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Background: The key pathophysiological changes in androgenetic alopecia (AGA) are limited to hair follicles (HFs) in frontal and vertex regions, sparing the occipital region. Objectives: To identify biological differences among HF subpopulations. Methods: Paired vertex and occipital HFs from 10 male donors with AGA were collected for RNA sequencing assay. Furthermore, HF and cell experiments were conducted on the identified key genes to reveal their roles in AGA. Results: Transcriptome profiles revealed that 506 mRNAs, 55 microRNAs and 127 long noncoding RNAs were differentially expressed in the AGA vertex HFs. Pathway analysis of mRNAs and microRNAs revealed involvement of the hypoxia‐inducible factor (HIF)‐1, Wnt/β‐catenin, and focal adhesion pathways. Differential expression of HIF‐1 prolyl hydroxylase enzymes (EGLN1, EGLN3) and Wnt/β‐catenin pathway inhibitors (SERPINF1, SFRP2) was experimentally validated. In vitro studies revealed that reduction of EGLN1, EGLN3, SERPINF1 and SFRP2 stimulated proliferation of dermal papilla cells. Ex vivo HF studies showed that downregulation of EGLN1, EGLN3 and SERPINF1 promoted HF growth, postponed HF catagen transition, and prolonged the anagen stage, suggesting that these genes may be potentially utilized as therapeutic targets for AGA. Conclusions: We characterized key transcriptome changes in male AGA HFs, and found that HIF‐1 pathway‐related genes (EGLN1, EGLN3) and Wnt pathway inhibitors (SERPINF1, SFRP2) may play important roles in AGA. What is already known about this topic?Multiple differentially expressed genes and signalling pathways have been found between hair follicles (HFs) in the balding area (frontal and vertex regions) and nonbalding area (occipital region) of individuals with androgenetic alopecia (AGA).A whole‐transcriptome atlas of the vertex and occipital region is lacking. What does this study add?We identified a number of differentially expressed genes and pathways between balding vertex and nonbalding occipital AGA HFs by using whole‐transcriptome analyses.We identified pathways not previously reported in AGA, such as the hypoxia‐inducible factor (HIF)‐1 signalling pathway.We verified that HIF‐1 pathway‐related genes (EGLN1, EGLN3) and Wnt pathway inhibitors (PEDF, SFRP2) played important roles in dermal papilla cell activity, hair growth and the hair cycle. What is the translational message?The EGLN1, EGLN3, SERPINF1 and SFRP2 genes may be potentially utilized as therapeutic targets for AGA. [ABSTRACT FROM AUTHOR]

Autonomous vehicles (AVs) are a vital direction for intelligent transportation; nevertheless, the current research is insufficient, and the aspects and mechanisms that influence individuals' adoption of AVs require additional investigation. This study examines the acceptance of the popularity of AVs from three perspectives: personal-psychological attributes, travel characteristics attributes, and latent variables. The descriptive statistical analysis revealed that the acceptance rate of AVs was 54.6% based on 304 valid questionnaires received through online questionnaires. And the proportion of the 18∼50 group in the article reached 92.8%; thus, this study takes the young group as the object to investigate the acceptance of AVs. A quantitative analysis of each factor's impact on the acceptability of AVs was conducted using the hybrid choice model (HCM), which was utilized to observe the link between latent variables. Results from parameter estimates demonstrate that the HCM's fitting impact when latent factors are taken into account is superior to that when latent variables are not taken into account. When latent variables are taken into account, the associated goodness ratio coefficient rises by 0.2337 to 0.2898, which is greater than the model as a whole. The three factors with the highest impact on AV acceptability among the five latent variables were attitude toward use, sense of use gain, and perceived trust, with matching z-test values of 2.42, 2.44, and 2.12, respectively. The development and marketing of AVs by pertinent businesses and government agencies would benefit greatly from this research as a source of reference. [ABSTRACT FROM AUTHOR]

A novel Gram-stain-negative, aerobic, yellowish-pigmented, non-motile, rod-shaped bacterial strain, designated strain BO-59T, was isolated from the activated sludge of a wastewater treatment plant in Hanam City, South Korea. Phylogenetic study based on the 16S rRNA gene sequence positioned BO-59T in a distinct lineage in the family Chitinophagaceae, sharing less than 92.8% sequence similarity with members of the closely related genera Ferruginibacter, Flavitalea, Pseudoflavitalea, Flavisolibacter, Niastella, and Terrimonas. Phylogenomic- and genomic relatedness analyses revealed that strain BO-59T is clearly distinguished from other genera in the family Chitinophagaceae by average nucleotide identity < 66.9%) and the genome-to-genome distance (< 29.5%) values. The strain BO-59T contained MK-7 as the predominant quinone, and iso-C15:0, iso-C17:0 3OH, and iso-C15:1 G as major fatty acids (> 10%). The DNA G + C content was 39.1 mol% based on genome sequence analysis. The polar lipids of strain BO-59T were phosphatidylethanolamine, an unidentified aminophospholipid and three unidentified polar lipids. 16S rRNA gene sequence similarity, physiological, and biochemical characteristics indicated that strain BO-59T represents a novel species of a new genus, for which the name Hanamia caeni gen. nov., sp. nov. is proposed. The type strain is BO-59T (= KACC 19646T = LMG 30865 T). [ABSTRACT FROM AUTHOR]

By virtue of the drug repurposing strategy, the anti-osteoporosis drug raloxifene was identified as a novel PPARγ ligand through structure-based virtual high throughput screening (SB-VHTS) of FDA-approved drugs and TR-FRET competitive binding assay. Subsequent structural refinement of raloxifene led to the synthesis of a benzothiophene derivative, YGL-12. This compound exhibited potent PPARγ modulation with partial agonism, uniquely promoting adiponectin expression and inhibiting PPARγ Ser273 phosphorylation by CDK5 without inducing the expression of adipongenesis associated genes, including PPARγ, aP2, CD36, FASN and C/EBPα. This specific activity profile resulted in effective hypoglycemic properties, avoiding major TZD-related adverse effects like weight gain and hepatomegaly, which were demonstrated in db/db mice. Molecular docking studies showed that YGL-12 established additional hydrogen bonds with Ile281 and enhanced hydrogen-bond interaction with Ser289 as well as PPARγ Ser273 phosphorylation-related residues Ser342 and Glu343. These findings suggested YGL-12 as a promising T2DM therapeutic candidate, thereby providing a molecular framework for the development of novel PPARγ modulators with an enhanced therapeutic index. In this study, SB-VHTS, structural optimization and comprehensive pharmacological evaluation lead to the identification of an anti-osteoporosis drug raloxifene-based candidate YGL-12 as the selective PPARγ modulator with a high therapeutic index for anti-diabetic drug discovery. [Display omitted] • Raloxifene is identified as the selective PPARγ modulator by SB-VHTS. • Structure-based optimization leads to the discovery of YGL-12 as the new and potent PPARγ modulating ligand. • YGL-12 demonstrates effective anti-diabetic effects with minimized TZD-associated side effects. • YGL-12 selectively up-regulates the expression of adiponectin and effectively blocks PPARγ Ser273 phosphorylation. • YGL-12 shows a unique binding mode that different from that of PPARγ full agonists such as Rosi. [ABSTRACT FROM AUTHOR]

Background: Platelet‐rich plasma (PRP) is effective in the treatment of androgenetic alopecia (AGA). Aims: The purpose of this study is to assess the effect of PRP on the proliferation of human follicle dermal papilla cells (HFDPCs), to observe the effect of PRP on the growth of hair follicles and hair shaft in vitro, to measure growth factors, and to evaluate the efficacy and safety of PRP injection. Patients/Methods: The effect of PRP on the proliferation of HFDPCs was observed. The length of hair follicle and hair shaft in vitro was measured. Then, the concentration of growth factors (EGF, FGF‐2, FGF‐7, IGF‐1, HGF, PDGF‐BB, and VEGF‐A) was evaluated. Half‐head injection of PRP was conducted to 10 males. Three treatments were conducted at 30‐day intervals. Digital photographs were taken; hair diameter, hair density, unit density of hair follicles, and terminal hair/ vellus hair were analyzed. Results: Platelet‐rich plasma significantly promoted the proliferation of HFDPCs. Under the PRP culture, the hair follicle and hair shaft were grown, and the hair growth length on the 3rd and 6th days was greater than that of the control. PRP contained growth factors such as EGF, FGF‐2, FGF‐7, IGF‐1, HGF, PDGF‐B, and VEGF‐A. Hair diameter, hair density, and unit hair follicle density on the PRP injection side peaked in the 6th month. The terminal hair/ vellus hair of the PRP injection side reached a peak in the 4th month. The average patient satisfaction during the entire treatment was 5.4 points (0‐10 points). Conclusion: Platelet‐rich plasma can promote hair growth. PRP injection is safe and effective for the treatment of AGA. [ABSTRACT FROM AUTHOR]

Interstitial lung disease (ILD) has been identified as a prevalent complication and significant contributor to mortality in individuals with pemphigus. In this study, a murine model of pemphigus was developed through the subcutaneous administration of serum IgG obtained from pemphigus patients, allowing for an investigation into the association between pemphigus and ILD. Pulmonary interstitial lesions were identified in the lungs of a pemphigus mouse model through histopathology, RT‐qPCR and Sircol assay analyses. The severity of these lesions was found to be positively associated with the concentration of IgG in the injected serum. Additionally, DIF staining revealed the deposition of serum IgG in the lung tissue of pemphigus mice, indicating that the subcutaneous administration of human IgG directly impacted the lung tissue of the mice, resulting in damage. This study confirms the presence of pulmonary interstitial lesions in the pemphigus mouse model and establishes a link between pemphigus and ILD. [ABSTRACT FROM AUTHOR]

Clumped-isotope analysis provides new constraints on the formation and evolution of methane. High-resolution isotope-ratio mass spectrometry (HR-IRMS) is a sensitive, precise, and stable analytical technique increasingly used in methane clumped-isotope analysis. However, the lack of standard reference frames hinders the comparison of data from different laboratories and the evaluation of accuracy. In this study, an absolute reference frame was introduced for HR-IRMS analysis of the multiply substituted methane isotopologues 13CH 3 D and 12CH 2 D 2. We evaluated the optimized performance of a Panorama (Nu Instruments, UK) HR-IRMS system by repeated analysis of an intra-laboratory standard gas, finding that these rare isotopologues can be analyzed separately with high precision, repeatability, and reproducibility. Internal precision (a key parameter in instrument performance) reached 0.15‰ − 0.25‰ for Δ13CH 3 D and 0.70‰ − 0.85‰ for Δ12CH 2 D 2 values, ensuring the reliability of data. Comparison of results before and after purification demonstrated that purification procedures caused negligible isotopic fractionation of clumped isotopes. Isotopic-exchange experiments revealed source effects in the MS ion source, depending on the difference in bulk H isotopic composition between sample and reference gas, but independent of bulk C isotopic composition. To improve analytical accuracy for methane isotopologues, an absolute reference frame was developed through experiments involving a suite of mixed gases of different H isotopic composition equilibrated at 100 °C and a standard gas equilibrated at 2 °C–500 °C. Based on the reference frame, raw data were processed with a non-linearity correction and converted to real values with empirical transformation functions. The reference frame was applied to analyses of two methane standard gases and three natural gases from Tarim Basin, China. Measured Δ13CH 3 D and Δ12CH 2 D 2 values for two standard gases were consistent with published values. Clumped-isotope signatures of natural gases preserve information related to the formation temperature of methane. • Clumped-isotope analysis provides new constraints on the formation and evolution of methane. • Isotopic-exchange experiments demonstrated the presence of source scrambling in Panorama. • An absolute reference frame was established to calibrate source scrambling to achieve the accurate clumped-isotope value. • We measured CH 4 clumped-isotope of natural gases and proved that the absolute reference frame is accurate and feasible. [ABSTRACT FROM AUTHOR]

The Tarim Basin is one of the most complex, ancient, and petroliferous deep craton basins in the world. Multiple sets of source rocks, stages of tectonism, and episodes of hydrocarbon generation and accumulation complicate the formation and evolutionary processes of hydrocarbons in the basin, especially for the deeply buried petroleum system at >6000 m depth. Paired clumped isotopes (Δ13CH 3 D and Δ12CH 2 D 2) allow the investigation of methane isotopic bond ordering, elucidating the methane generation mechanism and its post-generation processes, which can complement studies of the molecular and conventional stable isotopic compositions of gas hydrocarbons in constraining the origin and source of natural gas. This study focused on methane clumped isotopes, and chemical and conventional stable isotopic compositions of natural gas samples from four typical oil and gas regions of the Tarim Basin. Results indicate that these gases are thermogenic gases with relatively high stable isotopic δ values (i.e., −46.1‰ < δ13C–CH 4 < −25.9‰, −184‰ < δD-CH 4 < −140‰). Most exhibit equilibrium methane clumped isotope signatures at temperatures of 128–257 °C, consistent with the main oil-window to gas-window region. The clumped isotope apparent temperature of equilibrated methane was used to determine its formation temperature, which was applied for gas–source correlations and thermal maturity assessments of the natural gases based on the results of previous basin modeling. The clumped isotope compositions of two gas samples from the Keshen area of the basin are characterized by significant deficits in Δ12CH 2 D 2 values but with similar Δ13CH 3 D values to those of other equilibrated gases there, indicating the possibility of methane bond re-ordering at high temperatures (>300 °C) exceeding the methane "closure temperature". Non-equilibrium gases in the Tabei area yielded a plausible Δ13CH 3 D apparent temperature (<160 °C) with a pronounced deficit in Δ12CH 2 D 2 values, possibly owing to irreversible chemical kinetic processes in thermal cracking of organic matter at early thermal maturity (R o < 1.5‰) or mixing between thermogenic gases generated at two distinct temperatures (i.e., ∼200 °C and ∼120 °C). Equilibrium clumped isotope signatures also rule out the possible effects of secondary alteration on natural gases in the Hetianhe area that were previously considered in conventional isotope studies. Such findings demonstrate that methane clumped isotopes provide independent and effective indicators of gas–source correlations in deep basins while also elucidating secondary processes that are often under- or over-estimated in conventional stable isotope studies. • Natural gases in Tarim Basin are thermogenic gases with most at internal equilibrium. • Gases are generated at temperatures of 128–257 °C matching main oil to gas windows. • Clumped isotopes provide independent and robust proxies for source identification. • Clumped isotopes elucidate alterations un- or mis-recognized by conventional methods. [ABSTRACT FROM AUTHOR]

Systemic sclerosis (SSc) is an autoimmune disease mainly characterized by persistent inflammation and fibrosis. The receptor tyrosine kinase (RTK) signal pathway plays an important role in the process of SSc, and Grb2‐associated binding protein (GAB) is crucial in activating RTK signalling. A previous study found elevated levels of GAB1 in bleomycin (BLM)‐induced fibrotic lungs, but the effects of GAB1 in SSc remain unclear. Our aim was to investigate whether GAB1 was dysregulated and its potential role in SSc. Compared with healthy donors, we found GAB1 expression was 1.6‐fold higher in peripheral blood mononuclear cells (PBMC), 2.5‐fold higher in CD4 + T cells, and 2‐fold higher in skin from of SSc patients (P <.01). At the same time, the levels of type one collagen (COLI) were also significantly increased (1.8‐fold higher) in SSc skin. Additionally, BLM‐induced SSc mice showed mRNA levels of Gab1 2‐fold higher than saline‐treated controls, and Gab1 expression correlated positively with collagen content. A further in vitro study showed silencing of GAB1 suppressed inflammatory gene expression in TNF‐α induced fibroblasts. Additionally, GAB1 deficiency prominently inhibited cell proliferation and reduced COLI protein levels in TGF‐β induced fibroblasts. Taken together, these data suggest that GAB1 has a relatively high expression rate in SSc, and knockdown of GAB1 may attenuate SSc by stimulating inflammatory and fibrotic processes. [ABSTRACT FROM AUTHOR]

Abstract Systemic sclerosis (SSc) is a connective tissue disease characterized mainly by fibrosis of skin and internal organs. Our previous study has shown that salvianolic acid B (SAB), a bioactive component extracted from Salvia miltiorrhiza (SM), was one of the essential ingredients in the traditional Chinese medicine Yiqihuoxue formula, which has been used to treat SSc-related dermal and pulmonary fibrosis. The aim of the present study was to evaluate the effect of SAB on skin fibrosis and explore its underlying anti-fibrotic mechanism. We found that SAB was capable of alleviating skin fibrosis in a bleomycin-induced SSc mouse model, alleviating skin thickness and reducing collagen deposition. in vitro studies indicated that SAB reduced SSc skin fibroblast proliferation and downregulated extracellular matrix gene transcription and collagen protein expression. TGF-β/SMAD and MAPK/ERK pathway activation were also shown to be suppressed in SAB treated fibroblasts. Moreover, RNA-seq revealed that the anti-fibrotic effect of SAB might be related to antioxidant activity, the cell cycle, and the p53 signaling pathway. Taken together, our results suggest that SAB has the ability to alleviate SSc-related skin fibrosis both in vivo and in vitro. [ABSTRACT FROM AUTHOR]

Abstract Endothelial cell injury and subsequent inflammation play pivotal roles in the pathogenesis of pulmonary fibrosis, a progressive and fatal disorder. We found previously that salvianolic acid B (SAB) attenuated experimental pulmonary fibrosis. Pulmonary fibrosis is driven by inflammation, but the anti-inflammatory role and mechanism of SAB on the treatment of pulmonary fibrosis is still unknown. Here, our in vivo studies showed that SAB had a strong anti-inflammatory effect on bleomycin-instilled mice by inhibiting inflammatory cell infiltration and inflammatory cytokine production. Moreover, SAB protected endothelial cells against oxidative stress injury and inhibited endothelial cell apoptosis in bleomycin-treated mice. The in vitro studies also showed that SAB decreased the H 2 O 2 -induced overproduction of reactive oxygen species to protect EA.hy926 endothelial cells from oxidative damage, and further inhibited H 2 O 2 -induced permeability and overexpression of pro-inflammatory molecules. The next studies revealed that SAB inhibited the H 2 O 2 -induced cell apoptosis and attenuated the decrease of tight junction-related gene expression, resulting in a decrease of the endothelial permeability in injured endothelial cells. Furthermore, Western blot analysis suggested that SAB decreased endothelial cell permeability and expression of pro-inflammatory cytokines by inhibiting MAPK and NF-κB signaling pathways. Taken together, these data indicate that SAB exerted anti-inflammatory roles in pulmonary fibrosis by protection of the endothelial cells against oxidative stress injury, mediated by inhibition of endothelial permeability and expression of pro-inflammatory cytokine via the MAPK and NF-κB signaling pathways. Graphical abstract fx1 [ABSTRACT FROM AUTHOR]

This study explored the effects and mechanisms of petroleum-contaminated soil bioremediation using aged refuse (AR) from landfills. Three treatments of petroleum-contaminated soil (47.28 mg·g −1 ) amended with AR, sterilized aged refuse (SAR) and petroleum-contaminated soil only (as a control) were tested. During 98 days of incubation, changes in soil physicochemical properties, residual total petroleum hydrocarbon (TPH), biodegradation kinetics, enzyme activities and the microbial community were investigated. The results demonstrated that AR was an effective soil conditioner and biostimulation agent that could comprehensively improve the quality of petroleum-contaminated soil and promote microbial growth, with an 74.64% TPH removal rate, 22.36 day half-life for SAR treatment, compared with the control (half-life: 138.63 days; TPH removal rate: 22.40%). In addition, the petroleum-degrading bacteria isolation results demonstrated that AR was also a petroleum-degrading microbial agent containing abundant microorganisms. AR addition significantly improved both the biotic and abiotic conditions of petroleum-contaminated soil without other additives. The cooperation of conditioner addition, biostimulation and bioaugmentation in AR treatment led to better bioremediation effects (half-life: 13.86 days; TPH removal rate: 89.83%). In conclusion, AR amendment is a cost-effective, easy-to-use method facilitating in situ large-scale application while simultaneously recycling huge amounts of AR from landfills. [ABSTRACT FROM AUTHOR]

Eucheuma polysaccharides have varieties of biological activities. However, it is accompanied by problems like large molecular weight, high viscosity, and low utilization. Here, we first prepared fermented Eucheuma spinosum polysaccharides (F-ESP) by Lactobacillus fermentation, compared with low-temperature freeze-thaw ESP (L-ESP) prepared by the freeze-thaw method, explored the composition and structural characteristics of F-ESP and L-ESP, and evaluation of the ability of different samples to inhibit mast cell degranulation using classical mast cell model. Then, the activity of L-ESP and F-ESP in vivo was preliminarily evaluated using a passive cutaneous anaphylaxis model. Two kinds of F-ESP named F1-ESP-3 and F2-ESP-3 were obtained by fermentation of Eucheuma spinosum with the selected strains of Lactobacillus.sakei subsp.sakei and Lactobacillus.rhamnosus. Compared with the purified component L-ESP-3, the monosaccharide composition of F1-ESP-3 contains more glucuronic acid, the molecular weight reduced from >600 kDa (L-ESP-3) to 28.30 kDa (F1-ESP-3) and 33.58 kDa (F2-ESP-3), F1-ESP-3 has higher solubility and lower apparent viscosity. Fermentation did not destroy the functional groups and structure of ESP. Moreover, F1-ESP-3 significantly inhibited RBL-2H3 cell degranulation by reducing depolymerization of F-actin and Ca2+ influx. F1-ESP-3 reduced the symptoms of mast cell-mediated passive cutaneous anaphylaxis, indicating that F1-ESP-3 may have better anti-allergic activity in vivo. [Display omitted] [ABSTRACT FROM AUTHOR]

Objective: This study was aimed to explore the protective effect of electroacupuncture (EA) pretreatment at Zusanli point (ST36) on ventilation-induced lung injury (VILI) and its potential anti-inflammatory mechanism. Methods: High tidal volume ventilation was used to induce the VILI in mice, and EA pretreatment at ST36 was given for 7 consecutive days. The wet/dry ratio and pathological injury score of lung tissue, and total protein content of pulmonary alveolar lavage fluid (BALF) were detected after 4 h of mechanical ventilation (MV). Meanwhile, the expressions of TLR4 and NF- κB in lung tissue were evaluated by Western Blot, and the inflammatory factors in lung tissue were detected by ELISA. Results: After four hours of mechanical ventilation, mice with ventilator-induced lung injury showed significant increases in lung wet/dry ratio, tissue damage scores, and protein content in bronchoalveolar lavage fluid. Pro-inflammatory cytokines (IL-6, IL-1β, TNF-α) and TLR4/NF-κB expression levels in the lung were also markedly elevated (P < 0.05). Conversely, ST36 acupuncture point pre-treatment significantly reduced these parameters (P < 0.05). Conclusion: EA pretreatment at ST36 could alleviate the inflammatory response for VILI via inhibiting TLR4/NF- κB pathway. [ABSTRACT FROM AUTHOR]

The aim of this study is to assess the influence of various Er:YAG laser energies on dentin surface micromorphology and dentine-resin shear bond strength (SBS). Eighty dentin specimens were prepared and divided randomly into ten groups: control group (CG), phosphoric acid-etched group (AG), four laser-conditioned groups treated with various pulse energies of 40, 60, 80, and 100 mJ (L40, L60, L80, L100), and four laser-conditioned acid-etched groups (LA40, LA60, LA80, LA100). Two specimens from each group underwent scanning electron microscopy examination, while the remaining six were subjected to the dentin-resin SBS test. Statistical analyses included Welch's analysis of variance (ANOVA), followed by post hoc Tamhane's T2 multiple comparisons test, Pearson's correlation, and Fisher's exact test. Pulse energies of 60, 80, and 100 mJ fully exposed the dentin tubule orifices, although 100 mJ lead to microcracks. Laser-conditioned surfaces exhibited smaller tubule diameters compared to acid-etched surfaces, and tubule diameters positively correlated with dentin-resin SBS. Laser-conditioned groups showed lower SBS values, while laser-conditioned acid-etched groups demonstrated higher SBS values. No significant relationship was observed between dentin surface roughness and SBS. The range of laser energies used for dentin conditioning had limited effects on SBS or failure modes. Laser conditioning with energies ranging from 40 to 100 mJ effectively removes the smear layer from the dentin surface. However, to enhance dentin-resin bond strength, further acid etching of the laser-conditioned surface is necessary. [ABSTRACT FROM AUTHOR]

The prevalence of food allergy has increased in Asian countries. Marine algae have been proposed as the potential resource for anti-allergic therapeutics. The present study was aimed at isolating R-phycocyanin (RPC) from Porphyra haitanensis and determining the anti-allergy potential of RPC in antigen-sensitized mice and mast cells. In animal experiments, RPC could effectively reduce tropomyosin (TM)-specific immunoglobulin E (IgE) and histamine levels, alleviate allergy symptoms and jejunum tissue inflammation in mice, and inhibit the expression and release of cytokines (interleukin-4 (IL-4) and IL-13) in peritoneal lavage fluid. In spleen lymphocyte experiments, high purity of RPC skewed the immunological function of CD4 + T cells towards Th1 activity. A higher expression of interferon (IFN)-γ was induced by a synergistic effect of TM and RPC. Through the Jun N-terminal kinase and Janus kinase 2 signaling pathways, IFN-γ synthesis was induced by RPC in combination with TM. Anti-allergic effect of RPC was evaluated in IgE-mediated rat mast RBL-2H3 cells. The results demonstrated that RPC inhibited allergy markers, including the release of β-hexosaminidase, histamine and ROS in antigen-sensitized RBL-2H3 cells. RPC also suppressed the production of pro-inflammatory factors (IL-4 and tumor necrosis factor-α). In conclusion, RPC decreased allergic sensitization against TM by blocking Th2 cell polarization as well as suppressed the release of allergic-mediators in antigen-stimulated mast cells. It may be used as a functional food component or active pharmaceutical ingredient for allergic patients. [ABSTRACT FROM AUTHOR]

The classic Wnt/β-catenin pathway plays a crucial role in the differentiation and proliferation of osteoblasts. Any factor in the pathway can affect the proliferation and differentiation of osteoblasts. In recent years, a large number of studies show that R-spondins (RSPOs) is an important regulating factor in Wnt/β-catenin signaling pathway. This paper reviews the progress in Rspo1 regulation of osteoblast differentiation through Wnt/β-catenin signaling pathway. [ABSTRACT FROM AUTHOR]

Seaweeds are important "blue food" and some seaweeds have been demonstrated that have the immunoregulation activities and benefit for human health. However, which immune cell subsets are targeted and how immune processes are regulated by those seaweeds remain poorly understood. Here we identified sulfated oligosaccharide of Gracilaria lemaneiformis (GLSO) inhibits IFNγ production by T cells in ovalbumin (OVA) immunized mice and in vitro activation system of OVA-specific CD4+ T cells. Furthermore, GLSO predominantly targets T cells but not dendritic cells, and regulates the late stage of expression of T cell activation and differentiation markers. Mechanistically, results of transcriptomic and proteome analysis indicate that GLSO inhibits mTOR activity, glycolysis, cell cycle and DNA replication. Thus, GLSO has an immunomodulatory function in Th1 immune responses by restraining T cell activation. Our study unravels the anti-inflammatory mechanism of GLSO and provides a new insight for industrial development of seaweeds as health food. [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract: We study the single-polaron properties of the one-dimensional Holstein and SSH model. The dynamical coherent potential approximation (under the Hartree approximation) is applied to compute the polaron dispersion, the quasi-particle residue, and the polaronʼs Greenʼs functions. We compare our calculated results in comparison with those by the self-consistent Born approximation plus higher-order diagrams. [Copyright &y& Elsevier]

Abstract: A ginsenosidase specifically hydrolyzing multi-20-O-glycosides of protopanaxadiol type ginsenosides such as ginsenoside Rb1, Rb3, Rb2 and Rc, named ginsenosidase type II, was isolated and purified from Aspergillus sp.g48p strain. The molecular weight of the enzyme was 60kDa. Ginsenosidase type II was demonstrated to hydrolyze multi-20-O-glycoside of protopanaxadiol type ginsenoside Rb1, Rb3, Rb2 and Rc; i.e. the ginsenosidase type II hydrolyzes 20-O-β-glucoside of the ginsenoside Rb1, 20-O-β-xyloside of ginsenoside Rb3, 20-O-α-arabinoside(p) of ginsenoside Rb2 and α-arabinoside(f) of ginsenoside Rc to produce mainly ginsenoside Rd, and small amount of Rg3. However, it did not hydrolyze 3-O-β-glucosides of ginsenoside Rb1, Rb3, Rb2 and Rc which was different with the ginsenosidase type I previously reported, either did not hydrolyze the glycosides of protopanaxatriol type ginsenoside such as ginsenoside Re, Rf and Rg1, showing significant difference from all previously described glycosidases. [Copyright &y& Elsevier]

Abstract: The microstructure and mechanical properties of T10 steel treated with power ultrasonic during solidification are investigated. A self-developed experimental setup is built for the propagation of ultrasonic vibration into the melt along the horizontal direction. Experimental results indicate that the power ultrasonic applied in the melt can not only refine the microstructure remarkably but also enhance both tensile strength and ductility values of T10 steel. Furthermore, the finer grains can be obtained due to the higher incident ultrasonic power. SEM fractographs show that the sample with 600 W ultrasonic treatment exhibits a ductile fracture surface covered with deformation dimples, while the sample without ultrasonic treatment shows a brittle fracture surface. The effects of power ultrasonic on the melt are discussed. [Copyright &y& Elsevier]

ABSTRACT Background Objective Methods Results Conclusion The robotic hair transplant technology, ARTAS, has a series of fine mechanical structure and an intelligent recognition system that allows it to independently select hair follicular units (FUs) and effectively harvest hair. After entering China in 2016, ARTAS has attracted the attention of hair transplant surgeons and hair loss patients given its advantages in a short learning curve and simple operation.To compare the efficacy and safety between the ARTAS system and follicular unit excision (FUE) in the treatment of male androgenetic alopecia (AGA) and to further promote the improvement and upgrading of ARTAS technology concerning hair transplantation.Thirteen Chinese male patients with Norwood–Hamilton II–IV AGA aged 25–35 years were enrolled in this study. The donor site of each patient was randomly divided into left and right regions, receiving ARTAS on one side and FUE on the other. Yield, transection, and discard rates of hair FUs from both sides were compared. Safety of the procedures in whole, as well as follow‐up results were investigated and evaluated.The total yield rate on the ARTAS side was lower than on the FUE side (82.05% vs. 90.03%, p > 0.05); the total discard rate on the ARTAS side was higher than on the FUE side (10.71% vs. 5.46%, p < 0.05); the total transection rate on the ARTAS side was lower than on the FUE side (13.17% vs. 13.96%, p > 0.05). No significant difference was found in patient satisfaction (efficacy), and no side effects or complications were detected during or after all surgeries.The current iteration of Robotic hair transplant technology is effective and safe, and can be recommended for AGA hair transplantation surgery. [ABSTRACT FROM AUTHOR]

Unsaturated triflimides, especially homoallylic triflimide species, are rarely assessable. Herein, we disclose a Ca(NTf2)2/HFIP‐mediated direct chemo‐, regio‐, and stereoselective rearrangement of diverse cyclopropyl carbinols to exclusive E‐homoallylic triflimides in moderate to excellent yields at room temperature, in which Ca(NTf2)2 was used as both the OH activator and the triflimide anion source. This protocol shows excellent substrate/functional group tolerance with an emphasis on those substrates bearing strong electron‐withdrawing functional groups. [ABSTRACT FROM AUTHOR]

• Nine new and five known meroterpenoids were isolated the deep-sea-derived Penicillium allii-sativi. • The structures were elucidated by comprehensive analysis of their NMR, MS, ECD, and X-ray crystallography. • Compound 10 significantly decreased degranulation with the IC 50 value of 14.8 μM. • Compound 10 decreased the generation of histamine and TNF-α by reducing the accumulation of Ca2+. Andrastones are unusual 6,6,6,5-tetracyclic meroterpenoids that are rarely found in nature. Previously, three andrastones were obtained from the rice static fermentation extract of the deep-sea-derived fungus Penicillium allii-sativi MCCC 3A00580. Inspired by one strain many compounds (OSMAC) approach, the oat static fermentation on P. allii-sativi was conducted. As a result, 14 andrastones were isolated by UV-guided isolation. The chemical structures of the nine new compounds (1 – 9) was established by comprehensive analysis of the NMR, MS, ECD, and X-ray crystallography and the five known ones (10 – 14) were assigned by comparing their NMR, MS, and OR data with those reported in literature. Compound 1 bears a novel hemiketal moiety while 2 is the first example to possess a novel tetrahydrofuran moiety via C-7 and C-15. All isolates were tested for anti-allergic bioactivity. Compound 10 , 3-deacetylcitreohybridonol, significantly decreased degranulation with the IC 50 value of 14.8 μM, compared to that of 92.5 μM for the positive control, loratadine. Mechanism study indicated 10 could decrease the generation of histamine and TNF-α by reducing the accumulation of Ca2+ in RBL-2H3 cells. These findings indicate andrastones could be potential to discover new anti-allergic candidate drugs. [ABSTRACT FROM AUTHOR]

Background Skin fibrosis is the typical pathological manifestation of systemic sclerosis (SSc) and localized scleroderma (LS); it has an unclear aetiology and few effective treatments. Although excessive collagen secretion by fibroblasts is the primary cause of skin fibrosis, evidence has suggested that vascular damage is the initiating event and that various cell types, including fibroblasts, work together to contribute to the pathogenesis of skin fibrosis. Objectives To explore the relationship between vascular endothelial cell lesions and immune cell infiltration, along with the interactions between various cell types within the fibrotic skin ecosystem. Methods Single-cell RNA sequencing was performed on skin biopsies from three healthy donors and seven patients with SSc. Additional data from three patients with localized scleroderma available in the Gene Expression Omnibus (GSE160536) were integrated by Harmony. CellChat (version 1.5.0) was used to analyse the cell communication network. A Transwell® assay and a bleomycin (BLM) mouse model were used to explore the role of atypical chemokine receptor 1 (ACKR1; 'Duffy antigen') in immune cell infiltration. Milo single-cell Western blot was used to show fibroblast subcluster activation. Results A total of 62 295 cells were obtained and subpopulations of stromal and immune cells identified. Interaction network analysis found that multiple chemokines secreted by macrophages, pericytes and proinflammatory fibroblasts could bind with ACKR1, which was highly expressed by endothelial cells in lesional skin. The Transwell® assay revealed that overexpression of ACKR1 in human umbilical vein endothelial cells facilitated leucocyte infiltration following treatment with interleukin-8. BLM mice showed enhanced ACKR1 expression, massive immune cell infiltration and skin fibrosis that was attenuated by ACKR1 inhibition. Furthermore, infiltrated macrophages expressing high levels of transforming growth factor (TGF)-β1 or platelet-derived growth factor B (PDGFB) could activate secreted frizzled-related protein 2 (SFRP2)/asporin (ASPN)+ fibroblasts to contribute to the excessive accumulation of extracellular matrix. It was also found that the SOX4–ASPN axis plays an important role in the TGF-β signalling cascade and the aetiology of skin fibrosis. Conclusions Our results reveal that high expression of ACKR1 by endothelial cells in fibrotic skin tissue promotes immune cell infiltration and that SFRP2/ASPN+ fibroblasts synergize to exacerbate skin fibrosis. [ABSTRACT FROM AUTHOR]

Objectives Innate immunity significantly contributes to SSc pathogenesis. TLR8 is an important innate immune mediator that is implicated in autoimmunity and fibrosis. However, the expression, mechanism of action, and pathogenic role of TLR8 in SSc remain unclear. The aim of this study was to explore the roles and underlying mechanisms of TLR8 in SSc. Methods The expression of TLR8 was analysed, based on a public dataset, and then verified in skin tissues and skin fibroblasts of SSc patients. The role of TLR8 in inflammation and fibrosis was investigated using a TLR8-overexpression vector, activator (VTX-2337), inhibitor (cu-cpt-8m), and TLR8 siRNA in skin fibroblasts. The pathogenic role of TLR8 in skin inflammation and fibrosis was further validated in a bleomycin (BLM)-induced mouse skin inflammation and fibrosis model. Results TLR8 levels were significantly elevated in SSc skin tissues and myofibroblasts, along with significant activation of the TLR8 pathway. In vitro studies showed that overexpression or activation of TLR8 by a recombinant plasmid or VTX-2337 upregulated IL-6, IL-1β, COL I, COL III and α-SMA in skin fibroblasts. Consistently, both TLR8-siRNA and cu-cpt-8m reversed the phenotypes observed in TLR8-activating fibroblasts. Mechanistically, TLR8 induces skin fibrosis and inflammation in a manner dependent on the MAPK, NF-κB and SMAD2/3 pathways. Subcutaneous injection of cu-cpt-8m significantly alleviated BLM-induced skin inflammation and fibrosis in vivo. Conclusion TLR8 might be a promising therapeutic target for improving the treatment strategy for skin inflammation and fibrosis in SSc. [ABSTRACT FROM AUTHOR]

Treatments for pulmonary fibrosis (PF) are ineffective because its molecular pathogenesis and therapeutic targets are unclear. Here, we show that the expression of low‐density lipoprotein receptor (LDLR) was significantly decreased in alveolar type II (ATII) and fibroblast cells, whereas it was increased in endothelial cells from systemic sclerosis‐related PF (SSc‐PF) patients and idiopathic PF (IPF) patients compared with healthy controls. However, the plasma levels of low‐density lipoprotein (LDL) increased in SSc‐PF and IPF patients. The disrupted LDL–LDLR metabolism was also observed in four mouse PF models. Upon bleomycin (BLM) treatment, Ldlr‐deficient (Ldlr−/−) mice exhibited remarkably higher LDL levels, abundant apoptosis, increased fibroblast‐like endothelial and ATII cells and significantly earlier and more severe fibrotic response compared to wild‐type mice. In vitro experiments revealed that apoptosis and TGF‐β1 production were induced by LDL, while fibroblast‐like cell accumulation and ET‐1 expression were induced by LDLR knockdown. Treatment of fibroblasts with LDL or culture medium derived from LDL‐pretreated endothelial or epithelial cells led to obvious fibrotic responses in vitro. Similar results were observed after LDLR knockdown operation. These results suggest that disturbed LDL–LDLR metabolism contributes in various ways to the malfunction of endothelial and epithelial cells, and fibroblasts during pulmonary fibrogenesis. In addition, pharmacological restoration of LDLR levels by using a combination of atorvastatin and alirocumab inhibited BLM‐induced LDL elevation, apoptosis, fibroblast‐like cell accumulation and mitigated PF in mice. Therefore, LDL–LDLR may serve as an important mediator in PF, and LDLR enhancing strategies may have beneficial effects on PF. [ABSTRACT FROM AUTHOR]

Zifanocycline (KBP-7072) is a novel aminomethylcycline antibiotic with a broad spectrum of antibacterial activity. This study determined the pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of zifanocycline in mice and the optimal PK/PD index for efficacy against Acinetobacter baumannii in a neutropenic murine thigh infection model. Zifanocycline PK properties were characterized in plasma after single-dose subcutaneous injection in healthy mice at doses of 1, 4, 16, 64, and 256 mg/kg. PK/PD analyses were performed with zifanocycline against 8 clinical A. baumannii isolates in a neutropenic murine thigh infection model. Plasma total and free drug C max , AUC 0-inf , and AUC 0-24 increased with dose, where C max of total drug was 0.12–25.2 mg/L, AUC 0-inf was 1.13–234 h*mg/L, AUC 0-24 was 1.09–225 h*mg/L, and free drug C max was 0.03–5.68 mg/L, AUC 0-inf was 0.25–52.6 h*mg/L, and AUC 0-24 was 0.25–50.5 h*mg/L. MICs of zifanocycline against A. baumannii ranged from 0.06 to 0.5 mg/L, with significant activity against all 8 strains. Average daily doses of zifanocycline to achieve a static, 1-log 10 kill, and 2-log 10 kill effect were projected to be 6.92, 9.63, and 13.22 mg/kg, and the mean f AUC/MIC ratios were 6.91, 9.10, and 12.60, respectively. AUC/MIC was the optimal PK/PD index of zifanocycline against A. baumannii. The in vivo efficacy results and PK/PD analyses support the design of optimal dosing regimens in clinical studies and assist with determining clinical breakpoints for zifanocycline. [ABSTRACT FROM AUTHOR]

Background: Fibrosing alopecia in a pattern distribution (FAPD) is a distinct entity of primary cicatricial alopecia (PCA), mimicking diffuse hair loss of androgenetic alopecia (AGA) with trichoscopic and histopathologic features of both AGA and lichen planopilaris (LPP). Methods: Clinical, demographic, and histopathological data of 20 FAPD patients were retrospectively collected. Results: All patients presented with female pattern hair loss with a median Sinclair grade of 3. Trichoscopic findings revealed hair diameter variability (20/20), perifollicular erythema (mild 7/20, moderate 11/20, severe 2/20), peripilar casts (none 2/20, mild 12/20, moderate 5/20, severe 1/20), and loss of follicular ostia (+12/20, ±7/20, −1/20). Histopathologic examination revealed perifollicular lymphocytic infiltration at the infundibulum or isthmus level and an increase of vellus‐like hairs. All cases showed interface dermatitis with concentric perifollicular lamellar fibrosis and follicular scars. Infundibular or isthmic infiltration of mast cells was found. Conclusions: The uniqueness of our study lies in perifollicular mast cells and discovering that the young population is at higher risk than previously thought. Clinicopathological features of FAPD were identified, filling the void of much‐needed details for FAPD diagnosis tailored to the Chinese population. [ABSTRACT FROM AUTHOR]

Systemic Sclerosis (SSc) is an autoimmune disease characterized by vascular and immune system dysfunction, along with tissue fibrosis. Our previous study found GRB2 was downregulated by salvianolic acid B, a small molecule drug that attenuated skin fibrosis of SSc. Here we aim to investigate the role of GRB2 in SSc. The microarray data of SSc skin biopsies in Caucasians were obtained from the Gene Expression Omnibus (GEO) database. The expression of GRB2 was further detected in Chinese SSc and healthy controls. Bleomycin (BLM)-induced skin fibrosis mice were used to explore how GRB2 downregulation affected fibrosis. The apoptosis of EA.hy926 endothelial cells was induced by H 2 O 2 and apoptosis ratio was measured by flow cytometric. Transcriptome and phosphoproteomic analyses were performed to explore the regulated pathway. The expression of GRB2 was significantly enhanced in SSc patient skin, 1.51-fold in Caucasians and 1.40-fold in Chinese. Double immunofluorescence staining showed the endothelial cells of SSc patient's skin highly expressed GRB2. The in vivo study revealed that GRB2 knockdown alleviated skin fibrosis and apoptosis of endothelial cells in BLM mouse skin. The in vitro study showed that GRB2 downregulation inhibited the apoptosis of EA.hy926 and protected them from H 2 O 2 -induced hyperpermeability. Moreover, transcriptome and phosphoproteomic analysis suggested the focal adhesion pathway was enriched in GRB2 siRNA transfected endothelial cells. Our results demonstrated GRB2 highly expressed in endothelial cells of SSc skin, and inhibiting GRB2 could effectively attenuate BLM-induced skin fibrosis and endothelial cell apoptosis. GRB2 is expected to be a new therapeutic target for SSc. • Enhanced GRB2 in SSc patient skin, 1.51-fold in Caucasians and 1.40-fold in Chinese. • The endothelial cells of SSc patient skin highly expressed GRB2. • Inhibiting GRB2 attenuated BLM-induced skin fibrosis and endothelial cell apoptosis. • Inhibiting GRB2 protected EA.hy926 from apoptosis and H 2 O 2 -induced hyperpermeability. • Focal adhesion pathway was regulated by GRB2 to influence endothelial cell apoptosis. [ABSTRACT FROM AUTHOR]

Dear Editor, Fibrosis is characterized by fibroblast dysfunction and excessive deposition of cell-matrix that affect the normal functioning of the original tissue or organ.[1] The pathogenesis of keloids is complex and remains elusive. Fibroblasts interacted with endothelial cells via I ACKR1 i , while multiple chemokines ( I CXCL2 i , I CCL3L3 i ) secreted by myeloid cells interacted with I DPP4 i in fibroblasts (Figure 4D). (F) Interaction of macrophages and fibroblasts based on molecular patterns indicated that macrophages interact with fibroblasts via SPP1. CTHRC1+ fibroblasts are stimulated by macrophage-secreted SPP1 to induce excessive collagen deposition in keloids. [Extracted from the article]

In consideration of several serious side effects induced by the classical AF-2 involved "lock" mechanism, recently disclosed PPARγ-Ser273 phosphorylation mode of action has become an alternative and mainstream mechanism for currently PPARγ-based drug discovery and development with an improved therapeutic index. In this study, by virtue of structure-based virtual high throughput screening (SB-VHTS), structurally chemical optimization by targeting the inhibition of the PPARγ-Ser273 phosphorylation as well as in vitro biological evaluation, which led to the final identification of a chrysin-based potential hit (YGT-31) as a novel selective PPARγ modulator with potent binding affinity and partial agonism. Further in vivo evaluation demonstrated that YGT-31 possessed potent glucose-lowering and relieved hepatic steatosis effects without involving the TZD-associated side effects. Mechanistically, YGT-31 presented such desired therapeutic index, mainly because it effectively inhibited the CDK5-mediated PPARγ-Ser273 phosphorylation, selectively elevated the level of insulin sensitivity-related Glut4 and adiponectin but decreased the expression of insulin-resistance-associated genes PTP1B and SOCS3 as well as inflammation-linked genes IL-6, IL-1β and TNFα. Finally, the molecular docking study was also conducted to uncover an interesting hydrogen-bonding network of YGT-31 with PPARγ-Ser273 phosphorylation-related key residues Ser342 and Glu343, which not only gave a clear verification for our targeting modification but also provided a proof of concept for the abovementioned molecular mechanism. Through structure-based virtual high throughput screening, chemical modification by targeting the inhibition of the PPARγ-Ser273 phosphorylation as well as in vitro and in vivo biological evaluation, chrysin-derived YGT-31 is developed herein as a new and potent selective PPARγ modulator for the treatment of T2DM and hepatic steatosis. [Display omitted] • YGT-31 derived from chrysin was identified as the new and potent SPPARγM. • Potent anti -T2DM and anti-hepatic steatosis effect of YGT-31 was demonstrated. • YGT-31 up-regulated the expression of Glut4 and adiponectin selectively. • The PPARγ-Ser273 phosphorylation level, PTP1B and SOCS were effectively inhibited. • YGT-31 demonstrated an interesting hydrogen-bonding network with PPARγ LBD. [ABSTRACT FROM AUTHOR]

Objectives: Localized scleroderma (LSc) is a disease characterized by the excessive deposition of collagen and thereby thickening of the dermis. In recent years, studies reported that LSc demonstrated compromised skin barrier related to the progression of the disease. However, human studies examining epidermis in scleroderma are still sparse and lack systematic research. This study aims to investigate the structural and functional changes in the LSc epidermis and further explore the underlying mechanisms, providing a new angle to treat LSc in the clinic. Methods: A total of 136 skin sites, including lesion and non-lesion control, from 27 LSc patients were analyzed. Ultrasonic testing, trans-epidermal water loss (TEWL), and epidermal hydration were assessed to investigate the structural and functional alternations; correlations between these parameters were analyzed. To explore the underlying mechanism, skin-fibrosis mouse model and cellular model by bleomycin (BLM) were deployed. Results: The epidermal thickness was markedly increased, with a significant decline of hydration (dryness) in the LSc lesion skin. Epidermal hydration presented a negative correlation with the thickness. TEWL was not altered. The mouse model validated these morphological changes in the epidermis and indicated that interleukin-6 (IL-6) was significantly elevated. Furthermore, cellular study demonstrated that increased phosphorylation of p38 in keratinocyte promoted the secretion of IL-6, stimulating cell proliferation. Conclusion: This study characterized the epidermal alterations in LSc patients, suggesting that keratinocyte-derived abnormal IL-6 secretion can lead to the thickening of the epidermis, promoting dryness. The topical application of moisturizer may largely relieve dryness and related pruritus, thus improve the quality of life in LSc patients. Key Points • Epidermal thickness was increased in LSc lesion skin with declined hydration level. • Skin fibrosis mouse model validated the epidermal alteration in LSc patient. • p38-dependent IL-6 overexpression in keratinocyte result in epidermal thickening. [ABSTRACT FROM AUTHOR]

Highlights: [•] The ginsenoside Rg3(S) was obtained as a 100g unit with a high specificity, yield, and purity. [•] An enzymatic bioconversion method was developed using two glycoside hydrolases in series. [•] The produced Rg3(S) had the 78% chromatographic purity and the recovery ratio reached 88.3%. [ABSTRACT FROM AUTHOR]

In course recording, the audio recorded in different pickups and environments can be clearly distinguished and cause style differences after splicing, which influences the quality of recorded courses. A common way to improve the above situation is to use voice style unification. In the present study, we propose a voice style unification model based on generated adversarial networks (VSUGAN) to transfer voice style from the spectrogram. The VSUGAN synthesizes the audio by combining the style information from the audio style template and the voice information from the processed audio. And it allows the audio style unification in different environments without retraining the network for new speakers. Meanwhile, the current VSUGAN is implemented and evaluated on THCHS-30 and VCTK-Corpus corpora. The source code of VSUGAN is available at https://github.com/oy-tj/VSUGAN. In one word, it is demonstrated that the VSUGAN can effectively improve the quality of the recorded audio and reduce the style differences in kinds of environments. [ABSTRACT FROM AUTHOR]

With the development of urbanization, urban traffic has exposed many problems. To study the subway’s influence on urban traffic, this paper collects data on traffic indicators in Nanchang from 2008 to 2018. The research is carried out from three aspects: traffic accessibility, green traffic, and traffic security. First, Grey Relational Analysis is used to select 18 traffic indicators correlated with the subway from 22 traffic indicators. Second, the data is discretized and learned based on Bayesian Networks to construct the structural network of the subway’s influence. Third, to verify the reliability of using GRA and the effectiveness of Bayesian Networks (GRA-BNs), Bayesian Networks with full indicators analysis and other four algorithms (Naive Bayes, Random Decision Forest, Logistic and regression) are employed for comparison. Moreover, the receiver operating characteristic (ROC) area, true positive (TP) rate, false positive (FP) rate, precision, recall, F-measure, and accuracy are utilized for comparing each situation. The result shows that GRA-BNs is the most effective model to study the impact of the subway’s operation on urban traffic. Then, the dependence relations between the subway and each index are analyzed by the conditional probability tables (CPTs). Finally, according to the analysis, some suggestions are put forward. [ABSTRACT FROM AUTHOR]

Taken together, the percentages of MS2 cells were decreased in AS patients and might be recovered by TNF- blockers treatment in the good responders but not the poor responders, suggesting that MS2 cell proportion could be a potential indicator to the response to TNF- blocker treatment and MS2 cells might be beneficial for AS treatment. Data of NS5 are shown in Supporting Information figures gl In conclusion, we profiled the transcriptional landscape of monocytes and NK cells, which are two pivotal cell types of innate immunity in AS at single-cell resolution. Monocytes and NK cells were isolated from peripheral blood mononuclear cells using magnetic beads with high specificity (Supporting Information). Notably, the proportion of NS2 cells (FCER1G SP - sp FCGR3A SP + sp NK cells, similar to memory-like NK cells) differed significantly between AS patients and healthy controls and might serve as a potential indicator for AS (Figure 3C). [Extracted from the article]

• DAB2 expression was enhanced in the skin of SSc patients and DAB2 knockdown ameliorated skin fibrosis induced by BLM. • DAB2 knockdown suppressed the number of inflammatory cells and inflammatory gene expression in BLM-induced mouse skin. • DAB2 knockdown suppressed the activation of skin fibroblasts. • Transcriptome analysis of DAB2 siRNA transfected SSc skin fibroblasts. Systemic sclerosis (SSc) is a connective tissue disease characterized by inflammation and fibrosis. Our previous research found Disabled-2 (DAB2) expression was significantly downregulated by salvianolic acid B, a small molecular medicine which attenuated experimental skin fibrosis of SSc. These suggest that DAB2 plays an important role in SSc skin fibrosis, but the role of DAB2 in SSc remains unclear. To investigate the role of DAB2 in SSc. DAB2 expression level was detected in the skin and peripheral blood mononuclear cells of SSc patients. Bleomycin (BLM)-induced SSc mice and primary SSc skin fibroblasts were used to investigate the effect of DAB2 downregulation on fibrosis. RNA-seq transcriptome analysis was performed to underlie the mechanism of DAB2 in fibroblasts. DAB2 expression was enhanced in SSc lesion skin and was positively correlated with fibrotic genes, such as α-SMA and PAI-1. The in vivo study revealed that DAB2 downregulation alleviated skin fibrosis, alleviating skin thickness and reducing collagen deposition, and DAB2 knockdown ameliorated the inflammatory cell infiltration. The in vitro study showed that DAB2 knockdown reduced extracellular matrix genes and proteins expression. Moreover, Transcriptome analysis revealed TGF-β and focal adhesion signaling pathways were the main downregulated pathways involved in DAB2 siRNA treated fibroblasts. Taken together, our results revealed that DAB2 was increased in SSc skin, and DAB2 downregulation inhibited BLM-induced mouse skin fibrosis and SSc skin fibroblasts activation. DAB2 played an important role in the pathogenesis of SSc and DAB2 modulation may represent a potential therapeutic method for SSc. [ABSTRACT FROM AUTHOR]

The article discusses a study on a rare but high-risk pathogenic variants within several ankylosing spondylitis (AS) families by whole-exome sequencing and whether the rare variants exist in a larger sample population. Topics include clinical characteristics and relationships of six patients in the study from different families, finding on the number of osteoclasts present in the sample treated with interferon (IFN)ß stimulation, and mutant that plays a pathogenic role in AS.

Context: Tanshinone IIA, commercially produced from Salvia miltiorrhiza Bunge (C.Y.Wu) (Labiatae), has various biological benefits. Currently, this compound is mainly extracted from plants. However, because of the long growth cycle and the unstable quality of plants, the market demands can barely be satisfied. Objective: The genomic shuffling technology is applied to screen the high-yield tanshinone IIA strain, which could be used to replace the plant S. miltiorrhiza for the production of tanshinone IIA. The change in the production of tanshinone IIA is clarified by comparing it with the original strain. Materials and methods: Tanshinone IIA was extracted from Strains cells, which was prepared through 0.5 mL protoplast samples by using hypertonic solution I from two different strains. Then, it was analyzed by high-performance liquid chromatography at 30 °C and UV 270 nm. Total DNA from the strains was extracted for RAPD amplification and electrophoresis to isolate the product. Results: In this study, a high-yield tanshinone IIA strain F-3.4 was screened and the yield of tanshinone IIA was increased by 387.56 ± 0.02 mg/g, 11.07 times higher than that of the original strain TR21. Discussion: This study shows that the genetic basis of high-yield strains is achieved through genome shuffling, which proves that genome shuffling can shorten the breeding cycle and improve the mutagenesis efficiency in obtaining the strains with good traits and it is a useful method for the molecular breeding of industrial strains. [ABSTRACT FROM AUTHOR]

Highlights • It's the first time to evidence that Exendin-4 is effective in promoting ADSCs proliferation via PI3K-Akt-Wnt pathway. • Exendin-4 activates the PI3K-Akt-GSK3β signaling pathway. • Exendin-4 activates the Wnt signaling pathway. Abstract Adipose-derived stem cell (ADSC) transplantation has emerged as a potential tool for the treatment of cardiovascular disease and skin wounds. However, with a limited renewal capacity and the need for mass cells during the engraftment, strategies are needed to enhance ADSC proliferative capacity. In this study, we explored the effects of Exendin-4, a glucagon-like peptide-1 analog, on the growth of ADSCs, focusing in particular on phosphatidylinositol 3-kinase (PI3K)-protein kinase B (Akt) and Wnt signaling pathways. Firstly, ADSCs were isolated and cultured in vitro. Then, flow cytometry demonstrated that ADSCs were positive for CD44, CD90 and CD29 but negative for CD31, CD34, and CD45. Exendin-4 (0–200 nM) treatment increased ADSC proliferation. In order to examine specific signaling pathways, a western blotting assay was performed. Our results demonstrate that after treated with 50 nM Exendin-4 for 48 h, the phosphorylation of PI3K, Akt, and GSK3β were increased and phosphorylation of β-catenin was decreased. From these results, we concluded that PI3K-Akt and Wnt-β-catenin signaling pathways mediate Exendin-4 induced ADSC proliferation, the function of which might contribute to the regulation of ADSC proliferation. Our findings provided new insights into the function of the mechanisms underlying Exendin-4 of ADSCs. [ABSTRACT FROM AUTHOR]

A Gram-positive, rod-shaped, non-spore-forming, and aerobic bacterium (Gsoil 556T) was isolated from soil of a ginseng field and subjected to its taxonomic position. Based on 16S rRNA gene sequence similarity, strain Gsoil 556T was shown to belong to the genus Actinomadura of the family Thermomonosporaceae and was closely related to A. montaniterrae CYP1-1BT (99.3%), A. nitritigenes DSM 44137T (98.7%), and A. rudentiformis HMC1T (98.5%), while it showed less than 98.4% sequence similarity to the other species of this genus. Phylogenetic analysis based on the 16S rRNA gene sequence indicated that it is most closely related to A. rudentiformis HMC1T and A. nitritigenes DSM 44137T. The DNA G+C content was 73.1 mol%. The peptidoglycan was meso-diaminopimelic acid and the whole-cell sugar contained fucose, galactose, glucose, mannose, and ribose. The predominant menaquinone (KK) was MK-9(H8) [55%] and MK-9(H6) [45%]. The major cellular fatty acids were C14:0, C16:0, C18:1ω9c and summed feature 3 (C16:1ω6c/C16:1ω7c). All these data supported the affiliation of strain Gsoil 556T to the genus Actinomadura. The DNA-DNA hybridization between strain Gsoil 556T and its phylogenetically closest relatives were less than 40%. Furthermore, the results of physiological and biochemical tests enabled strain Gsoil 556T to be differentiated genotypically and phenotypically from currently known Actinomadura species. Therefore, strain Gsoil 556T represents a novel species of the genus Actinomadura, for which the name Actinomadura hankyongense sp. nov. is proposed. The type strain Gsoil 556T (=KACC 19438T=LMG 30327T). [ABSTRACT FROM AUTHOR]

Three new cyclopiane diterpenes ( 1 – 3 ) and one rare spirocyclolide ( 5 ) were isolated from the deep-sea-derived fungus Penicillium commune MCCC 3A00940, along with 11 known compounds. The planar structures of the new compounds were determined by extensive analysis of their NMR and HRESIMS spectra, and the absolute configurations were established on the basis of specific rotation data in association with calculated ECD spectra. Four of the cyclopiane diterpenes ( 1 – 4 ), with a rigid 6/5/5/5 fused tetracyclic ring framework, are rarely found in Nature. Notably, conidiogenone J ( 1 ) is the first naturally occurring enantiomer of the cyclopiane diterpenes. Additionally, penijanthine B ( 6 ) and 3-hydroxy-5-methoxystilbene ( 14 ) exhibited moderate antiallergic effects with IC 50 values of 30 and 33 μM, respectively. [ABSTRACT FROM AUTHOR]

GNB2L1 and its O-GlcNAcylation has been reported to play roles in gastric cancer metastasis. However, the roles of GNB2L1 in chemoresistance of gastric cancer has never been determined. In the present study, we found that GNB2L1 was downregulated in chemoresistant patients of gastric cancer, and observed the decrease of GNB2L1 in protein levels instead of mRNA levels in different chemoresistant gastric cancer cell lines. Further we proved that this downregulation of GNB2L1 was resulted from its elevated O-GlcNAcylation catalyzed by OGT in both cell lines and patients. Next, we investigate the function of GNB2L1 and its O-GlcNAcylation on gastric cancer metastasis during chemoresistance, and confirmed Ser124 as the major O-GlcNAcylation site on GNB2L1 that regulated its function on metastasis. Furthermore, our data demonstrated that GNB2L1 modulated EMT via regulating the translation of EMT-related proteins in the process of chemoresistance. In summary, this study indicated that GNB2L1 and its O-GlcNAcylation regulated metastasis via modulating the translation of EMT-related proteins in the chemoresistance of gastric cancer. [ABSTRACT FROM AUTHOR]

Background Systemic sclerosis (SSc) is a chronic autoimmune disease characterized by inflammation and fibrosis. Our previous research has indicated that Sirtuin1 (Sirt1) plays a role in the regulation of TNF-α-induced inflammation; however, whether Sirt1 may inhibit the progress of SSc by blocking inflammation remains unknown. Objective We aimed to investigate the function of Sirt1 in SSc. Methods The function and its mechanism of Sirt1 were evaluated in fibroblasts or scleroderma mice. The expression of Sirt1 and cytokines was analyzed using real-time PCR, western blot, ELISA and immunohistochemistry. Results We determined that fibroblasts of SSc patients were activated to exhibit inflammation. Sirt1, activated by resveratrol (Res), ameliorated cutaneous inflammation and fibrosis in bleomycin (BLM)-induced scleroderma mice. An improvement in mammalian target of rapamycin (mTOR) was identified in the fibroblasts of SSc patients and the skin lesions of BLM mice. Rapamycin, an mTOR specific inhibitor, substantially inhibited the induced inflammation and fibrosis. The enhancement of mTOR expression in the skin lesions of the BLM-treated mice was significantly inhibited by Sirt1 activation. However, in both the BLM-treated cells and mice, Res exerted an inhibitory function on the expression of inflammatory factors, and collagen was diminished following mTOR knockdown. These findings suggest that Res may inhibit inflammation and fibrosis via mTOR. Conclusion The modulation of Sirt1 activity may represent a potential therapeutic method for SSc. The mechanism may involve the inhibition of mTOR phosphorylation, whereas mTOR activity was shown to be a pathogenic culprit of SSc. [ABSTRACT FROM AUTHOR]

[Display omitted] • Dic was revealed to be a potent SPPARγM by SB-VHTS and assays in vitro. • Dic exhibited weaker promotion of adipose differentiation than TZD drugs. • Dic showed anti-diabetic effects without body and organ weight gains in db/db mice. • Dic regulated the insulin-relative genes by inhibiting pPPARγ Ser273. • Dic performed a unique binding mode with PPARγ LBD. PPARγ full agonists, thiazolidinediones (TZDs), have been known as a class of most effective drugs for the treatment of type 2 diabetes mellitus (T2DM). However, recently their therapeutic benefits have been compromised by several undesirable side effects. In this study, a host-based repurposing strategy and in combination with comprehensive biological evaluations were synergistically employed to seek for potent PPARγ ligands, which led to the identification of an anti-thrombotic drug, dicoumarol (Dic), as the novel and safer selectively PPARγ modulator (SPPARγM) with advantages over current TZD drugs. The results in vitro showed that Dic had a potent binding affinity and weakly agonistic activity for PPARγ and its downstream key genes. Moreover, in diabetic model, it significantly reduced blood glucose without leading to the weight gain of both body and main organ tissues. Further mechanistic investigations revealed that Dic possessed such desired pharmacological properties mainly through effectively inhibiting the phosphorylation of PPARγ-Ser273 and selectively regulating the expressions of insulin-sensitive and resistance genes. Finally, the docking studies on the analysis of the potent binding mode of Dic with PPARγ revealed a remarkable difference on interaction region compared with other developed PPARγ agonists, which not only gave a proof of concept for the abovementioned mechanism but also provided the molecular basis for the discrimination of Dic from other PPARγ ligands, especially TZD drugs. Taken together, our findings suggested that Dic could serve as a new and promising candidate with good therapeutic index for treating T2DM, especially for those T2DM patients with thrombosis. [ABSTRACT FROM AUTHOR]