silent” configuration of the wild-type receptor in each of the three clusters readily causes spontaneous receptor activity

A practical fabrication method of the gecko-inspired easy-removal skin adhesives

Easy-removal skin adhesives require a robust reversible adhesion. This requirement is addressed in this study with the fabrication of PDMS micro-patterned surfaces that inspired by gecko feet. The design of these gecko-inspired structures were aimed to maximize the ratio between pull-off strength and peel strength. They were fabricated using the laser cutting technology which is typically used for industrial manufacturing applications. Several kinds of PDMS specimens in triangular, square and hexagonal patterns, as well as triangular, square, diamond and circular cross-sections were made. The wetting properties of the gecko-inspired surfaces were evaluated by contact angle measurements. Pull-off strength and peel strength measurements were performed against a silicon skin substitute. Multiple attachments were achieved on a range of preloads. The averaged pull-off strength under a preload 10 N for 10 s can reach up to approximately five times of peel strength when the peel angle is 30 degree. Also compared with conventional Band-Aids, a slight enhancement in attachment ability and a significant decrease in peel strength between the skin and the adhesives were consistently observed. Therefore, the fabrication of the gecko-inspired structures on the micro-molding of PDMS appeared to offer a near-practical way for manufacturing an easy-removal skin adhesives, albeit in its present form with a comparable adhesion strength and a decreased peel strength. The originality of this work is the reverse de-molding approach based on the combination of the cost- and time-efficient laser cutting methods and the Teflon film as the mold material, which avoid the limitation caused by taking PDMS structure out of the molds, so that provide more variations of the tip geometry. As such, a further development of this fabrication method might be of significant interest in a number of practical applications in skin tissue industrial design

Human induced-T-to-natural killer cells have potent anti-tumour activities

Background: Adoptive cell therapy (ACT) is a particularly promising area of cancer immunotherapy, engineered T and NK cells that express chimeric antigen receptors (CAR) are being explored for treating hematopoietic malignancies but exhibit limited clinical benefits for solid tumour patients, successful cellular immunotherapy of solid tumors demands new strategies. Methods: Inactivation of BCL11B were performed by CRISPR/Cas9 in human T cells. Immunophenotypic and transcriptional profiles of sgBCL11B T cells were characterized by cytometer and transcriptomics, respectively. sgBCL11B T cells are further engineered with chimeric antigen receptor. Anti-tumor activity of ITNK or CAR-ITNK cells were evaluated in preclinical and clinical studies. Results: We report that inactivation of BCL11B in human CD8+ and CD4+ T cells induced their reprogramming into induced T-to-natural killer cells (ITNKs). ITNKs contained a diverse TCR repertoire; downregulated T cell-associated genes such as TCF7 and LEF1; and expressed high levels of NK cell lineage-associated genes. ITNKs and chimeric antigen receptor (CAR)-transduced ITNKs selectively lysed a variety of cancer cells in culture and suppressed the growth of solid tumors in xenograft models. In a preliminary clinical study, autologous administration of ITNKs in patients with advanced solid tumors was well tolerated, and tumor stabilization was seen in six out nine patients, with one partial remission. Conclusions: The novel ITNKs thus may be a promising novel cell source for cancer immunotherapy.This study was supported by the National Key Research and Development Plan (Nos. 2021YFE0202800 to P. L, 2017YFE0131600 to Y. L., and 2019YFA0111500 to X. L.), the National Natural Science Foundation of China (Nos. 81961128003 to P.L., 81972672 to P.L., 81773301 to Z. J., 81870121 to P. L., 81873847 to J. Y, 81872069 to Z. Z, and 32170946 to Z. J.), The Youth Innovation Promotion Association of the Chinese Academy of Sciences (No. 2020351 to Z. J.), the Guangdong Provincial Significant New Drugs Development (Nos. 2019B020202003 to P. L., 2019A1515010062 to Y. Y., and 2020A1515011516 to X. W.), the Guangzhou Science and Technology Plan Project (No. 201907010042 to P. L.), 2020B1212060052, the Frontier Research Program of the Guangzhou Regenerative Medicine and Health Guangdong Laboratory (No. 2018GZR110105003 to P. L.), Science and Technology Planning Project of Guangdong Province,China (2020B1212060052), the Science and Technology Program of Guangzhou, China (No. 202002020083 to X. L.), the Open project of the State Key Laboratory of Respiratory Disease (No. SKLRD-OP-202002 to Z. Z.), and the University Grants Committee/Research Grants Council of the Hong Kong (Project No. AoE/M-401/20), and Innovation and Technology Fund (ITF) from Hong Kong SAR Governmen

Comparison of ferric chloride and aluminum sulfate on phosphorus removal and membrane fouling in MBR treating BAF effluent of municipal wastewater

A membrane bioreactor (MBR) was used for treating biological aerated filter effluent in a municipal wastewater plant, and chemical phosphorus removal was accomplished in the MBR. The results showed that ferric chloride of 20 mg/L and aluminum sulfate of 30 mg/L were the optimal dosages for total phosphorus (TP) removal, and the TP removal efficiency was over 80%. In long-term continuous operations, both ferric chloride and aluminum sulfate effectively mitigated membrane fouling, with the corresponding growth rate of transmembrane pressure decreased to 0.08 and 0.067 kPa/d, respectively. Sludge particle sizes analysis demonstrated that the decrease of particle sizes lower than 50 μm was the main reason for membrane fouling control. Simultaneously, the proteins and polysaccharide (PS) concentrations in the MBR supernatant were analyzed, and the PS concentration significantly decreased to 2.02 mg/L at aluminum sulfate of 30 mg/L, indicating the flocculation of aluminum sulfate on PS was the main reason for mitigation of membrane fouling

Ethyl Acetate Extract of <i>Dracocephalum heterophyllum</i> Benth Ameliorates Nonalcoholic Steatohepatitis and Fibrosis via Regulating Bile Acid Metabolism, Oxidative Stress and Inhibiting Inflammation

Dracocephalum heterophyllum Benth is well-known for its ability to alleviate liver heat. In this study, Dracocephalum heterophyllum Benth ethyl acetate extracts were evaluated on mouse models of nonalcoholic steatohepatitis and liver fibrosis. After 6 and 8 weeks of treatment, serum parameters and gene expressions in tissue samples, as well as stained tissue sections, demonstrated that the ethyl acetate extracts were effective in treating these liver diseases. The principal bioactive constituent (rosmarinic acid) was identified and screened by high pressure liquid chromatography-1,1-diphenyl-2-picrylhydrazyl and affinity ultrafiltration-HPLC. The rosmarinic acid was separated from extracts with high purity by medium- and high-pressure liquid chromatography. Finally, the interactions between rosmarinic acid and the key targets of lipid metabolism, oxidative stress and inflammation were verified by molecular docking. Thereby, an indirect regulation of lipid and cholesterol metabolism and inhibition of liver inflammation and liver fibrosis by the studied extract has been observed. This study demonstrated that Dracocephalum heterophyllum Benth ethyl acetate extracts have the potential to treat nonalcoholic steatohepatitis and liver fibrosis, revealing their multi-target and multi-pathway therapeutic characteristics

Preparation and Antioxidant Activities of Phenylethanoids from Dracocephalum heterophyllum

The health benefits of Dracocephalum heterophyllum are widely reported in traditional Tibetan medicines, but the reported chemical composition is limited, probably due to difficulties in separating and purifying compounds. In this study, antioxidative phenylethanoids were isolated from an extract of Dracocephalum heterophyllum using medium- and high-pressure liquid chromatography, coupled with on-line HPLC&ndash;1,1-diphenyl-2-picrylhydrazyl recognition. Firstly, crude samples (1.3 kg) of Dracocephalum heterophyllum were pretreated via silica gel medium-pressure liquid chromatography to yield 994.0 g of Fr2, of which 10.8 g was then pretreated via MCI GEL&reg;CHP20P medium-pressure liquid chromatography. The resulting Fr23 and Fr25 were further separated and purified using high-pressure liquid chromatography, and yielded 8.08 mg of Fr2391, 9.76 mg of Fr2551, 16.09 mg of Fr2581, and 8.75 mg of Fr2582. Furthermore, analysis of the purity and structures of the phenylethanoids suggested that Fr2391, Fr2551, Fr2581, and Fr2582 corresponded to decaffeoylverbascoside, rosmarinic acid, acteoside, and 2&prime;-O-acetylplantamajoside, respectively, with all being over 95% pure. Finally, the antioxidant potential of the compounds was explored based on their ability to scavenge 1,1-diphenyl-2-picrylhydrazine, as well as through molecular docking of proteins related to antioxidant pathways. Altogether, our findings revealed that the proposed method is promising for separating pure antioxidative phenylethanoids from other natural compounds

Screening and Isolation of Potential Anti-Inflammatory Compounds from Saxifraga atrata via Affinity Ultrafiltration-HPLC and Multi-Target Molecular Docking Analyses

In this study, a 100 g sample of Saxifraga atrata was processed to separate 1.3 g of 11-O-(4&prime;-O-methylgalloyl)-bergenin (Fr1) after 1 cycle of MCI GEL&reg; CHP20P medium pressure liquid chromatography using methanol/water. Subsequently, COX-2 affinity ultrafiltration coupled with reversed-phase liquid chromatography was successfully used to screen for potential COX-2 ligands in this target fraction (Fr1). After 20 reversed-phase liquid chromatography runs, 74.1 mg of &gt;99% pure 11-O-(4&prime;-O-methylgalloyl)-bergenin (Fr11) was obtained. In addition, the anti-inflammatory activity of 11-O-(4&prime;-O-methylgalloyl)-bergenin was further validated through molecular docking analyses which suggested it was capable of binding strongly to ALOX15, iNOS, ERBB2, SELE, and NF-&kappa;B. As such, the AA metabolism, MAPK, and NF-&kappa;B signaling pathways were hypothesized to be the main pathways through which 11-O-(4&prime;-O-methylgalloyl)-bergenin regulates inflammatory responses, potentially functioning by reducing pro-inflammatory cytokine production, blocking pro-inflammatory factor binding to cognate receptors and inhibiting the expression of key proteins. In summary, affinity ultrafiltration-HPLC coupling technology can rapidly screen for multi-target bioactive components and when combined with molecular docking analyses, this approach can further elucidate the pharmacological mechanisms of action for these compounds, providing valuable information to guide the further development of new multi-target drugs derived from natural products